The Hippo Transducer YAP/TAZ as a Biomarker of Therapeutic Response and Prognosis in Trastuzumab-Based Neoadjuvant Therapy Treated HER2-Positive Breast Cancer Patients

  • Front Pharmacol. 2020 Aug 27;11:537265. doi: 10.3389/fphar.2020.537265.
Jia-Qi Yuan  1 ,  Nian-Hua Ding  2 ,  Zhi Xiao  1
Affiliations
  • 1. Clinical Research Center For Breast Cancer Control and Prevention in Hunan Province, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
  • 2. Department of Clinical Laboratory, The First Hospital of Changsha, Changsha, China.
PMID: 32973536 DOI: 10.3389/fphar.2020.537265
Abstract

Background: We explored the therapeutic and prognostic effect of YAP/TAZ intensityinHER2-positive breast Cancer patients. We also investigated the relationship between YAP/TAZ expression and Trastuzumab-resistance.

Methods: We collected clinicopathological information from 397 cases. We evaluated therapeutic and prognostic effect of YAP/TAZ and Other variables. We also cultivated Trastuzumab-resistance cell lines and explored relationship between YAP/TAZ and Trastuzumab-resistance.

Results: Over-expression of YAP/TAZ was remarkable in Trastuzumab-resistant cells, and so did HER3 and HER2/HER3 heterodimer. Inhibition of YAP/TAZ expression reversed Trastuzumab-resistance.YAP/TAZ deficiency contributed to favorable therapeutic response, and so did hormone receptor insufficiency and chemotherapy dosage inferiority. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival. Over-expression of YAP/TAZ was obvious in recurrent cases in comparison with their matching primary lesions. Prognostic superiority of insufficient YAP/TAZ intensity was more outstanding in hormone receptor negative cases. Over-expression of YAP/TAZ and HER3 was generally synchronous. Absence of HER3 expression in residual lesions might correlate with better breast cancer-free survival.

Conclusions: Over-expression of YAP/TAZ as well as HER-3 and HER2/HER3 heterodimer was synchronously remarkable in Trastuzumab-resistant cell lines. Inhibition of YAP/TAZ expression reversed Trastuzumab resistance. Deficient YAP/TAZ intensity as well as insufficient hormone receptor intensity and high chemotherapy dosage contributed to favorable therapeutic response. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival, and so did absence of HER3expression in residual lesions. Prognostic superiority of YAP/TAZ expression depended on hormone receptor status. Cases with synchronous over-expression of YAP/TAZ and HER3 suffered poor survival, which revealed the potential effect of YAP/TAZ-HER2/HER3 crosstalk in prognosis of HER2-positive patients.

Keywords
HER2/HER3 heterodimer; SKBR-3 cell lines; Trastuzumab-based neoadjuvant therapy; YAP/TAZ; breast cancer-free interval.
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