The TPD regimen (trastuzumab, pertuzumab and docetaxel) is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer (BC). BC is a very diverse disease regarding tumor biology with wide variation among individuals regarding sensitivity to anticancer drugs. Accordingly, to achieve maximum results from chemotherapy, it is necessary to predict the efficacy of treatment and select the optimum pharmacotherapy according to the characteristics of both the patient and the tumor. There is therefore a need for the identification of useful biomarkers that are capable of predicting the therapeutic effect when advanced HER2-BC is treated with the TPD regimen. 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-BC to the TPD regimen.
The subjects consisted of 29 cases in which TPD regimen chemotherapy was carried out. The expression levels of estrogen receptor (ER), progesterone receptor (PgR), Ki67, HER1-4 were evaluated using immunostaining employing needle biopsy specimens.
The HER1, HER3 and HER4 cut-off value for progression-free survival (PFS) was 28.6 (area under ROC curve (AUC), 0.566; sensitivity, 61.11%; specificity, 72.73%), 33.9 (AUC, 0.533; sensitivity, 83.33%; specificity, 54.55%), and 65.4 (AUC, 0.629; sensitivity, 61.11%; specificity, 72.73%), respectively. Of the 29 HER2-BC patients, 14 (48.3%) were in the HER1 positive group, 19 (65.5%) were in the HER3 positive group, and 14 (48.3%) were in the HER4 positive group. 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 PFS extension over the HER3 negative group (p = 0.042, log-rank). In univariate analysis, a high ORR (p = 0.004, hazard ratio=0.123) and positive HER3 expression (p = 0.023, hazard ratio=0.279) significantly contributed to extension of the PFS interval.
HER3 expression may be a useful factor for predicting the response of HER2-BC to the TPD regimen.
Clinical trial identification
Legal entity responsible for the study
Department of Surgical Oncology, Osaka City University Graduate School of Medicine
All authors have declared no conflicts of interest.