Domanda Alimentazione vegana e cancro: non protegge più ..

... di tanto....
non è quella che fa la differenza....


Alimentazione vegana e cancro
Alimentazione vegana, vegetariana e cancro: Cosa c'è di vero alla luce delle attuali conoscenze mediche?
Da anni ormai si sono diffuse le credenze che un'alimentazione vegana (cioè vegetariana in senso stretto, senza l'uso di proteine di origine animale) preservi dal cancro, che la carne rossa faccia venire i tumori ecc. Cosa c'è di vero alla luce delle attuali conoscenze mediche? 1) È parzialmente vero che l'alimentazione vegana diminuisce del 30% il rischio del cancro al colon e al retto. Chi consuma carne rossa o altri cibi animali grassi (formaggi grassi) è quindi più a rischio (a causa dei grassi contenuti in essa; il rischio diminuisce se si scelgono carni rosse magre e se si utilizzano metodi di cottura non traumatici, evitando per esempio lagriglia) per questi DUE tipi di tumore. Le più recenti ricerche dimostrano però che non sono i grassi saturi il fattore di rischio, ma il loro ABUSO: in soggetti normopeso il fattore di rischio non è aumentato. 2) È falso affermare che l'alimentazione vegana protegge da tutti i tumori. Per esempio, una ricerca condotta su 350.000 donne per un periodo di 6-15 anni da ricercatori della Harvard School of Public Health di Cambridge, nel Massachusetts, ha dimostrato che non c'è nessuna prova convincente di una significativa diminuzione del rischio di tumore del seno nelle donne che consumano frutta e verdura in abbondanza. La ricerca ha peraltro dimostrato come nelle donne obese il rischio di tumore al seno sia più alto. Perché questa ricerca è importante? Perché dimostra che il presunto ruolo anticancro di frutta e verdura è decisamente ridotto se si considerano individui "magri". In sostanza si deve modificare la precedente posizione secondo cui esisterebbero alimenti (come i grassi di origine animale) che favorirebbero i tumori in quella secondo cui alcuni alimenti sarebbero tanto più a rischio quanto più il soggetto è sovrappeso. Anche se preserva solo in parte dai tumori all'apparato digerente (anche i vegani muoiono di cancro), potrebbe essere un aiuto per tutti coloro che sono esposti a fattori di rischio o
sono geneticamente predisposti a questo tipo di tumori. Se però si traduce in numeri il punto 1) (su 100 morti si considerano quelle per tumore; su queste si considerano quelle per tumori all'apparato digerente e infine si considera il diminuito rischio del 30%, che non è poi molto) si scopre che un'alimentazione vegana non ha un'incidenza significativa sulla vita media, tenendo conto che comporta anche svantaggi dal punto di vista salutistico, altrettanto provati come la riduzione del rischio tumorale. La genetica ha ormai dimostrato che la frase "siamo ciò che mangiamo" è solo parzialmente vera perché è anche vero che "siamo ciò che nasciamo". 3) È falso che basta un'alimentazione vegana per proteggersi dai tumori all'apparato digerente. Infatti uno studio del dipartimento dell'Agricoltura statunitense su 71 tipi di broccoli ha rilevato che le quantità di glucorafanina (la sostanza che dovrebbe proteggere dal cancro) varia enormemente a seconda del tipo. In alcuni broccoli è addirittura assente. I nutrizionisti americani alla luce di queste scoperta pensano di realizzare ibridi ricchi di glucorafanina, addirittura con l'impiego della genetica. Ciò forse non piacerà ai vegani più naturalisti, ma il mondo va avanti. Infatti le varietà attuali più ricche di glucorafanina sono quelle più amare, meno appetibili (la glucorafanina è legata a un'altra sostanza dal sapore nettamente amarognolo) e quindi probabilmente non basteranno le tecniche tradizionali per ottenere ibridi che possano essere accolti favorevolmente dai consumatori. Lo stesso procedimento si pensa di attuarlo anche per i pomodori, aumentando il contenuto di licopene, un antiossidante che attacca i radicali liberi. Attualmente la quantità di licopene è proporzionale alla temperatura del luogo di coltivazione: i pomodori coltivati a Napoli contengono più licopene di quelli coltivati in Lombardia. 4) Veramente al sicuro? - Da ultimo la ricetta vegana contro il cancro non è scientifica. La morte per cancro di Linda McCartney (la moglie del celeberrimo Paul), vegana convinta, mise in crisi parecchi vegani che si ritenevano assolutamente al sicuro dalla malattia.

