Real-world assessment of breast cancer risk following hormonal therapy in endometriosis: A Global Collaborative Network propensity score matched analysis.

11143 Background: Research suggests endometriosis, an estrogen-dependent condition, may be a potential risk factor for breast cancer (BC) development. While oral contraceptives are the standard treatment, their efficacy is limited in symptom control. This study examines the relationship between hormonal therapy (HT) prescribed for endometriosis management and BC risk. Methods: Using TriNetX Global Collaborative Network, we compared 41 029 endometriosis patients receiving HT against 111 429 control patients without HT. We excluded patients with prior contraceptive use or neoplasm diagnosis. Through propensity score matching, we created 38 311 balanced pairs, accounting for demographics (age, race), medical history (pelvic disease, family cancer history, hypertension, diabetes), and clinical factors (pregnancies, body mass index). Additional analyses were conducted by type of HT: progestins (36 156 matched pairs) and LHRH analogues (7 700 matched pairs). BC incidence was measured using hazard ratios, starting 6 months post-endometriosis diagnosis. We evaluated the rate of pregnancies and we also conducted an analysis to assess the risk of major cardiovascular events according to HT treatment for endometriosis, including stroke, cardiac ischemia, thrombosis, and pulmonary embolism. Results: The matched cohorts had a mean age of 34 years (standard deviation 9.3). The study population was predominantly white (60%), with lower representation of Black American (10%) and Asian (3%) patients, while race was unknown for 19% of participants. Among patients with endometriosis treated with HT, 262 of them developed BC compared to 239 cases in the control group with a hazard ratio (HR) of 1.18 (95% CI 1.0-1.4, p = 0.064), showing no significant age-related differences. LHRHa treatment was associated with higher BC incidence (66 versus 36 cases, HR 1.7, 95% CI 1.14-2.6, p = 0.009). Age-stratified analysis of LHRHa patients showed no differences for those under 30 and 40 years, while patients under 50 showed a non-significant increase (25 versus 19 cases, HR 1.28, 95% CI 0.70-2.32, p = 0.42). Progestin treatment showed marginally increased BC risk (243 versus 216 cases, HR 1.2, 95% CI 1.0-1.4, p = 0.05) without age-related differences. Patients in the control group not receiving HT presented a lower chance to get pregnant (HR 1.32, 95% CI 1.3-1.4). No significant differences were observed in terms of major cardiovascular events. Conclusions: While overall HT showed no clear link to BC risk, both progestins and LHRHa were associated with increased risk. These findings warrant further investigation, particularly since these medications are typically prescribed to endometriosis patients with severe symptoms who share common reproductive and hormonal risk factors with BC.