Psico-oncologia e Nuova Medicina

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Cancro, la psico-oncologia e la Nuova Medicina Germanica® di Geerd Ryke Hamer.

Psiche e cancerogenesi: le attuali conoscenze mediche

Da molti secoli serpeggia in medicina il sospetto che fattori psicologici, sociali e comportamentali giocherebbero un ruolo nella psico-genesi del cancro e nella sopravvivenza di una tale patologia [1][2].

Che traumi psichici possano avere una qualche rilevanza nella genesi del cancro è un sospetto, quando non certezza, radicato in parte della popolazione anche se, al giorno d'oggi, si sa che tali rapporti sono molto deboli[3][4][5][6][7][8] (ma sembra esistano almeno per alcune patologie neoplastiche).

Il 40% degli australiani sono convinti che lo stress sia la causa del cancro al seno[9] ed in Canada è della stessa opinione il 38% delle donne[10]. Queste supposizioni vengono dibattute in TV, su riviste o su libri non scientifici.

Bisogna distinguere tra l'eventuale influenza diretta tra cervello da un lato e organo bersaglio dall'altro: lo stress, la vita emotiva, possono influenzare lo stato di attivazione del sistema immunitario con possibili conseguenze sulla genesi e la crescita tumorale.

D'altro canto esistono anche le influenze indirette: la nostra psiche determina le nostre abitudini quotidiane, il consumo di tabacco (cancerogeno), il consumo d'alcool (un fattore di rischio per alcuni tipi di cancro), la dieta (anch'essa gioca un ruolo nella cancerogenesi), il numero di visite mediche di controllo e di prevenzione, l'attività fisica, la vita sociale...[11].

La psiche influenza perciò anche la nostra esposizione verso fattori che espongono o proteggono dal rischio di ammalarci di cancro. C'è chi in uno stato d'ira, di depressione o di disperazione, fuma o beve di più e influenza cosi la propria esposizione al cancro. È difficile distinguere tra le conseguenze psichiche della malattia ed il profilo psicologico individuale di esposizione alla malattia.

Oggi la ricerca si orienta anche ai legami tra psiche e sistema immunitario (e secrezione ormonale), con una probabile importanza per la cancerogenesi e la crescita tumorale da parte del sistema immunitario. Le difese immunitarie giocano un ruolo determinante nella cancerogenesi (ad esempio: AIDS/sarcoma di Kaposi o virus HPV) e si sa che uno sforzo psico-sociale influenza allo stesso modo del sistema immunitario, un tipico esempio è l'herpes alle labra da HSV-1, che molti conoscono nella fase di preparzione ad un esame difficile o in occasioni simili. La psiconeuroimmunologia di oggi non è però in grado di spiegare in modo incontestabile lo sviluppo del cancro a partire da processi psichici. Non esiste una teoria comunemente accettata sulla psicosomatica della cancerogenesi. E non esistono prove scientifiche sulla realazione diretta causa-effetto tra sistema immunitario e sviluppo del cancro [12].

Le teorie attuali sul cancro si basano su un concetto multifattoriale, nel quale i fattori psico-sociali sono di importanza secondaria.

Cenni storici

Uno dei primi a formulare l'ipotesi di una psicogenesi del cancro fu il medico greco Ippocrate di Kos (nato 460 a.C. morto 377 a.C.) che introdusse una classificazione del cancro in maligno (denominazione di Ippocrate: karkinoma) e benigno [13].

Il medico Claudio Galeno di Pergamo (129 - 219 d.C.), medico dell'imperatore Marco Aurelio, ipotizzò nel 200, nel suo libro "De tumoribus praeter naturam", che le donne melancoliche fossero più vulnerabili e contrarrebbero più facilmente il cancro rispetto alle donne sanguigne.

Gli studi scientifici in proposito

All'inizio del settecento fecero la loro comparsa i primi testi scientifici che tematizzavano il legame tra cancro e lo stress[14].

Nel novecento si pensava che lo stress o l'esaurimento nervoso fossero in qualche modo all'origine del cancro. Circa 50 anni fa nacquero anzi diverse ipotesi su di una particolare personalità cancerosa (personalità a rischio neoplastico), anche denominata "di tipo C" (typus carcinomatosus o cancer prone), che faciliterebbe l'insorgenza del cancro, un esempio di studio che va in questo direzione è il lavoro di Wirsching del 1985[15].

La personalità di tipo C sarebbe caratterizzata da una abbondante gentilezza, un elevato grado di adattabilità sociale, tenderebbe alla depressione, altruista con tendenza al sacrificarsi e mostrerebbe una inibizione dell'aggressività ed una mancanza di espressività emozionale. Un contributo venne dato da Kissen e Eysenck [16] nel 1962 nel caso di uomini affetti dal cancro ai polmoni. Una tipologia (con 6 sub-tipi) particolare veniva sviluppata da Ronald Grossarth-Maticek, filosofo di origine ungherese. Con una personalità carcinomatosa, secondo Grossarth-Maticek (tipo 1), sarebbe un individuo che si espone spesso a sostanze cancerogene, farebbe spesso uso di farmaci, si riposasse poco, evitasse conflitti e fosse invece particolarmente vulnerabile ad offese e eventi traumatici. Grossarth-Maticek fu successivamente criticato per aver commesso gravi errori statistici nei suoi articoli: una seconda analisi dei suoi dati negli anni ottanta mostrò risultati completamente diversi rispetto a quelli delle sue pubblicazioni.

Le idee di una personalità cancerosa o tipizzazione psichica del paziente con cancro erano tra di loro contraddittorie e studi scientifici non hanno potuto dimostrare l'esistenza di una tale personalità. Di conseguenza le corrispondenti ipotesi sono state abbandonate e svolgono solo un ruolo storico nella medicina di oggi. (vedi [17] [18]. Lavori che contradicono la ipotesi dell'esistenza di una personalità cancerosa sono: [19][20][21][22][23][24][25][26][27][28]).

Secondo i ricercatori Gruhlke e Faller 1996 [29], le caratteristiche psichologiche attribuite alla personalità di tipo C sono piuttosto da considerarsi come la consequenza di una patologia traumatizzante invece di essere alla loro origine.


Nel secolo passato sono stati eleborati in psicologia (psicologia dinamica) anche modelli nevrotici della cancerogenesi (intasamento della libido, cancro come una forma del suicidio voluto, paragoni col parto e cosi via). Esistono anche legami tra alessitimia (incapacita di poter esprimere i propri sentimenti) e le ipotesi di una presunta personalità cancerosa. Un rapporto tra nevrosi e cancro appare invece nel lavoro di Nakaya [30] in Giappone, che viene pero contradetto in Danimarca da Hansen [31] nel 2005. Faragher [32] vide nel 1990 un possibile legame tra stress (personalità di tipo A) e cancro al seno. Jasmin, nel 1990 [33] vide nei suoi 77 soggetti una relazione tra prognosi psicosomatica e il rischio per il cancro.

La depressione non sembra facilitare la cancerogensi, potrebbe invece influenzare negativamente la mortalita (Wulsin [34] e vedi anche Chorot nel 1994 [35]).

Lo stress prolungato sembra avere un effetto sulla cangerogenesi [36] nel caso del cancro della cute. Lo stress cronico sembra pero anche avere un effetto prottetivo nel cancro al seno a causa della sua influenza ormonale [37][38].

Nel corso dell'ultimo ventennio la prospettiva psicosociale in oncologia ha preso corpo come ambito di studio a se, anche se sviluppatasi gia a partire dagli anni '50 quando, negli Stati Uniti, si costituirono le prime associazioni di pazienti laringectomizzati, colostomizzati e di donne operate al seno. Presso il Memorial Sloan-Kettering Center di New York nacque in questo periodo il primo Servizio autonomo finalizzato all' assistenza psicologica del paziente affetto da cancro. La psico-oncologia vera e propria nacque negli anni '70 e '80 del secolo scorso. In Italia, le prime tracce risalgono agli anni '70, nel 1980 viene istituito presso l' Istituto Nazionale per la Ricerca sul Cancro di Genova il primo servizio di psico-oncologia. Ricercatori prominenti sono ad esempio Jimmi Holland di New York.

Il 25-30% delle persone colpite da cancro presenta problemi di ordine emozionale, che nella maggior parte dei casi non vengono colti e presi in giusta considerazione. Circa 20% dei pazienti affetti da cancro mostrano sintomi di una depressione, che spesso non vengono diagnosticati (Secondo Faller). Lo psico-oncologo tedesco Volker Tschuschke lo conferma nel suo libro [39]. Tali problemi influenzano in maniera negativa la qualita della vita dei pazienti, l'aderenza alla terapie e i rapporti interpersonali. Si possono aggiungere sentimenti di colpa verso la famiglia o altri.

Argomentazione dell'oncologo italiano Prof. Umberto Veronesi, del 2006, a questo proposito e in relazione alle ipotesi di Geerd Ryke Hamer:

[...] non conosco il caso di Hamer ma mi fa piacere confrontarmi con lei sulla natura del cancro, anche se non voglio farlo ideologicamente ma scientificamente. Ho già avuto modo di esprimere su questo forum che io credo che tanto il benessere psichico come il suo opposto, la depressione profonda che porta ad una rinuncia alla vita, possono avere un'influenza sulla cura e sulla risposta del malato alla terapia. Sono anche d'accordo con lei che spesso i farmaci anticancro sono poco efficaci, tant'è vero che con il mio team ci stiamo impegnando nella ricerca di nuovi farmaci molecolari meno tossici per l'organismo e nella messa a punto di combinazioni di farmaci tradizionali che permettano l’utilizzo a basse dosi. Tuttavia nella cura del cancro anche il "poco" è importante. Sull'origine psicosomatica del cancro però non abbiamo alcuna evidenza scientifica e dunque, anche se la psicanalisi può sicuramente in alcuni casi far molto bene psicologicamente al paziente, io non mi sentirei mai come medico e come scienziato di considerarla un'alternativa alle cure che, pur con i loro limiti, oggi hanno dimostrato una qualche azione antitumorale. Ciò detto, io sono un gran sostenitore dell'importanza del lato psicologico e soggettivo della malattia, anche e soprattutto quelle più gravi e non mi stanco di ripetere che oggi vale al guarigione ma anche la qualità della guarigione e che la scienza medica non deve mai dimenticare l'attenzione "amorosa" alla persona..

Vedi anche: Umberto Veronesi: Il ricordo dello scienziato, Laura Dubini un simbolo della lotta al cancro.

Il ruolo dei life events (eventi traumatici)

Momenti particolarmente traumatici possono portare alla nascita di un cancro? La smentita delle rigide asserzioni di R.G. Hamer e delle leggi della Nuova Medicina Germanica arriva da parte della ricerca internazionale.

Il possibile impatto di eventi traumatici, come la morte di un familiare o di un amico, e specialmente eventi traumatici imprevisti come l'attacco alle Torri Gemelle del 11.9.2001 furono oggetto di ricerca per molti anni [40][41] e continuano ad esserlo [42].

Sapendo che circa 1 caso di cancro su 6 è causato da un virus (esempio HPV, HSV, HIV...), l'ipotesi immunitaria di eventi traumatici sull'insorgenza del cancro appare possibile attraverso la modulazione del sistema immunitario.

Gli studi': Forsen [43] ha analizzato 87 donne con cancro al seno, oltre ad un gruppo di controllo composto da donne non affette da tale patologia, per trovare un rapporto tra eventi traumatici e cancro.

Il suo lavoro retrospettivo mostra un numero più grande di eventi traumatici nel gruppo delle persone con cancro rispetto al gruppo di controllo nei 12 mesi precedenti la diagnosi.

Ramirez osservò, nel 1989, un rapporto tra eventi traumatici e ricadute nel caso del cancro al seno [44], venne però smentito da Barraclough [45] nel 1992 e nel 2002 da Graham [46] che conclude che le donne non dovrebbero avere paura di eventi traumatici come causa di una eventuale ricaduta della loro malattia.

Chen [47] trovò una relazione tra eventi traumatici e cancro al seno in Cina, in contrasto però con Protheroe [48].

Roberts [49] analizzò una eventuale relazione tra eventi traumatici ed il cancro al seno e nel suo studio del 1996, con 872 persone, non ha poté rilevare tale relazione e, al contrario, trovò un numero maggiore di persone che avevano perso una persona cara nel gruppo di controllo composto delle donne non aventi cancro.

Nel 1999 McKenna trovò un rapporto debole tra eventi traumatici e cancro al seno [50].

Anche Chorot [51] pensò ad una relazione tra psiche e cancro nel 1994. In una review del 2000, Butow vide solo un rapporto debole tra alessitimia, eventi traumatici e cancro [52], con correlazioni positive solo in studi con un numero ristretto di soggetti.

Nel 2001 l'australiano Price [53] paragonò donne con tumori benigni e donne con malignomi al seno. Dal suo studio su 514 donne risultò un rapporto positivo da eventi traumatici e malignomi (cancro) in assenza di un aiuto sociale. Il suo lavoro è in contrasto con quello di Maunsell del 2003 [54] che non trovò nessuna prova per tale asserzione nel caso del cancro al seno. I lavori di Protheroe del 1999 [55], di Lillberg del 2001 [56] in Finlandia, e di Duijts [57] in Olanda confermano quest'ultima teoria.

Dalla review di Dalton [58] del 2002 si deduce che non si conoscono studi scientifici che mostrano un relazione causale tra major life events (eventi traumatici), la depressione, o un particolare tipo individuale e il rischio di contrarre il cancro.

Dalton afferma che studi scientifici in questo campo contengono spesso un progetto metodologico debole.

Kvikstad, riferisce dalla Norvegia nel 1995 in un indagine su 14.231 donne che la morte del marito o il divorzio non modificano il rischio di cancro. Con alcune eccezioni [59] lo stesso autore, nel 1996, non notò nessuna differenza del rischio di contrarre il cancro in donne che avevano perso un bambino[60].

Lillberg affermò nel 2003 una relazione positiva tra eventi traumatici e cancro in Finlandia [61], Pereira (USA) affermò che tali eventi sono da considerarsi fattori di rischio nel 2003 [62] a base di una influenza del sistema immunitario sulle difese del corpo contro virus ongogeni, nello suo studio su pazienti affetti dal HIV.

Il crollo delle due torri del World Trade Center a New York l'11 Settembre 2001 fu un disastro imprevisto e molto traumatizzante per circa 400.000 persone (con almeno 188 donne incinte nel WTC), 71.000 di queste persone sono elencate nel World Trade Center Health Registry (WTCHR) per tenere sotto osservazione la loro salute. Secondo le "leggi" della nuova medicina questo evento avrebbe dovuto far emergere immediatamente molti nuovi casi di cancro e, visto che non si sa niente di una terapia tipo NMG per queste persone, non si puo ipottizzare che loro avessero potuto evitare in questo modo lo sviluppo di cancro.

Sono stati fatti alcune centinaia di studi dopo l'11/9 e alcune tematizzano un eventuale rapporto tra 11/9 e cancro. La ricerca di Rayne [63] mostra che dopo 4 anni dalla catastrofe, nella zona l'incidenza di cancro era solo leggermente superiore dopo l'attacco rispetto al "fondo", e questo si può anche spiegare con l'effetto di sostanze cancerogene che furono liberate nelle polveri dissipate durante la catastrofe ed i giorni seguenti (furono rilevati nelle polveri composti cancerogeni di idrocarburi policiclici, amianto e cosi via).

È da ricordare però che i periodi di latenza tra iniziazione e promozione di tumore e l'apparizione di sintomi puo essere molto lungo. Normalmente si tratta di periodi di latenza tra i 2 ed i 30 anni [64], in media dura 8 anni. Nel caso di un adulto, e nel caso del mesotelioma può estendersi fino a 70 anni. I periodi di latenza più brevi che si conoscono sono periodi di circa due anni nel caso di bambini con una leucemia.

Chen riferisce un periodo di cinque anni tra sintomo clinico del cancro al seno e prime modifiche osservabili al microscopio a luce [65], in realtà il periodo completo tra inizio e sintomo sarà ancora piu lungo. Ma in teoria un effetto psichico potrebbe anche influenzare in senso positivo la crescita di un tumore gia esistente e asintomatico, un contributo a tale ipotesi lo danno le osservazioni di Pereira [66] nel caso del carcinoma cervicale (2003). In queste condizioni il rapporto temporale potrebbe essere piu breve di 5 anni nel caso di adulti.

Eventi traumatici influenzano anche il comportamento: c'è chi si cura meno ed evita il contatto con servizi sanitari, in casi di elevato stress, con possibili consequenze sulla patologia stessa. In queste condizioni un intervento professionale putrebbe essere positivo.

In modo riassuntivo: eventi traumatizzanti non sembrano avere una importanza rilevante nella genesi del cancro [67][68][69]. I risultati degli studi effettuati all'inzio della psico-oncologia non erano sottoposti a condizioni tali da poter essere ripetuti per una verifica e sembrano essere parzialmente contaminati dalle aspettative dei ricercatori.

La ricerca attuale si concentra a partire degli anni '80, di consequenza più sulle possibilita di migliorare la qualità di vita (parole riassuntive di Jimmie Holland e Uwe Koch).

Da questo punto di vista si spiega la speranza in una nuova psico-oncologia orientata di più verso quello che si può fare in pratica per migliorare la qualità di vita dei ammalati di cancro.

fattori neuro-endocrini con una possibile importanza nella cancerogenesi

  • l'asse HPA / "asse dello stress"
  • Psiconeuroimmunologia e cancro, il concetto di controllo immunitario del cancro di 'Burnets. Tra ormoni coinvolti troviamo: cortisolo, prolatina, melatonina, GH, VIP e la sostanza P. Attualmente si conoscono sopratutto studi fatti su animali, e per l'uomo si conoscono quasi solo correlazioni tra stress e la crescita tumorale, e solo pocchi studi prospettivi.
  • Le cellule NK (natural killer cells): le cellule NK sono importanti nella difesa del corpo contro il cancro, sopratutto nelle fasi iniziali, ma anche nel caso delle metastasi. Lo stress influenza il numero delle cellule NK circolanti [70]

, e questo effetto sembra essere sotto controllo ipotalamico. Una stimolazione simpatica determina un abbassamento della concentrazione di cellule NK, betabloccanti possono impedire questo effetto. La morfina (e altri oppioidi) inibisce le cellule NK, d'altro lato si sa che la morfina ha un effetto protettiva nel caso dello stress causato da un intervento chirurugico [71][72].

Rapporto tra infiammazioni croniche e cancro: vedi Basak [73].