.....Da ultimo la ricetta vegana contro il cancro non è scientifica. La morte per cancro di Linda McCartney (la moglie del celeberrimo Paul), vegana convinta, mise in crisi parecchi vegani che si ritenevano assolutamente al sicuro dalla malattia.....

e come Lei ce ne sono migliaia....

Allora che cosa fa la differenza, se non l'alimentazione????

non avere infezioni!

atima ha scritto: non avere infezioni!

concordo sulle infezioni, l'alimentazione vegana non vuol dire sempre corretta, nel senso che spesso ho visto vegani abusare di dolci, seitan e altre cose ricche di zuccheri e glutine senza badarne, tanto ' non contengono prodotti animali'...
l'alcalinizzazione è per me fondamentale, la dieta vegana ha dimostrato che pero' a parita' di tossine si sviluppano meno tumori, perche' le proteine animali danno 1 qualche contributo negativo al processo degenerativo.

Ci sono altri fattori ad esempio avevo letto, mi pare da Pierpaoli o DiBella che si dovrebbe fare uno studio sui 'Cechi', i cechi in pochi lo sanno si ammalano molto poco di cancro rispetto alle altre persone, perche'?
sono tutti vegani? .....NO
sono tutti integrati al top? ....NO

rispettano di piu' i ritmi circadiani.

QUESTI SONO MATTI!!!!!!
LA STAMPA E' IMPAZZITA!!!!
NON ESISTE NESSUNA CORRELAZIONE SERIA TRA IL GENE IMPUTATO E IL CANCRO AL SENO.... NON PIù DELLE MAREEE E DELLA LUNA PIENA IN TERMINI DI ANALISI DELLA CORRELAZIONE E SERIE STORICA........ ASSURDO
ECCO COME CONVOGLIARE TUTTI VERSO LA CHEMIO E LA MEDICINA DA MECELLAIO.... STIAMO VIVENDO GLI ANNI DELLA LOBOCTONIA DEL SENO...

Cancro al seno, muore la zia della Jolie
E' deceduta domenica. 'Stesso gene difettoso dell'attrice'
27 maggio, 15:10

Muore di cancro la zia di Angelina Jolie

La zia materna di Angelina Jolie e' morta domenica di cancro al seno, quasi due settimane dopo che l'attrice ha annunciato di essersi sottoposta a una doppia mastectomia dopo aver saputo che aveva una elevata predisposizione ereditaria al cancro al seno. Debbie Martin, sorella minore della madre di Jolie, e' morta all'eta' di 61 anni al Palomar Medical center di Escondido, vicino a San Diego. Suo marito, Ron Martin, ha detto a Sky News che sua moglie aveva lo stesso gene difettoso BRCA1 della nipote attrice, che dà una elevatissima probabilità di contrarre la malattia. La madre di Jolie, Marcheline Bertrand (sorella maggiore di Debbie), era morta di cancro al seno nel 2007, all'eta' di 56 anni.


una delle ricerche che non significa assolutamente niente.... non sanno ancora niente e pretendono di spiegare...!!!!


"...danni al DNA di riparazione e regolazione trascrizionale. Valutiamo le conoscenze attuali di BRCA1 e BRCA2 funzioni ..."



