Abstract ES09-2: Metastatic breast cancer: An update on management and supportive care
Authors: Carey LA 
Published: August 2014

Triple negative breast cancer (TNBC), by virtue of having no estrogen (ER) or progesterone receptor (PR) expression nor HER2 expression/gene amplification, lacks any known targetable molecule. This presents a therapeutic challenge for both the adjuvant and metastatic setting, since we are curently reliant on chemotherapy for treatment.

Conventional chemotherapy is effective in TNBC, however, as with all stage IV disease, it is palliative and the duration of response is often short. Several studies have found median survival after diagnosis of stage IV disease of approximately 1-2 years. There are little clinical data supporting preferential use of any particular chemotherapy agent over another in metastatic TNBC compared with other subtypes. In the first-line setting, CALGB 40502 demonstrated that weekly paclitaxel was more effective than ixabepilone and less toxic than albumin-bound nab-paclitaxel, with similar results in TNBC as in the overall study population. In later lines there are a number of reasonable options. The EMBRACE study, which included approximately 20% TNBC, established the halichondrin B analogue eribulin in late (median 5th-line) treatment of unselected breast cancer. More recently, a phase III comparison of eribulin and capecitabine in 1st-3rd-line therapy demonstrated overall equivalence and a hint of better survival in the TNBC subset; given the subset nature and size of this analysis it is probably reasonable to conclude that both are reasonable choices. Alternatives include anthracyclines, platinum drugs, gemcitabine, and doublet regimens, among others.

Although preclinical and tissue studies suggested plausibility of antiangiogenic approaches in TNBC, clinical data in the metastatic setting have been conflicting, with some evidence of efficacy in pretreated TNBC subset of the RIBBON-2 study but no suggestion of an OS advantage in the pooled analysis of the first-line studies in the metastatic setting. TNBC itself is a clinical entity that encompasses all of the intrinsic subtypes, although most are of the basal-like subtype. Preclinical studies implicating aberrant DNA damage response in basal-like breast cancer, has led to hypotheses regarding particular sensitivity to direct DNA-damaging agents such as platinum drugs. While randomized clinical trials are ongoing, nonrandomized studies of with platinum-based chemotherapy in metastatic TNBC suggest reasonable, but modest, activity. Similarly, although clearly implicated in growth and proliferation in basal-like breast cancer models, in clinical trials targeting EGFR had only a modest impact in otherwise unselected TNBC. Although clinical data are still limited, directly targeting DNA damage repair with poly (ADP-ribose) polymerase (PARP) inhibition appears to have activity in tumors arising in patients with germline BRCA mutations, but not in sporadic TNBC. It is increasingly clear that within TNBC are a several biologic subsets with different target profiles including growth factor pathways, DNA damage repair deficiency, androgen receptor expression and immunologic mechanisms. To advance therapy in metastastic TNBC, we will need to better match the tumor to the target, it is unlikely that we will identify a biologic agent that is highly effective against unselected TNBC.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES09-2.