Analysis of HER Family (HER1-4) Expression as a Biomarker in Combination Therapy with Pertuzumab, Trastuzumab and Docetaxel for Advanced HER2-positive Breast Cancer

Background: Chemotherapy with trastuzumab, pertuzumab and docetaxel (TPD regimen) is now strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. In this study, we analyzed the expression of HER 1-4 proteins, and investigated whether or not their expression was predictive of the response of advanced HER2-positive breast cancer to chemotherapy with the TPD regimen. Patients and Methods: The study consisted of 29 cases in which TPD regimen chemotherapy was carried out from September 2013 to November 2015. The expression levels of estrogen receptor (ER), progesterone receptor (PgR), Ki67, HER1, HER2, HER3 and HER4 were evaluated using immunostaining employing needle biopsy specimens. Results: The overall response rate (ORR) was significantly higher in the HER3-positive group than in the HER3-negative group (p= 0.002). In prognostic analysis, the HER3-positive group showed a significant progression-free survival extension over the HER3-negative group (p= 0.042, log-rank). In univariate analysis, objective response (p= 0.004, hazard ratio(HR)= 0.123) and positive HER3 expression (p= 0.023, HR= 0.279) significantly contributed to extension of progression-free survival interval. Conclusion: HER3 expression may be a useful factor for predicting the response of HER2-positive breast cancer to chemotherapy with the TPD regimen.