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

Psiche e cancerogenesi: le ipotesi e i nessi che si conoscono attualmente in medicina

Natura sanat, medicus curat

Introduzione:

Da molti secoli gira in medicina il sospetto che fattori psicologici, sociali e comportamentali giocherrebbero un possibile ruolo in una eventuale psico-genesi del cancro e per la sopravvivenza di una tale patologia (rif 45 e 51). Il sospetto che traumi psichici potrebbero avere un importanza nella genesi del cancro è radicato in una parte della popolazione, anche se oggi si sa che un tale rapporto è solo debole (vedi rif 6, 15, 17, 18, 59, 102), ma sembra di esistere, almeno per alcune patologie neoplastiche. 40% dei australiani sono convinti che lo stress sarebbe la causa del cancro al seno (rif 51), e nel Canada il 38% delle donne lo pensa (rif 50). Tali supposizioni sono argomenti in TV e in riviste non scientifiche o libri non scientifici. Bisogna distinguere tra una eventuale influenza diretta tra cervello da un lato e un organo bersaglio: lo (dis-)stress, la vita emotiva, possono influenzare lo stato di attivazione del sistema immunitario con consequenze possibili sulla genesi e la crescita tumorale. E dall'altra parte le influenze indirette: la nostra psiche determina le nostre abitudini quotidiane, il consumo di tabacco (essendo 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 delle visite mediche, il numero delle visite mediche di controllo e di previsione, le nostre attività fisiche, la nostra vita sociale, le nostre emozioni cosi via (rif 47). La psiche influenza percio anche le nostre esposizioni verso fattori cancerogeni o fattori protettivi contro il cancro. Cè chi arrabiandosi, o in uno stato di depressione o di disperazione, fuma o beve di piu e influenza cosi il proprio rischio per il cancro. Però: spesso è difficile di distinguere tra le consequenze psichiche della malattia cancro ed il profilo psichologico individuale basale.
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 diffese immunitarie giocano un ruolo determinante nella cancerogenesi (esempio: AIDS/sarcoma di Kaposi o virus HPV) e si sa che uno sforzo psico-sociale influenza paramentri del sistema immunitario, un tipico esempio è il herpes delle labra da HSV-1, che molti conoscono nella fase di preparzione per un esame difficile o in occasiono simili. La psiconeuroimmunologia di oggi non è pero in grado di spiegare in un modo incontestato lo sviluppo di cancro a partire da processi psichici. Non esiste una accetata teoria psicosomatica della cancerogenesi. E non esiste una prova scientifica di una realazione diretta causa-effetto tra sistema immunitario e sviluppo del cancro (rif 126). Le teorie attuali sul cancro si basano su un concetto multifattoriale, anche con fattori psico-sociali di ordine secondario.

A l'inizio del settecento appaiano i primi testi scientifici che tematizzavano il legame tra cancro e lo stress (distress). (rif 1) Nel novecento si pensava che lo stress (nel senso di distress) o ''l'esaurimento nervoso'' sarrebbero eventualmente a l'origine del cancro. Circa 50 anni fa nascevano anzi diverse ipotesi di una particolare "personalità cancrosa'' (personalità a rischio neoplastico), anche denominata del tipo C (typus carcinomatosus o cancer prone), che faciliterebbe l'insorgenza del cancro, un esempio per uno studio che va in questo direzione e il lavoro di Wirsching del 1985 (rif 94). La persona di tipo C sarebbe caratterizzata da una abondante gentilezza, un elevato grado di addatazione sociale, sarebbe spesso depressivo, altruista con tendenza al sacrificarsri, e mostrerebbe una inibizione dell'agressione e una mancante espressività emozionale. Un contributo viene data da Kissen e Eysenck (rif 90) nel 1962 per uomini affetti dal cancro ai polmoni. Una tipologia (6 sub-tipi) particolare veniva sviluppata da Ronald Grossarth-Maticek, filosofo di origine ungarese. Il personaggio carcinomatoso secondo Grossarth-Maticek (tipo 1) sarebbe una persona che si esponesse spesso a sostanze cancerogene, farebbe spesso uso di farmaci, si riposesse poco, eviterebbe conflitti e sarebbe invece particolarmente vulnerabile per offese e eventi traumatici. Le idee di una ''personalita cancrosa'' o tipizzazione psichica del paziente con cancro erano tra di loro contraditori e studi scientifici non hanno potuto dimostrare l'esistenza di un tale personaggio, e di consequenza le corrispondenti ipotesi sono stati abandonati e hanno solo un ruolo storico nella medicina di oggi. (vedi rif 2 e 13). Lavori che contradicono la ipotesi dell'esistenza di una ''personalita cancrosa" sono: (riff 2, 9, 10, 12, 13, 14, 15, 16, 23, 127) Secondo i ricercatori Gruhlke e Faller 1996 (rif 72), le caratteristiche psichologiche attribuite al personaggio ''tipo C'' sono piutosto da considerare 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 un presunto personaggio cancroso. Un rapporto tra nevroticismo e cancro appare invece nel lavoro di Nakaya (rif 8) nel Giappone, che viene pero contradetto in Danimarca da Hansen (rif 10) nel 2005. Faragher (rif 35) vede nel 1990 un possibile legame tra distress (personaggio tipo A) e cancro al seno. Jasmin, nel 1990 (rif 56) vede 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 mortalità (Wulsin rif 75 e vedi anche Chorot nel 1994 rif 54). Lo (di-)stress prolungato sembra avere un effetto sulla cangerogenesi (rif 38) nel caso del cancro della cute. Stress chronico sembra pero anche avere un effetto prottetivo nel cancro al seno a causa della sua influenza ormonale (rif 79 e 91).

