Predictive markers of response to neoadjuvant chemotherapy in breast cancer

Several randomized prospective studies on breast cancer patients have proved the safety of neoadjuvant chemotherapy. These trials have also demonstrated that tumor down staging does indeed improve the eligibility for breast conservative surgery without increasing local recurrence rates with possibly an improved survival. However, complete pathologic remissions are noted in only 3-30% of patients. About 20% of patients do not benefit from different chemotherapy regimens currently in use and are thus subjected to toxic drugs. This often leads to progression of disease and thereby the surgeon may lose a window of opportunity to obtain durable locoregional control of disease. Identification of predictive markers associated with pathologic complete response can help to distinguish patients with high or low probability of a response to treatment so that an individualized treatment plan can be implemented. It could also streamline the development of new alternative regimens for those who are unlikely to benefit from existing drugs. It is expected that a combination of markers will be more informative than a single one. So far, several factors have been studied as predictors for response to cytotoxic treatment, viz., tumor size, hormone (estrogen and progesterone) receptor status, tumor type and differentiation, HER2/cerB-2, tumor proliferation Ki-67, apoptosis related genes p53, bcl-2 and BAX; certain subgroups of breast cancer, and the latest in this category is gene expression profiling. However, in terms of prediction of drug responsiveness, data reported are still very limited. This review aims to discuss the current relevant literature on the subject.