The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers

Abstract

BACKGROUND:The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC). METHODS: From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n ¼ 79) or with a history of unilateral BC (at risk of CBC; n ¼ 37) were selected. The control groups consisted of unaffected BRCA mutation carriers (n ¼ 351) or mutation carriers who had a previous unilateral BC (n ¼ 294), respectively. The risks of PBC and CBC were calculated using the Kaplan-Meier survival method with death considered as a competing risk event. RESULTS: Women with BRCA-associated OC had lower 2-year, 5-year, and 10-year risks of PBC (3%, 6%, and 11%, respectively) compared with unaffected mutation carriers (6%, 16%, and 28%, respectively; P ¼ .03), although they had a considerably higher mortality rate at similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%, respectively; P < .001). In BRCA mutation carriers with a previous unilateral BC, the 2-year, 5-year, and 10-year risks of CBC were nonsignificantly lower in patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%, 16%, and 34%, respectively; P ¼ .06), whereas the mortality rate was higher in patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%, respectively; P < .001). CONCLUSIONS: Patients with BRCA-associated OC had a lower risk of developing a subsequent PBC or CBC than mutation carriers without OC, whereas the risk of dying from OC was greater than the risk of developing BC. These data may facilitate more tailored counseling for this patient subgroup, although confirmative studies are warranted. Cancer 2013;119:955-62. V C 2012 American Cancer Society.KEYWORDS: BRCA, ovarian cancer, primary breast cancer, contralateral breast cancer, risk-reducing mastectomy. INTRODUCTIONWomen who have a germline mutation in the breast cancer susceptibility genes BRCA1 or BRCA2 have substantially elevated risks of developing both breast cancer (BC) and ovarian cancer (OC). It has been estimated that the cumulative 10-year risk of primary BC (PBC) ranges between 6% and 23% for BRCA1/BRCA2 mutation carriers, and the highest risk is observed between ages 40 and 50 years.1-6 After unilateral BC, the estimated 10-year risk of contralateral BC (CBC) is 29% to 39% for patients with BRCA1-associated BC and 23% to 35% for patients with BRCA2-associated BC. 1,[7][8][9][10] Factors that potentially affect the latter include age at first BC diagnosis (especially when diagnosed at ages <50 years),

Cumulative risk of second primary contralateral breast cancer in BRCA1/BRCA2 mutation carriers with a first breast cancer: A systematic review and meta-analysis

“…It is unlikely that BRCA1/ 2 carriers affected with ovarian cancer were included in those studies that specified ascertainment of first primary breast cancer cases [15e17,25e27, 29,34,37,40]. Women with BRCA-associated ovarian cancer have a lower risk of developing subsequent CBC than mutation carriers without ovarian cancer [60]. Studies that did not account for a first primary ovarian cancer might be therefore subjected to diluted effects of CBC cumulative risk.…”

Does perceived risk predict breast cancer screening use? Findings from a prospective cohort study of female relatives from the Ontario site of the Breast Cancer Family Registry

“…Classifications of familial breast cancer risk were based on data collected by the cancer FHQ completed by the proband, using previously referenced groups for familial breast cancer risk [12,41], with modifications based on key evidence [1,2,17,42–44] and expert opinion. Table 1 shows the criteria for classifying women as low, moderate or high risk.…”

Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer

“…This has been previously demonstrated as an hypothesized result of primary treatment with either RRSO or chemotherapy [ 38 ]. For a 50-year-old woman with a BRCA1 mutation and ovarian cancer, this resulted in a reduced lifetime risk of breast cancer from 24 to 14%.…”

“…Additionally, the majority of breast cancers were detected mammographically, questioning the value of MRI surveillance in this subset of women. Vencken et al 38 demonstrated a 6% 5-year risk of primary breast cancer in 79 women with BRCA-related ovarian cancer, compared with a 16% 5-year risk in unaffected BRCA mutation carriers. Domchek et al 40 reported excellent breast cancer-free survival in a cohort of 164 women with BRCA-related ovarian cancer.…”