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

BRCA1/2 mutation carriers are at a higher risk of breast cancer and of subsequent contralateral breast cancer (CBC). This study aims to evaluate the evidence of the effect of the BRCA1/2-carriership on CBC cumulative risk in female breast cancer patients.The literature was searched in Pubmed and Embase up to June 2013 for studies on CBC risk after a first primary invasive breast cancer in female BRCA1/2 mutation carriers. A qualitative synthesis was carried out and the methodological quality of the studies evaluated. Cumulative risks of CBC after 5, 10 and 15 years since the first breast cancer diagnosis were pooled by BRCA1/2 mutation status.A total number of 20 articles, out of 1324 retrieved through the search, met the inclusion criteria: 18 retrospective and 2 prospective cohort studies. Cumulative risks of up to five studies were pooled. The cumulative 5-years risk of CBC for BRCA1 and BRCA2 mutation carriers was 15% (95% CI: 9.5%–20%) and 9% (95% CI: 5%–14%), respectively. This risk increases with time since diagnosis of the first breast cancer; the 10-years risk increased up to 27% and 19%, respectively. The 5-years cumulative risk was remarkably lower in non-BRCA carriers (3%; 95% CI: 2%–5%) and remained so over subsequent years (5%; 95% CI: 3%–7%).In conclusion, risk of CBC increases with length of time after the first breast cancer diagnosis in BRCA1/2 mutation carriers. Studies addressing the impact of treatment-related factors and clinical characteristics of the first breast cancer on this risk are warranted.