Nel corso del ultimo ventennio la prospettiva psicosociale in oncologia prende corpo come ambito di studio a sé, anche se sviluppatasi già a partire dagli anni 50 quando, negli Stati Uniti, si costituiscono le prime associazioni di pazienti laringectomizzati, colostomizzati e di donne operate al seno. Presso il Memorial Sloan-Kettering Center di New York nasce in questo periodo il primo Servizio autonomo finalizzato all' assistenza psicologica del paziente affetto da cancro. La psicooncologia vera e propria e nata negli anni 70 e 80 del ultimo secolo. 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 psicooncologia. Ricercatori prominenti sono per esempio Jimmi Holland (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 di cancro mostrano sintomi di una depressione, che spesso non vengono diagnosticati (Secondo Faller). Il psico-oncologo tedesco Volker Tschuschke lo conferma nel suo libro (rif 25). Tali problemi influenzano in maniera negativa la qualità della vita dei pazienti, l'aderenza alla terapie e i rapporti interpersonali. Si possono aggiungere sentimenti di colpa verso la famiglia o altri.

Argomentazione del oncologo italiano Prof U. Veronesi nel 2006 a questo proposito e in relazione alle ipotesi di Geerd Ryke Hamer: Caro (omissis), 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. (citato da rif 62) Vedi anche rif 125.

Il 30 gennaio 2007 lo stesso Veronesi aggiunge: Re: arrabbiarsi fa male? "..."Cara Vera, come ho già avuto più volte occasione di scrivere su questo forum, non esistono prove scientifiche di un legame causa-effetto fra psiche e tumori e quindi non possiamo certamente affermare che il tumore sia una malattia psicosomatica. La scienza ha dimostrato che il rischio di ammalarsi di tumore dipende da fattori ambientali (stili di vita, esposizione a sostanze cancerogene etc.) e genetici. Non ci sono prove di legame fra atteggiamento psicologico (rabbia, dolore, depressione) e sviluppo di malattia. Questo non significa che non vi sia alcuna associazione fra mente e fisico, anche in campo oncologico, come per tutte le altre patologie, ma questo vale soprattutto quando la malattia è conclamata. 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."

maggiori ''life events'' / momenti traumatici: possono scattare il fenomeno cancro ? Smentita della asserzioni rigide di RG Hamer e della ''leggi'' della sua nuova medicina germanica da parte della ricerca internazionale.

L'impatto possibile di cosidetti ''life events'' traumatici (p.e. morte di un familiare/amico nel passato) e specialmente eventi traumatizzant imprevisti come l'attacco allo WTC del 11.9.2001 erano oggetto di ricerca per molti anni (rif 24 e 71) e continua ad essere (rif 119). Sapendo che circa un caso di cancro su 6 è causato da un virus (esempio HPV, HSV, HIV...), la ipotesi immunitaria di life events traumatici sull'insorgenza del cancro appare possibile (attraverso la modulazione del sistema immunitario).

