Fascin and Hormonal Therapy Response

Breast cancer can be classified into four major subtypes according to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 index. The four subtypes are luminal A (ER+ and/or PR+, HER2−, Ki-67 < 14%), luminal B (ER+ and/or PR+, HER2−, Ki-67 ≥ 14%; or ER+ and/or PR+, HER2+), HER2-enriched (ER−, PR−, HER2+) and triple negative breast cancer (TNBC; ER−, PR−, HER2−). Relatively, TNBC is an aggressive disease and is associated with poorer survival than other breast cancer subtypes, while luminal subtypes of cancer are less aggressive and generally correlate with better survival.

We have previously demonstrated the expression of an actin-bundling protein (fascin) in high percentage of TNBC, which was significantly associated with metastasis and drug resistance, key factors that promote disease progression and poor survival. Compared to TNBC, fascin is expressed only in smaller percentage of luminal tumors. While most of luminal A are sensitive to the anti-estrogen (hormonal) therapy, small percentage shows resistance and metastasis, leading to relapse of disease. Fascin expression and its contribution in luminal response to hormonal therapy has not been elucidated. This study will assess the effect of fascin expression on the response of luminal breast cancer to hormonal therapy and the consequence of this relationship on the disease progression. To delineate the underlying effect of fascin expression on the response to hormonal therapy in combination with other therapeutics, gain and loss of fascin expression in two luminal breast cancer cell lines (T-47D and MCF-7) will be tested in vitro. Understanding fascin role in luminal breast cancer patients’ response to hormonal therapies may offer a paradigm change in the treatment of this more common subtype of breast cancer.