Identifying genetic markers that can help select the right endocrine therapy in patients with hormone receptor-positive breast cancer. 

Impact

Every year, approximately one million women globally are diagnosed with estrogen receptor (ER)–positive breast cancers, which rely on estrogen to grow. This makes them a candidate for endocrine therapy, such as tamoxifen and aromatase inhibitors (AIs), which interfere with hormone signaling. While these therapies are successful in many patients, some do not experience the same benefit and side effects of these treatments can be so harsh that patients suspend therapy. Drs. Wang, Ingle, and their teams are studying how a patient’s genetic makeup can affect tolerance and response to endocrine therapy so that the most effective drugs can be selected. Their findings will ultimately enable doctors to select the best therapy to prevent breast cancer or breast cancer recurrence in individuals at high risk of the disease.  

Progress Thus Far

The team previously identified genetic alterations in specific genes that coincide with differences in a patients’ response to AIs. They subsequently found that these alterations modify the production of other genes, and they are exploring how those genes function within tumors and under the effect of AIs. In addition, they explored how breast cancer might become resistant to the AI anastrozole. They found that anastrozole treatment prevents the destruction of a protein called fatty acid synthase (FASN), which leads to increased breast cancer cell growth. High levels of FASN are associated with poor outcomes in anastrozole-treated patients, and FASN could serve as a new therapeutic target in endocrine-resistant breast cancer.  

What’s next

In addition to continuing their exploration of how genetics impacts patient response to AIs, the team is exploring the role of the androgen receptor (AR), another hormone receptor, in ER-positive breast cancers. They have found an interesting relationship between the ratio of androgen of two hormone receptors, AR and ER, that may dictate how a tumor responds to AR or ER-blocking therapies. In addition, they are exploring new ways that the AR-targeting therapy, enzalutamide, may function in ER-positive tumors, and they are exploring that further.