Forsen (rif 5) ha analizzato 87 persone aventi cancro al seno e no (gruppo controllo) per un eventuale rapporto tra eventi traumatici e cancro. Il suo lavoro retrospettivo mostra un numero piu grande di eventi traumatici nel gruppo delle persone con cancro rispetto al gruppo di controllo nei 12 mesi precedenti la diagnosi. Ramirez vede nel 1989 un rapporto tra life events e ricadute nel caso del cancro al seno (rif 19), viene pero smentito da Barraclough (rif 21) nel 1992 e nel 2002 da Graham (rif 20) che aggiunge che donne non dovrebbero avere paura da eventi traumatici come causa di una eventuale ricaduta. Chen (rif 11) trova una relazione tra eventi traumatici e cancro al seno in Cina (in contrasto con Protheroe rif 51). Roberts (rif 4) ha analizzato una eventuale relazione tra ''life events'' e il cancro al seno e nel suo studio con 872 persone nel 1996 non ha potuto trovare una tale relazione e ha trovato stranamente un numero maggiore di persone che hanno perso una persona cara nel gruppo delle donne non aventi cancro. 1999, McKenna trova un rapporto debole tra eventi stressanti e cancro al seno (rif 17). Anche Chorot (rif 54) pensa a una relazione tra psiche e cancro nel 1994. In un review del 2000, Butow vede solo un rapporto debole tra alessitimia, eventi stressanti e cancro (rif 6), con correlazioni positive solo in studi con un numero ristretto di soggetti. L' Australiano Price (rif 7) paragonava nel 2001 donne con processi benigni e donne con malignomi al seno. E dallo suo studio su 514 donne risulta un rapporto positivo da eventi stressanti e malignomi (cancro) in assenza di un aiuto sociale. Questo lavoro contradice invece quello di Maunsell nel 2003 (rif 50) che non trova nessuna prova per una tale asserzione nel caso del cancro al seno, e i lavori di Protheroe del 1999 (rif 51), di Lillberg (nel 2001 rif 52) in Finlandia, e di Duijts (rif 53) in Ollanda lo confermano. Dal review di Dalton (3) del 2002 appare 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 avere cancro. Dalton afferma che studi scientifici in questo campo contengono spesso un design metodologico debole. Kvikberg, riferisce dalla Norvegia nel 1995 in un indagine su 14231 donne che la morte del marito o il divorzio non modifica il rischio per il cancro, con alcune eccezioni (rif 92), lo stesso autore notera nel anno successivo 1996 nessuna differenza del rischio per cancro in donne che avevano perso un bambino in precedenza (rif 93). Lillberg afferma nel 2003 una relazione positiva tra eventi traumatici e cancro in Finlandia (rif 22), Pereira (USA) afferma che tali eventi sono da considerare fattori di rischio nel 2003 (rif 24) 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 dello World Trade Center a New York il 11.9.2001 fu un disastro imprevviso e molto traumatizzante per circa 400.000 persone (con almeno 188 donne incinte nel WTC), 71.000 di queste persone sono elencati nello World Trade Center Health Registry (WTCHR) per una osservazione della loro salute. Secondo le "leggi" della nuova medicina precisamente questo evento avrebbo dovuto scattare molti nuovi casi immediati 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 il 11-9 e alcune tematizzano un eventuale rapporto tra 11-9 e cancro. La ricerca di Rayne (rif 124) 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 puo anche spiegare con l'effetto di sostanze cancerogene che furono liberati nelle polveri dissipati durante la catastrofe ed i giorni consecutivi. (furono rilevati nelle polveri composti cancerogeni di idrocarburi policiclici, amianto e cosi via)
E da ricordare pero, 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 2 a 30 anni (rif 126), in media dura 8 anni. Nel caso di un adulto, e nel caso del mesotelioma puo estendersi fino a 70 anni. I periodi di latenza piu 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 (rif 11), in verità il periodo completo tra inizio e sintomo sara 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 per una tale ipotesi danno le osservazioni di Pereira (rif 24) nel caso del carcinoma cervicale nel 2003. In queste condizioni il rapporto temporale potrebbe essere piu breve di 5 anni nel caso di adulti. Eventi traumatici influenzano anche il comportamento: ce chi si cura meno, e evita il contatto con servizi sanitari nel caso di elevato distress, con possibili consequenze sulla patologia stessa. In queste condizioni un intervento professionale puo essere positivo.

