Emerging pathways in treating human epidermal growth factor receptor-2-negative breast cancer

Breast cancer remains the leading cause of new cancer cases in women and is responsible for the most cancer-related deaths in women worldwide. The goals of breast cancer treatment are to maintain or improve quality of life, prolong survival, and increase disease-free progression. The majority of breast cancer cases are estrogen receptor (ER)-positive and human epidermal growth factor receptor-2 (HER-2)-negative, and current treatment guidelines recommend multiple lines of endocrine therapy followed by chemotherapy in patients with locally recurrent or metastatic disease. Resistance to current therapies adds to the need for new therapeutic options. Translational research and preclinical data have provided insight into the identification of emerging signaling pathways for novel drug targets, and the development of a growing number of biologic targeted agents is currently underway to identify novel treatments. An alternative approach to improve patient benefit is to boost the efficacy and safety of existing agents by modifying their delivery or pharmacokinetics (ie, adding albumin to paclitaxel) as well as identifying new combination therapies. One combination therapy of interest is the addition of the 130 nm albumin-bound formulation of paclitaxel (nab-paclitaxel) to currently approved therapies or targeted agents in development. This review focuses on a number of key agents that are being investigated for the treatment of HER-2-negative breast cancer and the utilization of these agents as combination therapy to achieve prolonged disease control.

Focal points

• •

  Bedside

• ○ New therapeutic options are necessary for breast cancer patients with HER-2-negative and either hormone receptor positive or negative disease who develop resistance to current therapies. Recent insights into molecular pathways may soon expand the treatment options for all patients with HER-2-negative breast cancer.

• •

  Bench

• ○ Several rationally designed combinations of biologic targeted agents and next generation chemotherapeutic agents are currently under investigation to prolong disease control and overcome treatment resistance in patients with HER-2-negative breast cancer.