Chemosensitization role of fulvestrant in combination with chemotherapy in postmenopausal hormone receptor positive and human epidermal growth factor negative metastatic breast cancer

Abstract

In metastatic breast cancer (MBC), hormone receptor positive (HR+), human epidermal growth factor negative (HER2-) subtype accounts for the majority. With various new modalities available to prolong life span in this group of patients, the effect is distant from optimum. Prevalent strategy of treating postmenopausal HR+ HER2- MBC is application of chemotherapy (CT) after progression of disease on endocrine therapy (ET) of several lines. Generally, ET targets HR+ ingredients and CT works better with HR- tumor cells. HR+ MBC, though hormone-sensitive, has HR- portion which reacts poorly to ET. Thus, sequential use of ET and CT neglects its insensitive part and gives rise to drug resistance, while alleviation of tumor burden is the top priority in metastatic setting. Chemohormonal therapy (i.e. concomitant use of ET and chemotherapy) complements for the shortcoming of current therapy strategy targeting both HR+ and HR- ingredients theoretically. Fulvestrant, a pure estrogen receptor antagonist and down-regulator, could be a promising agent using concurrently with CT based on chemosensitizing character shown in preclinical and pilot clinical studies. It is hypothesized in this article that chemohormonal therapy with concurrent fulvestrant and CT would be a promising strategy in postmenopausal HR+ HER2- MBC patients. Proof of this hypothesis would help control evolvement of tumor burden and acquirement of drug resistance over a short period of time.