Three decades of breast cancer predisposition genetic testing at a comprehensive cancer center.

Abstract

e22633 Background: Uptake of germline genetic testing for breast cancer (BC) predisposition has expanded substantially over the past three decades. Temporal trends in pathogenic variant (PV) detection were assessed across Huntsman Cancer Institute’s (HCI) catchment area: Idaho, Montana, Nevada, Utah, and Wyoming. Methods: We conducted a retrospective observational study of individuals identified with BC predisposition PVs at HCI, describing demographics, rurality, and gene-specific PV detection across three time periods: 1994–2005, 2006–2015, and 2016–2025. Results: Among 16,169 patients who underwent germline genetic testing at HCI between 1994–2025, 3,179 (19.7%) were identified with PVs in BC predisposition genes; 3,097 with recorded testing date were included in temporal analyses. There was more than sixfold (612%) increase in identified PV carriers from the earliest to the most recent period (293 in 1994–2005 to 2,088 in 2016–2025). Mean age at testing among PV carriers was approximately 45 years and increased modestly in the most recent period compared with 2006–2015 (41.7 vs 45.9 years; p<0.001) (Table 1). Most PV carriers were White/Caucasian across all periods (84% overall), with minimal change in racial or ethnic diversity over time. BRCA1 and BRCA2 accounted for the largest number of PVs across successive periods ( BRCA1 : 195, 332, 360; BRCA2 : 117, 312, 611). Substantial growth was also observed in detected PVs in non- BRCA genes, including TP53 (15, 77, 213), ATM (0, 14, 320), CHEK2 (0, 11, 501), PALB2 (0, 11, 128), RAD51C (0, 4, 30), RAD51D (0, 1, 24), and STK11 (0, 5, 10). The geographic distribution of PV carriers broadened over time, with the number of counties represented increasing from 38 to 86. While approximately 80% of PV carriers resided in metropolitan areas, the absolute number of carriers from non-metropolitan areas increased 9.5-fold (47 to 448), with no significant change in proportional distribution (p>0.1) (Table 1). Conclusions: Detection of BC predisposition PVs increased markedly at HCI, with growing identification of carriers residing in both metropolitan and non-metropolitan areas, highlighting the need for strengthened infrastructure to support equitable care. PV carriers were identified at a mean age in the mid-40s, with a modest increase over time, suggesting missed opportunities for earlier identification to enable timely screening, risk reduction, and preconception counseling. Age and rurality by temporal changes among pathogenic variant (PV) carriers. Characteristics All PV carriers(n = 3,097) 1994-2005(n=293) 2006-2015(n=716) 2016-2025(n=2,088) Age, mean (SD) 44.7 (18.2) 43.8 (16.4) 41.7 (16.1) 45.9 (18.9) Rurality, n (%) Metropolitan* 2467 (79.7) 246 (84.0) 585 (81.7) 1636 (78.3) Micropolitan* 336 (10.8) 22 (7.5) 71 (9.9) 243 (11.6) Small Town* 100 (3.2) 5 (1.71) 20 (2.79) 75 (3.6) Rural Areas 189 (6.1) 20 (6.8) 39 (5.5) 130 (6.2) *Core, low and high commuting areas.