TO PUT THAT INTO CONTEXT
Debu Tripathy, MD
The University of Texas MD Anderson Cancer Center
Houston, TexasWhat Do We Already Know About Neoadjuvant Therapy for Breast Cancer?
Santa-Maria and colleagues review the evolving field of neoadjuvant therapy for breast cancer, nicely addressing the very practical questions of why and how this approach should be considered. They appropriately point out that neoadjuvant therapy should include adjuvant regimens proven to significantly lengthen disease-free or overall survival. The additional advantage of neoadjuvant therapy lies in its ability to downstage tumors and thereby enable selected patients to undergo breast-conserving surgery. The neoadjuvant approach may even enable patients who present with clinical N1 disease to avoid full axillary dissections, although this possibility is still being formally studied. The most responsive breast cancer subtypes are triple-negative and human epidermal growth factor receptor 2 (HER2)-positive (especially hormone receptor–negative) tumors, and in the case of inflammatory breast cancer, neoadjuvant chemotherapy has become the standard approach in the absence of controlled trials, because of the dismal historical results obtained with upfront surgery.What Holds Promise for the Future-And Why
One of the most interesting aspects of the neoadjuvant approach is the widening range of research opportunities. Several investigative groups are using the neoadjuvant platform to accelerate the development of relevant drugs and biomarkers/ signatures, given the strong link between pathologic complete response and long-term survival. However, very careful stratification by tumor subtype is necessary to confirm whether or not the neoadjuvant model can identify therapies with a high chance of success at improving survival in a large-scale trial. While the US Food and Drug Administration will consider this model as a pathway to accelerated drug approval, it must be coupled with definitive trials showing a disease-free survival benefit. The authors provide some examples of neoadjuvant research designs for triple-negative breast cancer, including the use of carboplatin, that have generated much interest and even premature changes in practice patterns. Accelerated approval of pertuzumab for neoadjuvant use in HER2-positive breast cancer, based on the results of NeoSphere, was also heavily supported by the large body of evidence of a survival benefit in the metastatic setting, as well as a favorable safety record. For platinum agents, the road will be different, as two large cooperative groups have launched definitive trials of post-neoadjuvant and adjuvant therapy for patients with early-stage breast cancer.