On Triple Negative Breast Cancer Day, the breast cancer community highlights a subtype of the disease defined by its aggressive nature and limited treatment options.
To talk about triple negative breast cancer, we first have to understand how breast cancer is classified. Breast tumors are broadly classified into three major subtypes: estrogen receptor positive, progesterone receptor positive and HER2 receptor positive.
Breast cancer tumors driven by estrogen and progesterone receptors are the most common form of the disease and the most treatable. Since the tumor cells express an abundance of hormone receptors driven by estrogen and/or progesterone, they can be targeted with anti-estrogen therapies like tamoxifen, fulvesterant and aromatase inhibitors, like anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®).These three classes of therapies have a distinct mechanism of action that blocks estrogen signaling and prevents tumor growth.
The second most common of the three major subtypes is driven by HER2 signaling. These cancers have an overabundance of the HER2 receptor on the surface of the tumor cells. About 20-25 percent of breast cancers fall into this category. Once an aggressive cancer with poor prognosis, HER2-positive breast cancer is now treatable with targeted therapies, including traztuzumab (Herceptin®), pertuzumab (Perjeta®), ado-trastuzumab-emtansine (Kadcyla®), and lapatinib (Tykerb®).
Patients with either hormone-positive or HER2-positive breast cancer have multiple options for first-line targeted therapies that can also be combined with chemo or radiation therapy. This means that if one therapy does not work, or if a patient stops responding to one of the drugs, another drug may work better.
Triple negative breast cancer (TNBC) is so named for the simple reason that the tumor cells do not express either of the hormone receptors or the HER2 receptor. About 10-15 percent of breast cancers fall into this category, including many hereditary breast cancers that are driven by mutations in the BRCA1 or BCRA2 genes. In contrast to the hormone-positive and HER2- positive breast cancers, chemotherapy is the only treatment option for TNBC as no targeted therapies are currently approved by the FDA.
There is an urgent need to develop effective targeted therapies for TNBC in order to improve outcomes, as targeted therapies have done in other breast cancers.
Over the last five years, a resurgence of interest in cancer immunotherapy has been driven by the discovery two immune regulatory pathways activated in tumors and the development and FDA-approval of targeted therapies to block them. Referred to as checkpoint inhibitors, anti-CTLA-4 and PD-1 therapies have demonstrated remarkable responses in some patients with melanoma, lung cancer, and other cancers. Though none are yet approved for breast cancer, clinical trials are ongoing to test these strategies as single agents or in combination with other immune therapies, chemo or radiation therapy in breast cancer, particularly TNBC.
Want to learn more about triple negative breast cancer? Read a conversation we held with two BCRF researchers conducting studies on TNBC.