La communicazione della diagnosi cancro: le consequenze per il paziente

Oggi, al contrario del passato, di solito viene communicata la diagnosi al paziente, anche se una diagnosi infausta puo provocare uno scioc profondo. Nei migliori casi, il paziente viene considerato un partner al quale si communica la verita e non una bugia, perche viene preso al serio. (vedi anche Ipocrate [74]). Questo perche spesso il paziente ha gia un sospetto da tempo e vuole sapere la verita, e questa sua volonta e da rispettare in una relazione rispettuosa e onesta tra medico e paziente. Ci sono medici che hanno il vizio di mandare prima una infermiera dal paziente mentendo e pretendendo di non conoscere la diagnosi e chiedendolo quale malattia avesse. Un metodo non compattibile con una relazione onesta tra paziente e terapeuta. Ma, spesso nel inzio del rapporto paziente-medico, quest' ultimo esitera per qualche tempo di communicare i suoi sospetti o anzi i primi risultati di una indagine, si parla nel gergo della "bugia della misericordia". Viene spesso concesso al paziente di cancro un periodo del non-sapere che puo creare gravi problemi di onesta nel rapporto e puo avere un effetto molto dannoso per il paziente [75], e che conduce ad una lenta communicazione a diversi passi successivi. Al contrario del passato, le speranze di vita media sono cresciute e in alcuni casi (tumore ai testicoli per esmepio) questa, dopo una terapia causale, potra essere uguale a quella di persone di stessa eta, in altri casi invece la situazione puo essere molto diversa. In Germania, il redditto medio dei medici e in calo rispetto a altri redditti e di consequenza e cambiato anche il rapporto medico-paziente, anche per altri motivi (medicina basata sempre di piu sulle prove e strumenti-apparecchi e meno su interventi suggestivi / cambiamenti politici e sociali) il ruolo del medico e cambiato (forse anche come quello del prete) e questo sta di meno al di sopra del paziente. Con la mancanza attuale dei medici (nel 2007 in Germania), la situazione potra cambiare pero.

I pazienti non sono uguali pero: ce chi chiede energicamente di essere informato su tutti i dettagli e dopo una diagnosi molto infausta reagira come un ragioniere organizzando la fine della sua vita scivendo un testamento e cosivia. Altre persone invece chiedono (spesso con un linguagio non-verbale) di non essere informati direttamente a proposito del esito probabile della patologia, e dal medico silenzioso capiscono la diagnosi, o come se questo parlasse in una lingua straniera. Nel silenzio si possono communicare tante verita. Si possono anche vedere diverse reazioni del rinegamento e del rifiuto della diagnosi. Una situazione difficile avviene quando il medico di famiglia ipotizza "qualche infezione" o "tumore benigno" e in un centro specializzato viene diagnosticato il contrario, o se un esamine ha un esito positivo falso.

La cura e lo 'coping style' - le differenti coping style e il loro effetto

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La terapia convenzionale del cancro e' di solito una terapia con una primaria orientazione somatica. Da partire dalle conoscenze moderne della psico-oncolgia (a partire dalla fine degli anni 70, partendo dagli stati uniti) tale terapia somatica viene piu spesso affiancata da interventi psicologici da psico-oncologi o psicologi con l'intenzione di migliorare la qualita di vita del paziente, ma anche per avere un eventuale effetto possibile sull'esito della patologia. Tutti i grandi centri ospedalieri hanno oggi un servizio psico-onlogico, almeno negli USA.

Esistono molte "coping style": lo "figthing spirit" - il spirito di combattimento da parte del paziente ma anche da parte dell' ambiente. La reazione attiva, orientata alla risoluzione razionale del problema. La reazione della disperazione, del sentimento di essere disarmato, fino al fatalismo e all' aresa. Il rinnegamento, si evita di voler sapere dettagli della proria patologia. La reazione depressiva, la paura in continuazione. La sopressione dei propri emozioni, la alessitemia. Spesso, con l'andamento della malattia, il paziente mostrera reazioni diverse in diversi momenti.

Lavori prospettivi (non retrospettivi) in questo campo:

influenza della situatione psicologica sul andamento della patologia
studio scientifico paese soggetti follow-up relazione
Lillberg 2001 [76] Finlandia 10.519 20 anni uguale / non esistente
Helgesson 2003 [77] Svezia 1462 24 anni aumentato
Kroenke 2004 [78] USA 69886 4-6 anni uguale / non esistente
Nielsen 2005 [79] Danimarca 6689 18 anni piu basso
Coyne JC et al nel 2007 [80] USA 1093 non esistente

I lavori di Nielsen e di Kroenke tra l'altro mostrano indipendentemente che elevato stress prolungato e quotidiano potrebbe avere un effetto protettivo contro il cancro al seno nel caso delle donne di eta media perche questo gruppo mostra una incidenza minore per questa patologia, forse a causa di una secrezione diversa degli ormoni estrogeni. Qui si possono osservare due fenomeni con un effetto opposto: elevate concentrazione di cortisolo a causa di una attivazione del'asse HPA (con un effetto di promozione per il cancro a causa delle conosciute consequenze per la reattivita' immunitaria) e l'abassamento contemporale dei ormoni estrogeni con un abassamento del rischio per il cancro al seno e sembra prevalere l'efetto prottetivo su quello di promozione. Stress acuto e stress cronico possono dunque avere effetti diversi sulle probabilita' di ammalarsi di cancro.

Relazione tra coping psicologico attivo e periodo di sopravivenza nel cancro del seno
Studio scientifico numero soggetti stadio effetto
Greer 1979 [81] 69 I - II positivo
Hislop 1987 [82] 133 I-IV positivo
Spiegel 1989 [83] studio retrospettivo, durata 1 anno 86 - positivo
Morris 1992 88 I-III non esistente
Buddeberg 1996 [84] 107 early stages non esistente
Giraldi 1997 [85] 95 I-II non esistente
Watson 1999 [86] 578 I-II non esistente
Reynolds 2000 [87] 847 I-IV non esistente
Goodwin 2001 [88] 235 - non esistente
Goodwin 2004 [89] 397 I-III non esistente

Si vede che i rapporti positivi si trovano sopratutto nei lavori piu vecchi, la qualita di vita e da distinguere dallo outcome / periodo di sopravivenza. Dal lavoro di Tschuschke [90]: L' impatto dello fighting spirit nel caso della terapia causale della leucemia (adulti) dopo trasplanto del midollo osseo (vedi immagine).

Le remissioni spontanee (RS)

Le remissioni spontanee RS sono guarizioni con nessun legame con una precedente terapia causale [91] e che si verificano spontaneamente. La prima RS che e diventata famosa nella storia della medicina e' quella di Pellegrino Laziosi di Forli (1265 - 1345 detto anche Pellegrino da Forli', in inglese Saint Peregrine) che si ammalo' di cancro alla tibia e guari completamente senza intervento medico. Pellegrino Laziosi e' diventato nel seguito Il Santo protettore degli ammalati di cancro, secondo la fede cattolica.

L' incidenza di una remissione spontanea nel caso di cancro (solo malignomi) e' purtroppo un fenomeno molto raro e occorre soltanto una volta su 60000-100000 dei casi (Bashford, Hirschberg). Nel 1992, Stoll [92] ipotizza che in tutto il mondo si possono verificare circa 20 nuovi casi all'anno. In tutta la storia della oncologia si conoscono solo all' incirca 1200 casi corrispondenti e pubblicati in tutto il mondo. Ulrich Abel (biologo e esperto di statistica di Heidelberg) stima che sarebbe molto difficile di stimare le probabilita' per una RS. Oggi si sa che le RS possono verificarsi in tutti i tipi di cancro che si conoscono, sono pero piu frequenti nel carcinoma renale, neuroblastoma, melanoma maligno e nel caso dei linfomi e delle leucemie [93][94]. Le RS sono anche piu frequenti nei bambini. In Germania esistono due gruppi di lavoro che si sono concentrati sulle RS (per esempio Klinikum Nurimberga). Queste remissioni spontanee rarissime non sono inducibili da una terapia conosciuta, anche dal punto di vista della psiconeuroimmunologia moderna. RS sono spesso stati osservati dopo infezioni con elevata febbre [95], e si hanno osservato tempi di maggiore sopravivenza nel caso di una malattia contemporale. Queste osservazioni hanno condotto a tentativi terapeutici immunologici o terapie che inducono la febbre, e hanno stimolato la ricerca dell'ipertermia terapeutica del cancro. (oggi praticamente abbandonata per mancanza di successi, e' rimasta in discussione e uso sola la ipertermia locale con-adiuvante e la ricerca continua). Tra i tentativi terapeutici della febbre e' da nominare la terapia di Coley con tossine di batteri, ora abbandonata [96] o tentativi terapeutici con una infezione artificiale della malaria. La vaccinazione BCG (Bacille Calmette Guerin), usata nella prevenzione della tuberculosi viene considerata tuttora efficace in modo co-adiuvante in certi tipi di tumori (tumori della vescica urinaria) [97]. Studi e meta-analisi retrospettivivi storici delle remissioni spontanee sono quelli di Rohdenburg nel 1918 [98] con 185 casi citati, Fauvet nel 1960/1964 (202 casi), Boyd W [99] nel 1966 (98 casi), Everson e Cole [100] nel 1966 (182 casi), Challis nel 1990 [101] (489 casi), O'Reagan e Hirschberg nel 1993 (216 casi). Le ricadute dopo una RS sono purtroppo frequenti [102][103]. Di consequenza occorre aspettare anni dopo una tale remissione per essere sicuro del successo, esattamente come nel caso di una terapia convenzionale del cancro. Il caso del paziente Wright [104] suscitava clamore nel mondo medico: nel suo caso farmaci placebo (causalmente inefficaci) erano efficaci contro linfomi per alcuni mesi, anche se il paziente e' decesso dopo la terapia.

Quali possono essere la cause della RS ? Esistono due spiegazioni: le ipotesi somatiche-fisiologiche e le ipotesi psicologiche. Le correlazioni delle RS con malattie infettive danno un contributo alle ipotesi somatiche, anche se non si sa con precisione quale e' l'influenza del puro caso. Un contributo alle ipotesi psicologiche danno le osservazioni che lo fighting spirit (lo spirito di battaglia dello paziente, la "grinta") e un ottimismo e un ottimo sostegno sociale/familiare (con consequenze sulla qualita' di vita) avevano un effetto positivo in una minorita' degli studi scientifici sulla terapia del cancro - un tale effetto psicologico sembra essere debole, e nella maggioranza degli studi corrispondenti non poteva essere dimostrato o ripetuto, vedi review di Petticrew del 1999 [105] e di Faller nel 2004 [106].

La prevenzione psico-sociale ed ambientale del cancro: esiste un stile di vita che potrebbe essere efficace a diminuire il rischio di riscontrare cancro ?

A scanso dei fattori a rischio ambientali e delle sostanze con conosciuto effetto cancerogeno, fattori psichici come causa di cancro non sembrano invece avere una importanza rilevante. E di consequenza non esiste una "ricetta psicologica" nella prevenzione del cancro. Nell' assistenza psicologica del cancro, la ricerca life-event da sostegno alla ipotesi che una vita caratterizata da un sufficiente sostegno sociale avrebbero un effetto protettivo nel caso del cancro [107][108]. Un tale rapporto sociale stabile puo avere un effetto positivo sul sistema immunitario con consequenze sulle difese del corpo contro virus che sono associati a patologie neoplastiche, sapendo che circa il 15% dei tumori sono da vedere in associazione con una infezione virale. Tipici esempi sono il carcinoma cervicale, sarcoma di Kaposi e alcuni tumori del fegato. Pero: una elevata reattivita' da parte del sistema immunitario, d'altro lato puo avere effetti negativi nel caso di malattie autoimmune come la poliartrite rheumatica. Rafforzare la reattivita immunitaria non e' sempre da consigliare. Evidenze che un cambiamento radicale dello stile di vita o il "pensare positivamente" potrebbero curare una patologia neoplastica non esistono.

Conclusione

Le ipotesi di Ryke Geerd Hamer e della sua nuova medicina germanica ® non sono compattibili con questa revisione della letteratura scientifica fatta a l'inzio del 2007. Hamer sostiene che il cancro, che non suddivide in maligno/benigno come veniva gia fatto ai tempi dei antichi greci, sia il tentativo del cervello di riparare (e quindi di guarire) un trauma psicologico inaspettato subito in precedenza. E che basti individuare il trauma sotto acusa e di disfarlo (attraverso una cosidetta soluzione) perche il cervello receda dalla sua azione riparatrice, arrestando quindi la proliferazione delle cellule neoplastiche una volta per tutte, visto che metastasi non esisterebbero secondo Hamer. Tutto questo ommetendo terapie convenzionali (a parte una minorita' degli interventi chirurgici) ed evitando una terapia analgetica effetuata con morfina o farmaci analoghi, esponendo i pazienti a soffererenze in buona parte evitabili con terapie moderne del dolore. Secondo Hamer, una tale sua strada terapeutica avrebbe un successo del 95-98%. Non e' in grado pero di dimostrarlo, scusandosi con interventi presunti da parte di loggie massoniche e dalla organizzazione B'nai Brith ebrea e da un complotto da parte della "medicina ufficiale". Dai numerosi lavori elencati non si puo trarre la conclusione certa di una psicogenesi per tutti i tipi di cancro. Una tale psicogenesi sarebbe inoltre non compattibile con i diversi tipi di cancro che hanno una accertata origine virale, origine genetica o una origine dal ambiente (raggi UV / radioattivita naturale) o da sostanze cangerogene (p.e. il fumo / amianto) o da radiazioni ionizzanti man-made. Anche l'esistenza dei tumori trasmissibili (nei animali) non e' compattibile con le "leggi" della Nuova Medicina Germanica". Da quello che si sa oggi, processi psichici possono solo avere un ruolo come fattori deboli facilitanti o protettivi, in alcuni estremi rari casi sono forse a l'origine di remissioni spontanee. A l'inzio degli anni 80, a l'epoca della nascita della NMG, la situazione non era cosi chiara come appare oggi. Si sapeva meno, ed erano in discussione modelli di una possibile psicogenesi del cancro. Il diffetto non scusabile di Hamer e' da cercare nella sua incapacita' di adattare le sue ipotesi-leggi progressivamente a quello che si puo osservare/misurare, di rispondere a nuovi risultati scientifici (anche a risultati deludenti propri), di non basarsi su lavori fatti e pubblicati in precedenza e riferirsi in un modo non-critico a racconti e aneddotti scelti, e di aggrapparsi alle sue leggi, in grande parte scurile. Altri errori non-scusabili (la questione dei artefatti TAC, asserzioni sbagliate nel argomento della lateralita umana e embriologia) si aggiungono a l'odore di antisemitismo (e vicinanza per movimenti di estrema destra come la NPD tedesca) che non e' compattibile con un rispetto fermo del essere umano (di ogni razza e confessione) e che deve per forza essere a la base della professione medica pratica. Le sue affermazioni di non essere razzista non convincono un lettore neutrale leggendo le sue lettere pubblicate o interviste, che di piu hanno indotto molti a pensare ad una mania con valore patologico in un uomo invelenito e racchiuso nel suo modo di pensare chiuso ermeticamente dal mondo 'esterno. L'esito fatale nel caso di numerosi pazienti che hanno creduto in un modo cieco alle promesse del medico o ex-medico charismatico con la sua voce rassicurante-simpatica e che presentavano gravi patologie e la contemporanea mancanza di prove per i presunti successi miracolosi del cancro non lasciano dubbi che la sua strada diagnostica e terapeutica non e' idonea per pazienti affetti da una grave patologia.

Pazienti affetti da cancro dovrebbero cercare aiuto competente e professionale e stare lontani dalla terapie della NMG !

La si puo considerare invece come alternativa nel caso di infezioni blandi o disturbi psicosomatici banali, per chi le convinzioni anti-ebrei di Hamer non sono un argomento da stargli lontano.

