Dr. Gradishar says that at the present time, evidence-based decision making would provide little differences in approach to chemotherapy recommendations between TNBC and non-TNBC. For most patients, single agents in sequence are appropriate, while for those with rapidly progressive disease or a visceral crisis, combination therapy could be considered. Emerging data suggests that platinum-based therapy may be useful in TNBC.

William J. Gradishar, MD: Chemotherapy Combinations with TNBC

William J. Gradishar, MD: Main Choices for TNBC

Dr Gradishar says that the results of this trial remain to be seen; however, it may show that one combination is better than another.

William J. Gradishar, MD: Standard of Care for Patient 

Dr. Yardley says that the benefits of cytotoxic chemotherapy in TNBC neoadjuvant, adjuvant, or metastatic treatment are well established, with numerous studies demonstrating the effectiveness of chemotherapy in these settings. Polychemotherapy in ER-poor early disease was evident in both the younger and older patients from The Early Breast Cancer Trialists&rsquo; Collaborative Group overview, demonstrating that a substantial risk reduction in recurrence and death from breast cancer is consistent with the notion that TNBC derives substantial benefit from polychemotherapy. In further support, a retrospective analysis of 3 large Cancer and Leukemia Group B (CALGB) trials concluded that ER-tumors derive substantially greater improvements in outcome from modern intensive and extensive chemotherapy regimens.

In the advanced disease setting, combination chemotherapy offers higher response rates and prolonged time to disease progression compared with single- agent chemotherapy. It is often reserved for those with very symptomatic disease, rapid tempo of progression, or those with high tumor burdens and/or visceral crisis.

Denise A. Yardley, MD: Chemotherapy Combinations with TNBC

Dr. Yardley cites a variety of approved noncross-resistant agents, such as nab-paclitaxel, gemcitabine, vinorelbine, capecitabine, eribulin, ixabepilone, and/or the platinums. In anthracycline-pretreated patients, combination chemotherapy platforms based on microtubule inhibitor doublets partnered with some of these antineoplastic agents have demonstrated superior efficacy, including survival. In addition, the platinums have gained increasing attention and popularity based on the strong association of TNBC tumors with germ-line mutations in the BRCA1 gene, with at least 10% of TNBC tumors having a BRCA 1 mutation. In later lines of metastatic breast cancer therapy, other agents, such as eribulin, have also demonstrated efficacy specifically in anthracycline- and taxane-pretreated patients. Capecitabine in combination with ixabepilone demonstrated superior responses in the TNBC subset. However, overall outcomes still remain poor for TNBC, and while administration of sequential single agents is not likely to require dose reductions or treatment delaysno single agent has demonstrated superiority&mdash; treatment decisions can be selected on the basis of efficacy, toxicity profiles, schedule, and/or route of administration.

Denise A. Yardley, MD: Main Choices for TNBC

Trials such as tnAcity will help determine a standard for patients like Rebecca B., who received appropriate anthracycline- and taxane-based therapy for her early-stage disease and unfortunately relapsed. As she is greater than 12 months from her exposure to a microtubule inhibitor, this remains a reasonable option and backbone to therapy. Given her young age and symptomatic visceral relapse, a clinical trial evaluating combination chemotherapy regimens seems reasonable and appropriate. By assessing regimens that demonstrate noncross-resistance and offer great therapeutic options for her aggressive TNBC subtype, such as tnAcity, it is hoped that a better understanding of the impact of combination chemotherapy on her disease will establish additional treatment options.

Triple-Negative Breast Cancer: Case 1

William J. Gradishar, MD: Chemotherapy Combinations with TNBC

William J. Gradishar, MD: Main Choices for TNBC

William J. Gradishar, MD: Standard of Care for Patient

Denise A. Yardley, MD: Chemotherapy Combinations with TNBC

Denise A. Yardley, MD: Main Choices for TNBC

Denise A. Yardley, MD: Standard of Care for Patient