. Hum Mol Genet 2001 Aprile; 10 (7) :705-13.
BRCA1 e BRCA2 e la genetica del cancro al seno e alle ovaie.
Welcsh PL , Re MC .
Fonte
Dipartimenti di Medicina e Genetica, Box 357.720, Università di Washington, Seattle, WA 98.195-7720, Stati Uniti d'America. piri@u.washington.edu
Estratto
Mutazioni germinali in geni oncosoppressori BRCA1 e BRCA2 predispongono gli individui a seno e alle ovaie. I progressi nella determinazione della funzione di BRCA1 e BRCA2 suggerisce che essi sono coinvolti in due processi cellulari fondamentali: danni al DNA di riparazione e regolazione trascrizionale. Valutiamo le conoscenze attuali di BRCA1 e BRCA2 funzioni per spiegare perché le mutazioni in BRCA1 e BRCA2 portano specificamente per cancro al seno e alle ovaie. Il geni BRCA1 e BRCA2 contengono insolitamente alta densità di elementi ripetitivi. Queste caratteristiche delle regioni genomiche BRCAs contribuiscono all'instabilità cromosomica di questi geni. Proponiamo che le alterazioni somatiche di BRCA1 e BRCA2 sono comuni e guidato da riarrangiamenti tra elementi ripetitivi. Ereditata e mutazioni somatiche avvengono in BRCA1 e BRCA2; praticamente tutte le mutazioni somatiche sono il risultato di grandi riarrangiamenti genomici. Quali sono le conseguenze di tali grandi mutazioni somatiche dei geni BRCA1 e BRCA2 in donne con o senza mutazioni ereditarie? Il seno e ovaio sono tessuti estrogeno-responsive. Cominciando in pubertà, l'epitelio mammario prolifera rapidamente in risposta fluttuanti livelli di estrogeni. Vi presentiamo un modello genetico che illustra come le cellule di BRCA-deficienti possono guadagnare proliferazione incontrollata che porta alla formazione del tumore. Al centro di questo modello di tumorigenesi BRCA-mediata sono estrogeno-mediata proliferazione di epitelio mammario e ovarico e il contesto genomico distintivo dei geni BRCA.

---

Gene BRCA1 nel carcinoma mammario.
Rosen EM , Fan S , Pestell RG , Goldberg ID .
Fonte
Dipartimento di Radioterapia Oncologica, Long Island Jewish Medical Center, New York, New York, USA. erosen@lij.edu
Estratto
Il gene BRCA1 è stato identificato e clonato nel 1994 fondato il suo legame con il cancro al seno ad insorgenza precoce e le sindromi di cancro al seno-ovarico nelle donne. Mentre le mutazioni ereditarie di BRCA1 sono responsabili di circa il 40-45% dei tumori al seno ereditari, queste mutazioni rappresentano solo il 2-3% di tutti i tumori al seno, in quanto il gene BRCA1 è raramente mutato nei tumori al seno sporadici. Tuttavia, l'espressione BRCA1 è frequentemente ridotta o assente nei tumori sporadici, suggerendo un ruolo molto più ampio nella carcinogenesi mammaria. Poiché BRCA1 è stato clonato nel 1994, la sua funzione molecolare è stata oggetto di intense ricerche. Questi studi hanno rivelato molteplici funzioni del BRCA1 che possono contribuire alla sua attività di soppressore del tumore, tra cui ruoli in: progressione del ciclo cellulare, diversi processi altamente specializzati di riparazione del DNA, DNA damage-reattiva ciclo cellulare punti di controllo, regolazione di una serie di specifiche trascrizionale percorsi, e apoptosi. Molte di queste funzioni sono legate alla proteina: proteina coinvolgono diverse porzioni del 1.863 amminoacidi (aa) proteina BRCA1. Funzioni di BRCA1 nella progressione del ciclo cellulare e della risposta al danno del DNA sembrano essere regolata da eventi di fosforilazione distinte e specifiche, ma i meccanismi molecolari attivati ​​da queste fosforilazioni stanno solo iniziando a essere svelato. Inoltre, la ragione per cui i portatori di mutazioni BRCA1 sviluppare specifici tipi di tumore (mammella e alle ovaie nelle donne e, eventualmente, tumori della prostata negli uomini) non sia chiaramente compreso. Delucidazione delle funzioni molecolari precise del prodotto del gene BRCA1 permetterà di migliorare notevolmente la nostra comprensione della patogenesi della ereditaria così come sporadici carcinogenesi mammaria.



ma come... le probabilità di contrarre il cancro non dovevano essere dell87%

siamo al casino'!!!!!!!!