riferimenti

  • Targ EF, Levine EG., The efficacy of a mind-body-spirit group for women with breast cancer: a randomized controlled trial, Gen Hosp Psychiatry. 2002 Jul-Aug;24(4):238-48.
  • Spiegel D, Kramer H, Bloom JR, et al. Effects of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet. 1989;2:888-891
  • Wallace Sampson Controversies in cancer and the mind: Effects of psychosocial support Seminars in Oncology Volume 29, Issue 6, pagine 595-600 (December 2002)
  1. ↑ Reynaert C, Psychogenesis" of cancer: between myths, misuses and reality. Bull Cancer, 2000 Sep;87(9):655-64 Summary : Since a long time, hypothesis of links between psychological factors and cancer, have been established in our culture. So far, numerous researches have tempted to indicate stress, coping facing the disease, depression or "type C" personality as factors participating to the onset and/or the course of the cancer. A review of those studies, mainly retrospective, has mostly brought debated results, as well as prospective researches including large sample of population or people awaiting a diagnosis; therefore making oldfashioned every area strictly "psychogenetic" of cancer at first sight. Explicative indirect hypothesis are suggested by the psycho-neuro-endocrino-immunology. Various researches in this field proved that external factors such as stress, depression or social support have significative influences on components of the immune system which in turn influence the onset and/or the course of the cancer. The links between psychological factors and cancer are extremely complex, bringing numerous biological, psychological or even sociological systems in interactions. The psycho-neuro-endocrino-immunology constitutes an early interdisciplinary way of mediation, capable of account for the connections between psychology and cancer.
  2. ↑ Protheroe D, Stressful life events and difficulties and onset of breast cancer: case-control study, BMJ, 1999 Oct 16;319(7216):1027-30 OBJECTIVE: To determine the relation between stressful life events and difficulties and the onset of breast cancer. DESIGN: Case-control study. SETTING: 3 NHS breast clinics serving west Leeds. Participants: 399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents. MAIN OUTCOME MEASURES: Odds ratios of the risk of developing breast cancer after experiencing one or more severe life events, severe difficulties, severe 2 year non-personal health difficulties, or severe 2 year personal health difficulties in the 5 years before clinical presentation. RESULTS: 332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1. 81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump. CONCLUSION: These findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.
  3. ↑ Butow PN, Epidemiological evidence for a relationship between life events, coping style, and personality factors in the development of breast cancer, J Psychom res, 2000 Sep;49(3):169-81,OBJECTIVE: Review empirical evidence for a relationship between psychosocial factors and breast cancer development. METHODS: Standardised quality assessment criteria were utilised to assess the evidence of psychosocial predictors of breast cancer development in the following domains: (a) stressful life events, (b) coping style, (c) social support, and (d) emotional and personality factors. RESULTS: Few well-designed studies report any association between life events and breast cancer, the exception being two small studies using the Life Events and Difficulties Schedule (LEDS) reporting an association between severely threatening events and breast cancer risk. Seven studies show anger repression or alexithymia are predictors, the strongest evidence suggesting younger women are at increased risk. There is no evidence that social support, chronic anxiety, or depression affects breast cancer development. With the exception of rationality/anti-emotionality, personality factors do not predict breast cancer risk. CONCLUSION: The evidence for a relationship between psychosocial factors and breast cancer is weak. The strongest predictors are emotional repression and severe life events. Future research would benefit from theoretical grounding and greater methodological rigour.
  4. ↑ Garssen B, Psychological factors and cancer development: evidence after 30 years of research, clin psychol rev, 2004 Jul;24(3):315-38 The question whether psychological factors affect cancer development has intrigued both researchers and patients. This review critically summarizes the findings of studies that have tried to answer this question in the past 30 years. Earlier reviews, including meta-analyses, covered only a limited number of studies, and included studies with a questionable design (group-comparison, cross-sectional or semiprospective design). This review comprises only longitudinal, truly prospective studies (N=70). It was concluded that there is not any psychological factor for which an influence on cancer development has been convincingly demonstrated in a series of studies. Only in terms of 'an influence that cannot be totally dismissed,' some factors emerged as 'most promising': helplessness and repression seemed to contribute to an unfavorable prognosis, while denial/minimizing seemed to be associated with a favorable prognosis. Some, but even less convincing evidence, was found that having experienced loss events, a low level of social support, and chronic depression predict an unfavorable prognosis. The influences of life events (other than loss events), negative emotional states, fighting spirit, stoic acceptance/fatalism, active coping, personality factors, and locus of control are minor or absent. A methodological shortcoming is not to have investigated the interactive effect of psychological factors, demographic, and biomedical risk factors.
  5. ↑ McKenna MC, Psychosocial factors and the development of breast cancer: a meta-analysis, health psychol, 1999 Sep;18(5):520-31, A meta-analysis examined the relationship between psychosocial factors and the development of breast cancer. Average effect sizes (Hedges's g) were calculated from 46 studies for 8 major construct categories: anxiety/depression, childhood family environment, conflict-avoidant personality, denial/repression coping, anger expression, extraversion-introversion, stressful life events, and separation/loss. Significant effect sizes were found for denial/repression coping (g = .38), separation/loss experiences (g = .29), and stressful life events (g = .25). Although conflict-avoidant personality style was also significant (g = .19), the effect size was less robust, and a moderate number of future studies with null results would reduce the significance. Results overall support only a modest association between specific psychosocial factors and breast cancer and are contrary to the conventional wisdom that personality and stress influence the development of breast cancer.
  6. ↑ Edwards JR, The relationship between psychosocial factors and breast cancer: some unexpected results, Behav med, 1990 Spring;16(1):5-14 A growing body of research suggests a link between psychosocial factors and breast cancer. Research in this area often contains methodological problems, however, such as small sample size, inadequate comparison groups, omission of important control variables, inclusion of only a few psychosocial variables, and failure to analyze moderating effects. To overcome these problems, the present study examined the link between breast cancer and multiple psychosocial variables (life events, coping, Type A behavior pattern, availability of social support) among 1,052 women with and without breast cancer. After controlling for history of breast cancer and age, we found very few significant relationships between psychosocial variables and breast cancer. Furthermore, the relationship between life events and breast cancer was not moderated by coping, Type A, or availability of social support. Methodological and substantive reasons for these findings are discussed.
  7. ↑ Garssen B, On the role of immunological factors as mediators between psychosocial factors and cancer progression, psychiatry res, 1999 Jan 18;85(1):51-61 Thirty-eight prospective studies on the role of psychological factors in cancer initiation and progression are reviewed. Despite the availability of many prospective studies, there is no certainty about the role of any specific factor. An important reason might be that the interactions among several psychological factors, and the interactions of psychological and biomedical risk factors, have rarely been studied. Some evidence has been found that a low level of social support, a tendency towards helplessness, and repression of negative emotions are factors that promote cancer progression. The effect of psychological factors has been more convincingly demonstrated with respect to cancer progression than cancer initiation, and more convincingly in intervention than in natural history studies. Possible mechanisms mediating associations between psychological factors and disease outcome are discussed. The role of immunosurveillance seems modest overall, and alternative pathways are suggested.
  8. ↑ Edwards AG, Psychological interventions for women with metastatic breast cancer, Cochrane Database Syst Rev, 2004;(2):CD004253 BACKGROUND: There have been conflicting results from systematic reviews of psychological interventions for patients with cancer, some showing benefits for patients and others not. One early study appeared to show significant survival benefits as well as psychological benefits from a psychological intervention given to women with metastatic breast cancer. Some further studies have been undertaken, again with conflicting results. OBJECTIVES: To assess the effects of psychological interventions (educational, individual cognitive behavioural or psychotherapeutic, or group support) on psychological and survival outcomes for women with metastatic breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Trials Register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1966-October 2003), CancerLit (1983-2000), CINAHL (1982-October 2003), PsycInfo (1974-November 2003), and SIGLE (1980-November 2003). SELECTION CRITERIA: Randomised controlled trials (RCTs) of psychological interventions for women with metastatic breast cancer. Studies were included even if they were not 'intention to treat', owing to the nature of the patient group under study and the likely high loss of follow-up data. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Data about the nature and setting of the intervention, and the relevant outcome data were extracted, along with items relating to methodological quality. MAIN RESULTS: Five primary studies were identified, all group psychological interventions. Two of these were cognitive behavioural interventions and three evaluated support-expressive group therapy. The five studies of group psychological therapies for women with metastatic breast cancer showed very limited evidence of benefit arising from these interventions. Although there was evidence of short-term benefit for some psychological outcomes, in general these were not sustained at follow-up. A clearer pattern of psychological outcomes could not be discerned as a wide variety of outcome measures and durations of follow-up were used in the included studies. The possible longer survival times in women allocated to receive psychological intervention in the early study have not been replicated in the subsequent four studies (including one by members of the first study group), and overall the effects of these interventions on survival are not statistically significant (for example, odds ratio for 5 year survival 0.83 (95% confidence interval [CI] 0.53 - 1.28). REVIEWERS' CONCLUSIONS: There is insufficient evidence to advocate that group psychological therapies (either cognitive behavioural or supportive-expressive) should be made available to all women diagnosed with metastatic breast cancer. Any benefits of the interventions are only evident for some of the psychological outcomes and in the short term. The possibility of the interventions causing harm is not ruled out by the available data.
  9. ↑ Protheroe D, Stressful life events and difficulties and onset of breast cancer: case-control study, BMJ, 1999 Oct 16;319(7216):1027-30, OBJECTIVE: To determine the relation between stressful life events and difficulties and the onset of breast cancer. DESIGN: Case-control study. SETTING: 3 NHS breast clinics serving west Leeds. Participants: 399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents. MAIN OUTCOME MEASURES: Odds ratios of the risk of developing breast cancer after experiencing one or more severe life events, severe difficulties, severe 2 year non-personal health difficulties, or severe 2 year personal health difficulties in the 5 years before clinical presentation. RESULTS: 332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1. 81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump. CONCLUSION: These findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.
  10. ↑ Maunsell E, Stressful life events and survival after breast cancer, Psychosom Med, 2001 Mar-Apr;63(2):306-15 http://www.psychosomaticmedicine.org/cgi/reprint/63/2/306?ijkey=c89eedfd5ea3b5021d6d4b83a3ccfe4539246efa OBJECTIVE: This study assessed the relation of stressful life events with survival after breast cancer. METHODS: This study was based on women with histologically confirmed, newly diagnosed, localized or regional stage breast cancer first treated in 1 of 11 Quebec City (Canada) hospitals from 1982 through 1984. Among 765 eligible patients, 673 (88%) were interviewed 3 to 6 months after diagnosis about the number and perceived impact of stressful events in the 5 years before diagnosis. Three scores were calculated: number of events; number weighted by reported impact; and for almost 80% of events, number weighted by community-derived values reflecting adjustment required by the event. Scores were divided into quartiles to assess possible dose-response relationships. Survival was assessed in 1993. Hazard ratios and 95% confidence intervals (CIs) comparing all-cause and breast cancer-specific mortality were calculated with adjustment for age, presence of invaded axillary nodes, adjuvant radiotherapy, and systemic therapy (ie, chemotherapy and hormone therapy). RESULTS: When quartiles 2, 3, and 4 were compared with the appropriate lowest quartile, adjusted hazard ratios for all-cause mortality were 0.99 (CI = 0.70-1.38), 0.97 (CI = 0.73-1.31), and 1.04 (CI = 0.78-1.40) for number, number weighted by impact, and number weighted by community-derived values, respectively. Results were essentially similar for the relation between stressful life events limited to those occurring within the 12 months before diagnosis and overall mortality and between stressful life events in the 5 years before diagnosis and breast cancer-specific mortality. CONCLUSIONS: Stress was conceptualized as life events presumed to be negative, undesirable, or to require adjustment by the person confronting them. We found no evidence indicating that this kind of stress during the 5 years before diagnosis negatively affected survival among women with nonmetastatic breast cancer. Evidence from this study and others on the lack of effect of this type of stress on survival may be reassuring for women living with breast cancer.
  11. ↑ Spiegel D, Kato PM, Psychosocial influences on cancer incidence and progression, Harv rev psychiatry, 1996 May-Jun;4(1):10-26 The impact of psychosocial factors on the incidence and progression of cancer has become an area that demands attention. In this article recent evidence of psychosocial effects on cancer incidence and progression is reviewed in the context of past research. Psychosocial factors discussed include personality, depression, emotional expression, social support, and stress. Mechanisms that could mediate the relationship between psychosocial conditions and cancer incidence and progression are also reviewed. These include alterations in diet, exercise, and circadian cycles; variations in medical treatment received; and physiological mechanisms such as psychoendocrinologic and psychoneuroimmunologic effects. We conclude that there is a nonrandom relationship among various psychosocial factors and cancer incidence and progression that can only partially be explained by behavioral, structural, or biological factors. Suggestions for future research are discussed.
  12. ↑ http://www.meb.uni-bonn.de/cancernet/600317.html National Cancer Institute: Psychological Stress and Cancer
  13. ↑ http://www.aerzteblatt.de/v4/archiv/artikeldruck.asp?id=49834 Sonnenmos, Marion: Psychosoziale Aspekte onkologischer Erkrankungen: „Der Einfluss der Psyche ist sekundär“
  14. ↑ LeShan L, psychological states in the development of malignous disease: a critical review. J nat cancer inst 1959:22 1-18
  15. ↑ Wirsching M, Prebioptic psychological characteristics of breast cancer patients, Psychother Psychosom, 1985 43(2) 69-76, 63 women were examined the day before breast biopsy using psychological ratings, speech analysis and questionnaire testings. Ratings revealed differences (benign vs. malignant, a = 5%) in 8 of 10 scales, cancer patients being inaccessible, altruistic, suppressing feelings, rationalizing and harmonizing. The biopsy's result was predicted in 75% of all cases. Questionnaire testing showed differences in 7 of 16 scales. It proved cancer patients to be more dependent, anxious, aggressive, health-conscious, family-bound and antisexual. A discriminant analysis correctly identified 77% of cancer and 87% of benign patients. Speech analysis (Gottschalk-Gleser) revealed only minor differences: fewer aggressive and more anxious utterances from cancer patients. Conclusions are drawn for the care and treatment of breast cancer patients.
  16. ↑ Kissen DM Eysenck HJ, Personality in male lung cancer patients, J Psychosom Res, 1962 apr-june 6 123
  17. ↑ Schwarz R, Die Krebspersönlichkeit, libro: 1994 Schattauer Stuttgard New York.
  18. ↑ Sampson W, Controversies in cancer and the mind: effects of psychosocial support, Semin Oncol, 2002 Dec;29(6):595-600, In the last decades of the twentieth century, interest in effects of consciousness on health and illness generated several lines of investigation into effects on cancer. Animal studies showed sensitivity of some cancers to hormonal and stressful influences. However, those findings did not translate into effects on humans, nor did they lead to advances in understanding of human cancer. The proposal that emotional state or stress, mediated through psycho-neuro-immunologic mechanisms would affect cancer generation or growth, resulted in conflicting information. Major surveys found no relationship. The proposal of a cancer personality (Type C) also was not confirmed. Initial observations that depression and stress affected human cancer seem to have best been explained by misinterpretations of cause and effect. By the mid 1990s, a remaining thesis--effect of psychosocial support on longevity and the course of cancer--was yet to be resolved. Initial positive results, especially findings in two popularly quoted studies, were not confirmed; they seem to have been due to inadequate numbers (chance) or to artifacts in study design or implementation. Psychosocial support may result in better adjustment and quality of life, but it does not directly affect the evolution of human cancer.
  19. ↑ Schwarz R, Die Krebspersönlichkeit, libro: 1994 Schattauer Stuttgard New York.
  20. ↑ Nakaya N, Personality and the risk of cancer, j natl cancer inst, 2003 Jun 4;95(11):799-805, http://jnci.oxfordjournals.org/cgi/reprint/95/11/799?ijkey=79f30310e4da10c9c341265b0cecde7e0f4cee4d BACKGROUND: The role of personality in the causation of cancer has been controversial. We examined this question in a large, prospective study. METHODS: From June through August 1990, 30 277 residents of Miyagi Prefecture in northern Japan completed a Japanese version of the short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits. There were 671 prevalent cases of cancer at baseline, and 986 incident cases of cancer were identified during 7 years of follow-up, through December 1997. We used Cox proportional hazards regression to estimate the relative risk (RR) of incident cancer (total, stomach, colorectal, breast, and lung) according to four levels of each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for sex, age, education, smoking, alcohol use, body mass index, and family history of cancer. Statistical tests were two-sided. RESULTS: Multivariable RRs of total cancer for individuals in the highest level of each personality subscale as compared with those in the lowest were 0.9 for extraversion (95% confidence interval [CI] = 0.7 to 1.1; P(trend) =.32), 1.1 for psychoticism (95% CI = 0.9 to 1.3; P(trend) =.96), 0.9 for lie (95% CI = 0.7 to 1.0; P(trend) =.19), and 1.2 for neuroticism (95% CI = 1.0 to 1.4; P(trend) =.06). There were no associations between any personality subscale and risk of specific cancers. Neuroticism showed statistically significant positive, linear associations with prevalent cancer at baseline (P(trend)<.001) and with the 320 incident cancer cases diagnosed within the first 3 years of follow-up (P(trend) =.03); however, it showed no association with the 666 cases diagnosed during the fourth through the seventh years of follow-up (P(trend) =.43). CONCLUSION: Our data do not support the hypothesis that personality is a risk factor for cancer incidence. The association between neuroticism and prevalent cancer may be a consequence, rather than a cause, of cancer diagnosis or symptoms.
  21. ↑ Hansen PE, Personality traits, health behavior, and risk for cancer: a prospective study of Swedish twin court, Cancer, 2005 Mar 1;103(5):1082-91 BACKGROUND: The authors conducted a prospective investigation into the relation between personality traits and the risk for cancer. METHODS: The study cohort consisted of 29,595 Swedish twins from the national Swedish Twin Registry who were ages 15-48 years at time of entry. In 1973, the twins completed a questionnaire eliciting information on personality traits and health behavior. The Eysenck Personality Inventory was used to measure neuroticism and extroversion as two personality dimensions. A Cox proportional hazards model was used to estimate hazard ratios and 95% confidence intervals for extroversion and neuroticism separately as well as for their joint effect, and conditional logistic regression analyses were conducted to estimate the relation between personality traits and risks for cancer in twin pairs who were discordant for cancer. All analyses were conducted for six etiologically different groups of cancers: hormone-related organ cancers, virus-related and immune-related cancers, digestive organ cancers (excluding liver), respiratory organ cancers, cancers in other sites, and all cancer sites. RESULTS: Follow-up in the Swedish Cancer Registry for 1974-1999 revealed 1898 incidents of primary cancer. The authors found no significant association between neuroticism, extroversion, their joint effects and the risk for any cancer group. CONCLUSIONS: The current results did not support the hypothesis that certain personality traits are associated with cancer risk. 2005 American Cancer Society.
