New agents in locally advanced breast cancer.

PURPOSE OF REVIEW: Sequential anthracycline/taxane regimens are routinely used as neoadjuvant therapy (NAT) for locally advanced breast cancer. Unfortunately, the majority of patients do not achieve a pathological complete response (pCR). Efforts to improve pCR rates include the addition of novel targeted agents. The purpose of this article is to review recent developments in this area and to demonstrate the clinical and research advantages of a neoadjuvant platform for the evaluation of novel targeted therapy. RECENT FINDINGS: Dual human epidermal growth factor 2 (HER2)-targeting concurrent with chemotherapy has demonstrated superiority over chemotherapy with trastuzumab alone. Bevacizumab appears to have a modest effect on pCR rates and its role in neoadjuvant treatment remains uncertain. Despite promising preclinical signals, mTOR inhibition in combination with chemotherapy has yet to yield a benefit in the neoadjuvant setting and trials are ongoing. In contrast, mTOR inhibition in combination with endocrine therapy has demonstrated potential as NAT. SUMMARY: Dual HER2-targeting considerably improves pCR rates. Thus, far incorporation of non-HER2 targeted agents has been less successful. NAT provides an opportunity to evaluate novel agents, and thereby assist the development of a rationale adjuvant strategy, and facilitates the collection of samples for correlative research into breast cancer biology and predictive biomarkers/pathways.