Breast cancer prevention in women with a BRCA1 or BRCA2 mutation
KELLY A METCALFE, STEVEN A NAROD
Kelly A Metcalfe is an assistant professor at the Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, and an adjunct scientist at Women’s College Research Institute, Toronto, Ont. Steven A Narod is a geneticist at the Women’s College Research Institute, Toronto, Ont.
Competing interests: None declared.
Counselling women about the resources that are available to them to assess their risk of breast cancer and providing advice on appropriate screening and risk-reduction strategies can be challenging for clinicians. This article discusses genetic risk factors for breast cancer, how to take a family history, and how to counsel and organize appropriate referrals for patients who may be at an increased risk of breast cancer because of a mutation in the BRCA1 or BRCA2 gene. In addition, it provides information on counselling women who have been identified as having a mutation in BRCA1 or BRCA2.

Case
A 40-year-old patient informs you that her sister has been diagnosed with breast cancer at the age of 38. The patient’s mother, at age 65, is healthy and has never had a cancer diagnosis. The patient knows of no other family history of breast cancer on her mother’s side of the family; her father’s grandmother possibly had breast cancer, but she died before the patient was born. The patient also mentions a paternal aunt who died of ovarian cancer. She is of Ashkenazi Jewish descent. The patient inquires whether she should be concerned about her sister’s breast cancer diagnosis and if she is too young to begin breast screening. How would you advise her?

Assessing breast cancer risk
Several models are available to help assess a woman’s risk of breast cancer. The Gail Model calculates a woman’s breast cancer risk over the next five years, in addition to her lifetime risk ( www.cancer.gov/bcrisktool/ ). The model considers age, ethnicity, history of breast cancer in first-degree relatives, age of menarche, and previous history of breast biopsies and benign breast disease.

Clinicians should be familiar with the process of taking a detailed family history (pedigree) to assess cancer risk. This involves collecting information with regard to types of cancer, the ages at which cancer diagnoses were made, and the vital status of three generations of relatives within a family. In addition, family ethnicities should be recorded. There are many resources available to help clinicians assess genetic family histories, including a detailed list on the University of Kansas Medical Center website.

Genetic testingfor BRCA1 and BRCA2 mutations helps physicians identify women who are at significantly increased risk of developing breast and ovarian cancer. For BRCA1 carriers, the estimated cumulative risks to age 70 years are 65% for breast cancer and 39% for ovarian cancer. The corresponding risks for BRCA2 carriers are 45% for breast cancer and 11% for ovarian cancer.1 In comparison, the average woman in the general population has an 11% lifetime risk of developing breast cancer and a 1.5% risk of developing ovarian cancer (Table 1). After the initial diagnosis of breast cancer in a BRCA1 or BRCA2 carrier, the risk of cancer in the opposite breast (a new primary cancer) increases by approximately 3% per year.2-4

About 1 in 200 women in North America carries a BRCA1 or BRCA2 mutation,5-7 but among several ethnic groups the prevalence is considerably higher. Notably, the frequency in those of Ashkenazi Jewish ancestry is 1 in 50.7,8 Other groups with high frequencies of mutations include women from Iceland9 and Poland.10 These high prevalence rates are explained by the presence of founder mutations. (Founder mutations are one or more specific mutations in a population that have been inherited from a common ancestor, and that have become amplified through chance effects, often aided by geographic isolation of the population.)

Patients identified as being at increased risk for any familial cancers should be referred for genetic counselling. The Ontario Medical Review published guidelines for the referral of patients with a family history of cancer to cancer genetics clinics.11 These guidelines identify risk factors for inherited breast and ovarian cancer (Textbox 1). The presence of one or more of these factors in an individual’s personal or family history may suggest an increased risk for hereditary cancer and warrants a referral for genetic counselling. Information on genetic counselling centres within Canada can be found at www.cagc-accg.ca .