  22. ↑ Bleiker EM, Personality factors and breast cancer development: a prospective longitudinal study, J natl cancer inst, 1996 Oct 16;88(20):1478-82 http://jnci.oxfordjournals.org/cgi/reprint/88/20/1478?ijkey=ba8a8b7de087a2eb6604b0724ae2f4276bc33545&keytype2=tf_ipsecsha BACKGROUND: It has been estimated that approximately 25% of all breast cancers in women can be explained by currently recognized somatic (i.e., hereditary and physiologic) risk factors. It has also been hypothesized that psychological factors may play a role in the development of breast cancer. PURPOSE: We investigated the extent to which personality factors, in addition to somatic risk factors, may be associated with the development of primary breast cancer. METHODS: We employed a prospective, longitudinal study design. From 1989 through 1990, a personality questionnaire was sent to all female residents of the Dutch city of Nijmegen who were 43 years of age or older. This questionnaire was sent as part of an invitation to participate in a population-based breast cancer screening program. Women who developed breast cancer among those who returned completed questionnaires were compared with women without such a diagnosis in regard to somatic risk factors and personality traits, including anxiety, anger, depression, rationality, anti-emotionality (i.e., an absence of emotional behavior or a lack of trust in one's own feelings), understanding, optimism, social support, and the expression and control of emotions. Conditional logistic regression analysis was used to identify variables that could best explain group membership (i.e., belonging to the case [breast cancer] or the control [without disease] group). RESULTS: Personality questionnaires were sent to 28 940 women, and 9705 (34%) were returned in such a way that they could be used for statistical analyses. Among the 9705 women who returned useable questionnaires, 131 were diagnosed with breast cancer during the period from 1989 through 1994. Seven hundred seventy-one age-matched control subjects (up to six per case patient) were selected for the analyses. Three variables were found to be statistically significantly associated with an increased risk of breast cancer: 1) having a first-degree family member with breast cancer (versus not having an affected first-degree relative, odds ratio [OR] = 4.05; 95% confidence interval [CI] = 1.76-9.31); 2) nulliparity (i.e., having no children) (versus having had a child before the age of 30 years, OR = 2.67; 95% CI = 1.26-5.68); and 3) a relatively high score on the personality scale of anti-emotionality (versus a low score, OR = 1.19; 95% CI = 1.05-1.35). CONCLUSIONS AND IMPLICATIONS: With the exception of a weak association between a high score on the anti-emotionality scale and the development of breast cancer, no support was found for the hypothesis that personality traits can differentiate between groups of women with and without breast cancer. We recommend that this study be continued and that other studies be encouraged to explore possible relationships between personality factors and the risk of breast cancer.
  23. ↑ Sampson W, Controversies in cancer and the mind: effects of psychosocial support, Semin Oncol, 2002 Dec;29(6):595-600 In the last decades of the twentieth century, interest in effects of consciousness on health and illness generated several lines of investigation into effects on cancer. Animal studies showed sensitivity of some cancers to hormonal and stressful influences. However, those findings did not translate into effects on humans, nor did they lead to advances in understanding of human cancer. The proposal that emotional state or stress, mediated through psycho-neuro-immunologic mechanisms would affect cancer generation or growth, resulted in conflicting information. Major surveys found no relationship. The proposal of a cancer personality (Type C) also was not confirmed. Initial observations that depression and stress affected human cancer seem to have best been explained by misinterpretations of cause and effect. By the mid 1990s, a remaining thesis--effect of psychosocial support on longevity and the course of cancer--was yet to be resolved. Initial positive results, especially findings in two popularly quoted studies, were not confirmed; they seem to have been due to inadequate numbers (chance) or to artifacts in study design or implementation. Psychosocial support may result in better adjustment and quality of life, but it does not directly affect the evolution of human cancer.
  24. ↑ Schwarz R, Social and psychological differences between cancer and noncancer patients: cause or consequence of the disease? Psychother Psychosom, 1984;41(4):195-9 83 female patients with breast tumors were interviewed prior to biopsy. The interview contained a psychological instrument measuring action control as an indicator for the patients' reaction to stress together with questions about the expected diagnosis. Using multiple-regression analysis we estimated the explained variance of the variables relating to the histological result of the biopsy. Since most of the patients gave a correct prognosis of the nature of their disease-this variable proved to be very important-most of the social psychological findings have to be interpreted as consequences rather than causes of cancer.
  25. ↑ Garssen B, Psychological factors and cancer development: evidence after 30 years of research, clin psychol rev, 2004 Jul;24(3):315-38 The question whether psychological factors affect cancer development has intrigued both researchers and patients. This review critically summarizes the findings of studies that have tried to answer this question in the past 30 years. Earlier reviews, including meta-analyses, covered only a limited number of studies, and included studies with a questionable design (group-comparison, cross-sectional or semiprospective design). This review comprises only longitudinal, truly prospective studies (N=70). It was concluded that there is not any psychological factor for which an influence on cancer development has been convincingly demonstrated in a series of studies. Only in terms of 'an influence that cannot be totally dismissed,' some factors emerged as 'most promising': helplessness and repression seemed to contribute to an unfavorable prognosis, while denial/minimizing seemed to be associated with a favorable prognosis. Some, but even less convincing evidence, was found that having experienced loss events, a low level of social support, and chronic depression predict an unfavorable prognosis. The influences of life events (other than loss events), negative emotional states, fighting spirit, stoic acceptance/fatalism, active coping, personality factors, and locus of control are minor or absent. A methodological shortcoming is not to have investigated the interactive effect of psychological factors, demographic, and biomedical risk factors.
  26. ↑ Zander E, Cancer--a psychosomatic disease?, Z Psychosom Med Psychoanal, 1983;29(4):363-79 Taking psychoanalytical aspects of psychologically caused symptoms into consideration it is discussed, whether in a narrower sense human cancer can be regarded as a psychosomatic disease or not. Research results in molecular biology including genetics are taken into account. It is held that psychogenesis as a primary cause explains only a minor part of the incidence rate of human cancer. Psychological--or neurotic--influences on the course of the disease are regarded as relatively well proved, but not as specific to cancer. Against hasty psychological explanations of cancer should be warned.
  27. ↑ Lillberg K, Personality characteristics and the risk of breast cancer: a prospective cohort study. int j cancer, 2002 Jul 20;100(3):361-6 Various personality characteristics have been suggested to increase the risk of breast cancer but reliable epidemiologic data on this issue are limited. We prospectively investigated the relationship between personality characteristics and the risk of breast cancer in 12,499 Finnish women aged 18 years or more. In health questionnaires in 1975 and 1981, these women completed at least one of the following personality scales: Eysenck extroversion, Bortner type A behaviour and author-constructed measure of hostility. They also reported about other potential breast cancer risk factors. From 1976-1996, 253 cases of breast cancer were identified by record linkage with the Finnish Cancer Registry. Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The multivariable HRs of breast cancer for women with intermediate level (scores 3-6) and high level (7-9) of extroversion in 1975 were 1.18 (95% CI 0.87-1.60) and 0.97 (95% CI 0.64-1.47), respectively, compared to those with low level (0-2). These results remained unaltered when the level of extroversion was determined as the average of the 1975 and 1981 reports. There was also no increase in breast cancer risk in relation to type A behaviour and hostility. Furthermore, we observed no substantial joint effects of personality characteristics on the risk of breast cancer. In conclusion, our data do not support the existence of an important role for personality in the aetiology of breast cancer. These findings are reassuring to those who have believed the contrary.
  28. ↑ http://www.aerzteblatt.de/v4/archiv/artikeldruck.asp?id=49834 Sonnenmos, Marion: Psychosoziale Aspekte onkologischer Erkrankungen: „Der Einfluss der Psyche ist sekundär“
  29. ↑ Faller H, cancer personality" attribution--an expression of maladaptive coping with illness?, Z Klin Psychol Psychiatr Psychother, 1996 44(1) 104 In psycho-oncology, the concept of a "cancer-prone personality" has gained some attention. This notion means that persons who try to stay pseudo-normal in spite of severe life stress, suppress negative emotions, particularly anger, and sacrifice themselves for other people without uttering any personal demands, are at a high risk to develop cancer. However, it has been demonstrated by previous research that features of the cancer-prone personality could only be found if the ill person was convinced to suffer from cancer, irrespective of what the factual diagnosis was. Thus it can be concluded that at least some aspects of the so called cancer personality might be the results of coping with the belief of having cancer. The present study had the objective to describe causal attributions to psychosocial factors in cancer patients, and to find out if these were connected with emotional state and coping. N = 120 newly diagnosed lung cancer patients were included in the study. The instruments consisted of a semi-structured interview, a check-list of subjective causal factors, self-reports and interviewer ratings on emotional state and standardised questionnaires about depression and coping. Patients who made a psychosocial causal attribution proved to suffer from greater emotional distress, to be more depressed and less hopeful than other patients. This difference seemed to be mediated by a depressive way of coping with the illness (brooding, wrangling). Thus, an attribution of the illness to psychological factors seems indicative of a maladaptive way of coping with illness. This result is supported by similar findings of previous research. The question is put up to discussion if the psychosomatic concept of a cancer personality may reflect patients' subjective theories which in turn may be the expression of their depressive coping modes.
  30. ↑ Nakaya N, Personality traits and cancer survival: a Danish cohort study, Br j cancer, 2006 Jul 17;95(2):146-52. Epub 2006 Jul 4 We conducted a population-based prospective cohort study in Denmark to investigate associations between the personality traits and cancer survival. Between 1976 and 1977, 1020 residents of the Copenhagen County completed a questionnaire eliciting information on personality traits and various health habits. The personality traits extraversion and neuroticism were measured using the short form of the Eysenck Personality Inventory. Follow-up in the Danish Cancer Registry for 1976-2002 revealed 189 incidents of primary cancer and follow-up for death from the date of the cancer diagnosis until 2005 revealed 82 deaths from all-cause in this group. A Cox proportional-hazards model was used to estimate the hazard ratios (HRs) of death from all-cause according to extraversion and neuroticism adjusting for potential confounding factors. A significant association was found between neuroticism and risk of death (HR, 2.3 (95% CI=1.1-4.7); Linear trend P=0.04) but not between extraversion and risk of death (HR, 0.9 (0.4-1.7); Linear trend P=0.34). Similar results were found when using cancer-related death. Stratification by gender revealed a strong positive association between neuroticism and the risk of death among women (Linear trend P=0.03). This study showed that neuroticism is negatively [corrected] associated with cancer survival. Further research on neuroticism and cancer survival is needed.
  31. ↑ Hansen PE, Personality traits, health behavior, and risk for cancer: a prospective study of Swedish twin court, Cancer, 2005 Mar 1;103(5):1082-91 BACKGROUND: The authors conducted a prospective investigation into the relation between personality traits and the risk for cancer. METHODS: The study cohort consisted of 29,595 Swedish twins from the national Swedish Twin Registry who were ages 15-48 years at time of entry. In 1973, the twins completed a questionnaire eliciting information on personality traits and health behavior. The Eysenck Personality Inventory was used to measure neuroticism and extroversion as two personality dimensions. A Cox proportional hazards model was used to estimate hazard ratios and 95% confidence intervals for extroversion and neuroticism separately as well as for their joint effect, and conditional logistic regression analyses were conducted to estimate the relation between personality traits and risks for cancer in twin pairs who were discordant for cancer. All analyses were conducted for six etiologically different groups of cancers: hormone-related organ cancers, virus-related and immune-related cancers, digestive organ cancers (excluding liver), respiratory organ cancers, cancers in other sites, and all cancer sites. RESULTS: Follow-up in the Swedish Cancer Registry for 1974-1999 revealed 1898 incidents of primary cancer. The authors found no significant association between neuroticism, extroversion, their joint effects and the risk for any cancer group. CONCLUSIONS: The current results did not support the hypothesis that certain personality traits are associated with cancer risk. 2005 American Cancer Society.
  32. ↑ Faragher EB, Type A stress prone behaviour and breast cancer, Psychol Med, 1990 Aug;20(3):663-70 Department of Medical Statistics, University Hospital of South Manchester, Withington. This quasi-prospective study of 2163 women attending breast-screening clinics (and controls), indicates that there is a link between personality factors and breast disease. Certain aspects of Type A behaviour seem to be associated with breast-disease states.
  33. ↑ Jasmin C, Le MG, Marty P, Herzberg R, Psycho-Oncologic between certain psychol Group. Evidence for a linogical factors and the risk of breast cancer in a case control study. Ann Oncol 1990;1:22-9 Unite d'Oncogenese Appliquee, INSERM U 268, Hopital Paul Brousse, Villejuif, France The relationship between psychosomatic characteristics and the risk of breast cancer was studied in women aged from 35 to 65 years, presenting with a clinically palpable breast tumor. To permit a double-blind design, the psychosomatic evaluation obtained by a long open-ended interview was completed before any diagnostic procedure. On the basis of this evaluation, the psychosomatician concluded that the patient was at high or low risk of serious disease. Several other psychological parameters were also recorded, and the diagnosis was then established by cytology or histology. Nineteen of the 77 patients finally included in the study had histologically verified breast cancer. The relative risk (RR) of breast cancer associated with psychosomatic factors was estimated by multivariate unconditional logistic regression, taking into account age at interview, family history of breast cancer, parity and age at first delivery. A significant relationship (p = 0.02) was found between psychosomatic prognosis and the relative risk of breast cancer. Both the low and high risk groups identified by the psychosomaticians had a similar mean age (46.1 versus 47.6 years). Fundamental mental structure played a predominant role in the risk of breast cancer, since no case was observed among the 18 patients with well organized neurosis, and all the 19 malignant tumors were observed among patients with poorly organized neurosis or psychosis (RR = 7.8, p = 0.009). In addition, excessive self-esteem (RR = 10.0, p = 0.02), hysterical disposition (RR = 7.5, p = 0.02), and unresolved recent grief (RR = 8.2, p = 0.05), were found to be significantly related to the risk of breast cancer....
  34. ↑ Wulsin LR, A systematic review of the mortality of depression, Psychosom Med, 1999 Jan 61 (1) 18, OBJECTIVE: The literature on the mortality of depression was assessed with respect to five issues: 1) strength of evidence for increased mortality, 2) controlling for mediating factors, 3) the contribution of suicide, 4) variation across sample types, and 5) possible mechanisms. METHOD: All relevant English language databases from 1966 to 1996 were searched for reviews and studies that included 1) a formal assessment of depressive symptoms or disorders, 2) death rates or risks, and 3) an appropriate comparison group. RESULTS: There were 57 studies found; 29 (51%) were positive, 13 (23%) negative, and 15 (26%) mixed. Twenty-one studies (37%) ranked among the better studies on the strength of evidence scale used in this study, but there are too few comparable, well-controlled studies to provide a sound estimate of the mortality risk associated with depression. Only six studies controlled for more than one of the four major mediating factors. Suicide accounted for less than 20% of the deaths in psychiatric samples, and less than 1% in medical and community samples. Depression seems to increase the risk of death by cardiovascular disease, especially in men, but depression does not seem to increase the risk of death by cancer. Variability in methods prevents a more rigorous meta-analysis of risk. CONCLUSION: The studies linking depression to early death are poorly controlled, but they suggest that depression substantially increases the risk of death, especially death by unnatural causes and cardiovascular disease. Future well-controlled studies of high risk groups may guide efforts to develop treatments that reduce the mortality risk of depression.
  35. ↑ Chorot P, Life events and stress reactivity as predictors of cancer, coronary heart disease and anxiety disorders, int j psychosom, 1994;41(1-4):34-40 The topic relative to the differential psychobiological mechanisms between cancer and coronary illness has been showing for the last years. In this sense, some theoretical models which have been formulated by relevant authors have suggested the possibility of differentiating cancer and cardiovascular disease, both the onset and the progression, from coping strategies, personality variables and affective states, as well as the different categories of psychosocial stress. Likewise, the implication of psychological distress, such as anxiety, anger and depression for the occurrence of somatic disease has been reported frequently. This research was designed to analyze the psychosocial patterns which could explain the incidence of heart disease, cancer and anxiety based disorders. Measures of life events and stress reactivity were obtained from a total of 109 patients diagnosed as having breast cancer (37), infarct (37), and anxiety (35), and from 72 normal control subjects. Our data tend to show that the cancer group was strongly predicted by lost and illness events, while the coronary group was more associated with work events. The anxiety disorders group lacked a life events dimension, but shared the same category of the infarct group. We also found a strong relationship between depressive reactions and cancer in contrast to the anxiety-anger variable that was more relevant in the infarct patients. The interaction between internal and external stress factors in the etiology of disease is also discussed.
  36. ↑ Saul AN, Chronic stress and susceptibility to skin cancer, J natl cancer inst, 2005 Dec 7;97(23):1760-7 http://jnci.oxfordjournals.org/cgi/reprint/97/23/1760?ijkey=9c9216b7d06ed0474b50ec0632122cdca08f851f BACKGROUND: Studies have shown that chronic stress or UV radiation independently suppress immunity. Given their increasing prevalence, it is important to understand whether and how chronic stress and UV radiation may act together to increase susceptibility to disease. Therefore, we investigated potential mediators of a stress-induced increase in emergence and progression of UV-induced squamous cell carcinoma. METHODS: SKH1 mice susceptible to UV-induced tumors were unexposed (naive, n = 4) or exposed (n = 16) to 2240 J/m2 of UVB radiation three times a week for 10 weeks. Half of the UVB-exposed mice were left nonstressed (i.e., they remained in their home cages) and the other half were chronically stressed (i.e., restrained during weeks 4-6). UV-induced tumors were measured weekly from week 11 through week 34, blood was collected at week 34, and tissues were collected at week 35. mRNA expression of interleukin (IL)-12p40, interferon (IFN)-gamma, IL-4, IL-10, CD3epsilon, and CCL27/CTACK, the skin T cell-homing chemokine, in dorsal skin was quantified using real-time polymerase chain reaction. CD4+, CD8+, and CD25+ leukocytes were counted using immunohistochemistry and flow cytometry. All statistical tests were two-sided. RESULTS: Stressed mice had a shorter median time to first tumor (15 versus 16.5 weeks, difference = 1.5 weeks, 95% confidence interval [CI] = -3.0 to 3.3 weeks; P = .03) and reached 50% incidence earlier than controls (15 weeks versus 21 weeks). Stressed mice also had lower IFN-gamma ( mean = 0.03 versus mean = 0.07, difference = 0.04, 95% CI = 0.004 to 0.073; P = .02), CCL27/CTACK (mean = 101 versus mean = 142, difference = 41, 95% CI = 8.1 to 74.4; P = .03), and CD3epsilon (mean = 0.18 versus mean = 0.36, difference = 0.18, 95% CI = 0.06 to 0.30; P = .007) gene expression and lower numbers of infiltrating CD4+ cells (mean = 9.40 versus mean = 13.7, difference = 4.3, 95% CI = 2.36 to 6.32; P = .008) than nonstressed mice. In addition, stressed mice had more regulatory/suppressor CD25+ cells infiltrating tumors and more CD4+ CD25+ cells in circulation (mean = 0.36 versus mean = 0.17, difference = 0.19, 95% CI = 0.005 to 0.38; P = .03) than nonstressed mice. CONCLUSIONS: Chronic stress increased susceptibility to UV-induced squamous cell carcinoma in this mouse model by suppressing type 1 cytokines and protective T cells and increasing regulatory/suppressor T cell numbers.
