Adjuvant therapy of triple negative breast cancer

Abstract

Patients with the triple negative subtype of breast cancer have an overall poor outcome, with earlier relapses, distinct patterns of metastases, and lack of specific targets for treatment selection. Classification of these tumors has begun to be modified by inclusion of immunohistochemistry for various markers, and gene profiling. Further characterization of this subtype of breast cancer may aid in the identification of new targeted therapies. Anthracyclines and taxanes remain the standard of care in the adjuvant setting. However, novel anti-angiogenesis, anti-tubulin, and DNA repair agents are already under evaluation in (neo) adjuvant trials. Molecular characterization is being included in trials to identify optimal adjuvant strategies. The aim of this manuscript is to review data concerning the molecular characterization of triple negative breast cancers as well as the clinical outcomes of treating patients with existing adjuvant treatments, and to highlight newer adjuvant research strategies in development.

Figure 1. “Triple Negative” Disease in the Context of “Basal-like” Breast Cancer

Classification of so called triple negative breast cancers is beginning to be modified by inclusion of immunohistochemistry for various markers. Triple negative breast cancers exhibit a range of molecular and clinical properties that suggest that they are comprised of several subtypes. There is a tendency to equate basal-like tumors with triple negative due to ER/PR negative status and no amplification and/or overexpression of HER2, yet as many as 10–20% of triple negative tumors exhibit a non-basal genomic profile and there appear to be at least 5 molecular subtypes. Evaluating the molecular characteristics, between the different subtypes may be essential to understanding the natural histories and their responsiveness to treatment.

Figure 2. Potential Therapeutic Targets for Triple Negative Breast Cancer [27, 36, 70, 71]

The majority of therapeutic targets currently under investigation fall within three broad categories: anti-angiogenesis (bevacizumab and other anti-VEGF compounds), stabilization of microtubules (MSAs such as ixabepilone) and deoxyribonucleic acid (DNA) repair (including platinums and PARP inhibitors, such as olaparib and BSI-120).