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MAP3K1 is a MAPK family serine-threonine kinase that is frequently mutated in human cancer. The association between mutations in the MAP3K1 gene and the clinicopathological characteristics and prognosis of patients with breast cancer remain unclear in the Chinese population. Thus, the aim of the present retrospective study was to investigate the possible role and function of MAP3K1 in breast cancer. Data obtained from 412 consecutive patients with breast cancer were selected from Guangdong Provincial People's Hospital (GDPH) for analysis in the present study. Mutations were assessed using next-generation sequencing. The association between MAP3K1 mutations and clinicopathological features were analyzed and further compared with the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort and data from The Cancer Genome Atlas (TCGA). In the GDPH cohort, a total of 45 mutations MAP3K1 were identified in 8.5% (n=35) of the 412 patients, compared with 9.7% (n=244) in METABRIC and 7.9% (n=88) in TCGA. The majority of the mutations identified in the in three cohorts were truncating mutations, followed by mis-sense mutations. Mutations in MAP3K1 were predominant in patients with the luminal A and B breast cancer subtypes in METABRIC datasets (P

Additional file 1: Table S1. Mutations in other members of the HER family detected from our cohort. Figure S1. Somatic mutation landscape of the cohort. Figure S2. Comparison of mutational profile of the HER2 subgroups. Figure S3. Distribution of TP53 mutations among the HER2 subgroups. Figure S4. Distribution of PIK3CA mutations among the HER2 subgroups. Figure S5. Genes frequently mutated across HER2 subgroups according to hormone receptor (HR) status. Figure S6. Comparison of TP53 (A) and PIK3CA (B) mutation rates across HER2 subgroups according to hormone receptor (HR) status. Figure S7. Genes frequently mutated across immunohistochemistry-based molecular subgrouping between HER2-low and HER2-zero subgroups. TNBC, triple negative breast cancer. Figure S8. Comparison of TP53 (A) and PIK3CA (B) mutation rates between HER2-zero and HER2-low subgroups according to immunohistochemistry-based molecular subgrouping. Figure S9. Comparison of genes (top 11) and signaling pathways (top 5) differentially mutated between HER2-low and HER2-zero subgroups according to immunohistochemistry-based molecular subgrouping: A. triple negative breast cancer (TNBC), B. luminal A, and C. luminal B. Figure S10. Tumor mutational burden (TMB) were comparable across HER2 subgroups. TMB were not statistically different among patients with HER2-zero (IHC 0), HER2-low (IHC1+ or IHC 2+/FISH-negative), and HER2-positive (IHC 3+ or IHC 2+/FISH-positive) breast tumors. Figure S11. Distribution of ERBB/HER family mutations according to HER2 status. Figure S12. Molecular clustering across hormone receptor (HR) status (A) and immunohistochemistry-based molecular subgrouping (B). Figure S13. Pathological complete response (pCR) rate is comparable between HER2-low and HER2-zero subgroups across hormone receptor (HR) status (A-B) and immunohistochemistry-based molecular subgrouping (C-E). Figure S14. Disease-free survival (DFS) was comparable between women with HER2-low and HER2-zero tumors as shown by Kaplan-Meier survival plot of the whole cohort (A) and when considering only the relapsed patients per group (B). Figure S15. Disease-free survival (DFS) was comparable between HER2-zero and HER2-low subgroups regardless of pathological complete response (pCR) status. Figure S16. Disease-free survival (DFS) was comparable between HER2-zero and HER2-low subgroups regardless of hormone receptor (HR) status. Figure S17. Disease-free survival (DFS) was comparable between HER2-zero and HER2-low subgroups across immunohistochemistry-based molecular subgrouping.