In modo riassuntivo: eventi traumatizzanti non sembrano avere una importanza rilevante nella genesi del cancro, vedi conferma nei riferimenti 20, 40 e 73. Risultati da studi fatti all'inzio della psico-oncologia non potevano essere ripetuti e sembrano parzialmente essere ''contaminati'' dalle aspettative dei ricercatori. La ricerca attuale si concentra a partire degli anni 80 di consequenza di piu sulle possibilità di migliorare la qualita 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 piu verso quello che si puo 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 (rif 114), 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 (rif 115 e 116).

Rapporto tra infiammazioni croniche e cancro: vedi Basak (rif 106).

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 verità e non una bugia, perche viene preso al serio. (vedi anche Ipocrate rif 98) Questo perche spesso il paziente ha gia un sospetto da tempo e vuole sapere ''la verità'', e questa sua volonta è 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 cosa pensa di avere. 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 un indagine, si parla nel gergo della "bugie 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 (rif 97), 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) questa, dopo una terapia causale, potra essere uguale a quella di persone di stessa età, in altri casi invece la situazione puo essere molto diversa. In Germania, il redditto medio dei medici è 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 ''sopra'' il 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 verità. 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.

Opinione di Umberto Veronesi a questo proposito: (corriere della sera 25 gennaio 2007): La comunicazione della diagnosi, ..."Caro Renato, riprendo quanto ho già scritto su questo argomento in risposta a un messaggio già pubblicato su questo forum. E' diritto del malato conoscere la verità circa il suo stato, ed è dovere di chi lo cura comunicargliela. Una persona malata per guarire, oltre ad aver bisogno di cure, ha bisogno di vivere un rapporto di fiducia con chi si prende cura di lei. Proprio perché il rapporto del malato con il proprio medico è una priorità, non può fondarsi sull'imprecisione o sull'equivoco. Quindi dire la verità sulla diagnosi è fondamentale, con tatto, ma va detta.
Informare un paziente però non vuol dire togliergli la speranza o il coraggio, anzi. E questo dipende moltissimo dalla comunicazione da parte del medico: ci sono casi in cui, in un difficile equilibrio, il medico deve saper anche discernere come, cosa e quanto comunicare. A volte, percependo che questo è l'aiuto reale per il suo paziente, può anche decidere di assumere su di sé le responsabilità, di raccontare senza dire, ma sempre aiutando, confortando e incoraggiando. Inoltre, la mia esperienza di medico me l'ha insegnato, quando il malato è messo di fronte alla realtà della sua condizione – con la dovuta accortezza e attenzione alla sua sensibilità - dopo un primo momento di sconcerto reagisce per lo più in modo costruttivo e matura una determinazione a guarire molto più forte di quella che può avere un malato incerto o dubbioso sulla natura del proprio male.
Bisogna però distinguere sempre e nettamente la diagnosi dalla prognosi. Se non si può barare sulla diagnosi, nella prognosi dobbiamo essere sempre un po' ottimisti, anche perché non abbiamo mai certezze. Non dimentichiamo che la medicina, nel bene e nel male, non è una scienza certa: al di là dei dati statistici ed epidemiologici, e perfino al di là della valutazione clinica della persona malata, in realtà nessun medico potrà mai stabilire con certezza quale sarà l'evoluzione esatta della sua malattia. Inoltre oggi il varco della speranza è diventato più ampio. Per esempio, mentre anni fa dare una speranza a un malato di cancro poteva apparire una forzatura, oggi guarisce il cinquantacinque per cento dei malati, e nelle donne colpite dal cancro al seno la percentuale sale fino all'ottanta per cento."

curando il cancro: interventi psicologici per pazienti e i loro ambiente
le differenti coping style e il loro effetto

La terapia convenzionale del cancro è 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:

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 età 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 reattività 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 probabilità di ammalarsi di cancro.

Relazione tra coping psicologico attivo e periodo di sopravivenza nel cancro del seno:

Si vede che i rapporti positivi si trovano sopratutto nei lavori piu vecchi, la qualità di vita è da distinguere dallo outcome / periodo di sopravivenza.

