First-line Treatment of Triple-Negative and Basal-Like Breast Cancers

Question

What is the best first-line treatment for advanced basal-like triple-negative metastatic breast cancer in circumstances in which radiation is not possible? Is one of the platinum agents a good option?

Response From the Expert

Ting Bao, MD and Antonio C. Wolff, MD
Ting Bao, MD, Oncology Fellow, Breast Cancer Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland

Antonio C. Wolff, MD, Associate Professor of Oncology, Breast Cancer Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland

Although the terms are often used interchangeably, it is important to remember that a triple-negative breast cancer (TNBC) phenotype (ER/PR and HER2-negative) is not exactly synonymous with basal-like breast cancer (BLBC). BLBC is defined by gene expression profiling and describes breast cancers that in most cases are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), and are positive for cytokeratins 5/6 and epithelial growth factor receptor (EGFR). Although the majority of cases of BLBC are triple-receptor-negative, 5% to 15% are not. Moreover, TNBC tumors are histologically heterogeneous and may include infiltrating ductal carcinoma (basal-like and non-basal-like breast cancers) and other subtypes such as medullary, squamous, and apocrine.^[1] However, BLBC and TNBC overlap significantly, and in everyday usage the term TNBC is commonly understood to include BLBC.

TNBC is associated with a more aggressive clinical course and worse clinical outcomes than is non-TNBC. A recent cohort study of 1601 patients with breast cancer demonstrated that those with TNBC had a greater risk for systemic recurrence and death than did those with non-TNBC.^[2] These events occurred mostly within the first 5 years after diagnosis, as the risk for systemic recurrence for patients with TNBC peaked at 3 years and declined rapidly afterwards, whereas non-TNBC patients' risk for recurrence was constant.^[2] Patients with TNBC have a higher rate of visceral metastasis and their tumors are more likely to harbor abnormalities in the p53 and BRCA1 genes compared with patients with non-TNBC.^[1]

Because patients with TNBC are not likely to benefit from antiestrogen or anti-HER2 therapy, first-line treatment usually consists of conventional cytotoxic chemotherapy. Although TNBCs are quite sensitive to taxane- and anthracycline-containing regimens in the preoperative setting, they are nevertheless associated with poor long-term outcomes.^[1] In a recent large retrospective clinical trial of 1118 stage I-III breast cancer patients treated with preoperative chemotherapy, those with TNBC had a higher rate of pathologic complete response (pCR) than did those with non-TNBC (22% vs 11%; P = .034), but they had lower rates of 3-year progression-free survival (P < .0001) and overall survival (P < .0001). Of note, TNBC patients who achieved a pCR had a survival rate similar to that of non-TNBC patients.^[3]

Although there is no standard first-line chemotherapy regimen for metastatic TNBC, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including taxanes, platinum agents, antiangiogenic agents, and EGFR inhibitors, are currently being tested in clinical trials.^[1] Cisplatin exerts a modest degree of antitumor activity in unselected patients with metastatic disease, but few data are available specifically in patients with TNBC. At the 2008 meeting of the American Society of Clinical Oncology, Yi and colleagues^[4] reported the results of a retrospective evaluation of clinical outcomes in patients with metastatic breast cancer treated with a platinum-containing regimen. They found similar activity in patients with TNBC and in those with non-TNBC. At that same meeting, Carey and coworkers^[5] presented the results from a Translational Breast Cancer Research Consortium trial (TBCRC 001) that assessed the clinical efficacy of the EGFR inhibitor cetuximab alone or combined with carboplatin as first-line therapy for metastatic TNBC. Cetuximab alone had minimal activity in TNBC; only 6% of patients (2 of 31) responded, although these 2 responses lasted more than 40 weeks. In the combination arm, 18% of patients (13 of 71) showed a response. The TBCRC now plans to conduct a trial examining single-agent carboplatin or cisplatin in TNBC patients. In the meantime, there is no preferred standard first-line therapy in patients with metastatic TNBC.

This activity is supported by an independent educational grant from Susan G. Komen for the Cure.