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The discovery of the BRCA1 and BRCA2 mutation identifies a group of nearly homogeneous patients at substantially increased risk of breast cancer. The risk of breast cancer by age 70 in BRCA1 mutation carriers is estimated to range from 44% to 78% and for BRCA2 mutation carriers from 31% to 56%.1,2 Bilateral prophylactic mastectomy (BPM) is thus an important consideration for this population. Alternative approaches that have been investigated include frequent surveillance that includes the use of breast magnetic resonance imaging (MRI) and chemoprevention using tamoxifen.

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Meijers-Heijboer and colleagues compared breast cancer related outcomes among BRCA1/2 mutation carriers who opted for BPM and compared this with those who chose to undergo surveillance.3 Many of the patients who underwent surveillance also had regular MRI of the breast. Among the 76 women who underwent BPM, no cases of breast cancer were identified after 2.9 years of follow-up. In contrast, 8 of 63 women who opted for a surveillance approach were diagnosed with breast cancer during this follow-up period. Importantly, among these 8 women, 1 death from breast cancer was also reported. Thus the authors estimated that the 5-year risk of breast cancer in the surveillance group was 12% with BPM reducing this risk by 66% to 100% (Fig. 65-1). In addition, although more women who underwent BPM also underwent prophylactic oophorectomy, the benefits of BPM in reducing breast cancer events was still significant even after controlling for this difference. Although data from this cohort suggested substantial benefit to BPM, the number of patients in the study as well as the follow-up was small, with a resulting wide estimate of risk reduction conferred by BPM. Thus this study leaves open the possibility that BPM in BRCA1/2 mutation carriers may confer less of an advantage than estimated by these initial findings.

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Figure 65-1
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Actuarial incidence of breast cancer among women with a BRCA1 or BRCA2. Mutation after prophylactic mastectomy or during surveillance. The surveillance group includes data obtained before prophylactic mastectomy in 76 of the 139 women. The dashed line represents the probability of breast cancer during surveillance, and the dotted lines represent the 95% confidence interval. Values were calculated with the use of an exponential model in which the hazard rate was assumed to be constant. [Reproduced, with permission, from Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2001;345(3):159-164.]

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Breast cancer related outcomes in a larger population of BRCA1/2 mutation carriers was reported by the PROSE study group.4 In this multicenter study, 483 women with deleterious BRCA1 or BRCA2 mutations were followed for a mean of 6.4 years. Of the 105 women who elected to undergo BPM, 2 cases of breast cancer (1.9%) were reported compared with 184 ...

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