Beyond cytotoxic chemotherapy for the first-line treatment of HER2-negative, hormone-insensitive metastatic breast cancer: Current status and future opportunities

As reflected In its varied clinical behavior, appearances under the light microscope, and differential patterns of gene expression, metastatic breast cancer (MBC) is a heterogeneous disease. Systemic treatment decisions are guided by specific tumor characteristics and individual patient factors. For patients with hormone therapies, cytotoxic chemotherapy has been the mainstay of systemic treatment. For hormone-insensitive, HER2-positive MBCs, the addition of trastuzumab to chemotherapy has resulted in improved outcomes. Hormone-insensitive MBC lacking HER2 overexpression includes the subset of patients with estrogen receptor/progesterone receptor/HER2-negative (so-called triple-negative) disease, which represents a significant minority of all breast cancers. Therapeutic options for such patients are limited by the lack of specific targeted approaches, and this heterogeneous group will be considered collectively as well as separately in this overview of existing and emerging treatment strategies. Conventional cytotoxic chemotherapy, alone or in combination, has been the standard first-line treatment for patients with MBC not amenable to antiestrogen or trastuzumab therapy. The recent evaluation of new targeted therapies in combination with cytotoxic agents has created a new type of combination regimen. Agents targeting angiogenesis, the epidermal growth factor receptor, and various signal transduction pathways have been combined with chemotherapy and possess biologic activity in MBC. As these combinations are being investigated, parallel correlative studies aimed at enriching the population who will benefit most are under way.