Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

• Published in: British journal of cancer Vol. 104; no. 9; pp. 1384 - 1392
• Main Authors: Metcalfe, K, Gershman, S, Lynch, H T, Ghadirian, P, Tung, N, Kim-Sing, C, Olopade, O I, Domchek, S, McLennan, J, Eisen, A, Foulkes, W D, Rosen, B, Sun, P, Narod, S A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.04.2011; Nature Publishing Group
• Subjects: 631/67/68; 692/699/67/1347; 692/700/565/545/546; Adult; Age; Age Factors; Aged; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer; Cancer Research; Clinical Study; Cohort Studies; Drug Resistance; Epidemiology; Female; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Genetics; Heterozygote; Humans; Middle Aged; Molecular Medicine; Mortality; Mutation; Neoplasms, Second Primary - diagnosis; Neoplasms, Second Primary - genetics; Neoplasms, Second Primary - mortality; Neoplasms, Second Primary - prevention & control; Odds Ratio; Oncology; Ovariectomy; Predictive Value of Tests; Risk Assessment; Risk Factors; Risk reduction; Survival Analysis; breast cancer; BRCA1; BRCA2; contralateral breast cancer
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2011.120

Purpose: The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk. Patients and methods: Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. Results: Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8%; P =0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36%; P =0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30–0.76; P =0.002). Conclusion: The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.