Table 1. Lifetime breast cancer risk [view]
Case revisited
The patient’s family history suggests a possible BRCA1 or BRCA2 mutation. She has a sister with premenopausal breast cancer, a paternal grandmother with breast cancer who died at a young age, and a paternal aunt with ovarian cancer. Her Ashkenazi Jewish descent may also increase her risk of a mutation. Information is collected on 3 generations within the family and presented in a genetic pedigree (Figure 1), which proves to be suggestive of hereditary breast cancer. You refer your patient for genetic counselling and testing, and also suggest that her sister with breast cancer seek genetic counselling. Models are available to assess an individual’s risk of having a mutation in the BRCA1 or BRCA2 genes ( www4.utsouthwestern.edu/breasthealth/cagene/ ). Your patient’s genetic counseller, using the BRCAPRO model, determines that she has a 30% lifetime risk of breast cancer and a 42% chance of having a BRCA1 or BRCA2 mutation. She then receives genetic testing and is found to have a BRCA1 mutation. Your patient returns to consult you and wants to know what she can do to prevent the development of breast cancer. What would you tell her?

Figure 1. A family history of cancer. The patient (arrow) is considered the proband [view]
Cancer prevention options
Ultimately, the value of genetic testing for BRCA1 and BRCA2 mutations comes from reducing the number of women who develop breast cancer and the number of women who die of the disease. Women with a BRCA1 or BRCA2 mutation may consider several options for breast cancer prevention. The three main options are prophylactic mastectomy, prophylactic oophorectomy, and chemoprevention (tamoxifen or raloxifene). In addition, a woman may elect to undergo routine screening (secondary prevention) with the goal of detecting any cancers at an early, treatable stage.

Prophylactic mastectomy. The goal of prophylactic mastectomy is to prevent breast cancer, thereby eliminating the potential for metastatic spread and death from the disease. The effectiveness of prophylactic mastectomy in preventing breast cancer in BRCA1 and BRCA2 mutation carriers has been established in a small prospective study and in historical cohort studies of primary and contralateral breast cancers. In the small prospective study of 26 women with a BRCA1 or BRCA2 mutation, observed numbers of cancer were compared to expected numbers of breast cancer based on penetrance estimates. Statistical analysis demonstrated that prophylactic mastectomy offered at least an 89% risk reduction of breast cancer in BRCA1 and BRCA2 carriers.12 Meijers-Heijboer and colleagues observed no cases of breast cancer over 3 years among 76 women who underwent prophylactic mastectomy.13 Rebbeck and colleagues observed 2 cases of breast cancer among 191 women after mastectomy, compared to 184 cases among 378 women who did not choose mastectomy (p < 0.0001).14 Metcalfe and colleagues studied the development of contralateral breast cancer in 491 women treated for hereditary breast cancer using various standard surgical and adjuvant therapies.2 Only one contralateral breast cancer was observed among 146 women who had undergone a contralateral mastectomy, versus 33 expected with no contralateral mastectomy (p < 0.0001). These studies suggest that the residual breast cancer risk after mastectomy is minimal (less than 5%), and much less than the risk of breast cancer in the general population.

Total mastectomy is currently recommended over subcutaneous or nipple-sparing mastectomy; in the latter procedure, some breast tissue must remain below the nipple-areola complex to maintain the blood and nerve supply, and therefore there is the potential for breast cancer to develop in this residual tissue. However, one systematic review previously reported that in all of the case studies in the literature reporting a failure of a subcutaneous mastectomy in the prevention of breast cancer, the majority of cancers did not occur in this residual tissue.15 As such, the risks and benefits of both surgical options should be discussed with patients.

Although prophylactic mastectomy offers the best protection against developing breast cancer, it is known that the majority of women in Canada are unwilling to exercise this option.16

Prophylactic oophorectomy. It has been shown that BRCA1-associated breast cancers are hormonally associated.17 The purpose of an anti-hormonal therapy is to eliminate or block the effect of ovarian estrogen, and probably progesterone, or to prevent aromatization of androgen to estrogen. Anti-hormonal approaches include therapy with tamoxifen, raloxifene and other selective estrogen receptor modulators (SERMs), ovarian ablation (oophorectomy, radiation or chemical ablation with gonadotropin-releasing hormone [GNRH] agonists) and aromatase inhibition (with an agent such as anastrozole or letrozole). Of these, only tamoxifen and oophorectomy have been well studied in women with BRCA1 or BRCA2 mutations.

