How do I Treat “Triple-Negative” Disease

Abstract

Over the recent years, there has been an increasing recognition that triple-negative breast cancer constitutes a separate, albeit heterogeneous, entity arising from distinct oncogenic pathways. Despite its aggressive clinical behavior, triple-negative disease responds favorably to cytotoxic chemotherapy resulting in high response rates. Nonetheless, the relapse rates are high and, in the absence of targeted therapies to significantly alter its natural history, the prognosis can be poor. Most of the trials conducted in the past that led to the formulation of the current guidelines have indiscriminately lumped triple-negative disease with receptor-positive subtypes. Therefore, there are relatively scant data regarding how standard approaches specifically apply for triple-negative disease. By virtue of its chemosensitive nature and high probability of achieving a complete pathologic response, neoadjuvant chemotherapy in early-stage/operable and locally-advanced/inoperable triple-negative disease is highly recommended. The indications for adjuvant chemotherapy are the same as in receptor-positive tumors, although endocrine therapies or agents targeting Her2 signaling have no established role in triple-negative disease. The optimal chemotherapy is not entirely clear; however, by virtue of their efficacy in breast cancer in general, anthracycline-containing regimens are the most widely used. The incorporation of taxanes in the regimen is supported by retrospective analyses. There is scant evidence to recommend any particular agent in the metastatic setting, although the combination of ixabepilone with capecitabine was shown to be active specifically in triple-negative disease. Given the uncertainty in the optimal management of triple-negative disease, the shortcomings of contemporary regimens, and the strong rationale of novel therapies, participation in clinical trials should be strongly considered at any stage of the disease.