Abstract
Background: The relationship between oral contraceptive (OC) use and breast cancer risk is highly debated. Recent publications support a slight increase in overall breast cancer risk among OC user women, in particular among the current users. Women with inherited BRCA1 (Breast cancer type 1) or BRCA2 (Breast cancer type 2) gene mutations are at increased risk of breast and ovarian cancers, which is often mistakenly attributed to their elevated endogenous estrogen levels. The aim of presented meta-analysis was to assess the effects of OC use on breast cancer risk in BRCA mutation carrier women with minimal bias. Methods: A systematic search strategy was used to identify relevant studies, Stata (version 15) was used for meta-analysis. Results: Individual datasets from 13 studies totaling 20,202 patients were analyzed. The combined results showed no significant increase in risk of breast cancer in BRCA mutation carriers who had ever used oral contraceptive (HR = 1.09, 95% CI: 0.71–1.69 among BRCA1 mutation carriers and HR = 1.19, 95% CI: 0.73–1.95 among BRCA2 mutation carriers, respectively). However, in correlation with long-term (>5 years) OC users, the breast cancer risk was significantly increased in both BRCA1 mutation carriers (HR = 1.39, 95% CI: 1.19–1.60) and BRCA1 mutation carriers (HR = 1.61, 95% CI: 1.25–1.96). Conclusion: The presented results indicate that in BRCA mutation carriers women who have defective liganded activation of estrogen receptors (ERs), the use of synthetic estrogens means an additive factor for ER deregulation further increasing the risk for breast cancer. Long term OC use in BRCA mutation carriers results in a significantly increased risk for breast cancer by exhausting the compensatory genome defending process.
Highlights
Breast cancer is the most common malignancy among women, while ovarian cancer is considered one of the most lethal malignancies
When I2 > 35%, we considered it as heterogeneity and used random effect (I–V heterogeneity)
Preliminary search identified 16 studies that compared the breast cancer risks in BRCA mutation carriers with oral contraceptives or not, after full text were reviewed (Fig. 1). Three of these were found to be ineligible, because the data was from small sample size less of than 30 participants [11,12,13]
Summary
Breast cancer is the most common malignancy among women, while ovarian cancer is considered one of the most lethal malignancies. Women with BRCA mutations have higher risk of breast cancer as well as ovarian cancer [1]. The lifetime risk of breast cancer in general population is about 10%, while it is 37–85% in women with BRCA mutations by the age of 70 years. Conclusion: The presented results indicate that in BRCA mutation carriers women who have defective liganded activation of estrogen receptors (ERs), the use of synthetic estrogens means an additive factor for ER deregulation further increasing the risk for breast cancer. Long term OC use in BRCA mutation carriers results in a significantly increased risk for breast cancer by exhausting the compensatory genome defending process
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