Adjuvant and neoadjuvant systemic therapies for early-stage breast cancer

Background: While surgery is still the cornerstone treatment for early stage breast cancer, a deeper understanding in breast cancer biology has led to improvements in systemic therapies that improve patient outcomes. Methods: This chapter will review the different subtypes of breast cancer and how receptor status influences therapeutic strategies. The evolution of adjuvant cytotoxic chemotherapy will be discussed, including how gene expression profiling can help identify patients with hormone receptor positive breast cancer most likely to benefit from therapy. Adjuvant targeted therapies will be reviewed. Considerations for adjuvant versus neoadjuvant approaches will be discussed. Results: Breast cancer can be clinically subtyped based on the presence of hormone receptors and human epidermal growth factor receptor 2-neu (HER2). Numerous clinical trials have been conducted to determine the optimal adjuvant chemotherapy regimens. The benefit of chemotherapy in hormone positive disease may be assessed using gene expression profiling. In hormone receptor positive breast cancer, antihormone therapy such as tamoxifen or aromatase inhibitors can reduce the risk of relapse substantially. The advent of anti-HER2 therapies, including trastuzumab and pertuzumab, has led to improved survival in patients with HER2-positive disease. A neoadjuvant approach can make inoperable tumors operable, or increase the chance of breast conserving therapy in those not eligible for it at diagnosis, and is considered the standard for inflammatory breast cancers. Conclusion: Systemic therapies in early breast cancer can improve patient outcomes, particularly when targeting key oncogenic drivers.