Abstract 263P
Background
The effectiveness of CDK4/6i and ET in patients (pts) with germline pathogenic variants (gPV) in genes implicated in the HRR is unknown and the current evidence is conflicting.
Methods
This is a retrospective study of 250 consecutive pts with hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer treated with CDK4/6i and ET in Hospital Clinic of Barcelona between 2016-2021. gPV were determined using the Trusight assay. Intrinsic subtypes and gene expression were assessed in formalin-fixed paraffin-embedded tumor samples. The objectives were to determine the associations of gPV with intrinsic subtype and clinical outcomes. The association between gPV and objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated with logistic (ORR) and Cox (PFS/OS) regression models.
Results
31% (n=78) of pts fulfilled germline testing criteria for the Hereditary Breast and Ovarian Cancer Syndrome. gPV were found in 14(18%) pts: BRCA2 (58%), CHEK2 (14%), ATM (7%), BRIP1 (7%), PTEN (7%), RAD51C (7%). Three groups were analyzed according to gPV BRCA2 status: mutated (BRCA2-PV)(n=8), wild-type (BRCA2-WT)(n=70), and unknown (nontested) (BRCA2-UNK)(n=172). The mean age in pts with BRCA2-PV and BRCA2-UNK was 51 vs 66 years respectively (p=0.010). Intrinsic subtype was analyzed in 60% (n=151) of pts. The proportion of basal-like (25%) and HER2-enriched (38%) intrinsic subtypes in pts BRCA2-PV was higher than in pts BRCA2-WT (1.4% and 8.5%) and BRCA2-UK (4.6% and 8.7%) (p=0.003). No differences in ORR were seen across BRCA2 groups (p=0.500). Median PFS was 12.1, 12.6 and 13.6 months in BRCA2-PV, BRCA2-WT and BRCA2-UNK respectively (p>0,050). OS was 28.8, not reached and 35.8 months in BRCA2-PV, BRCA2-WT and BRCA2-UNK respectively (p>0,050, probably due to the low number of BRCA2-PV).
Conclusions
We observed for the first time a substantially higher proportion of non-luminal subtypes (63%) in BRCA2-PV compared to BRCA2-WT/UNK tumors (12%), in patients with advanced HR+/HER2- breast cancer. This observation could explain the previously reported association of BRCA1/2 mutations with poor prognosis in this context.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hospital Clinic of Barcelona.
Funding
This work has been funded by Contractec Clinic de Recerca “Clínic-La Pedrera\".
Disclosure
All authors have declared no conflicts of interest.