Hormone-receptor Expression and Activity of Trastuzumab with Chemotherapy in HER2-positive Advanced Breast Cancer Patients

Background: The relationship between quantitative immunohistochemical hormone receptor expression and response to the combination of trastuzumab with chemotherapy in HER2-positive advanced breast cancer is currently unknown.

Methods: Estrogen receptor (ER) and progesterone receptor expression was studied both as a dichotomous variable (positivity set at ≥ 1% of positive cells) and as a continuous variable. The effect of hormone receptor expression on overall response rate and progression-free survival in patients receiving trastuzumab-based treatment was studied by univariate and multivariate analysis.

Results: One hundred eleven of 227 consecutive advanced breast cancer patients treated at 2 Institutions had hormone receptor-positive tumors (49%). High expression of ER (≥ 30% of tumor cells) predicted reduced probability of tumor response to trastuzumab plus chemotherapy (multivariate odds ratio, 0.422; 95% confidence interval [CI], 0.222-0.803; P = .009). In patients with hormone receptor-positive tumors (≥ 1% of tumor cells), maintenance endocrine therapy added to trastuzumab upon the completion of chemotherapy was associated with a significant progression-free survival benefit (hazard ratio, 0.521; 95% CI, 0.3325-0.836; P = .007).

Conclusions: Our results suggest a predictive role of hormone receptor expression in HER2-positive tumors. Further investigation in this patient subset is warranted to optimize the use of HER2-targeting agents, chemotherapy, and endocrine therapy.