Association between FGFR1 copy numbers, MAP3K1 mutations, and survival in axillary node-positive, hormone receptor-positive, and HER2-negative early breast cancer in the PACS04 and METABRIC studies

Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2−) early breast cancer (BC) is the most prevalent BC subtype with substantial biological heterogeneity. Although clinicopathological (CP) characteristics have a clear prognostic value, additional biomarkers could refine survival prediction and guide treatment decision. Copy number aberrations and somatic driver mutations were obtained with OncoScan CGH array and sequencing of 36 genes on HR+/HER2− node-positive early BC patients treated with chemotherapy from the PACS04 trial. We built a two-gene genomic score (GS) associated with distant disease-free survival (DDFS), whose prognostic value was assessed on the external METABRIC data (n = 1413) using overall survival (OS) and breast cancer-specific survival (BCSS). In the PACS04 trial (n = 327), the median follow-up for DDFS (65 events) was 9.6 years. FGFR1 amplifications ($${\text{HR}}_{\text{Amplification}}$$ = 2.44, 95% CI [1.25; 4.76], p = 0.009) and MAP3K1 mutations ($${\text{HR}}_{\text{Mutation}}$$ = 0.10, [0.01; 0.78], p = 0.03) were associated with DDFS beyond CP characteristics. A prognostic GS combining FGFR1 amplifications and MAP3K1 mutations added more information to CP model ($$\chi_{\text{DDFS}}^{2}$$ = 12.97, $$p_{\text{DDFS}}$$