Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer

Hartmann, Lynn C.; Schaid, Daniel J.; Woods, John E.; Crotty, T. P.; Myers, Jeffrey L.; Arnold, Phillip G.; Petty, Paul M.; Sellers, Thomas A.; Johnson, Joanne L.; McDonnell, Shannon K.; Frost, Marlene H.; Jenkins, Robert B.

doi:10.1056/nejm199901143400201

Cited by 1,257 publications

(303 citation statements)

References 30 publications

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“…20,21 The present findings extend and confirm the preliminary report from the same series. 5 The results indicate that groups of patients may benefit differently from the surveillance programmes and treatment given so far.…”

Section: Discussionsupporting

confidence: 92%

Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy

Møller

Borg

Evans

et al. 2002

Intl Journal of Cancer

102

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Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaN0) and 26% had cancer with spread (CaN؉). Five-year survival was 100% for CIS, 94% for CaN0 and 72% for CaN؉ (p ‫؍‬ 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p ‫؍‬ 0.04). For CaN0 patients, mutation carriers had 75% 5-year disease-free survival vs. 96% for noncarriers (p ‫؍‬ 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but 1 relapse occurred in the 15 who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p ‫؍‬ 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.

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Section: Discussionsupporting

confidence: 92%

Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy

Møller

Borg

Evans

et al. 2002

Intl Journal of Cancer

102

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“…Identification of these individuals before they present with cancer is important since prophylactic surgery can reduce morbidity and mortality in these individuals (Struewing et al, 1995;Rebbeck et al, 1999;Hartmann et al, 1999;Hartmann et al, 2001;Meijers-Heijboer et al, 2001;Kauff et al, 2002;Rebbeck et al, 2004). Unfortunately, genetic testing is expensive, family history of breast cancer is common and BRCA mutations are rare (Ford et al, 1994;Peto et al, 1999;Antoniou et al, 2002).…”

mentioning

confidence: 99%

Evaluation of models to predict BRCA germline mutations

et al. 2006

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The selection of candidates for BRCA germline mutation testing is an important clinical issue yet it remains a significant challenge. A number of risk prediction models have been developed to assist in pretest counselling. We have evaluated the performance and the inter-rater reliability of four of these models (BRCAPRO, Manchester, Penn and the Myriad-Frank). The four risk assessment models were applied to 380 pedigrees of families who had undergone BRCA1/2 mutation analysis. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operator characteristic (ROC) curve were calculated for each model. Using a greater than 10% probability threshold, the likelihood that a BRCA test result was positive in a mutation carrier compared to the likelihood that the same result would be expected in an individual without a BRCA mutation was 2.10 (95% confidence interval (CI) 1.66 -2.67) for Penn, 1.74 (95% CI 1.48 -2.04) for Myriad, 1.35 (95% CI 1.19 -1.53) for Manchester and 1.68 (95% CI 1.39 -2.03) for BRCAPRO. Application of these models, therefore, did not rule in BRCA mutation carrier status. Similar trends were observed for separate BRCA1/2 performance measures except BRCA2 assessment in the Penn model where the positive likelihood ratio was 5.93. The area under the ROC curve for each model was close to 0.75. In conclusion, the four models had very little impact on the pre-test probability of disease; there were significant clinical barriers to using some models and risk estimates varied between experts. Use of models for predicting BRCA mutation status is not currently justified for populations such as that evaluated in the current study.

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“…However, studies have suggested that total mastectomy provides the greatest breast cancer risk reduction due to removal of more breast tissue [19]. These surgeries are highly effective as bilateral prophylactic mastectomy has been shown to reduce the risk of breast cancer by at least 95% in women who have a deleterious mutation in the BRCA1 gene or the BRCA2 gene [20][21][22][23], while bilateral prophylactic salpingo-oophorectomy has been shown to reduce the risk of breast cancer by approximately 50% in women who have high risk of developing the disease [19].…”

Section: Risk-reducing Surgerymentioning

confidence: 99%

Indian Solutions for Indian Problems—Association of Breast Surgeons of India (ABSI) Practical Consensus Statement, Recommendations, and Guidelines for the Treatment of Breast Cancer in India

Somashekhar

Agarwal²,

Deo

et al. 2017

Indian J Surg

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Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer

Abstract: In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer.

Cited by 1,257 publications

References 30 publications

Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy

Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy

Evaluation of models to predict BRCA germline mutations

Indian Solutions for Indian Problems—Association of Breast Surgeons of India (ABSI) Practical Consensus Statement, Recommendations, and Guidelines for the Treatment of Breast Cancer in India

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