Patients with triple negative breast cancer: Is there an optimal adjuvant treatment?

Abstract

Chemotherapy is the mainstay of adjuvant treatment for triplenegative breast cancer (TNBC), and is highly effective in preventing breast cancer recurrence and improving survival. Triple-negative tumors, by definition, lack expression of estrogen receptor (ER) and HER2, the established markers used to select patients for adjuvant endocrine therapy or trastuzumab therapy, respectively. For these reasons, optimizing adjuvant chemotherapy for TNBC has been a high priority. Large clinical trials have attempted to define the optimal adjuvant chemotherapy regimens. Most of these studies included patients based on clinical stage, and irrespective of tumor hormonereceptor or HER2 status. Retrospective subset analyses have attempted to characterize outcomes for patients defined by tumor ER and/or HER2 status. However, such analyses were in almost all cases post hoc subset examinations, and have frequently lacked power to rigorously characterize outcomes in TNBC, as opposed to other types, of breast cancer. In addition, many such retrospective studies have reported on outcomes by ER status or by HER2, but have not always specified TNBC cancers (i.e. ER negative and HER2 negative) as a distinct subset. Such methodological problems have meant that it has been hard to define the optimal adjuvant chemotherapy regimen by breast cancer subset, particularly for older clinical trials. The Early Breast Cancer Trialists’ Collaborative Group has demonstrated that both anthracyclines and taxanes are effective adjuvant chemotherapeutic agents in hormone-receptor negative breast cancers, with anthracycline-based regimens conferring modest benefits over non-anthracycline, CMF-type regimens, and taxane-based regimens being superior to non-taxane alternatives [1]. Large, multicenter clinical trials such as ECOG 1199 and NSABP B-30 have proven the benefit of sequential chemotherapy regimens – anthracycline/cyclophosphamide followed by taxane eincluding hormone-receptor negative tumors [2,3]. US Oncology group trial 9735, a comparison of AC vs TC chemotherapy, showed a survival advantage for the inclusion of the taxane among patients with ER negative breast cancer [4].