In vitro chemoresponse assay based on the intrinsic subtypes in breast cancer

Abstract

Objective: In vitro chemotherapy response assays are not widely accepted in making decisions regarding cytotoxic drugs. To evaluate the usefulness of chemotherapy response assays in breast cancer, we compared the chemotherapy response assay results according to subtypes. Human epidermal growth factor receptor-2 and Ki67 associated with chemosensitivity were also analyzed.

Methods: Four hundred and ninety-six patients were enrolled, and chemotherapy response assays based on adenosine triphosphate were performed in 500 tumors. Patients were classified as five subtypes: luminal A, luminal B/human epidermal growth factor receptor-2 negative, luminal B/human epidermal growth factor receptor-2 positive, human epidermal growth factor receptor-2 and triple negative. The cell death rate for various drugs was calculated.

Results: The mean cell death rate of the luminal A subtype was the lowest, and the mean cell death rates of the human epidermal growth factor receptor-2 and triple-negative subtypes were the highest for all tested drugs, except 5-fluorouracil and methotrexate. The cell death rate differed significantly among the subtypes in the types of drugs (doxorubicin, epirubicin, paclitaxel, docetaxel, gemcitabine, vinorelbine and cisplatin). In triple-negative tumors, the mean cell death rate of cisplatin was the highest among the tested drugs, and which was not observed in the other subtypes. Human epidermal growth factor receptor-2 positive tumors are associated with higher cell death rates for anthracyclines. High Ki67 expression (a cutoff of 14%) was associated with a high response in several tested drugs including epirubicin, paclitaxel, docetaxel, gemcitabine, vinorelbine and cisplatin.

Conclusions: Our findings suggest that in vitro chemoresponse assays for breast tumors could effectively reflect the tumor response to chemotherapies observed in neoadjuvant settings.

Keywords: HER-2; breast cancer; chemosensitivity; chemotherapy; intrinsic subtype.