284P - Clinical and molecular characteristics of early-stage triple-negative breast cancer (eTNBC) patients with germline pathogenic variants in homologous recombination repair genes

Background

The impact of germline pathogenic variants (GPVs) in homologous recombination repair (HRR) genes on the prognosis and treatment outcomes of early-stage triple-negative breast cancer (eTNBC) remains uncertain. This study explores clinical and pathological profiles of eTNBC patients, both with and without HRR gene PVs.

Methods

This is a retrospective study including 185 consecutive patients treated for eTNBC between 2000 and 2022, who underwent germline testing at the Hereditary Cancer Unit, Hospital Clinic Barcelona. Our primary goal was to identify clinicopathological and molecular differences in patients harbouring a GPV in any HRR gene. We utilized Chi-squared or Fisher's exact tests to examine distributions, alongside univariate and multivariable logistic regression, and Cox regression models to assess the impact of clinicopathological and molecular factors on pathological complete response (pCR) and relapse-free survival (RFS).

Results

GPVs were present in 37 (20%) patients, predominantly in BRCA1 (64%), followed by BRCA2 (11%), BRIP1 (11%), PALB2 (5%), BARD1 (3%), CHEK2 (3%), and TP53 (3%). The median follow-up duration was 68 months (95% CI: 60.0-81.4 months). Patients with HRR-GPVs were notably younger (median age 43.5 vs 49.2 years, p=0.002), with higher incidences of previous cancer diagnosis (43% vs 18%, p=0.005) and bilateral breast cancer (16% vs 2%, p=0.002). No differences were observed between carriers and non-carriers with respect to Ki67 (60% vs 60%, p=0.900) and tumor-infiltrating lymphocytes (TILs) (28% vs 37%, p=0.310).The variables linked to pCR were the neoadjuvant carboplatin chemotherapy use (OR 2.9, CI 1.3-6.6, p=0.003), Ki67% (OR 1.02, CI 1.01-1.05, p=0.032) and TILS% (OR 1.03, CI 1.01-1.06, p=0.022). pCR was associated with better RFS (hazard ratio 0.26, CI 0.09-0.92, p=0.021). GPV-HRR genes were not associated with pCR or RFS.

Conclusions

Patients with eTNBC and an HRR-GPV presented at an earlier age. No association of GPVs with pCR or RFS was identified, whereas carboplatin increased pCR rates, regardless of GPVs. Detailed gene expression data, including profiles of immune genes, will be presented at the conference.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.