"Triple positive" breast cancer - a novel category?

Breast cancer (BC) biology is of outmost importance for its therapeutic management and for establishing patients' outcome. Breast cancer has been divided in subtypes depending on the presence of hormone receptors (HRs) for estrogen and progesterone and human epidermal growth factor receptor 2 (HER2) gene amplification. Recently, a distinct subcategory has been analyzed from the group of HER2-enriched BC with positive HR, namely HER2 positive with high levels of hormone receptor expression, suggestively named "triple positive" breast cancer. We aim to review current evidence on this subtype of BC, from the molecular mechanisms regulating its behavior to the current standard treatment outcome in order to establish whether it qualifies as a new distinct subtype of BC. Its biology is dominated by the crosstalks between HR pathway and HER2 pathway, which might be responsible for the development of rapid resistance to treatment, because of estrogen receptor up-regulation and alternate regulatory pathways activation when anti-HER2 agents are used. "Triple positive" subtype has apparently similar outcome when treated with chemotherapy alone, compared to chemotherapy and anti-HER2 agents treatment. It resembles more to luminal A breast cancer, with positive HR and HER2 negative. However, most of the clinical evidence is provided by retrospective trials with multiple potential biases. Treatment of "triple positive" subtype of BC with anti-HER2 agents and chemotherapy remain standard until stronger evidence will be available. Whether "triple positive" category should be regarded as a separate entity with distinct characteristics and management has to be demonstrated in future better designed trials.