  37. ↑ Nielsen NR, Self reported stress and risk of breast cancer: prospective cohort study, BMJ 2005 sept 10 331(7516) OBJECTIVE: To assess the relation between self reported intensity and frequency of stress and first time incidence of primary breast cancer. DESIGN: Prospective cohort study with 18 years of follow-up. SETTING: Copenhagen City heart study, Denmark. PARTICIPANTS: The 6689 women participating in the Copenhagen City heart study were asked about their perceived level of stress at baseline in 1981-3. These women were followed until 1999 in the Danish nationwide cancer registry, with < 0.1% loss to follow-up. MAIN OUTCOME MEASURE: First time incidence of primary breast cancer. RESULTS: During follow-up 251 women were diagnosed with breast cancer. After adjustment for confounders, women with high levels of stress had a hazard ratio of 0.60 (95% confidence interval 0.37 to 0.97) for breast cancer compared with women with low levels of stress. Furthermore, for each increase in stress level on a six point stress scale an 8% lower risk of primary breast cancer was found (hazard ratio 0.92, 0.85 to 0.99). This association seemed to be stable over time and was particularly pronounced in women receiving hormone therapy. CONCLUSION: High endogenous concentrations of oestrogen are a known risk factor for breast cancer, and impairment of oestrogen synthesis induced by chronic stress may explain a lower incidence of breast cancer in women with high stress. Impairment of normal body function should not, however, be considered a healthy response, and the cumulative health consequences of stress may be disadvantageous.
  38. ↑ Kroenke CH, Caregiving stress, endogenous sex steroid hormone levels, and breast cancer incidence, Am J Epidemiol 2004 june 1 159(11) 1019, Stress is hypothesized to be a risk factor for breast cancer. The authors examined associations of hours of, and self-reported levels of stress from, informal caregiving with prospective breast cancer incidence. Cross-sectional analyses of caregiving and endogenous sex steroid hormones were also conducted. In 1992 or 1996, 69,886 US women from the Nurses' Health Study, aged 46-71 years at baseline, answered questions on informal caregiving; 1,700 incident breast cancer cases accrued over follow-up to 2000. A subset of 665 postmenopausal women not taking exogenous hormones returned a blood sample in 1990. Numbers of hours of care provided to an ill adult or to a child were each summed and analyzed as 0 (reference), 1-14, and >/=15 per week. Cox proportional hazards models were used in prospective analyses and linear models in cross-sectional analyses. High numbers of caregiving hours and self-reported stress did not predict a higher incidence of breast cancer. However, compared with women providing no adult care, women providing >/=15 hours of adult care (median, 54) had significantly lower levels of estradiol (geometric mean, 9.21 pg/ml vs. 7.46 pg/ml (95% confidence interval: 6.36, 8.76)) and bioavailable estradiol (geometric mean, 1.86 pg/ml vs. 1.35 pg/ml (95% confidence interval: 1.00, 1.82)). Stress from caregiving did not appear to increase breast cancer risk.
  39. ↑ Tschuschke V: Pschoonkologie - Psychologische Aspekte der Entstehung und Bewältigung von Krebs. Stuttgard Schattauer 2002
  40. ↑ Pereira DB, Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus, Psychosom Med, 2003 May-Jun;65(3):427-34, http://www.psychosomaticmedicine.org/cgi/reprint/65/3/427?ijkey=0bd20bb958e7d5a62e1589bb41f88f55d0892e95 OBJECTIVE: Human immunodeficiency virus (HIV)-infected women are at risk for cervical intraepithelial neoplasia (CIN) and cancer due to impaired immunosurveillance over human papillomavirus (HPV) infection. Life stress has been implicated in immune decrements in HIV-infected individuals and therefore may contribute to CIN progression over time. The purpose of this study was to determine whether life stress was associated with progression and/or persistence of squamous intraepithelial lesions (SIL), the cytologic diagnosis conferred by Papanicolaou smear, after 1-year follow-up among women co-infected with HIV and HPV. METHOD: Thirty-two HIV-infected African-American and Caribbean-American women underwent a psychosocial interview, blood draw, colposcopy, and HPV cervical swab at study entry. Using medical chart review, we then abstracted SIL diagnoses at study entry and after 1-year follow-up. RESULTS: Hierarchical logistic regression analysis revealed that higher life stress increased the odds of developing progressive/persistent SIL over 1 year by approximately seven-fold after covarying relevant biological and behavioral control variables. CONCLUSIONS: These findings suggest that life stress may constitute an independent risk factor for SIL progression and/or persistence in HIV-infected women. Stress management interventions may decrease risk for SIL progression/persistence in women living with HIV.
  41. ↑ Antoni MH, Host moderator variables in the promotion of cervical neoplasia--II. Dimensions of life stress, J Psychosom Res, 1989;33(4):457-67, Controllability and predictability have been shown to mediate the aversive impact of life events on health. This study examined the relationship of these parameters (along with coping style) to the promotion of cervical intraepithelial neoplasia (CIN) to invasive squamous cell carcinoma of the cervix. Seventy-five female patients participated while awaiting the results of colposcopically directed biopsy performed during work-up of an abnormal Pap smear. The Million Behavioral Health Inventory, a modified form of the Life Experience Survey, and a semi-structured interview were administered before subjects learned of their biopsy results. Subjects defined as susceptible by previous research had positive (through generally nonsignificant) correlations between life events and promotion while resilient subjects had negative correlations. The relationship between controllability of life events and CIN was moderated beneficially by a sociable and confident style and detrimentally by an inhibited style and a pessimistic attitude. Life event predictability did not contribute to CIN promotion beyond the effects of controllability.
  42. ↑ Yehuda R, Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy, J Clin Endocrin Metab 2005 Jul;90(7):4115-8. Epub 2005 May 3 http://jcem.endojournals.org/cgi/reprint/90/7/4115?ijkey=3fb94906118ae5ce99eaee74d30221b9e54bd4f1 CONTEXT: Reduced cortisol levels have been linked with vulnerability to posttraumatic stress disorder (PTSD) and the risk factor of parental PTSD in adult offspring of Holocaust survivors. OBJECTIVE: The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001 during pregnancy. DESIGN: Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-yr-old babies at awakening and at bedtime. RESULTS: Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters. CONCLUSIONS: The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD.
  43. ↑ Forsen A, Psychosocial stress as a risk for breast cancer, Psychother Psychosom, 1991;55(2-4):176-85 Life events, important emotional losses, difficult life situations, and psychological characteristics were investigated in a case-control study of 87 breast cancer patients and their controls. In a second part, the effect of stressful life events preceding cancer diagnosis on survival was studied in an 8-year follow-up of the breast cancer group. The control group was selected from the general female population and matched for sex, age, number of child-births, and language. The findings showed that breast cancer patients had significantly more life events, important losses, and difficult life situations prior to the discovery of the breast tumor than controls. The analysis indicated that important losses during a 6-year prodromal period and life event scores prior to examination on both the 12-month and modified 6-year Social Readjustment Rating Scale were associated with subsequent development of breast cancer. The association persisted after adjustment for marital status, education, and social class. The findings of the survival analyses indicated that life events in the 12 months preceding the onset of breast cancer and lower social class were associated with a smaller chance of disease-free and overall survival after controlling for clinical factors.
  44. ↑ Ramirez AJ, Craig TKJ, Watson JP, Fentiman IS, North WRS, Rubens RD. Stress and relapse of breast cancer. BMJ 1989;298:291-3, To elucidate the association between stressful life events and the development of cancer the influence of life stress on relapse in operable breast cancer was examined in matched pairs of women in a case-control study. Adverse life events and difficulties occurring during the postoperative disease free interval were recorded in 50 women who had developed their first recurrence of operable breast cancer and during equivalent follow up times in 50 women with operable breast cancer in remission. The cases and controls were matched for the main physical and pathological factors known to be prognostic in breast cancer and sociodemographic variables that influence the frequency of life events and difficulties. Severely threatening life events and difficulties were significantly associated with the first recurrence of breast cancer. The relative risk of relapse associated with severe life events was 5.67 (95% confidence interval 1.57 to 37.20), and the relative risk associated with severe difficulties was 4.75 (1.58 to 19.20). Life events and difficulties not rated as severe were not related to relapse. Experiencing a non-severe life event was associated with a relative risk of 2.0 (0.62 to 7.47), and experiencing a non-severe difficulty was associated with a relative risk of 1.13 (0.38 to 3.35). These results suggest a prognostic association between severe life stressors and recurrence of breast cancer, but a larger prospective study is needed for confirmation.
  45. ↑ Barraclough J, Pinder P, Cruddas M, Osmond C, Taylor I, Perry M. Life events and breast cancer prognosis. BMJ 1992;304:1078-81 OBJECTIVE--To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN--Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING--Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS--204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES--Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS--After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION--These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.
  46. ↑ Graham J, Stressful life experiences and risk of relapse of breast cancer: observational cohort study, BMJ, 2002 Jun 15;324(7351):1420 http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=115851&blobtype=pdf OBJECTIVE: To confirm, using an observational cohort design, the relation between severely stressful life experiences and relapse of breast cancer found in a previous case-control study. DESIGN: Prospective follow up for five years of a cohort of women newly diagnosed as having breast cancer, collecting data on stressful life experiences, depression, and biological prognostic factors. SETTING: NHS breast clinic, London; 1991-9. PARTICIPANTS: A consecutive series of women aged under 60 newly diagnosed as having a primary operable breast tumour. 202/222 (91%) eligible women participated in the first life experiences interview. 170 (77%) provided complete interview data either up to 5 years after diagnosis or to recurrence. MAIN OUTCOME MEASURE: Recurrence of disease. RESULTS: We controlled for biological prognostic factors (lymph node infiltration and tumour histology), and found no increased risk of recurrence in women who had had one or more severely stressful life experiences in the year before diagnosis compared with women who did not (hazard ratio 1.01, 95% confidence interval 0.58 to 1.74, P=0.99). Women who had had one or more severely stressful life experiences in the 5 years after diagnosis had a lower risk of recurrence (0.52, 0.29 to 0.95, P=0.03) than those who did not. CONCLUSION: These data do not confirm an earlier finding from a case-control study that severely stressful life experiences increase the risk of recurrence of breast cancer. Differences in case control and prospective methods may explain the contradictory results. We took the prospective study as the more robust, and the results suggest that women with breast cancer need not fear that stressful experiences will precipitate the return of their disease.
  47. ↑ Chen CC, Adverse life events and breast cancer: case-control study, BMJ, 1995 Dec 9;311(7019):1527-30 OBJECTIVE--To investigate the strength of association between past life events and the development of breast cancer. DESIGN--Case-control study. A standardised life events interview and rating was administered before a definitive diagnosis. SETTING--Breast Cancer Screening Assessment Unit and surgical outpatient clinics at King's College Hospital, London. SUBJECTS--119 consecutive women aged 20-70 who were referred for biopsy of a suspicious breast lesion. MAIN OUTCOME MEASURES--Odds ratio of the risk of developing breast cancer after life events in the preceding five years after adjustment for confounders. RESULTS--41 women were diagnosed as having malignant disease while the remainder had benign conditions. Severe life events increased the risk of breast cancer. The crude odds ratio was 3.2 (95% confidence interval 1.35 to 7.6). After adjustment for age and the menopause and other potential confounders this rose to 11.6 (3.1 to 43.7). Multiple logistic regression analysis showed that all severe events and coping with the stress of adverse events by confronting them and focusing on the problems significantly predicted a diagnosis of breast cancer. Non-severe life events and long term difficulties had no significant association. CONCLUSION--These findings suggest an aetiological association between life stress and breast cancer.
  48. ↑ Protheroe D, Stressful life events and difficulties and onset of breast cancer: case-control study, BMJ, 1999 Oct 16;319(7216):1027-30 OBJECTIVE: To determine the relation between stressful life events and difficulties and the onset of breast cancer. DESIGN: Case-control study. SETTING: 3 NHS breast clinics serving west Leeds. Participants: 399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents. MAIN OUTCOME MEASURES: Odds ratios of the risk of developing breast cancer after experiencing one or more severe life events, severe difficulties, severe 2 year non-personal health difficulties, or severe 2 year personal health difficulties in the 5 years before clinical presentation. RESULTS: 332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1. 81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump. CONCLUSION: These findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.
  49. ↑ Roberts FD, Self-reported stress and risk of breast cancer, Cancer, 1996 Mar 15;77(6):1089-93 BACKGROUND: Many women attribute the development of their breast cancer to psychosocial factors such as stress and depression. Yet investigations of the relationship between breast cancer and stressful life events have had inconsistent outcomes, due in part to studies with small sample sizes and reliance on hospital-based populations. METHODS: As part of a population-based, case-control study of breast cancer etiology, we evaluated the association between stressful life events and the risk of breast cancer among 258 breast cancer patients and 614 randomly selected population-based controls. Information on 11 stressful life events was collected in telephone interviews with women aged 50-79 who were participating in the ongoing study. RESULTS: Breast cancer patients and controls experienced the same number of stressful life events in the five years prior to diagnosis or an equivalent reference date (controls), averaging 2.4 and 2.6 events, respectively. After adjustment for known breast cancer risk factors, there was no association between weighted stressful life event scores and the risk of breast cancer (odds ratio [OR] = 0.90 per unit increase; 95% confidence interval [CI], 0.78-1.05). Only one life event, death of a close friend, was significantly more often reported by controls (OR = 0.72; 95% CI, 0.52-1.00). Other life events were inconsistently and nonsignificantly associated with breast cancer risk. CONCLUSIONS. The results of this retrospective study do not suggest any important associations between stressful life events and breast cancer risk.
  50. ↑ McKenna MC, Psychosocial factors and the development of breast cancer: a meta-analysis, health psychol, 1999 Sep;18(5):520-31 A meta-analysis examined the relationship between psychosocial factors and the development of breast cancer. Average effect sizes (Hedges's g) were calculated from 46 studies for 8 major construct categories: anxiety/depression, childhood family environment, conflict-avoidant personality, denial/repression coping, anger expression, extraversion-introversion, stressful life events, and separation/loss. Significant effect sizes were found for denial/repression coping (g = .38), separation/loss experiences (g = .29), and stressful life events (g = .25). Although conflict-avoidant personality style was also significant (g = .19), the effect size was less robust, and a moderate number of future studies with null results would reduce the significance. Results overall support only a modest association between specific psychosocial factors and breast cancer and are contrary to the conventional wisdom that personality and stress influence the development of breast cancer.
  51. ↑ Chorot P, Life events and stress reactivity as predictors of cancer, coronary heart disease and anxiety disorders, int j psychosom, 1994;41(1-4):34-40 The topic relative to the differential psychobiological mechanisms between cancer and coronary illness has been showing for the last years. In this sense, some theoretical models which have been formulated by relevant authors have suggested the possibility of differentiating cancer and cardiovascular disease, both the onset and the progression, from coping strategies, personality variables and affective states, as well as the different categories of psychosocial stress. Likewise, the implication of psychological distress, such as anxiety, anger and depression for the occurrence of somatic disease has been reported frequently. This research was designed to analyze the psychosocial patterns which could explain the incidence of heart disease, cancer and anxiety based disorders. Measures of life events and stress reactivity were obtained from a total of 109 patients diagnosed as having breast cancer (37), infarct (37), and anxiety (35), and from 72 normal control subjects. Our data tend to show that the cancer group was strongly predicted by lost and illness events, while the coronary group was more associated with work events. The anxiety disorders group lacked a life events dimension, but shared the same category of the infarct group. We also found a strong relationship between depressive reactions and cancer in contrast to the anxiety-anger variable that was more relevant in the infarct patients. The interaction between internal and external stress factors in the etiology of disease is also discussed.
  52. ↑ Butow PN, Epidemiological evidence for a relationship between life events, coping style, and personality factors in the development of breast cancer, J Psychom res, 2000 Sep;49(3):169-81 OBJECTIVE: Review empirical evidence for a relationship between psychosocial factors and breast cancer development. METHODS: Standardised quality assessment criteria were utilised to assess the evidence of psychosocial predictors of breast cancer development in the following domains: (a) stressful life events, (b) coping style, (c) social support, and (d) emotional and personality factors. RESULTS: Few well-designed studies report any association between life events and breast cancer, the exception being two small studies using the Life Events and Difficulties Schedule (LEDS) reporting an association between severely threatening events and breast cancer risk. Seven studies show anger repression or alexithymia are predictors, the strongest evidence suggesting younger women are at increased risk. There is no evidence that social support, chronic anxiety, or depression affects breast cancer development. With the exception of rationality/anti-emotionality, personality factors do not predict breast cancer risk. CONCLUSION: The evidence for a relationship between psychosocial factors and breast cancer is weak. The strongest predictors are emotional repression and severe life events. Future research would benefit from theoretical grounding and greater methodological rigour. Recommendations are given.
  53. ↑ Price MA, The role of psychosocial factors in the development of breast carcinoma: Part II. Life event stressors, social support, defense style, and emotional control and their interactions, Cancer, 2001 Feb 15;91(4):686-97 BACKGROUND: The evidence supporting an association between life event stress and breast carcinoma development is inconsistent. METHODS: Five hundred fourteen women requiring biopsy after routine mammographic breast screening were interviewed using the Brown and Harris Life Event and Difficulties Schedule. Other psychosocial variables assessed included social support, emotional control, and defense style. Biopsy results identified 239 women with breast carcinoma and 275 women with benign breast disease. Multiple logistic regression analysis was used to distinguish between breast carcinoma subjects and benign breast disease controls based on these psychosocial variables and their interactions. RESULTS: The findings of the current study revealed a significant interaction between highly threatening life stressors and social support. Women experiencing a stressor objectively rated as highly threatening and who were without intimate emotional social support had a ninefold increase in risk of developing breast carcinoma. CONCLUSIONS: Although there was no evidence of an independent association between life event stress and breast carcinoma, the findings of the current study provided strong evidence that social support interacts with highly threatening life stressors to increase the risk of breast carcinoma significantly.
