Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers

Abstract

The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I -IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (Po0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P ¼ 0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far. Women identified as carriers of a mutation in one of the breast and ovarian cancer-susceptibility genes BRCA1 or BRCA2 have strongly elevated risks of developing breast or ovarian cancer (Ford et al, 1998). A recent meta-analysis (Antoniou et al, 2003) including 22 studies, revealed an average cumulative risk of 65% for breast cancer and 39% for ovarian cancer in BRCA1 mutation carriers by age 70 years. The corresponding estimates for women with a mutation in BRCA2 were 45 and 11%. Once diagnosed with breast cancer, these women are also at high risk of developing breast cancer in the contralateral breast. Early reports of The Breast Cancer Linkage Consortium estimated a contralateral breast cancer cumulative risk of 50 -60% at age 70 years in BRCA1 or BRCA2 mutation carriers (Easton et al, 1995; The Breast Cancer Linkage Consortium, 1999). Later studies estimated even higher incidences of contralateral breast cancer within the first 5 years of follow-up after the primary breast cancer: 12 -33% among BRCA1 or BRCA2 mutation carriers (2.4 -6.5% per year) (Robson et al, 1998;Verhoog et al, 1998Verhoog et al, , 1999) as compared to a 0.4 -1% per year for breast cancer patients in general (Fisher et al, 1984).Owing to the elevated risks and fear of contralateral breast cancer, some women opt for contralateral prophylactic mastectomy (CPM). No stu...

Mastectomy and Contralateral Prophylactic Mastectomy Rates: An Institutional Review

“…2 Contralateral prophylactic mastectomy (CPM) reduces the risk of breast cancer by 91-96%. 3,4 Although a significant improvement in survival has not been identified in most studies, a more recent study has demonstrated a modest survival benefit for women under 50. 5,6 Prophylactic mastectomy is usually reserved for patients who are at high risk for developing a contralateral breast cancer.…”

Improved overall survival after contralateral risk‐reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: A prospective analysis

“…Some studies showed improved survival after CRRM, 14,17,[19][20][21] while others did not. 11,13,16,18 Also, previous studies often suffered from small sample sizes, 11,13,18 short follow-up 13,18,20 and heterogeneous study populations consisting of mixtures of sporadic, high-risk and BRCA-associated PBC patients. 16,18 In fact, only three studies exclusively reported on BRCA1/2 mutation carriers.…”

“…16,18 In fact, only three studies exclusively reported on BRCA1/2 mutation carriers. 13,19,21 More knowledge on the efficacy of CRRM after BRCAassociated PBC is important as this allows for more accurate and tailored genetic and oncologic counselling for respective patients. In view of the limitations of previous studies, we designed a well-powered prospective study to establish the efficacy of CRRM after BRCA-associated PBC on overall survival.…”

“…This procedure significantly reduces the risk of CBC by 83-100%, both in the sporadic breast cancer population and in high-risk and BRCA-associated PBC patients. [11][12][13][14][15][16][17][18][19] Still, the ultimate goal of contralateral risk-reducing mastectomy (CRRM) is to improve survival. So far, data on survival of PBC patients who opt for subsequent CRRM are inconsistent.…”

The Importance of Quality of Life to Patient Decision Making in Breast Cancer Care

“…Patients who carry mutations in the BRCA genes may have more limited treatment options; their lifetime risk of recurrence in either the affected or unaffected breast is high enough that they benefit from double mastectomy [2]. Another group whose options may be limited comprises younger women, who tend to be diagnosed with later-stage disease because there is less routine screening of this population.…”