Association of germline genetic testing results with chemotherapy regimens received by women with early-stage breast cancer.

Abstract

10518 Background: Germline genetic testing is widespread after breast cancer diagnosis and increasingly informs treatment decisions; however, guidelines do not advise selecting chemotherapy regimens based on genetic testing results. It is unknown whether women with pathogenic variants (PVs) in BRCA1, BRCA2 ( BRCA1/2) or other cancer risk genes receive different chemotherapy regimens than women with negative genetic testing results. Methods: We linked Surveillance, Epidemiology and End Results (SEER) registry records from Georgia and California to clinical germline genetic testing results from four participating laboratories (Ambry, Bioreference/GeneDx, Invitae, and Myriad). For this analysis, we included patients who: 1) were diagnosed with stages I-III breast cancer, either hormone receptor-positive and HER2-negative (HR+HER2-) or triple-negative, in Georgia or California from 2013-2017; 2) received chemotherapy based on SEER records; and 3) linked to a genetic testing result. We further selected cases by genetic testing results: 50% PVs in BRCA1/2 or another cancer risk gene, 25% variant of uncertain significance (VUS) only and 25% negative. We extracted details of chemotherapy regimens from SEER text fields completed by registrars. We categorized regimens by drug classes reported (anthracycline, taxane, platinum, nitrogen mustard, other). We used multivariable models that controlled for age, race/ethnicity, stage, grade, surgical procedure, radiotherapy receipt and geographic site to test whether PV carriers received a more intensive chemotherapy regimen. For HR+HER2-, a more intensive regimen was defined as at least three drugs including an anthracycline and for triple-negative, as at least four drugs including an anthracycline and a platinum (versus fewer drugs). Results: 2,293 women were included, 1,451 with HR+HER2- and 842 with triple-negative disease. On multivariable analysis, receipt of a more intensive chemotherapy regimen was associated with having a BRCA1/2 PV among women with HR+HER2- disease (odds ratio 1.22, p = 0.036), but not among women with triple-negative disease. Moreover, platinum use was elevated in BRCA1/2 PV carriers with HR+HER2- disease (from an adjusted model: BRCA1/2 PV 10.9%, other PV 3.6%, VUS 5.6%, negative 5.7%), while in BRCA1/2 PV carriers with triple-negative disease, platinum use did not vary significantly by genetic results ( BRCA1/2 27.7%, other PV 27.7%, VUS 20.9%, negative 20.7%; p = 0.025 for interaction between genetic result and subtype). Conclusions: Compared to women with negative genetic testing results, women with BRCA1/2 PVs more often received a platinum and/or an anthracycline in chemotherapy regimens for early-stage, HR+HER2- breast cancer. This suggests potential over-treatment. No differences in chemotherapy regimen by genetic testing result were observed in triple-negative disease.