Dal lavoro di Tschuschke (rif 76): L' impatto dello fighting spirit nel caso della terapia causale della leucemia (adulti) dopo trasplanto del midollo osseo:

Le remissioni spontanee (RS)

Le remissioni spontanee RS sono guarizioni con nessun legame con una precedente terapia causale (rif 34) e che si verificano spontaneamente. La prima RS che e diventata famosa nella storia della medicina è quella di Pellegrino Laziosi di Forli (1265 - 1345 detto anche Pellegrino da Forlì, in inglese Saint Peregrine) che si ammalò di cancro alla tibia e guari completamente senza intervento medico. Pellegrino Laziosi è 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) è purtroppo un fenomeno molto raro e occorre soltanto una volta su 60000-100000 dei casi (Bashford, Hirschberg). Nel 1992, Stoll (26) 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 (rif 33 e 63). 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 (rif 29), 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, è rimasta in discussione e uso sola la ipertermia locale con-adiuvante e la ricerca continua). Tra i tentativi terapeutici della febbre è da nominare la terapia di Coley con tossine di batteri, ora abbandonata (rif 49) 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) (rif 67). Studi e meta-analisi retrospettivivi storici delle remissioni spontanee sono quelli di Rohdenburg nel 1918 (rif 64) con 185 casi citati, Fauvet nel 1960/1964 (202 casi), Boyd W (rif 66) nel 1966 (98 casi), Everson e Cole (rif 68) nel 1966 (182 casi), Challis nel 1990 (rif 69 - 489 casi), O'Reagan e Hirschberg nel 1993 (216 casi). Le ricadute dopo una RS sono purtroppo frequenti (rif 49 e 65). 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 (rif 27) suscitava clamore nel mondo medico: nel suo caso farmaci placebo (causalmente inefficaci) erano efficaci contro linfomi per alcuni mesi, anche se il paziente è 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 è 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 qualità di vita) avevano un effetto positivo in una minorità 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 (rif 73) e di Faller nel 2004 (rif 74).

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 (rif 44 e 60). 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 reattività 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 è 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, 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) perché 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 minorità 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 è 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 è 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 è da cercare nella sua incapacità 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 è 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 è 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:

(1) LeShan L, psychological states in the development of malignous disease: a critical review. J nat cancer inst 1959:22 1-18

(2) Schwarz R, Die Krebspersönlichkeit, libro: 1994 Schattauer Stuttgard New York.

(3) 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.

(4) 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.

(5) 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.

(6) 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.

(7) 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.

(8) 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.

(9) 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.

(10) 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.

(11) 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.

(12) 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.

(13) 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.

(14) 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.

(15) 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.

(16) 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.

(17) 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.

(18) 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.

(19) 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.

(20) 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.

(21) 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.

(22) 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.

(23) 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.

(24) 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.

(25) Tschuschke V: Pschoonkologie - Psychologische Aspekte der Entstehung und Bewältigung von Krebs. Stuttgard Schattauer 2002

(26) 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.

(27) 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.)

(27-2) 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.

(28) Sarkar RR, Cancer self remission and tumor stability-- a stochastic approach, Math biosci 2005 Jul, 196 (1) 65
The paper aims to express the spontaneous regression and progression of a malignant tumor system as a prey--predator like system. The model is a three dimensional deterministic system, consisting of tumor cells, hunting predator cells and resting predator cells. Local stability analysis is performed along with numerical simulations to support the analytical findings. Moreover, the deterministic model is extended to a stochastic one allowing random fluctuations around the positive interior equilibrium. The stochastic stability properties of the model are investigated both analytically and numerically. The thresholds obtained from our study may be helpful to control the malignant tumor growth.

(29) 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.

(30) Bodey B, The spontaneous regression of neoplasms in mammals: possible mechanisms and their application in immunotherapy, In Vivo 1998 Jan-feb 12(1) 107
In mammalian cells, neoplastic transformation is directly associated with the expression of oncogenes, with the mutation, loss or simple inactivation of the function of tumor suppressor genes, and the production of certain growth factors. 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 cancers. Telomerase activation is regarded as essential for cell immortalization and its inhibition may result in the 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 be neither complete nor 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.

