Breast (Apr 2025)
Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer
Abstract
Background: The rate of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC) varies, and adjuvant therapy treatment for residual cancer remains a challenge. The aim of our study was to assess the added value of FoundationOne®CDx (F1CDx) testing in the non-metastatic TNBC in predicting responses to NACT and disease outcomes. Methods: Ninety-three eligible patients with stage II-III TNBC were treated with NACT without immunotherapy. Response to NACT was evaluated postoperatively. Comprehensive genomic profiling with NGS-based molecular test F1CDx was performed on diagnostic biopsies (N = 93). Hierarchical clustering and logistic regression were applied for data analysis. Results: Genomic profiling and data clustering revealed heterogeneous genetic landscapes of TNBC with subsets displaying multilayered co-amplifications of oncogenes and overlapping changes in crucial signaling pathways. TP53 mutations were detected in 95 % of all TNBCs. BRCA1/BRCA2 mutations were significant molecular factors in predicting favorable responses to NACT (OR = 0.09, p = 0.002), while CCNDs co-mutations with FGFs (OR = 13.4, p = 0.016) and PI3Ks family mutations in AR-positive cases (OR = 6.1, p = 0.008) – poor responses. Low tumor mutational burden (TMB) ≤ 3 (OR = 9.4, p = 0.009) was a significant factor for the disease progression after NACT. Conclusions: This study suggests that comprehensive CDx testing can be explored as a prognostic tool in early-stage TNBC to predict responses to NACT and disease progression. Based on these results, genomic analysis should be performed early in the patient journey, possibly guiding adjuvant treatment choices and participation in randomized clinical trials, mainly when pCR is not achieved, as the ultimate goal is improving patient outcomes.
