Breast cancer diagnosis, management, and outcomes in transgender, nonbinary, and gender-diverse individuals: A multicenter cohort.

1516 Background: Paucity of data on breast cancer (BC) in transgender, nonbinary, and gender-diverse (TGD) individuals leads to suboptimal screening and treatment algorithms. We developed a national multicenter retrospective cohort to describe demographic, clinicopathologic, and treatment characteristics of TGD individuals with BC and report outcomes. Methods: The cohort included TGD persons age ≥18yrs with stage 0–IV BC treated at 22 US centers from 1990–2023. Demographic and clinicopathologic characteristics were evaluated and compared to BC patients in the SEER 2016–21 dataset. Wilcoxon rank sum tests, χ 2 tests, and KM analysis were used to compare variables and estimate 5-yr BC-specific survival (BCSS). Results: 112 TGD persons with 113 BCs were included. Median age at diagnosis was 42.5yrs (IQR 36.5–51), 92.9% were female sex at birth (FSAB), 73.2% were NH-White, and 38.4% used gender-affirming hormones pre-BC. Of those FSAB (n=104), 61.5% were premenopausal and 11.5% had undergone gender-affirming top surgery (GATS) pre-BC. Most BCs (51.8%) were self-detected, 27.7% were screen-detected (48.2% underwent screening pre-BC), 13.4% were incidentally found on GATS pathology, 3.6% were provider-detected, and 2.7% were incidentally found on other imaging. Of 84 (75%) tested patients, 16/84 (19%) had a pathogenic germline variant, with BRCA2 (25%) and BRCA1 (18.8%) being most common. Most tumors were HR+ (85.7%) and early stage (25.7% DCIS and 45.1% stage I). Regarding local treatment, most (61.6%) underwent mastectomy, with 63.8% omitting reconstruction; after lumpectomy, 29% omitted radiation (RT). 41.1% received systemic chemotherapy and while endocrine therapy (ET) was recommended for 79, only 81% (64/79) received ET. There was no difference in surgery type ( p = 0.22) or ET receipt ( p = 0.32) by SAB. Compared to patients in SEER (N = 401,311), the TGD cohort was younger (median age 42.5 vs 62yrs), more frequently NH-White (75.2% vs 65.1%), more often had PR+ disease (79.5% vs 70.7%), and had a higher proportion of males (MSAB) (7.1% vs 0.8%) ( p <0.01 for all); but there was no difference in disease stage ( p = 0.39). At 38 months median follow-up: 12 (10.7%) had a locoregional recurrence (LRR), and 2 died of metastatic BC. 5-yr BCSS probability was 96.2% (95% CI 85.3–99.0%). Conclusions: The first multicenter cohort study of TGD individuals with BC identified they were younger and had a higher proportion MSAB compared to BC patients in SEER. Most tumors were self-detected, and the pathogenic germline variant rate was high – suggesting a possible role for earlier screening in high-risk TGD persons regardless of SAB. The elevated LRR rate along with low ET and RT uptake indicates opportunities to improve adherence to guideline concordant care. Findings underscore the necessity for prospective research to inform gender-inclusive evidence-based BC screening and treatment guidelines.