  54. ↑ Maunsell E, Stressful life events and survival after breast cancer, Psychosom Med, 2001 Mar-Apr;63(2):306-15 http://www.psychosomaticmedicine.org/cgi/reprint/63/2/306?ijkey=c89eedfd5ea3b5021d6d4b83a3ccfe4539246efa OBJECTIVE: This study assessed the relation of stressful life events with survival after breast cancer. METHODS: This study was based on women with histologically confirmed, newly diagnosed, localized or regional stage breast cancer first treated in 1 of 11 Quebec City (Canada) hospitals from 1982 through 1984. Among 765 eligible patients, 673 (88%) were interviewed 3 to 6 months after diagnosis about the number and perceived impact of stressful events in the 5 years before diagnosis. Three scores were calculated: number of events; number weighted by reported impact; and for almost 80% of events, number weighted by community-derived values reflecting adjustment required by the event. Scores were divided into quartiles to assess possible dose-response relationships. Survival was assessed in 1993. Hazard ratios and 95% confidence intervals (CIs) comparing all-cause and breast cancer-specific mortality were calculated with adjustment for age, presence of invaded axillary nodes, adjuvant radiotherapy, and systemic therapy (ie, chemotherapy and hormone therapy). RESULTS: When quartiles 2, 3, and 4 were compared with the appropriate lowest quartile, adjusted hazard ratios for all-cause mortality were 0.99 (CI = 0.70-1.38), 0.97 (CI = 0.73-1.31), and 1.04 (CI = 0.78-1.40) for number, number weighted by impact, and number weighted by community-derived values, respectively. Results were essentially similar for the relation between stressful life events limited to those occurring within the 12 months before diagnosis and overall mortality and between stressful life events in the 5 years before diagnosis and breast cancer-specific mortality. CONCLUSIONS: Stress was conceptualized as life events presumed to be negative, undesirable, or to require adjustment by the person confronting them. We found no evidence indicating that this kind of stress during the 5 years before diagnosis negatively affected survival among women with nonmetastatic breast cancer. Evidence from this study and others on the lack of effect of this type of stress on survival may be reassuring for women living with breast cancer.
  55. ↑ Protheroe D, Stressful life events and difficulties and onset of breast cancer: case-control study, BMJ, 1999 Oct 16;319(7216):1027-30 OBJECTIVE: To determine the relation between stressful life events and difficulties and the onset of breast cancer. DESIGN: Case-control study. SETTING: 3 NHS breast clinics serving west Leeds. Participants: 399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents. MAIN OUTCOME MEASURES: Odds ratios of the risk of developing breast cancer after experiencing one or more severe life events, severe difficulties, severe 2 year non-personal health difficulties, or severe 2 year personal health difficulties in the 5 years before clinical presentation. RESULTS: 332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1. 81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump. CONCLUSION: These findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.
  56. ↑ Lillberg K, Stress of daily activities and risk of breast cancer: a prospective cohort study in Finland, int j cancer, 2001 Mar 15;91(6):888-93 The belief that life stress enhances breast cancer is common, but there are few prospective epidemiological studies on the relationship of life stress and breast cancer. We have investigated the association between stress of daily activities (SDA) and breast-cancer risk in a prospective cohort study of 10,519 Finnish women aged 18 years or more. SDA measures a subject's own appraisal of daily stress. It was assessed in 1975 and 1981 by a self-administered questionnaire, which also provided information on subject characteristics and other known breast-cancer risk factors. Follow-up data for breast cancer from 1976 to 1996 were attained through record linkage to the Finnish Cancer Registry. Study subjects were divided into 3 groups based on their SDA scores in 1975: no stress (23% of subjects), some stress (68%) and severe stress (9%). Hazard ratios (HRs) and respective 95% confidence intervals (CIs) for incidence of breast cancer by level of SDA were obtained from the Cox proportional hazards model. We identified 205 incident breast cancers in the cohort. Multivariable-adjusted HRs for breast-cancer risk were 1.00 (reference), 1.11 (95% CI 0.78-1.57) and 0.96 (95% CI 0.53-1.73) by increasing level of stress. Neither shifting of the SDA cut-off points nor restricting the analysis to women who reported the same level of SDA in 1975 and 1981 materially altered the results. We found no evidence of an association between self-perceived daily stress and breast-cancer risk.
  57. ↑ Duijts SF, The association between stressful life events and breast cancer risk: a meta-analysis, int j cancer, 2003 Dec 20;107(6):1023-9 Breast cancer is the most prevalent cancer in women in Western societies. Studies examining the relationship between stressful life events and breast cancer risk have produced conflicting results. The purpose of this meta-analysis was to identify studies on this relationship, between 1966 and December 2002, to summarize and quantify the association and to explain the inconsistency in previous results. Summary odds ratios and standard errors were calculated, using random effect meta-regression analyses, for the following categories: stressful life events, death of spouse, death of relative or friend, personal health difficulties, nonpersonal health difficulties, change in marital status, change in financial status and change in environmental status. The presence of publication bias has been explored, and sensitivity analyses were performed to identify heterogeneity, using calculation of the percentage of variability due to heterogeneity, meta-regression analyses and stratification. Only the categories stressful life events (OR = 1.77, 95% CI 1.31-2.40), death of spouse (OR = 1.37, 95% CI 1.10-1.71) and death of relative or friend (OR = 1.35, 95% CI 1.09-1.68) showed a statistically significant effect. Publication bias was identified in both stressful life events (p = 0.00) and death of relative or friend (p = 0.02). Sensitivity analyses resulted in the identification of heterogeneity in all categories, except death of spouse. The results of this meta-analysis do not support an overall association between stressful life events and breast cancer risk. Only a modest association could be identified between death of spouse and breast cancer risk. Copyright 2003 Wiley-Liss, Inc.
  58. ↑ Dalton SO, Mind and cancer. Do psychological factors cause cancer? in: Eur J Cancer. 2002 Jul;38(10):1313-23 We have reviewed the evidence for an association between major life events, depression and personality factors and the risk for cancer. We identified and included only those prospective or retrospective studies in which the psychological variable was collected independently of the outcome. The evidence failed to support the hypothesis that major life events are a risk factor for cancer. The evidence was inconsistent for both depression and personality factors. Chance, bias or confounding may explain this result, as many of the studies had methodological weaknesses. The generally weak associations found, the inconsistency of the results, the unresolved underlying biological mechanism and equivocal findings of dose-response relationships prevent a conclusion that psychological factors are established risk factors. However, certain intriguing findings warrant further studies, which must, however, be well conducted and large and include detailed information on confounders.
  59. ↑ Kvikstad A, Widowhood and divorce in relation to overall survival among middle-aged Norwegian women with cancer, Br J Cancer 1995 june 71(6) 1343, The aim of the study was to examine the relations between widowhood and divorce and overall survival among women with cancer. All Norwegian women born between 1935 and 1954, and diagnosed with cancer between 1966 and 1990, were followed up until 1991. In all, 14,231 cases were followed up for a median length of approximately 4.5 years (mean = 6 years), and 4311 women died during follow-up. In addition to overall cancer, separate analyses have been made for cancer at specific sites. Widows had a risk of dying which was nearly identical to that of married women for all sites except colorectal cancer, for which widows had a 2-fold increased death rate compared with married women. Divorced women had an overall increased hazard ratio of 1.17 (95% CI 1.07-1.27), which was confined to cancer of the breast, lung and cervix. With few clear exceptions women with children had a better survival than nulliparous women (overall hazard ratio = 0.80, 95% CI 0.74-0.87).
  60. ↑ Kvikstad A, Risk and prognosis of cancer in middle-aged women who have experienced the death of a child. Int J Cancer, 1996 july 17 67(2) 165, First, we studied the relative risk of cancer among women born between 1935 and 1954 who had experienced a child's death, compared with women without this experience. Second, we examined whether survival was any different between cancer patients in the 2 groups. The study was a population-based nested case-control study that included 14,669 cancer cases and 29,750 age-matched controls. The women who were included as incident cases were further analyzed using Cox regression in a study of total survival. The overall relative risk of cancer among women who had lost a child was nearly identical to that of women who had not lost a child (OR = 0.96, 95% confidence interval 0.87-1.07), after adjustment for age and parity. In the analysis of specific cancer sites, there was no difference in relative risk between the 2 groups. In relation to cancer survival, we found that patients who had lost a child had an overall risk of dying that was nearly identical to patients who had not had this experience (HR = 1.08, 95% confidence interval 0.92-1.26), after adjustment for age and stage at diagnosis. For specific sites of cancer, the results also showed no difference in survival between the 2 groups. In conclusion, risk and survival of cancer were not different among women who had experienced the death of a child from the risk and survival among women without this experience.
  61. ↑ Lillberg K, Stressful life events and risk of breast cancer in 10,808 women: a cohort study, Am j epidemiol, 2003 Mar 1;157(5):415-23 http://aje.oxfordjournals.org/cgi/reprint/157/5/415?ijkey=0b9693306207f4d2e7dd1f46e798450a51bc7ead The authors prospectively investigated the relation between stressful life events and risk of breast cancer among 10,808 women from the Finnish Twin Cohort. Life events and breast cancer risk factors were assessed by self-administered questionnaire in 1981. A national modification of a standardized life event inventory was used, examining accumulation of life events and individual life events and placing emphasis on the 5 years preceding completion of the questionnaire. Through record linkage with the Finnish Cancer Registry, 180 incident cases of breast cancer were identified in the cohort between 1982 and 1996. The multivariable adjusted hazard ratio for breast cancer per one-event increase in the total number of life events was 1.07 (95% confidence interval (CI): 1.00, 1.15). This risk estimate rose to 1.35 (95% CI: 1.09, 1.67) when only major life events were taken into account. Independently of total life events, divorce/separation (hazard ratio (HR) = 2.26, 95% CI: 1.25, 4.07), death of a husband (HR = 2.00, 95% CI: 1.03, 3.88), and death of a close relative or friend (HR = 1.36, 95% CI: 1.00, 1.86) were all associated with increased risk of breast cancer. The findings suggest a role for life events in breast cancer etiology through hormonal or other mechanisms.
  62. ↑ Pereira DB, Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus, Psychosom Med, 2003 May-Jun;65(3):427-34 http://www.psychosomaticmedicine.org/cgi/reprint/65/3/427?ijkey=0bd20bb958e7d5a62e1589bb41f88f55d0892e95 OBJECTIVE: Human immunodeficiency virus (HIV)-infected women are at risk for cervical intraepithelial neoplasia (CIN) and cancer due to impaired immunosurveillance over human papillomavirus (HPV) infection. Life stress has been implicated in immune decrements in HIV-infected individuals and therefore may contribute to CIN progression over time. The purpose of this study was to determine whether life stress was associated with progression and/or persistence of squamous intraepithelial lesions (SIL), the cytologic diagnosis conferred by Papanicolaou smear, after 1-year follow-up among women co-infected with HIV and HPV. METHOD: Thirty-two HIV-infected African-American and Caribbean-American women underwent a psychosocial interview, blood draw, colposcopy, and HPV cervical swab at study entry. Using medical chart review, we then abstracted SIL diagnoses at study entry and after 1-year follow-up. RESULTS: Hierarchical logistic regression analysis revealed that higher life stress increased the odds of developing progressive/persistent SIL over 1 year by approximately seven-fold after covarying relevant biological and behavioral control variables. CONCLUSIONS: These findings suggest that life stress may constitute an independent risk factor for SIL progression and/or persistence in HIV-infected women. Stress management interventions may decrease risk for SIL progression/persistence in women living with HIV.
  63. ↑ Rayne S, Using exterior building surface films to assess human exposure and health risks from PCDD/Fs in New York City, USA, after the World Trade Center attacks, J Hazard Mater 2005 Dec 9;127(1-3):33-9 Concentrations of tetra- through octa-chlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined in exterior window films from Manhattan and Brooklyn in New York City (NYC), USA, 6 weeks after the World Trade Center (WTC) attacks of 11 September 2001. High concentrations of the 2,3,7,8-substituted congeners (P(2378)CDD/Fs) were observed, at levels up to 6600 pg-TEQ g(-1) nearest the WTC site. An equilibrium partitioning model was developed to reconstruct total gas + particle-phase atmospheric concentrations of P(2378)CDD/Fs at each site. The reconstructed atmospheric and window film concentrations were subsequently used in a preliminary human health risk assessment to estimate the potential cancer and non-cancer risks posed to residents of lower Manhattan from these contaminants over the 6 week exposure period between the WTC attacks and sampling dates. Residents of lower Manhattan appear to have a slightly elevated cancer risk (up to 1.6% increase over background) and increased P(2378)CDD/F body burden (up to 8.0% increase over background) because of above-background exposure to high concentrations of P(2378)CDD/Fs produced from the WTC attacks during the short period between 11 September 2001, and window film sampling 6 weeks later.
  64. ↑ http://www.meb.uni-bonn.de/cancernet/600317.html National Cancer Institute: Psychological Stress and Cancer
  65. ↑ Chen CC, Adverse life events and breast cancer: case-control study, BMJ, 1995 Dec 9;311(7019):1527-30 OBJECTIVE--To investigate the strength of association between past life events and the development of breast cancer. DESIGN--Case-control study. A standardised life events interview and rating was administered before a definitive diagnosis. SETTING--Breast Cancer Screening Assessment Unit and surgical outpatient clinics at King's College Hospital, London. SUBJECTS--119 consecutive women aged 20-70 who were referred for biopsy of a suspicious breast lesion. MAIN OUTCOME MEASURES--Odds ratio of the risk of developing breast cancer after life events in the preceding five years after adjustment for confounders. RESULTS--41 women were diagnosed as having malignant disease while the remainder had benign conditions. Severe life events increased the risk of breast cancer. The crude odds ratio was 3.2 (95% confidence interval 1.35 to 7.6). After adjustment for age and the menopause and other potential confounders this rose to 11.6 (3.1 to 43.7). Multiple logistic regression analysis showed that all severe events and coping with the stress of adverse events by confronting them and focusing on the problems significantly predicted a diagnosis of breast cancer. Non-severe life events and long term difficulties had no significant association. CONCLUSION--These findings suggest an aetiological association between life stress and breast cancer.
  66. ↑ Pereira DB, Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus, Psychosom Med, 2003 May-Jun;65(3):427-34 http://www.psychosomaticmedicine.org/cgi/reprint/65/3/427?ijkey=0bd20bb958e7d5a62e1589bb41f88f55d0892e95 OBJECTIVE: Human immunodeficiency virus (HIV)-infected women are at risk for cervical intraepithelial neoplasia (CIN) and cancer due to impaired immunosurveillance over human papillomavirus (HPV) infection. Life stress has been implicated in immune decrements in HIV-infected individuals and therefore may contribute to CIN progression over time. The purpose of this study was to determine whether life stress was associated with progression and/or persistence of squamous intraepithelial lesions (SIL), the cytologic diagnosis conferred by Papanicolaou smear, after 1-year follow-up among women co-infected with HIV and HPV. METHOD: Thirty-two HIV-infected African-American and Caribbean-American women underwent a psychosocial interview, blood draw, colposcopy, and HPV cervical swab at study entry. Using medical chart review, we then abstracted SIL diagnoses at study entry and after 1-year follow-up. RESULTS: Hierarchical logistic regression analysis revealed that higher life stress increased the odds of developing progressive/persistent SIL over 1 year by approximately seven-fold after covarying relevant biological and behavioral control variables. CONCLUSIONS: These findings suggest that life stress may constitute an independent risk factor for SIL progression and/or persistence in HIV-infected women. Stress management interventions may decrease risk for SIL progression/persistence in women living with HIV.
  67. ↑ Graham J, Stressful life experiences and risk of relapse of breast cancer: observational cohort study, BMJ, 2002 Jun 15;324(7351):1420 http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=115851&blobtype=pdf OBJECTIVE: To confirm, using an observational cohort design, the relation between severely stressful life experiences and relapse of breast cancer found in a previous case-control study. DESIGN: Prospective follow up for five years of a cohort of women newly diagnosed as having breast cancer, collecting data on stressful life experiences, depression, and biological prognostic factors. SETTING: NHS breast clinic, London; 1991-9. PARTICIPANTS: A consecutive series of women aged under 60 newly diagnosed as having a primary operable breast tumour. 202/222 (91%) eligible women participated in the first life experiences interview. 170 (77%) provided complete interview data either up to 5 years after diagnosis or to recurrence. MAIN OUTCOME MEASURE: Recurrence of disease. RESULTS: We controlled for biological prognostic factors (lymph node infiltration and tumour histology), and found no increased risk of recurrence in women who had had one or more severely stressful life experiences in the year before diagnosis compared with women who did not (hazard ratio 1.01, 95% confidence interval 0.58 to 1.74, P=0.99). Women who had had one or more severely stressful life experiences in the 5 years after diagnosis had a lower risk of recurrence (0.52, 0.29 to 0.95, P=0.03) than those who did not. CONCLUSION: These data do not confirm an earlier finding from a case-control study that severely stressful life experiences increase the risk of recurrence of breast cancer. Differences in case control and prospective methods may explain the contradictory results. We took the prospective study as the more robust, and the results suggest that women with breast cancer need not fear that stressful experiences will precipitate the return of their disease.
  68. ↑ Bleiker EM - van der Ploeg, Psychosocial factors in the etiology of breast cancer: review of a popular link, Pat Educ Couns, 1999 Jul;37(3):201-14 Breast cancer is the most frequently occurring type of cancer in women in the western world. The etiology of a large proportion of breast cancers is still unexplained, and the possibility that psychosocial factors could play a role is not ruled out. Already in pre-Christian times, it was assumed that psychological factors might play a significant role in the development of breast cancer. However, studies have failed to produce conclusive results. There is still a lack of knowledge on the relationship between breast cancer development and psychosocial factors such as stressful life events, coping styles, depression, and the ability to express emotions. The results of this review show that there is not enough evidence that psychosocial factors like 'ways of coping' or 'non-expression of negative emotions', play a significant role in the etiology of breast cancer.
  69. ↑ Petticrew M, Cancer-stress link: the truth, 1999 Nurs Times Mar 3-9 95
  70. ↑ Besedovsky HO, Psychoneuroimmunology and cancer: fifteenth Sapporo Cancer Seminar, Cancer res, 1996 Sep 15;56(18):4278-81 http://cancerres.aacrjournals.org/cgi/reprint/56/18/4278?ijkey=f9e6ec7bd08e32d5a719b5b2b21441f363b22767&keytype2=tf_ipsecsha
  71. ↑ Sacerdote P, Opioids and the immune system, Palliat Med 2006;20 Suppl 1:s9-15, Opioid compounds such as morphine produce powerful analgesia that is effective in treating various types of pain. In addition to their therapeutic efficacy, opioids can produce several well known adverse events, and, as has recently been recognized, can interfere with the immune response. The immunomodulatory activities of morphine have been characterized in animal and human studies. Morphine can decrease the effectiveness of several functions of both natural and adaptive immunity, and significantly reduces cellular immunity. Indeed, in animal studies morphine is consistently associated with increased morbidity and mortality due to infection and worsening of cancer. However, from several animal studies it emerges that not all opioids induce the same immunosuppressive effects, and evaluating each opioid's profile is important for appropriate analgesic selection. Buprenorphine is a potent opioid that is frequently prescribed for chronic pain. Acute intracerebroventricular administration of buprenorphine has been shown in rats not to affect cellular immune responses, while a statistically significant inhibition of the immune response was observed with morphine. In mouse studies, chronic administration of buprenorphine led to immune parameters important for antimicrobial responses or for anti-tumour surveillance (lymphoproliferation, natural killer (NK)-lymphocyte activity, cytokine production, lymphocyte number) being unaffected. In contrast, levels of these immune markers were significantly reduced when the potent micro-agonist fentanyl was administered, but recovered after longer periods as tolerance developed. Because the intrinsic immunosuppressive activity varies between individual opioids, predicting the outcome on immunity can be difficult. To study this, the effects of morphine, fentanyl and buprenorphine on NK-lymphocyte activity depressed by experimental surgery were examined in rats. Treating animals immediately after surgery with equianalgesic doses of morphine and buprenorphine significantly reduced surgery-induced immunosuppression. However, buprenorphine reverted NK-lymphocyte activity to preoperative levels, while in morphine-treated rats NK-lymphocyte activity was ameliorated, although not completely. In contrast, fentanyl did not prevent immunosuppression induced by surgery. Overall, from several animal studies it emerges that buprenorphine has the more favourable profile, being a potent analgesic devoid of intrinsic immunosuppressive activity.
  72. ↑ Beilin B, Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period, Anesth Analg 1996 Mar;82(3):492-7, Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC). This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large- (LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined.
