Association between hysterectomy, oophorectomy, and risk of breast cancer: a meta-analysis

Abstract Objectives This meta-analysis seeks to clarify the relationship between hysterectomy, oophorectomy, and the subsequent risk of developing breast cancer. Methods A comprehensive literature search was conducted across PubMed, the Cochrane Library, and Embase to identify relevant studies. The quality of the included studies was assessed using the Newcastle–Ottawa Scale (NOS). Statistical analyses were performed using Stata software (version 14.0), with hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) calculated. Publication bias was assessed using funnel plots and Egger’s test. Results A total of 12 studies were included, comprising 9 cohort studies and 3 case–control studies, with publication years ranging from 1988 to 2023, involving 5,868,660 participants, predominantly from the United States. The analysis revealed that both hysterectomy and oophorectomy are associated with a reduced risk of breast cancer, lowering the risk by 16% (HR 0.84; 95% CI: 0.76–0.92; I 2 = 76.5%; P < 0.001). Standalone hysterectomy was associated with a 13% reduction in breast cancer risk (HR 0.87; 95% CI: 0.77–0.99; I 2 = 82.3%; P = 0.033), while bilateral oophorectomy reduced the risk by approximately 19% (HR 0.81; 95% CI: 0.68–0.96; I 2 = 61.7%; P = 0.016). In contrast, unilateral oophorectomy did not significantly affect the risk of breast cancer (HR 0.89; 95% CI: 0.71–1.11; I 2 = 45.5%; P = 0.288). Patients who underwent bilateral oophorectomy and received hormone therapy experienced a 20% reduction in breast cancer risk (HR 0.80; 95% CI: 0.68–0.93; I 2 = 38.5%; P = 0.005), whereas those who did not receive hormone therapy showed no significant risk reduction (HR 0.87; 95% CI: 0.69–1.10; I 2 = 48.5%; P = 0.254). Premenopausal bilateral oophorectomy was associated with a 13% decrease in breast cancer incidence risk (HR 0.87; 95% CI: 0.79–0.96; I 2 = 0%; P = 0.004), while postmenopausal bilateral oophorectomy had no significant impact (HR 0.95; 95% CI: 0.88–1.03; I 2 = 1.2%; P = 0.196). Conclusions This meta-analysis suggests that both hysterectomy and oophorectomy are significantly associated with a reduction in breast cancer risk. The effectiveness of bilateral oophorectomy appears to be modulated by hormone therapy and menopausal status. Further research is needed to clarify these associations and to explore the underlying biological mechanisms.