Breast cancer is the most frequently diagnosed cancer worldwide, with over a million new cases diagnosed each year in the U.S. alone (Siegel, Cancer statistics, 2018).
Although cases of breast cancer are often discussed in aggregate, breast cancer is quite heterogeneous, both at the molecular level and in terms of clinical outcomes. Each individual’s cancer cells express different levels of certain receptors that can impact the responsiveness to therapy and overall prognosis. These receptors include the estrogen receptor (ER), progesterone receptor (PR), and Her2/neu receptor (HER2). Breast cancer subtypes can thus be broken down into hormone receptor positive (ER/PR+), HER2 overexpressing, and triple-negative breast cancers (TNBCs). As the name implies, TNBCs are characterized by the absence of these three receptors.
Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer. Women with TNBC have significantly reduced survival compared to women with other forms of breast cancer for every tumor stage at presentation (Bauer, Cancer, 2007). Because targeted therapies do not exist for TNBCs, the mainstays of therapy include surgery, radiotherapy, and chemotherapy. Traditional chemotherapy is often met with rapid resistance and consequently poor response rates (Yu, Clin Canc Res, 2013).
TNBCs represent roughly 13% of all breast cancers (Parise, Breast J, 2009) and have substantially worse clinical outcomes than other breast cancer subtypes. Specifically, patients with TNBCs have a lower overall and breast cancer specific survival than hormone receptor positive cancers. Strikingly, this increased mortality risk peaks dramatically within the first two years following diagnosis, with TNBC patients possessing approximately six-times greater risk of death compared to hormone receptor positive cancers, even after adjusting for age, race, stage, tumor size, grade, and nodal status (Lin, Cancer, 2012). Additionally, patients with TNBCs have higher rates of both local and distant recurrence over shorter time intervals (Lin, Cancer, 2012; Dent, Clin Cancer Res, 2007). The increased risk of death and recurrence seems to dissipate over time.
Additional therapeutic avenues are desperately needed to combat this aggressive form of breast cancer.