The Role of Reproductive Risk Factors in Hereditary Breast Cancer within BRCA Mutation Carriers: Systematic Review and Meta-Analysis

Abstract

Background: BRCA1 and BRCA2 are tumor suppressor genes that play a pivotal role in DNA repair. Mutations of these genes are associated with increased risk of several cancers, including breast, ovarian, prostate, and other malignancies. While the prevalence of these mutations is relatively low, affecting less than 1% of the general population, certain racial and ethnic groups have much higher mutation rates. BRCA mutations make up nearly 10% of all breast cancer diagnoses affecting women under age 40, and these cancers are typically more aggressive. With the increasing prevalence of these BRCA cancers in younger women, there is a growing need for reproductive guidelines for this population. This project aims to address this gap by analyzing the effect of reproductive risk factors between BRCA carriers and the general population. Methods: We conducted a systematic review and meta-analysis to describe the association of pregnancy associated breast cancer risk factors and disparities within BRCA carriers. A comprehensive literature search was performed using PubMed, OVID, and CINAHL to evaluate the role of parity, age at first full-term pregnancy, incomplete pregnancies, and breastfeeding on breast cancer risk in BRCA carriers. Statistical analyses were performed using Revman 5.4, and subsequent forest plots and tables were generated. Results: Eighteen eligible articles were identified through our literature search. We found no association between parity, breastfeeding, spontaneous or therapeutic abortions, and breast cancer risk in BRCA1/2 carriers. These findings are different from breast cancer risk associated with these reproductive factors in the general population. However, our study found younger age at first full-term pregnancy (