Open AccessSomatic alterations of TP53 , ERBB2 , PIK3CA and CCND1 are associated with chemosensitivity for breast cancers
Author(s) -
Yang Libo,
Ye Feng,
Bao Longlong,
Zhou Xiaoyan,
Wang Zhe,
Hu Peizhen,
Ouyang Nengtai,
Li Xiaojuan,
Shi Yi,
Chen Gang,
Xia Peiyi,
Chui Meiying,
Li Wencai,
Jia Ying,
Liu Yueping,
Liu Junjun,
Ye Junyi,
Zhang Zhe,
Bu Hong
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13976
Subject(s) - breast cancer , oncology , cancer research , cancer , medicine
The correlation of genetic alterations with response to neoadjuvant chemotherapy (NAC) has not been fully revealed. In this study, we enrolled 247 breast cancer patients receiving anthracycline‐taxane‐based NAC treatment. A next generation sequencing (NGS) panel containing 36 hotspot breast cancer‐related genes was used in this study. Two different standards for the extent of pathologic complete response (pCR), 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 to 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 had 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 study may shed light on the molecular characteristics of breast cancer for prediction of NAC expectations when breast cancer is first diagnosed by biopsy.