The rationale for an anti-hormonal approach comes from the observation that oophorectomy prevents breast cancer in BRCA1 and BRCA2 carriers. Cohort studies estimate the reduction in hereditary breast cancer risk associated with a premenopausal oophorectomy to be about 50%.18-20 A recent case-control study reported that this risk reduction may be greater if oophorectomy is performed before age 40 and that the duration of protection is approximately 15 years.21 Short-term use of estrogen for menopausal symptom relief in young women after oophorectomy might abrogate some of the breast cancer protection associated with oophorectomy but may be important to a woman’s quality of life. In one study the effectiveness of prophylactic oophorectomy was not reduced by the addition of hormone replacement therapy.20 Women who elect for prophylactic mastectomy should receive routine screening for osteoporosis associated with low estrogen.

There are no comparable data on the degree of protection against breast cancer offered by other forms of ovarian ablation such as radiation or GNRH agonists. GNRH agonists are a reversible form of ovarian suppression and thus may be preferred by a woman who wishes to preserve her fertility, but the use of these drugs in BRCA carriers is not widespread and their effectiveness in reducing breast cancer risk is unknown. There remains the concern that these non-surgical approaches to ovarian ablation do not address the risk for ovarian or fallopian tube cancers, which are also elevated in BRCA1 and BRCA2 carriers.

Selective estrogen receptor modulators. Tamoxifen is a selective estrogen receptor modulator (SERM) that competes with estrogen for binding to the estrogen receptor. In humans, tamoxifen acts as an estrogen antagonist in breast tissue, inhibiting the growth of estrogen-dependent breast tumours.22 On theoretical grounds, tamoxifen should not reduce the incidence of estrogen-receptor (ER) negative breast cancers, and most breast cancers that occur in BRCA1 (but not BRCA2) carriers are ER negative. An attempt to understand the preventative role of tamoxifen was made in the National Surgical Adjuvant Breast and Bowel Project — P1 trial.23 In this study, the authors compared the incidence of breast cancer among women who took tamoxifen with the incidence among those who took a placebo. In the cohort of 288 women who developed breast cancer during the study, 8 women were found to have a BRCA1 mutation and 11 were found to have a BRCA2 mutation. When cancer incidence was examined in this group of women with BRCA1 and BRCA2 mutations, it was concluded that tamoxifen was protective against breast cancer in women with a BRCA2 mutation, but not in those with a BRCA1 mutation. No protective effect was seen with tamoxifen for BRCA1 carriers, but the number of cases is too small for the study to be definitive. In a large case-control study, tamoxifen was found to reduce the incidence of contralateral breast cancer in affected BRCA1 and BRCA2 carriers by about one-half (odds ratio = 0.5; 95% confidence interval 0.30–0.85).24 If we assume that contralateral cancers in carriers are representative of all new primary breast cancers, the results of this study might be extrapolated to the prevention of first primary breast cancers. But this conclusion would be invalid if the 2 primary cancers were not independent — for example, if tamoxifen were given only to ER positive patients, and if the ER status of bilateral cancers were highly correlated. In a recent study by Weitzel and colleagues, the majority of contralateral breast cancers after ER-positive breast cancer were in fact, estrogen-receptor negative, suggesting that tamoxifen prevents ER-negative contralateral breast cancers.25

There are risks associated with taking tamoxifen: for every 10,000 women who take tamoxifen there are 15 endometrial cancers, 2 uterine sarcomas, 4 cerebrovascular events, and 5 pulmonary emboli per year above that expected in those not on tamoxifen.26

Screening. The goal of screening is to identify breast cancer at a stage when surgical cure is likely. For women in the general population, this outcome would pertain to small (< 1 cm) node-negative tumours with no evidence of distant spread. However, BRCA1-associated breast tumours are typically high grade and are estrogen-receptor negative,2 which may impart higher risk even when they are detected early. Although several small studies have been done of breast-cancer-specific survival in women with a BRCA1 or BRCA2 mutation,27 there is little consensus on survival outcomes in this group of women. In one study involving BRCA1 carriers, little correlation was found between tumour size and lymph-node positivity, as would be expected with sporadic breast cancer. About one-third of BRCA1 carriers had lymph node metastases detected at diagnosis, regardless of tumour size,28 making it difficult to predict the benefit of screening using survival data generated from a comparison group of non-carriers.

