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.