TY - JOUR
T1 - Genetic mutation profile of Chinese HER2-positive breast cancers and genetic predictors of responses to Neoadjuvant anti-HER2 therapy
AU - Li, Kai
AU - Liao, Ning
AU - Chen, Bo
AU - Zhang, Guochun
AU - Wang, Yulei
AU - Guo, Liping
AU - Wei, Guangnan
AU - Jia, Minghan
AU - Wen, Lingzhu
AU - Ren, Chongyang
AU - Cao, Li
AU - Mok, Hsiaopei
AU - Li, Cheukfai
AU - Lin, Jiali
AU - Chen, Xiaoqing
AU - Zhang, Zhou
AU - Hou, Ting
AU - Li, Min
AU - Liu, Jing
AU - Balch, Charles M.
AU - Liao, Ning
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Purpose: Despite the therapeutic success of existing HER2-targeted therapies, tumors respond quite differently to them. This study aimed at figuring out genetic mutation profile of Chinese HER2-positive patients and investigating predictive factors of neoadjuvant anti-HER2 responses. Methods: We employed two cohorts. The first cohort was comprised of 181 HER2-positive patients treated at Guangdong Provincial People’s Hospital from 2012 to 2018. The second cohort included 40 patients from the first cohort who underwent HER2-targeted neoadjuvant chemotherapy. Genetic mutations were characterized using next-generation sequencing. We employed the most commonly used definition of pathological complete response (pCR)-eradication of tumor from both breast and lymph nodes (ypT0/is ypN0). Results: In Chinese HER2-positive breast cancer patients, TP53 (74.6%), CDK12 (64.6%) and PIK3CA (46.4%) have the highest mutation frequencies. In cohort 2, significant differences were found between pCR and non-pCR groups in terms of the initial Ki67 status, TP53 missense mutations, TP53 LOF mutations, PIK3CA mutations and ROS1 mutations (p = 0.028, 0.019, 0.005, 0.013, 0.049, respectively). Furthermore, TP53 LOF mutations and initial Ki67 status (OR 7.086, 95% CI 1.366–36.749, p = 0.020 and OR 6.007, 95% CI 1.120–32.210, p = 0.036, respectively) were found to be predictive of pCR status. Conclusion: TP53 LOF mutations and initial Ki67 status in HER2-positive breast cancer are predictive of pCR status after HER2-targeted NACT.
AB - Purpose: Despite the therapeutic success of existing HER2-targeted therapies, tumors respond quite differently to them. This study aimed at figuring out genetic mutation profile of Chinese HER2-positive patients and investigating predictive factors of neoadjuvant anti-HER2 responses. Methods: We employed two cohorts. The first cohort was comprised of 181 HER2-positive patients treated at Guangdong Provincial People’s Hospital from 2012 to 2018. The second cohort included 40 patients from the first cohort who underwent HER2-targeted neoadjuvant chemotherapy. Genetic mutations were characterized using next-generation sequencing. We employed the most commonly used definition of pathological complete response (pCR)-eradication of tumor from both breast and lymph nodes (ypT0/is ypN0). Results: In Chinese HER2-positive breast cancer patients, TP53 (74.6%), CDK12 (64.6%) and PIK3CA (46.4%) have the highest mutation frequencies. In cohort 2, significant differences were found between pCR and non-pCR groups in terms of the initial Ki67 status, TP53 missense mutations, TP53 LOF mutations, PIK3CA mutations and ROS1 mutations (p = 0.028, 0.019, 0.005, 0.013, 0.049, respectively). Furthermore, TP53 LOF mutations and initial Ki67 status (OR 7.086, 95% CI 1.366–36.749, p = 0.020 and OR 6.007, 95% CI 1.120–32.210, p = 0.036, respectively) were found to be predictive of pCR status. Conclusion: TP53 LOF mutations and initial Ki67 status in HER2-positive breast cancer are predictive of pCR status after HER2-targeted NACT.
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U2 - 10.1007/s10549-020-05778-0
DO - 10.1007/s10549-020-05778-0
M3 - Article
C2 - 32638235
AN - SCOPUS:85088475349
SN - 0167-6806
VL - 183
SP - 321
EP - 332
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -