Potential role of antiestrogens in treating ovarian cancer

Ovarian cancer is the deadliest of all gynecologic malignancies and remains the fifth leading cause of cancer related deaths among women (1). High-grade serous ovarian cancer (HGSOC) is the most predominant and lethal subtype accounting for about 70% of ovarian cancer cases (2). The standard of care involves platinum and taxol based cytotoxic chemotherapy which has remained unchanged for the past 3 decades (3,4). Development of individualized targeted therapies catering to the specific tumor characteristics is needed. Andersen and colleagues report the presence of a subset of estrogen dependent HGSOC and have identified estrogen responsive features, which can be used to determine patient cohorts who can benefit from endocrine therapy. Endocrine based therapies have been found to be effective when targeting estrogen receptor (ER) in ER positive metastatic breast cancer (5). Inhibition of ER is considered as an alternative in recurrent ovarian cancer patients who are resistant to the carbo-taxol based standard chemotherapy (6). However, changes in expression of ER have been reported between matched primary and recurrent ovarian cancer (7). Therefore, it is essential to take this into account while planning therapies involving ER inhibition. In their article Andersen and colleagues suggest that many OC patients exhibit high expression of ERα and have identified an ER dependent gene expression signature (8). They further report that the selective ER-alpha down-regulator (SERD) fulvestrant is more effective than the selective ER modulator (SERM) 4-Hydroxytamoxifen (4OHT) in inhibiting the growth of ERα expressing ovarian cancer.