  73. ↑ Basak S, A Fourth IkappaB Protein within the NF-kappaB Signaling Module, Cell 2007 jan 26 128(2) 369, Inflammatory NF-kappaB/RelA activation is mediated by the three canonical inhibitors, IkappaBalpha, -beta, and -varepsilon. We report here the characterization of a fourth inhibitor, nfkappab2/p100, that forms two distinct inhibitory complexes with RelA, one of which mediates developmental NF-kappaB activation. Our genetic evidence confirms that p100 is required and sufficient as a fourth IkappaB protein for noncanonical NF-kappaB signaling downstream of NIK and IKK1. We develop a mathematical model of the four-IkappaB-containing NF-kappaB signaling module to account for NF-kappaB/RelA:p50 activation in response to inflammatory and developmental stimuli and find signaling crosstalk between them that determines gene-expression programs. Further combined computational and experimental studies reveal that mutant cells with altered balances between canonical and noncanonical IkappaB proteins may exhibit inappropriate inflammatory gene expression in response to developmental signals. Our results have important implications for physiological and pathological scenarios in which inflammatory and developmental signals converge.
  74. ↑ Der beste Arzt scheint mir der zu sein, der sich auf Voraussicht versteht. Denn wenn er den gegenwärtigen und den ihm vorhergegangenen und den küfftigen Stand einer Krankheit schon vorher erkennt und den Kranken vorhersagt und ihnen erklärt, was sie unterlassen haben, dann werden sie ihm vertrauen, weil er ihren Zustand besser als sie selber erkennt, sodass die Menschen es wagen, sich dem Arzt anzuvertrauen. Ihre Therapie wird er aber am richtigsten vornehmen, wenn er aus dem gegenwärtigen Stand ihrer Krankheit deren künftigen Verlauf vorhersagt. Dal Corpus Hippocraticum di Ipocrate.
  75. ↑ Fallowfield LJ, Truth may hurt but deceit hurts more: communication in palliative care, Palliat Med, 2002 Jul;16(4):297-303 Healthcare professionals often censor their information giving to patients in an attempt to protect them from potentially hurtful, sad or bad news. There is a commonly expressed belief that what people do not know does not harm them. Analysis of doctor and nurse/patient interactions reveals that this well-intentioned but misguided assumption about human behaviour is present at all stages of cancer care. Less than honest disclosure is seen from the moment that a patient reports symptoms, to the confirmation of diagnosis, during discussions about the therapeutic benefits of treatment, at relapse and terminal illness. This desire to shield patients from the reality of their situation usually creates even greater difficulties for patients, their relatives and friends and other members of the healthcare team. Although the motivation behind economy with the truth is often well meant, a conspiracy of silence usually results in a heightened state of fear, anxiety and confusion--not one of calm and equanimity. Ambiguous or deliberately misleading information may afford short-term benefits while things continue to go well, but denies individuals and their families opportunities to reorganize and adapt their lives towards the attainment of more achievable goals, realistic hopes and aspirations. In this paper, some examples and consequences of accidental, deliberate, if well-meaning, attempts to disguise the truth from patients, taken verbatim from interviews, are given, together with cases of unintentional deception or misunderstandings created by the use of ambiguous language. We also provide evidence from research studies showing that although truth hurts, deceit may well hurt more. 'I think the best physician is the one who has the providence to tell to the patients according to his knowledge the present situation, what has happened before, and what is going to happen in the future' (Hippocrates).
  76. ↑ Lillberg K, Stress of daily activities and risk of breast cancer: a prospective cohort study in Finland, int j cancer, 2001 Mar 15;91(6):888-93 The belief that life stress enhances breast cancer is common, but there are few prospective epidemiological studies on the relationship of life stress and breast cancer. We have investigated the association between stress of daily activities (SDA) and breast-cancer risk in a prospective cohort study of 10,519 Finnish women aged 18 years or more. SDA measures a subject's own appraisal of daily stress. It was assessed in 1975 and 1981 by a self-administered questionnaire, which also provided information on subject characteristics and other known breast-cancer risk factors. Follow-up data for breast cancer from 1976 to 1996 were attained through record linkage to the Finnish Cancer Registry. Study subjects were divided into 3 groups based on their SDA scores in 1975: no stress (23% of subjects), some stress (68%) and severe stress (9%). Hazard ratios (HRs) and respective 95% confidence intervals (CIs) for incidence of breast cancer by level of SDA were obtained from the Cox proportional hazards model. We identified 205 incident breast cancers in the cohort. Multivariable-adjusted HRs for breast-cancer risk were 1.00 (reference), 1.11 (95% CI 0.78-1.57) and 0.96 (95% CI 0.53-1.73) by increasing level of stress. Neither shifting of the SDA cut-off points nor restricting the analysis to women who reported the same level of SDA in 1975 and 1981 materially altered the results. We found no evidence of an association between self-perceived daily stress and breast-cancer risk.
  77. ↑ Helgesson O, Self-reported stress levels predict subsequent breast cancer in a cohort of Swedish women, Eur J Cancer Prev, 2003 12(5) 377, The association between stress and breast cancer has been studied, mostly using case-control designs, but rarely examined prospectively. The purpose of this paper is to describe the role of stress as a predictor of subsequent breast cancer. A representative cohort of 1,462 Swedish women aged 38-60 years were followed for 24 years. Stress experience at a baseline examination in 1968-69 was analysed in relation to incidence of breast cancer with proportional hazards regression. Women reporting experience of stress during the five years preceding the first examination displayed a two-fold rate of breast cancer compared with women reporting no stress (age-adjusted relative risk 2.1; 95% CI [1.2-3.7]). This association was independent of potential confounders including reproductive and lifestyle factors. In conclusion, the significant, positive relationship between stress and breast cancer in this prospective study is based on information that is unbiased with respect to knowledge of disease, and can be regarded as more valid than results drawn from case-control studies.
  78. ↑ Kroenke CH, Caregiving stress, endogenous sex steroid hormone levels, and breast cancer incidence, Am J Epidemiol 2004 june 1 159(11) 1019, Stress is hypothesized to be a risk factor for breast cancer. The authors examined associations of hours of, and self-reported levels of stress from, informal caregiving with prospective breast cancer incidence. Cross-sectional analyses of caregiving and endogenous sex steroid hormones were also conducted. In 1992 or 1996, 69,886 US women from the Nurses' Health Study, aged 46-71 years at baseline, answered questions on informal caregiving; 1,700 incident breast cancer cases accrued over follow-up to 2000. A subset of 665 postmenopausal women not taking exogenous hormones returned a blood sample in 1990. Numbers of hours of care provided to an ill adult or to a child were each summed and analyzed as 0 (reference), 1-14, and >/=15 per week. Cox proportional hazards models were used in prospective analyses and linear models in cross-sectional analyses. High numbers of caregiving hours and self-reported stress did not predict a higher incidence of breast cancer. However, compared with women providing no adult care, women providing >/=15 hours of adult care (median, 54) had significantly lower levels of estradiol (geometric mean, 9.21 pg/ml vs. 7.46 pg/ml (95% confidence interval: 6.36, 8.76)) and bioavailable estradiol (geometric mean, 1.86 pg/ml vs. 1.35 pg/ml (95% confidence interval: 1.00, 1.82)). Stress from caregiving did not appear to increase breast cancer risk.
  79. ↑ Nielsen NR, Self reported stress and risk of breast cancer: prospective cohort study, BMJ 2005 sept 10 331(7516) OBJECTIVE: To assess the relation between self reported intensity and frequency of stress and first time incidence of primary breast cancer. DESIGN: Prospective cohort study with 18 years of follow-up. SETTING: Copenhagen City heart study, Denmark. PARTICIPANTS: The 6689 women participating in the Copenhagen City heart study were asked about their perceived level of stress at baseline in 1981-3. These women were followed until 1999 in the Danish nationwide cancer registry, with < 0.1% loss to follow-up. MAIN OUTCOME MEASURE: First time incidence of primary breast cancer. RESULTS: During follow-up 251 women were diagnosed with breast cancer. After adjustment for confounders, women with high levels of stress had a hazard ratio of 0.60 (95% confidence interval 0.37 to 0.97) for breast cancer compared with women with low levels of stress. Furthermore, for each increase in stress level on a six point stress scale an 8% lower risk of primary breast cancer was found (hazard ratio 0.92, 0.85 to 0.99). This association seemed to be stable over time and was particularly pronounced in women receiving hormone therapy. CONCLUSION: High endogenous concentrations of oestrogen are a known risk factor for breast cancer, and impairment of oestrogen synthesis induced by chronic stress may explain a lower incidence of breast cancer in women with high stress. Impairment of normal body function should not, however, be considered a healthy response, and the cumulative health consequences of stress may be disadvantageous.
  80. ↑ Coyne JC et al,Emotional well-being does not predict survival in head and neck cancer patients, Cancer 2007 Volume 110, Issue 11 , pag. 2568 - 2575. A patient's positive or negative emotional state has no direct or indirect effect on cancer survival or disease progression, according to a large scale new study. Published in the December 1, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study found that emotional well-being was not an independent factor affecting the prognosis of head and neck cancers. The question of whether or not the mind, through psychological state and emotional status, has the ability to heal organic disease in the body continues to be reviewed and tested in human health research. A large body of evidence strongly suggests that, for life-threatening diseases such as advanced cancer, it does not. However, this debate continues in popular and scientific circles. Particular importance has been attached to the question because of the belief that if it can be shown that emotions affect the outcome of cancer, then psychotherapy might be able to aid in the fight against cancer. Dr. James Coyne and colleagues from the University of Pennsylvania say previous studies used patients with many different diseases, small sample sizes and an inadequate number of deaths to be conclusive. Dr. Coyne's team analyzed data from two community studies of patients with head and neck cancer "to examine whether emotional well being at study entry predicted survival." Their approach had the methodological strengths of using a homogenous population and many deaths to detect even small statistically significant effects. The sample included 1,093 patients with head and neck cancer who completed a quality of life questionnaire during their treatment. Of that group, 646 died during the length of the study. The analysis showed that emotional status was not associated with survival rate. Emotional status was not associated with survival even after investigating several other factors, such as gender, tumor site or disease stage. In one of the methodologically strongest studies to date, Dr. Coyne and co-authors found that emotional status "neither directly affected progression or death, nor functioned as a lurking variable." While this study may not end the e debate, it does provide the strongest evidence to date that psychological factors are not independently prognostic in cancer management. Moreover, a recent comprehensive review by Dr, Coyne and Dr, Stephen Palmer of the University of Pennsylvania and Michael Stefanek of the American Cancer Society failed to find credible evidence in the available studies for the claim that cancer patients' participation in psychotherapy or support groups prolonged their lives. That review was published in Psychological Bulletion. Dr. Coyne noted that "The hope that we can fight cancer by influencing emotional states appears to have been misplaced. If cancer patients want psychotherapy or to be in a support group, they should be given the opportunity to do so. There can be lots of emotional and social benefits. But they should not seek such experiences solely on the expectation that they are extending their lives."
  81. ↑ Greer S, Psychological response to breast cancer: effect on outcome, Lancet 1979 oct 13(2) A prospective, multidisciplinary, 5-year study of 69 consecutive female patients with early (T0,1N0,1M0) breast cancer was conducted. Patients' psychological responses to the diagnosis of cancer were assessed 3 months postoperatively. These responses were related to outcome 5 years after operation. Recurrence-free survival was significantly common among patients who had initially reacted to cancer by denial or who had a fighting spirit than among patients who had responded with stoic acceptance or feelings of helplessness and hopelessness.
  82. ↑ Hislop TG, The prognostic significance of psychosocial factors in women with breast cancer, Chron Dis 1987 40(7) 729, One hundred and thirty three recently diagnosed breast cancer patients completed a self-administered questionnaire which measured 16 psychosocial variables. After 4 years, three variables (expressive activities at home, extroversion, low anger) were significant prognostic factors for overall survival independent of clinical and other psychosocial factors; likewise three variables (expressive activities at home, expressive activities away from home, low cognitive disturbance) were significant independent prognostic factors for disease-free survival. These findings support the prognostic importance of the social emotional network.
  83. ↑ Spiegel D, Effect of psychosocial treatment on survival of patients with metastatic breast cancer, Lancet, 1989 Oct 14;2(8668):888-91 The effect of psychosocial intervention on time of survival of 86 patients with metastatic breast cancer was studied prospectively. The 1 year intervention consisted of weekly supportive group therapy with self-hypnosis for pain. Both the treatment (n = 50) and control groups (n = 36) had routine oncological care. At 10 year follow-up, only 3 of the patients were alive, and death records were obtained for the other 83. Survival from time of randomisation and onset of intervention was a mean 36.6 (SD 37.6) months in the intervention group compared with 18.9 (10.8) months in the control group, a significant difference. Survival plots indicated that divergence in survival began at 20 months after entry, or 8 months after intervention ended.
  84. ↑ Buddeberg C, Are coping strategies related to disease outcome in early breast cancer? J Psychosom Res 1996 mar 40(3) 255, A consecutive series of 107 women with early breast cancer were investigated for coping strategies and disease outcome 5 to 6 years after primary surgical treatment (mastectomy or lumpectomy). Coping was assessed several times during a 3-year investigation period by the Zurich and Freiburg Questionnaires of Coping with Illness (ZQCI, FQCI). Data analysis revealed no significant correlations between coping strategies and the target variable "death from breast cancer". However, significant relations were found between postsurgical tumour size (p < or = 0.01), positive histological node status (p < or = 0.01) and death from breast cancer. The results of a discriminant analysis also indicated that somatic parameters are more important for the course of breast cancer disease than psychological aspects of coping. The role of psychosocial variables for the outcome of cancer disease remains unclear and further studies in this field are necessary.
  85. ↑ Giraldi T, Psychosocial factors and breast cancer: a 6-year Italian follow-up study, Psychother Psychosom 1997 66(5) 229, BACKGROUND: Over the last 20 years contradictory results have been obtained as regards to the role of psychosocial factors in favouring the onset of breast cancer and/or in influencing disease progression. METHODS: The present study prospectively investigated the association between psychosocial variables and breast cancer in 95 out-patients. Within 3 months from the diagnosis the patients completed a series of questionnaires to evaluate psychological disturbances, emotional repression, adjustment to cancer, social support and occurrence of life events in the past. At a distance of 6 years from the first assessment, the patients' charts were re-examined in order to evaluate the course of cancer. RESULTS: A higher volume of primary tumour at surgery was shown in patients who had had stressful events in the 6 months preceding cancer diagnosis. At follow-up, no relationship was found between psychosocial variables and the course of disease. The analysis of the frequency of relapses and deaths, and the survival analysis indicated that positivity of loco-regional lymph nodes, infiltrating histotype of the tumour and tumour stage were the only significant predictors of the time of death. CONCLUSIONS: The study suggests that clinical and biological rather than psychosocial factors exert a major role in breast cancer progression.
  86. ↑ Watson M, Influence of psychological response on survival in breast cancer: a population-based cohort study, Lancet, 1999 Oct 16;354(9187):1331-6, BACKGROUND: The psychological response to breast cancer, such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease, has been suggested as a prognostic factor with an influence on survival. We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer. METHODS: 578 women with early-stage breast cancer were enrolled in a prospective survival study. Psychological response was measured by the mental adjustment to cancer (MAC) scale, the Courtauld emotional control (CEC) scale, and the hospital anxiety and depression (HAD) scale 4-12 weeks and 12 months after diagnosis. The women were followed up for at least 5 years. Cox's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response, with adjustment for known clinical factors associated with survival. FINDINGS: At 5 years, 395 women were alive and without relapse, 50 were alive with relapse, and 133 had died. There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression (hazard ratio 3.59 [95% CI 1.39-9.24]). There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category (1.55 [1.07-2.25]). There were no significant results found for the category of "fighting spirit". INTERPRETATION: For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect. A high score for depression is linked to a significantly reduced chance of survival; however, this result is based on a small number of patients and should be interpreted with caution.
  87. ↑ ) Reynolds P, Use of coping strategies and breast cancer survival: results from the Black/White Cancer Survival Study, Am J Epidemiol 2000 nov 15 152(10) 940, This analysis was designed to evaluate the association between coping strategies and breast cancer survival among Black and White women in a large population-based study. A total of 442 Black and 405 White US women diagnosed with invasive breast cancer during 1985-1986 and actively followed for survival through 1994 were administered a modified Folkman and Lazarus Ways of Coping questionnaire. Coping strategies were characterized via factor analyses of the responses. Hazard ratios associated with coping strategies were estimated using Cox proportional hazards models, with adjustment for age, race, tumor stage, study location, tumor hormone responsiveness, comorbidity, health insurance status, smoking, relative body weight, and alcohol consumption. Emotion-focused coping strategies were significantly associated with survival. Expression of emotion was associated with better survival (hazard ratio = 0.6; 95% confidence interval: 0.4, 0.9). When it was considered jointly with the presence or absence of perceived emotional support, women reporting low levels of both emotional expression and perceived emotional support experienced poorer survival than women reporting high levels of both (hazard ratio = 2.5; 95% confidence interval: 1.7, 3.7). Similar risk relations were evident for Blacks and Whites and for patients with early and late stage disease. These results suggest that the opportunity for emotional expression may help improve survival among patients with invasive breast cancer.
  88. ↑ Goodwin PJ, The effect of group psychosocial support on survival in metastatic breast cancer, NEJM, 2001 Dec 13;345(24):1719-26 BACKGROUND: Supportive-expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival. METHODS: In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive-expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires. RESULTS: Women assigned to supportive-expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological score was found (P</=0.003 for the comparison of mood variables; P=0.04 for the comparison of pain); women who were more distressed benefited, whereas those who were less distressed did not. The psychological intervention did not prolong survival (median survival, 17.9 months in the intervention group and 17.6 months in the control group; hazard ratio for death according to the univariate analysis, 1.06 [95 percent confidence interval, 0.78 to 1.45]; hazard ratio according to the multivariate analysis, 1.23 [95 percent confidence interval, 0.88 to 1.72]). CONCLUSIONS: Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer. It improves mood and the perception of pain, particularly in women who are initially more distressed.
  89. ↑ Goodwin PJ, Health-related quality of life and psychosocial status in breast cancer prognosis: analysis of multiple variables, J Clin Oncol 2004 oct 15 22(20), PURPOSE: Evidence that psychosocial status and health-related quality of life (HRQOL) are associated with breast cancer (BC) outcomes is weak and inconsistent. We examined prognostic effects of these factors in a prospective cohort study. PATIENTS AND METHODS: Three hundred ninety-seven women with surgically resected T1 to T3, N0/N1, M0 BC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (Core 30 items), Profile of Mood States, Psychosocial Adjustment to Illness Scale, Impact of Events Scale, Mental Adjustment to Cancer Scale, and the Courtauld Emotional Control Scale 2 months after diagnosis and 1 year later. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records, and Cox survival analyses were performed. RESULTS: Mean age was 52.0 +/- 9.9 years. Two hundred twenty-five women had T1, 136 women had T2, 16 women had T3, and 20 women had TX tumors; 127 were N1. One hundred thirteen women received adjuvant chemotherapy, 130 received hormone therapy, 45 received both, and 109 received neither. We investigated 140 prognostic associations; four were found to be statistically significant at a P value of </= .05 (three fewer than expected by chance). Two were in the hypothesized direction of effect, and two were in the opposite direction. All arose from measurements 1 year after diagnosis, which were most susceptible to confounding by treatment. There was no evidence of consistency of associations across outcomes or questionnaires. These results are in keeping with chance as the explanation for our statistically significant findings. CONCLUSION: HRQOL and psychosocial status at diagnosis and 1 year later are not associated with medical outcome in women with early-stage BC.
