Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 were associated with chemosensitivity for breast cancers

Summary

The correlation of genetic alterations with responding to neoadjuvant chemotherapy (NAC) is not fully revealed. In this study, we enrolled 247 breast cancers receiving anthracycline‐taxane‐based NAC treatment. Next generation sequencing (NGS) panel containing 36 hot spot breast cancer related genes was used in this study. Two different extent of pathologic complete response (pCR) standards, which were ypT0/isypN0 and ypT0/is, were used as indicators for NAC treatment. TP53 mutation (n = 149, 60.3%), PIK3CA mutation (n = 109, 44.1%) and MYC amplification (n = 95, 38.5%) were frequently detected in enrolled cases. TP53 mutation (P = 0.019 for ypT0/isypN0 and P = 0.003 for ypT0/is) and ERBB2 amplification (P <0.001 for both ypT0/isypN0 and ypT0/is) were related with higher pCR rates. PIK3CA mutation (P = 0.040 for ypT0/isypN0) and CCND2 amplification (P = 0.042 for ypT0/is) showed reduced sensitivity to NAC. Patients with MAPK pathway alteration shows pretty low pCR rates (P = 0.043 for ypT0/is). Patients with TP53 mutation (‐) PIK3CA mutation (‐) ERBB2 amplification (+) CCND1 amplification (‐), TP53 mutation (+) PIK3CA mutation (‐) ERBB2 amplification (+) CCND1 amplification (‐) or TP53 mutation (+) PIK3CA mutation (+) ERBB2 amplification (+) CCND1 amplification (‐) had significantly higher pCR rates (P <0.05 for ypT0/isypN0 and ypT0/is) than wild type genotype tumors. Some cancer genetic alterations as well as pathway alterations were associated with chemosensitivity to NAC treatment. Our data may shed light on molecular diagnosis of breast cancer for prediction of NAC expectations when first time diagnosed by biopsy.

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