145P Pathological complete response in young women with breast cancer in connection with pathogenic germline BRCA1 variants and subtype

Young age and pathogenic germline BRCA1 variants (gBRCA1m) are associated with high chemosensitivity and high rates of pathological complete response (pCR), meaning no residual tumor at surgical excision in breast or axilla after neoadjuvant chemotherapy. Yet, there is little data on how these factors interact regarding pCR and clinical subtypes. The study included retrospective real-world data of young women with breast cancer before the age of 40 undergoing neoadjuvant chemotherapy. All patients were diagnosed between 2008-2019 and presented at Charité – Universitaetsmedizin Berlin. Patients with missing germline testing, pathogenic germline variants in BRCA2, or other high-risk cancer susceptibility gene variants were excluded from analysis. The association of pCR and gBRCA1m vs. wild-type BRCA1 variants (gBRCA1wt) was explored using a binary logistic regression model. The association was further investigated subtype-specifically with Chi-square tests. A total of 143 cases were included in the analysis, of which 62 (43.4%) achieved pCR. gBRCA1m was most prevalent in triple-negative patients (38/79) and less prevalent in HR+/Her2- (10/33) and Her2+ patients (2/31). Patients with gBRCA1m achieved pCR more often than patients with gBRCA1wt (58.0% vs. 35.5%). This was associated with a crude odds ratio of 2.51 (95% CI 1.24-5.08, p=0.010). The associated increase of the pCR-rate varied across clinical subtypes. gBRCA1m was associated with a significant increase of the pCR-rate in patients with HR+/Her2- subtype (60.0% vs. 8.7%, p=0.002) and a not significant increase in triple-negative patients (60.5% vs. 39.0%, p=0.056). Among Her2+ patients, both gBRCA1m patients did not achieve pCR and gBRCA1wt patients had a pCR rate of 51.7%. Triple-negative and especially HR+/Her2- breast cancer in young women might be more chemosensitive if associated with a pathogenic germline variant in BRCA1. Therefore, the germline BRCA1 status should be included in evaluations of pCR in young women with breast cancer.