(31) Horino T, Spontaneous remission of small cell lung cancer: a case report and review in the literature, lung cancer, 2006 Aug;53(2):249-52. Epub 2006 Jun 21
Spontaneous remission (SR) of cancer, especially of lung tumor, is a rare biological event. Only seven cases in which small cell lung cancer (SCLC) regressed spontaneously had been previously reported. We report here a rare case of complete SR of SCLC in an 86-year-old man. Paraneoplastic sensory neuronopathy (PSN) is a rare syndrome, which is associated with malignancy such as SCLC and starts with dysesthetic pain and numbness in the distal extremities, then spreading all four limbs and trunk causing severe sensory ataxia. In the previous reports, SR of SCLC is suggested to result from surgical trauma or PSN, which may be able to enhance anti-tumoral immunity. Our report is the case of SR of SCLC, without any therapies nor any invasive examinations. Although the reason of SR of SCLC in the present case is unknown, PSN could be one of the diagnosis by exclusion.

(32) Horii R, Spontaneous " healing" of breast cancer, Breast cancer, 2005;12(2):140-4
http://www.jstage.jst.go.jp/article/jbcs/12/2/140/_pdf
BACKGROUND: Healing is a phenomenon by which the intraductal component of breast cancer disappears and is replaced by fibrous tissue. Focally localized healing often prevents confirmation of the continuity of intraductal carcinoma. OBJECTIVE: To clarify the clinicopathological characteristics of breast cancer with healing. PATIENTS AND METHODS: At our hospital, 308 patients (311 breasts) underwent breast conservation therapy without neoadjuvant chemotherapy for breast cancer in 2000. These surgical specimens were histopathologically investigated with 5 mm serial sections. We assessed the proportion and the characteristics of breast cancer with healing. RESULTS: (1) The proportion of breast cancer with healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and the mean diameter was 2.8 cm. (3) The histological type of the breast cancer varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5, solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular carcinoma in 1, and Paget's disease in 1. However in all cases, the histologic type of the intraductal carcinoma foci was the comedo/solid type and the nuclear grade of cancer cells was high. (4) In cases with healing, areas of healing were seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in 8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was seen at the surgical margin of the partial mastectomy specimen. CONCLUSION: The proportion of breast cancer cases with healing was 7% and these cases were intraductal carcinoma of the comedo/solid type, consisting of highly malignant cancer cells.

(33) 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.

(34) 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.

(35) 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.

(36) Dalton SO, Depression and cancer risk: a register-based study of patients hospitalized with affective disorders, Denmark, 1969-1993, American journal epidem., 2002 Jun 15;155(12):1088-95

(37) Bryla CM, The relationship between stress and the development of breast cancer: a literature review, Oncol Nurs Forum, 1996 Apr;23(3):441-8

(38) 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.

(39) Baltrusch HJ, Stress, cancer and immunity. New developments in biopsychosocial and psychoneuroimmunologic research, acta neurol (Napoli), 1991 Aug;13(4):315-27

(40) 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.

(41) Hilakivi-Clarke L, Psychosocial factors in the development and progression of breast cancer, breast cancer res treat, 1994 Feb;29(2):141-60

(42) Cooper CL, Psychosocial stress and breast cancer: the inter-relationship between stress events, coping strategies and personality, Psychol med 1993 Aug;23(3):653-62

(43) Fox BH, The role of psychological factors in cancer incidence and prognosis, Onclology (Williston Park), 1995 Mar;9(3):245-53

(44) 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.

(45) 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.

(46) Jadoulle V, Cancer, a defect of the psyche?, Bull Cancer, 2004 Mar;91(3):249-56

(47) 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.

(48) Lambley P, The role of psychological processes in the aetiology and treatment of cervical cancer: a biopsychological perspective, Br J Med Psychol, 1993 Mar;66 ( Pt 1):43-60
Cervical cancer is one of the most serious illnesses affecting women today, particularly in developing societies. Despite medical advances in treatment and the success of cervical screening programmes in detection, the incidence of the disease is increasing. In this paper it is argued that one of the reasons for this is that the aetiological model employed for cervical cancer takes little account of psychological and psychophysiological factors. Both of these factors are now thought to play important roles in disease processes. Research in these areas is reviewed and a new aetiological model for cervical cancer described. This model incorporates existing epidemiological and medical formulations into a new multifactor framework. The implications of this model for treatment are explored and it is suggested that psychological interventions could play a much greater role than they have in the past.

(49) 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.

(50) 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.

(51) 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.

(52) 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.

(53) 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.

(54) 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.

(55) Byrnes DM, Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer, Psychosom Med, 1998 Nov-Dec;60(6):714-22
OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

(56) 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....