Association of Fibroids, Endometriosis, and Gynecologic Surgeries with Breast Cancer Incidence and Hormone Receptor Subtypes.

ABSTRACT

BACKGROUND: Fibroids and endometriosis are sex hormone-mediated and exhibit cancer-like behavior. Breast cancer may be more common in women who have had these conditions, but the literature is conflicting and does not always address factors like hysterectomy/oophorectomy status, race/ethnicity, menopause, and hormone receptor subtypes. METHODS: Data are from the Sister Study, a cohort of 50,884 U.S. women enrolled in 2003 to 2009 and followed through 2020. Cox proportional hazards models with time-varying exposures and covariates assessed the relationship of fibroids or endometriosis with breast cancer. Logistic regression examined the association with estrogen receptor (ER) status among cases. RESULTS: Fibroids (19,932 cases) were positively associated with breast cancer [fully adjusted HR 1.07; 95% confidence interval (CI) 1.01-1.14], notably among Black participants (HR 1.34; 95% CI 1.07-1.69) and women who had a hysterectomy (HR 1.18; 95% CI 1.05-1.31). Endometriosis (3,970 cases) was not associated with breast cancer (HR 0.99; 95% CI 0.91-1.08). Among 4,419 breast cancer cases, fibroids were positively associated with ER+ subtypes (OR 1.34; 95% CI 1.10-1.65), while endometriosis was negatively associated with ER+ subtypes (OR 0.78; 95% CI 0.61-1.01). CONCLUSIONS: We observed a modest positive association between fibroids and breast cancer, particularly ER+ breast cancer. No relationship with endometriosis and breast cancer incidence was found. IMPACT Fibroids, even in those with a family history of breast cancer, might modify breast cancer risk stratification tools. Future studies should further assess this link and interrogate shared risk factors.