Neoadjuvant therapy for breast cancer: controversies in clinical trial design and standard of care.

Neoadjuvant therapy for breast cancer has been increasingly used in recent years as first-line treatment for operable breast cancer-serving as both a management strategy and a research tool. In addition to the established clinical benefits of down-staging more locally advanced cancers and improving breast-conservation rates, investigators have recognized the potential advantages of this approach in developing new therapies. Preoperative systemic therapy provides the opportunity for in vivo assessment of pharmacodynamic markers to assess biologic effects and allows new compounds to be tested in a more responsive, treatment-naive population. In addition, early surrogates of response, such as pathologic complete response (pCR) and residual cancer burden, provide proximate measures that correlate with long-term outcomes, thus potentially shortening the time needed to identify effective adjuvant therapies. Despite the advantages of neoadjuvant therapy for research and clinical practice, its use is characterized by persistent controversy and healthy debate regarding how to optimally use research findings and when to integrate them into the standard of care for daily management. Among the controversies surrounding neoadjuvant therapy use are questions about defining the best endpoint for assessing treatment efficacy, deciding when results from research should be used in daily clinical practice, and how the growing use of neoadjuvant therapy affects locoregional treatments.