Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation carriers: results from ten studies

Abstract

Although reproductive factors are among the most well-established risk factors for breast cancer in the general population, it is still a matter for debate whether these factors act as risk modifiers among BRCA1 or BRCA2 mutation carriers. This meta-analysis is the first to be performed to determine the relationship between reproductive factors and breast cancer risk among BRCA1 and BRCA2 mutation carriers. We searched the PubMed database up to February 2013. A total of ten studies met the inclusion criteria. The results showed that the reproductive factors may be associated with breast cancer risk only among BRCA1 mutation carriers. No association was found between parity and breast cancer risk. Compared with women at the youngest age in the first-birth category, women in the oldest age category were at a 38% lower risk of breast cancer (RR=0.62, 95%CI=0.45-0.85). Breastfeeding for at least 1 or 2 years was associated with a 37% reduction in breast cancer risk (RR=0.63, 95%CI=0.46-0.86). Women at the oldest age in the menarche category were at a 34% lower risk of breast cancer (RR=0.66, 95%CI=0.53-0.81) than women in the youngest age category. However, none of the reproductive factors were associated with breast cancer risk among BRCA2 mutation carriers. In conclusion, late age at first birth, breastfeeding, and late age at menarche protect against breast cancer in BRCA1 mutation carriers only. Further studies are needed to explore the mechanisms.

Keywords: Age at first birth; BRCA1 or BRCA2; Breast cancer; Breastfeeding; Menarche; Parity.