  90. ↑ Tschuschke el al, Associations between coping and survival time of adult leukemia patients receiving allogeneic bone marrow transplantation: results of a prospective study, J Psychosom Res 2001 50, 277 BACKGROUND: To investigate associations between coping strategies and length of survival in a sample of 52 adult leukemia patients receiving allogeneic bone marrow transplantation (BMT). METHODS: 52 adult patients, diagnosed with acute (AML) and chronic myeloid leukemia (CML) admitted for allogeneic BMT to a university hospital BMT unit in preparation for a transplantation of genotypically matched HLA donor marrow, were interviewed immediately after informed consent and prior to preparatory treatment for transplantation. Semistructured interviews were conducted and recorded for analysis to assess coping styles and were evaluated by a new content analytic coping measure [Ulm Coping Manual (UCM)]. Patients were a random sample of all eligible patients on the BMT unit between May 1990 and May 1994. RESULTS: Complete audiotaped interviews were rated by blind raters, employing a newly developed content analysis for the identification of patients' coping strategies. Multivariate analysis using a Cox model revealed three pretransplant variables that demonstrated a statistically significant influence on 5-year survival: Stage of Disease at transplant (P < .012), Distraction (P < .007), and Fighting Spirit as coping modalities (P < .013). CONCLUSIONS: The results of this prospective study document the impact of certain psychological variables, notably coping style on survival with BMT. This suggests the necessity of utilizing psychosocial interventions to address stress and anxiety in patients awaiting transplantation in order to reduce anxieties and to employ more effective coping techniques to deal more appropriately with their situation and to enhance Fighting Spirit. The effects on survival of such psychosocial interventions need to be tested in a randomized controlled study.
  91. ↑ Kaiser HE, Spontaneous neoplastic regression: the significance of apoptosis, In Vivo, 2000 Nov-Dec;14(6):773-88 In mammalian cells, neoplastic transformation has a direct relationship with the expression of oncogenes, the production of certain growth factors and with the mutation, loss or simple inactivation of the function of tumor suppressor genes. Genes for suppression of the development of the malignant immunophenotype, as well as inhibitory growth factors have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently observed in various types of neoplastic cell transformation. Telomerase activation is regarded as essential for cell immortalization and its inhibition may result in spontaneous regression (SR) of neoplasms. SR of neoplasms occurs when the malignant tumor mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic disease. This definition makes it clear that the term SR applies to neoplasms in which the malignant disease is not necessarily cured, and to cases where the regression may not be complete or permanent. A number of possible mechanisms of SR are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualized anticancer immunotherapy (biotherapy) is also discussed. In conclusion, of all the possible mechanisms of SR of neoplasms, programmed cell death (PCD) or apoptosis is involved in each. The immunological mechanism is probably the main effector mechanism of SR in human neoplasms with its trigger being apoptosis. The treatments of the tumor, such as with various anti-neoplastic drugs or radiation or immunotherapy, all include the basic mechanism of programmed cell death or apoptosis. Without apoptosis, there is practically no tumor regression, none of any kind.
  92. ↑ Stoll BA, Spontaneous regression of cancer: new insights, Biotherapy, 1992;4(1):23-30 Suppression of oncogene expression and of host- or tumour-expressed growth factors and receptors may precipitate spontaneous regression or dormancy in human cancer. Loss of oncogenes necessary for progressive proliferation can lead to differentiation changes. Both natural factors and chemical agents can trigger such a change, and of the naturally occurring agents, growth factors and immunological factors have been most studied. We may find new clues to biological methods of prolonging arrest of cancer, by looking for cytogenetic abnormalities, alterations in oncogene expression and immunocytological composition, in patients showing prolonged dormancy of cancer.
  93. ↑ Papac RJ, Spontaneous regression of cancer: possible mechanisms, In Vivo, 1998 Nov-Dec;12(6):571-8 Spontaneous regression of cancer is reported in virtually all types of human cancer, although the greatest number of cases are reported in patients with neuroblastoma, renal cell carcinoma, malignant melanoma and lymhomas/leukemias. Study of patients with these diseases has provided most of the data regarding mechanisms of spontaneous regression. Mechanisms proposed for spontaneous regression of human cancer include: immune mediation, tumor inhibition by growth factors and/or cytokines, induction of differentiation, hormonal mediation, elimination of a carcinogen, tumor necrosis and/or angiogenesis inhibition, psychologic factors, apoptosis and epigenetic mechanisms. Clinical observations and laboratory studies support these concepts to a variable extent. The induction of spontaneous regression may involve multiple mechanisms in some cases although the end result is likely to be either differentiation or cell death. Elucidation of the process of spontaneous regression offers the possibility of improved methods of treating and preventing cancer.
  94. ↑ Cole WH, Spontaneous regression of cancer and the importance of finding its cause, Natl Cancer Inst Monogr, 1976 Nov, 44 A few years ago Everson and I assembled all the examples of spontaneous regression in the world medical literature from 1900 to 1960 and added numerous cases from expriences of our friends. Our figure was 176. We excluded squamous cell carcinoma of the skin, leukemia, Hodgkin's disease, and a large number of cases that did not fulfill the prerequisites of confirmed diagnosis and no significant treatment. The four most common examples of regression were carcinoma of the kidney (31), neuroblastoma (29), malignant melanoma (19), and choriocarcinoma (19); these constituted more than half the group. We did not require that the regression be permanent because it appeared that the explanation of temporary regression would be just as important as the cause of permanent regression. There was no proven specific cause of the regression, but the following mechanisms had a possible relationship: immunologic action, elimination of carcinogens, trauma (altering the antigen-antibody relationship), hormones, irradiation, infection and/or fever, and drugs or chemicals. The most applicable of these is elimination of the carcinogen. Immunologic reactions seem to offer the best explanation, and the potential of humoral immunity is more impressive than that of cellular immunity.
  95. ↑ Hobohm U, Fever therapy revisited, Br J Cancer 2005 feb 14, 92(3) 421, The phenomenon of spontaneous regression and remission from cancer has been observed by many physicians and was described in hundreds of publications. However, suggestive clues on cause or trigger are sparse and not substantiated by much experimental evidence. In this review, literature is surveyed and summarised and possible causes are discussed. At least in a larger fraction of cases a hefty feverish infection is linked with spontaneous regression in time and is investigated as putative trigger. Epidemiological and immunological evidence is put into perspective.
  96. ↑ Cann - Van Netten, Dr William Coley and tumour regression: a place in history or in the future, Postgrad Med J, 2003 Dec 79 (938) 672 Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. This phenomenon inspired the development of numerous rudimentary cancer immunotherapies, with a history spanning thousands of years. Coley took advantage of this natural phenomenon, developing a killed bacterial vaccine for cancer in the late 1800s. He observed that inducing a fever was crucial for tumour regression. Unfortunately, at the present time little credence is given to the febrile response in fighting infections-no less cancer. Rapidly growing tumours contain large numbers of leucocytes. These cells play a part in both defence and repair; however, reparative functions can also support tumour growth. Intratumoural infections may reactivate defensive functions, causing tumour regression. Can it be a coincidence that this method of immunotherapy has been "rediscovered" repeatedly throughout the centuries? Clearly, Coley's approach to cancer treatment has a place in the past, present, and future. It offers a rare opportunity for the development of a broadly applicable, relatively inexpensive, yet effective treatment for cancer. Even in cases beyond the reach of conventional therapy, there is hope.
  97. ↑ Cole WH, Relationship of causative factors in spontaneous regression of cancer to immunologic factors possibly effective in cancer, J Surg Oncol, 1976 8 (5) 391 In a book written by Everson and Cole (1966) on spontaneous regression 176 examples of the phenomenon were encountered in the medical literature from 1900 to 1964, supplemented by cases referred by friends. No common denominator of explanations were found. Various types of trauma (e.g., biopsy, incomplete excision), transfusions, infection, hormone changes, drugs, etc. were encountered as possible causative factors. Most significant of all factors was encountered in the 13 examples of spontaneous regression of the bladder; in this series regression of the tumor occurred in 10 after transplantation of the ureters out of the bladder. A consideration and discussion of various reactions in human beings associated with therapeutic regressions have been reviewed hoping to develop a correlation between the two types of regression. At the time of publication of our monograph 9 years ago we were unable to suggest any mechanisms which might explain the regressions. However, since that time so many advances have been made in immunology that it appears now that a stimulation of the immune process might explain most of the regressions. We are just beginning to learn a few methods of stimulating the immune process. Use of BCG is one of the best examples of this stimulating process; other bacterial agents, or fractions, are known to have this action. No doubt there are innumerable others unknown, some of which might explain spontaneous regressions. It would appear that hormonal changes might be responsible for many of the regressions but this author doubts it explains many. More is known at the present time about cellular immunity than humoral immunity, but greater possibilities surely lie in humoral immunity. The blocking and unblocking activities developed by the Hellstroms and associates are no doubt important. Immunoglobulins exert a very important role in the immune process; antibodies may consist of immunoglobulins but much more needs to be known before this relationship can be understood. The recent report (Amery, 1975) that levamisole (given at the time of resection of the lung for carcinoma) improves patient survival is exciting. Amery believes the drug may prevent the hematogenous spread of the tumor during surgery and/or may decrease the immunosuppression caused by a major operation.
  98. ↑ Rohdenburg, Fluctuations in the growth energy of tumors in man, with esspecial reference to spontaneous recession, 1918 J Cancer Res 1918;3:193-225
  99. ↑ Boyd W. The spontaneous regression of cancer. Charles Thomas, Publ., Springfield Ill. 1966
  100. ↑ Cole WH - Everson TC: Spontaneous Regression of Cancer (WB Saunders, Philadelphia, PA) 1966
  101. ↑ Challis GB, The spontaneous regression of cancer. A review of cases from 1900 to 1987, Acta Oncol, 1990 29 (5) 545, The literature on the spontaneous regression of cancer is reviewed from 1966 to 1987 to update reviews by Everson & Cole and by Boyd. These authors reviewed all cases of spontaneous regression from 1900 to 1965. We then report the entire series from 1900 to 1987. We also attempted to determine what attributions for spontaneous regressions have been reported. Although almost half of the authors failed to speculate or specify a possible cause for the spontaneous regression, the remainder postulated responsible factors such as immunological or endocrine, surgical, necrosis, infection, or operative trauma. The only unorthodox treatment to appear in the literature was the psychological. We conclude that the literature on the spontaneous regression of cancer is still unable to provide unambiguous accounts of the mechanisms operating to affect these regressions.
  102. ↑ Cann - Van Netten, Dr William Coley and tumour regression: a place in history or in the future, Postgrad Med J, 2003 Dec 79 (938) 672, Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. This phenomenon inspired the development of numerous rudimentary cancer immunotherapies, with a history spanning thousands of years. Coley took advantage of this natural phenomenon, developing a killed bacterial vaccine for cancer in the late 1800s. He observed that inducing a fever was crucial for tumour regression. Unfortunately, at the present time little credence is given to the febrile response in fighting infections-no less cancer. Rapidly growing tumours contain large numbers of leucocytes. These cells play a part in both defence and repair; however, reparative functions can also support tumour growth. Intratumoural infections may reactivate defensive functions, causing tumour regression. Can it be a coincidence that this method of immunotherapy has been "rediscovered" repeatedly throughout the centuries? Clearly, Coley's approach to cancer treatment has a place in the past, present, and future. It offers a rare opportunity for the development of a broadly applicable, relatively inexpensive, yet effective treatment for cancer. Even in cases beyond the reach of conventional therapy, there is hope.
  103. ↑ Nauts HC, The beneficial effects of bacterial infections on host resistance to cancer, cancer res int 1980
  104. ↑ Il caso Wright del 1957: Cancro e l'effetto placebo. "Psychologist Bruno Klopfer was treating a man named Wright who had advanced cancer of the lymph nodes. All standard treatments had been exhausted and Wright appeared to have little time left. His neck, armpits, chest, abdomen, and groin were filled with tumors the size of oranges, and his spleen and liver were so enlarged that two quarts of milky fluid had to be drained out of his chest every day. Wright heard about an exciting new drug called Krebiozen, and he begged his doctor to let him try it. At first the doctor refused because the drug was being tried on people with a life expectancy of at least three months. Finally the doctor gave in and gave Wright an injection of Krebiozen on Friday, but in his heart of hearts he did not expect Wright to last the weekend. "To his surprise, on the following Monday he found Wright out of bed and walking around. Klopfer reported that his tumors had 'melted like snowballs on a hot stove' and were half their original size. Ten days after Wright's first treatment, he left the hospital and was, as far as his doctors could tell, cancer free. When he entered the hospital he had needed an oxygen mask to breathe, but when he left, he was well enough to fly his own plane at 12,000 feet with no discomfort. "Wright remained well for about two months, but then articles began to appear asserting that Krebiozen actually had no effect on cancer of the lymph nodes. Wright, who was rigidly logical and scientific in his thinking, became very depressed, suffered a relapse, and was readmitted to the hospital. This time his physician decided to try an experiment. He told Wright that Krebiozen was every bit as effective as it had seemed, but that some of the initial supplies of the drug had deteriorated during shipping. He explained, however, that he had a new highly concentrated version of the drug and could treat Wright with this. The physician used only plain water and went through an elaborate procedure before injecting Wright with the placebo. "Again the results were dramatic. Tumor masses melted, chest fluid vanished, and Wright was quickly back on his feet and feeling great. He remained symptom-free for another two months, but then the AMA announced that a nationwide study of Krebiozen had found the drug worthless for the treatment of cancer. This time Wright's faith was completely shattered. His cancer blossomed anew and he died two days later." (Brono Klopfer, Psychological Variables in Human Cancer, Journal of Prospective Techniques 31, 1957, pp. 331-40.). - The best known sample of the placebo response, is perhaps the case of Mr Wright, documented in 1957 by Dr Phillip West and Dr Bruno Klopfer. Mr Wright had advanced widespread lymphosarcoma, and as standard treatment has failed, he was expected to live no more than a few weeks. A then new drug (Krebiozen) was being tested as a potential cancer cure, and on Mr Wright`s request, he was included in the trial. Shortly after the first injection of the drug, the patient`s tumor masses “melted like snowballs on a hot stove”. Wright was soon released, apparently free of malignancy. Two months later, shortly after the worthlessness of the drug was being published in newspapers, Mr Wright`s tumours returned. Dr Klopfer, suspecting that this was due to Wright`s expectations, again involved Mr Wright, pretending to give him a double-strength of a new, more active form of the drug, while merely treating him with distilled water. Again the tumours disappeared and Mr Wright was symptom-free for another two months. Then a report from the American Medical Association stating beyond doubt that Krebiozen was worthless, was published in the newspapers. Wright`s tumours reappeared and he died within two days. It is said that it was his total belief in the efficacy of a worthless drug that mobilized a healing placebo response by activating all the major systems of mind-body communication and healing, namely endocrine, autonomic nervous and immune systems. Riferimenti per questo caso: http://webspace.quinnipiac.edu/thomas/InformedConsentPlaceboEffectACLMversion2.pdf Rossi, EL (1986). The psychobiology of mind-body healing. (First edition) WW Norton & Company, Inc. Watkins, A (1997). Mind-body medicine. A clinicians guide to psychoneuroimmunology. (First edition) Churchill &Livingston.
  105. ↑ Petticrew M, Cancer-stress link: the truth, 1999 Nurs Times Mar 3-9 95
  106. ↑ Faller H, Prognostic value of depressive coping and depression in survival of lung cancer patients, Psychooncology 2004 May 13 (5) 359 The aim of this investigation was to determine whether depressive coping and depression predict shorter survival among lung cancer patients. We conducted a prospective study using an inception cohort with a 3-5-year follow-up. The sample consisted of n = 59 (of n = 69 invited to participate) patients (mean age 65 years, S.D. = 9.7; 81% male) newly diagnosed with small cell lung cancer or non-small cell lung cancer Stage III or IV who were scheduled for later chemotherapy and/or radiotherapy at a tertiary care centre. Patients were investigated after their diagnosis and before the beginning of treatment. Depressive coping and depression were assessed using standardized self-report questionnaires (Freiburg Questionnaire of Coping with Illness; Hospital Anxiety and Depression Scale). Depressive coping was associated with shorter survival (hazard ratio 1.75, 95% confidence interval 1.04-2.93, p = 0.034) after adjusting for age, sex, stage, histological classification, and Karnofsky performance status but not treatment type, using the Cox proportional hazards regression. Depression, however, was not linked with survival (hazard ratio 1.05, 95% confidence interval 0.98-1.13, p = 0.18). To conclude, the prognostic value of depressive coping was partially confirmed, warranting further examination of the robustness of this relationship.
  107. ↑ Schüssler G Schubert C, The influence of psychosocial factors on the immune system (psychoneuroimmunology) and their role for the incidence and progression of cancer, Z psychosom Med Psychother, 2001;47(1):6-41 Psychoneuroimmunological research investigates the influence of psychosocial factors on the immune systems. We reviewed clinical studies dealing with the following three topics: life events, psychological/psychopathological factors and social support, and their influence on cellular and humoral immune activity. There is strong evidence that stressful life events (especially losses) have a decreasing effect on immunity. Depression has a similar effect and may be the mediator between life events and the immune systems. Results dealing with the influence of social support on immune functions are still inconclusive. In the second part, we reviewed prospective studies concerning the role of psychosocial factors on cancer incidence and progression. Most of the life event studies reviewed have methodological problems, thus the results are heterogenous. There is some evidence that psychological/psychopathological factors can promote cancer progression. This is even more obvious in case of insufficient social support.
  108. ↑ Kiekolt-Glaser JK, Psychoneuroimmunology and cancer: fact or fiction? Eur j cancer, 1999 Oct;35(11):1603-7 There is substantial evidence from both healthy populations as well as individuals with cancer linking psychological stress with immune downregulation. This discussion highlights natural killer (NK) cells, because of the role that they may play in malignant disease. In addition, distress or depression is also associated with two important processes for carcinogenesis: poorer repair of damaged DNA, and alterations in apoptosis. Conversely, the possibility that psychological interventions may enhance immune function and survival among cancer patients clearly merits further exploration, as does the evidence suggesting that social support may be a key psychological mediator. These studies and others suggest that psychological or behavioural factors may influence the incidence or progression of cancer through psychosocial influences on immune function and other physiological pathways.
  • Vedi anche: Quirino Zangrilla: Cancro e psiche: tra intervento scientifico e posizione di onnipotenza
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