Triple-negative (basal-like) breast cancer: a new entity

Unsupervised gene expression array profiling has provided biological evidence for the heterogeneity of breast cancer through the identification of intrinsic subtypes such as luminal A, luminal B, HER2+/ER- and the basal-like subtype. The basal-like subtype is characterized by low expression of both the ER and HER2 clusters of genes, so is typically ER-negative, PR-negative, and HER2-negative on clinical testing; for this reason, it is often referred to as 'triple-negative' breast cancer.

Basal-like breast cancer has some unique characteristics. It is the type of breast cancer that BRCA1 mutation carriers generally develop, although most basal-like breast cancers are sporadic. It comprises approximately 15% of all breast cancers, but is overrepresented among young African-American women who develop breast cancer, in whom it comprises 39%. Although it does not occur at higher stages than other breast cancer subtypes, it is usually high grade and highly proliferative, which may explain the poor prognosis associated with this subtype in several series. Given the triple-negative status of basal-like breast cancer, it cannot be treated with ER-targeted or HER2-targeted therapies, so is primarily treated with chemotherapy. Fortunately, advances in adjuvant therapy appear to benefit ER-negative breast cancer even more than ER-positive breast cancer, and women with the basal-like subtype have similarly benefited. In addition, in cohorts of breast cancer treated with neoadjuvant chemotherapy, the pathologic complete response to anthracycline/taxane-based therapy was significantly higher among basal-like breast cancers than luminal breast cancers. The women with pathologic complete response have good outcome; the poor prognosis of basal-like breast cancer appears to relate to a particularly high risk of early distant relapse among those that had residual disease. Among the targeted agents for breast cancer, bevacizumab added to paclitaxel in a randomized phase III trial appeared to have similar benefit in the triple-negative subset as the other breast cancer phenotypes, suggesting effectiveness in basal-like breast cancer. Current investigations into other therapeutic options for this subtype include confirmation of effectiveness of VEGF targeting, examination of EGFR-targeted strategies, determining whether the association of basal-like breast cancer with BRCA1 mutations means that this DNA repair pathway is dysfunctional in all basal-like breast cancer, and determining whether specific chemotherapy agents have greater or lesser efficacy in this subtype. Future studies should also focus upon identifying whether there are particular genetic or environmental risk factors for basal-like breast cancer that differ from other subtypes, and whether there are metastatic or predictive signatures that can be identified within the basal-like subtype.