Professor of Medicine, Harvard Medical School
Director, Center for Functional Cancer Epigenetics
Dana-Farber Cancer Institute
The goal of this project is to determine the role played by male hormones, androgens, in breast cancer. Scientists now understand that rather than being a single disease, there are several different types of breast cancer that depend for their growth and spread on different factors. While it has been appreciated for many years that the female hormone estrogen is critical for the growth of the most common type of breast cancer that contain the receptor for estrogen, so-called ER+ breast cancer, it is only in recent years that it has been appreciated that male hormones, androgens, also play an important role in breast cancer growth. Specifically, Dr. Brown and others have found that depending on breast cancer type, androgens can either stimulate or inhibit breast cancer growth. In the coming year, he seeks to understand how this occurs.
This study is important to breast cancer patients as new classes of drugs that block the action of androgens have been recently developed for the treatment of prostate cancer. These drugs would be potentially effective in those breast cancers that depend on androgen for growth. In contrast, other new drugs that mimic the activity of androgens in the breast without unwanted masculinizing side effects could provide a new option for the treatment of the subset of breast cancers that are growth inhibited by androgens. For these new agents to be appropriately developed for breast cancer, a detailed understanding of the complexities of androgen signaling is required. Dr. Brown’s goal is to precisely elucidate the mechanisms underlying the subtype selective actions of androgens in breast cancer so that new therapies can be developed.
It is widely appreciated that breast cancer is often dependent on the female hormone estrogen and therapies that block the action of estrogen are among the most effective and least toxic therapies. The effectiveness of these therapies is limited to the breast cancers that express the estrogen receptor, so-called ER+ breast cancer. Our current view of breast cancer has evolved from simply two types, ER+ and ER–, to include characterization of other genes including the progesterone receptor, PR, and the HER2 oncogene. Dr. Brown’s group has found that in addition to estrogen that male hormones androgens that act through the androgen receptor, AR, also play important roles in breast cancer. They have found that, depending on breast cancer type, androgens can either stimulate or inhibit breast cancer growth. This project is aimed at understanding how this occurs. Progress in the prostate cancer field has led to the development of new drugs that more completely block the action of androgens. The researchers plan on testing whether these drugs will be effective in those breast cancers that depend on androgen for growth. In contrast, other drugs that mimic the activity of androgens in the breast without unwanted masculinizing side effects could provide a new option for the treatment of the subset of breast cancers that are growth inhibited by androgens. These new drugs targeting AR have the potential to provide additional patients with breast cancer the benefits of endocrine therapy.