A Prospective Study of Endometriosis and Breast Health: Findings From the Nurses' Health Study II

Endometriosis is a chronic gynecologic disease affecting approximately ten percent of women in the United States. Endometriosis lesions depend on estrogen for growth and maintenance and it is hypothesized that women with endometriosis have an altered hormonal and inflammatory state. Emerging evidence suggests that women with endometriosis may be at increased risk of breast cancer. Using data from the Nurses’ Health Study II, a prospective cohort of 116,430 women, this thesis investigates endometriosis and breast health. Specifically we investigated whether endometriosis influences risk of breast cancer and benign breast disease and alters mammographic density. Lastly, we investigated whether breastfeeding duration influenced endometriosis risk. \n\tAcross all analyses, endometriosis was confirmed using laparoscopy, considered the clinical diagnostic gold standard. Information on breast cancer and benign breast disease was collected every two years and confirmed by medical record or pathology slides respectively. Mammographic density was measured from mammograms of a subset of participants without breast cancer using a computer assisted thresholding technique. Detailed breastfeeding information was collected between 1997-2001. Cox proportional hazard models were used to calculate Hazard Ratios (HR) and 95% confidence intervals (CI) and linear regression using generalized estimating equations was used to estimate difference in mammographic density measurements. \n\tWe found that while women with endometriosis were not at increased risk of overall breast cancer (HR:1.05, CI:0.95-1.16), they did appear to be at an increased risk of ER+/PR- tumors (HR:1.72, CI:1.27-2.32). Endometriosis moderately increased risk of biopsy confirmed benign breast disease, both proliferative (HR:1.23, CI:1.01-1.51) and non-proliferative lesions (HR:1.25, CI:0.93-1.69). Endometriosis did not significantly alter mammographic density. History of breastfeeding was inversely associated with endometriosis (P-value, test for linear trend: <0.0001), which was partially, but not fully mediated through postpartum amenorrhea. \n\tOur findings report novel associations with endometriosis and ER+/PR- breast tumors and benign breast disease lesions and no difference in mammographic density. This may elucidate avenues of research on how endometriosis lesions may alter chronic disease risk. Given the debilitating symptoms and few known modifiable risk factors of endometriosis, our findings of an inverse relationship with breastfeeding and endometriosis may inform treatments and prevention strategies for endometriosis in the future.