Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis

• Published in: Familial cancer 2015-12, Vol.14 (4), p.531-538
• Main Authors: Basu, N. N., Ingham, S., Hodson, J., Lalloo, F., Bulman, M., Howell, A., Evans, D. G.
• Format: Article
• Language: English
• Subjects: Adult; Biomedical and Life Sciences; Biomedicine; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer Research; Cross-Sectional Studies; Epidemiology; Female; Follow-Up Studies; Genetic Predisposition to Disease; Heterozygote; Human Genetics; Humans; Middle Aged; Neoplasm Staging; Original Article; Polymorphism, Single Nucleotide - genetics; Prognosis; Prospective Studies; Retrospective Studies; Risk Factors; Time Factors; United Kingdom - epidemiology; Young Adult
• ISSN: 1389-9600; 1573-7292
• DOI: 10.1007/s10689-015-9825-9

BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2–3 % per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.