Treatment patterns and clinical outcomes of germline BRCA mutation (gBRCAm)-associated breast cancer (BC): A matched, case-control study

Up to 10% of early BC occur in gBRCAm carriers. Whether gBRCAm-related and sporadic BC have different outcomes is controversial. Consecutive patients (pts) who underwent surgery for BC at Dana-Farber Brigham Cancer Center between 1/2016 and 8/2021 and had known gBRCA status were included. gBRCAm cases were matched 1:3 with non-gBRCAm controls by age groups, stage, hormone receptor (HR) status and year of diagnosis. HER2-negative BC were excluded. Clinicopathologic features, treatments, and outcomes of gBRCAm carriers and non-gBRCAm controls were compared. We identified 189 gBRCAm (107 BRCA1, 82 BRCA2) carriers and 567 matched non-gBRCAm controls. Median age was 43 years (yrs) in carriers and 46 yrs in controls. Most pts had stage I (41.7%) or II (44.7%) BC; 55% of BC were HR+ (38 in gBRCA1m, 66 in gBRCA2m; 312 in non-gBRCAm). Compared to controls, gBRCAm carriers had higher tumor grade (p<0.001), higher recurrence score in HR+ (median 25 vs 19, p<0.001), were more likely to receive chemotherapy (CT) (81 vs 67.4%, p<0.001), including platinum-based regimens (17.6 vs 9.2%, p=0.007). 11 gBRCAm carriers and 3 controls received PARPi. At a median follow up of 42.3 months, invasive disease-free survival (iDFS) and relapse-free survival (RFS) did not differ between gBRCAm and controls after adjusting for age, grade, and CT administration (Table). In triple-negative BC (TNBC), risk of relapse was lower for gBRCAm vs controls (p=0.025).Table: 285PN (%)Events3-yr IDFSAdjusted hazard ratio [95% CI]p-valueAll746 (100)95gBRCAm = 88.4% [83.3, 93.9]Non-gBRCAm = 88.9% [86.2, 91.7]0.82 [0.46,1.44]0.49HR+ BC411 (55)47gBRCAm = 88.4% [83.3, 93.9]Non-gBRCAm = 88.9% [86.2, 91.7]1.44 [0.55, 3.81]0.46TNBC335 (45)48gBRCAm = 91.8% [85.6, 98.5]Non-gBRCAm = 84.3% [79.7, 89.3]0.53 [0.22, 1.31]0.17N (%)Events3-yr RFSAdjusted hazard ratio [95% CI]p-valueAll748 (100)83gBRCA = 92.2% [87.8, 96.9]Non-gBRCA = 89.4% [86.8, 92.2]0.57 [0.30, 1.08]0.085HR+ BC412 (55)40gBRCA = 90.6% [84.1, 97.6]Non-gBRCA = 93.6% [90.7, 96.5]1.14 [0.41, 3.21]0.80TNBC336 (45)43gBRCA = 94.4% [89.1, 100.0]Non-gBRCA = 84.3% [79.7, 89.3]0.25 [0.07, 0.84]0.025 Open table in a new tab . Pts with BRCA-associated BC have higher-risk pathologic features and are more often treated with CT compared to matched non-gBRCAm BC. After adjusting for treatment and clinicopathologic variables, short-term outcomes did not differ in gBRCAm carriers vs controls overall. However, in TNBC pts, risk of relapse was significantly lower among carriers than controls. Our results provide risk estimates for gBRCAm carriers that could inform the design of future clinical trials.