A number of advisory groups in the United States and Europe have published recommendations for surveillance for women at hereditary risk for breast cancer and ovarian cancer.29-31 In general, these guidelines called for annual mammography beginning around age 25, as well as monthly breast self-examinations (BSE) and clinical breast examination (CBE) once to twice a year.

Certain histological features of BRCA1-associated breast cancer (e.g., the appearance of pushing margins) and high breast density (characteristic of young women) in women with a BRCA1 or BRCA2 mutation32 may make BRCA-associated tumours difficult to detect mammographically. Studies conducted in the US and in the United Kingdom of women under 50 with a family history of breast cancer reported mammography sensitivities of 63%–70%33 and 44%,34 respectively. Goffin and colleagues35 found that only 2 of 8 breast cancers (25%) in BRCA1 carriers were detectable by mammogram at diagnosis, versus 27 of 35 (77%) among non-carrier controls (p = 0.01). In a large cohort at a single centre (n = 251), of 12 breast tumours diagnosed in BRCA mutation carriers, fewer than half were detected by mammogram.36 Breast magnetic resonance imaging (MRI) offers the promise of a greatly improved sensitivity of detection of breast cancers in those at high risk. Early studies reported sensitivities in the range of 100% for invasive breast cancer, but later studies that included ductal carcinoma in situ (DCIS) reported lower sensitivities.36-43 In the largest series reported to date, the sensitivity of MRI was 83% for invasive disease but was only 71% overall.44 However, the benefit attributable to finding cases of DCIS (versus early invasive cancers) has not been established. In a study with longitudinal follow-up, MRI detected 9 breast tumours that were missed by the other screening modalities.45 Of note, only 2 of the 22 women with breast cancer (9%) detected in this Canadian trial had lymph node metastases. Thus, we feel that MRI has a role in screening BRCA mutations carriers. It is not clear if the addition of mammography to MRI improves the sensitivity of screening.

Case revisited
Your patient is BRCA1 positive, and women with a BRCA1 or BRCA2 mutation represent the group at highest risk for breast cancer. She should be made aware of her options to reduce her cancer risk. Prophylactic mastectomy has the greatest likelihood of preventing cancer but is not acceptable to many women. The risk reductions resulting from tamoxifen and prophylactic oophorectomy are lower (approximately 50% risk reduction for each) and are associated with the side effects of hormone withdrawal and infertility. For these reasons, for many women screening is the preferred option.

References
Antoniou A, Pharoah PDP, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003;72(5):1117–30. [PubMed] [Full Text]
Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2004;22(12):2328–35. [CrossRef] [PubMed]
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Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997;336(20):1401–8. [PubMed] [Full Text]
Oddoux C, Struewing JP, Clayton CM, Neuhausen S, Brody LC, Kaback M, et al. The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%. Nat Genet 1996;14(2):188–90. [CrossRef] [PubMed]
Thorlacius S, Struewing JP, Hartge P, Olafsdottir GH, Sigvaldason H, Tryggvadottir L, et al. Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 1998;352(9137):1337–9. [PubMed]
Górski B, Jakubowska A, Huzarski T, Byrski T, Gronwald J, Grzybowska E, et al. A high proportion of founder BRCA1 mutations in Polish breast cancer families. Int J Cancer 2004;110(5):683–6. [CrossRef] [PubMed]
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Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 2001;93(21):1633–7. [PubMed] [Full Text]
Meijers-Heijboer H, van Geel B, van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345(3):159–64. [PubMed] [Full Text]
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