Abstract
Preoperative systemic therapy, though primarily used to downstage breast cancers, can offer, using pathologic complete response (pCR) as an endpoint, a rapid assessment of efficacy of a given therapeutic approach, particularly in triple-negative (TNBC) and HER2-positive breast cancers. Recently, this approach resulted in the approval of pertuzumab for HER2-positive cancers, in a considerably quicker timeline than would have been possible with its assessment in the adjuvant setting. However, the use of preoperative systemic therapy remains controversial, as the higher response rates noted with newer approaches have not routinely translated into improved longer-term outcomes, nor have they been confirmed in larger adjuvant trials. Almost all trials have demonstrated that pCR is a robust prognostic marker in patients with TNBC and HER2-positive cancers, so part of this discrepancy may be due to inadequate power in the preoperative trials and/or due to the heterogeneous nature of breast cancers. PCR following preoperative chemotherapy is not prognostic in many hormone receptor (HR)-positive breast cancers, especially those with a luminal A phenotype, which typically has minimal response to chemotherapy. Given this lack of response to chemotherapy, there is considerable interest in the use of neoadjuvant endocrine therapy (NET). The rate of pCR to NET in HR-positive cancers is low, leading to the use of surrogate markers, including changes in Ki-67 and the preoperative endocrine prognostic index (PEPI) score, as biomarkers of efficacy. Overall, the use of neoadjuvant approaches offers a rapid assessment of efficacy of novel therapies and remains a useful research tool for drug evaluation.
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More From: American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
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