Preventative intervention uptake among women with breast cancer and pathogenic germline variants.

Abstract

10570 Background: Risk-reducing (RR) interventions in patients (pts) with pathogenic germline variants (PGV) in breast cancer (BC) risk genes include RR mastectomy (RRM), RR salpingo-oophorectomy (RRSO) and pancreatic cancer surveillance (endoscopic ultrasound [EUS] and/or MR cholangiopancreatography [MRCP]). Gene-specific intervention uptake was stratified by family history (FHx) of cancer in 1903 BC pts with PGV in high/moderate BC risk genes ( ATM, BARD1, BRCA1/2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C/D, SK11, TP53 ). Methods: Germline genetic testing (GGT) and insurance claims data were analyzed female DCIS/BC pts diagnosed 2015-24, GGT <120 days after diagnosis and ≥1 year of claims pre/post-GGT (uptake measured within 1 year of GGT). Inclusion/exclusion criteria followed prior work (PMID 32027353). Following NCCN (Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic and Prostate v2.2025) guidelines, PGV were in genes in the following categories: 1) gene-specific criteria (GSC): eligible for intervention +/- FHx; 2) gene and FHx-specific criteria (GFHxSC): consider (RRM, RSSO) or eligible (EUS/MRCP) for intervention if pt has relevant FHx or 3) Other: no specific intervention eligibility. Multivariable logistic regression models compared odds of intervention uptake for pts stratified by the categories above and by relevant cancer FHx (RRM: breast, RRSO: ovarian, EUS/MRCP: pancreatic). Results: 1903 pts with BC had ≥ 1 PGV. Clinico-demographics included were: 70% White, 74% BC FHx, 16% ovarian FHx, 35% pancreatic FHx, and mean (range) age at GGT, 50 (21-90). RRM had the highest uptake (56% overall, 75% in those with GSC PGV). RRSO uptake: 23% overall, 37% in pts with GSC PGV. EUS/MRCP uptake was 9% in pts with GSC PGV or GFHxSC PGV (+) FHx. Pts with GSC PGV (+) FHx had 5x higher odds of RRM vs. pts with GFHxSC PGV (-) FHx. Compared to pts with Other PGV (-) FHx, pts with GSC PGV (+) FHx had 18x higher odds of RRSO and 6x higher odds of MRCP/EUS (Table). Conclusions: In this retrospective analysis, intervention uptake generally followed NCCN guidelines, with uptake consistently higher in pts with PGV in GSC genes and positive FHx. Other factors in the shared decision-making process should be studied to identify gaps in quality of care. Association of model variables with intervention uptake. RRM OR (CI) RRSO OR (CI) MRCP/EUS OR (CI) PGV/FHx ref: GFHxSC PGV (-) FHx ref: Other PGV (-) FHx GSC PGV (+) FHx 5 (3-8) 18 (11-30) 6 (3-13) GSC PGV (-) FHx 3 (2-6) 16 (10-24) 3 (1-6) GFHxSC PGV (+) FHx NS 7 (2-22) 6 (2-13) GFHxSC (-) FHx NA 3 (2-5) NS Other PGV (+) FHx NA NS NS Age NS 1.5 (1-2) 1.2 (1.0-1.4) Ethnicity (ref: White) Hispanic:2 (1-5) Ashkenazi Jewish:0.2 (0-0.7)Asian: 0.4 (0.2-0.9) Multiracial:2 (1-4) Lymph node disease 1.6 (1-2) 0.7 (0.5-1) NS OR, odds ratio; CI, 95% confidence interval; NS, not significant (p≥0.05); NA, not applicable; other variables not shown: insurance, DCIS, age2, days from diagnosis to GGT.