Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer

603 Background: While most patients with breast cancer receiving neoadjuvant chemotherapy (NCT) have some tumor response, a small proportion progress during therapy. Although several groups have looked at markers for response, none have specifically evaluated markers for progression. The goal of this study was to identify predictors of tumor progression during NCT with the ultimate aim of identifying the subset of patients who may benefit from a first-line surgical approach. Methods: Patients with stage I-III breast cancer treated at a single comprehensive cancer center with NCT between 1994 and 2007 were included. Data was obtained from a review of medical records of patients in a prospectively acquired database. Chemotherapy consisted of anthracycline and/or taxane-based regimens. Statistical analysis was performed using univariate and multivariate analysis with logistic regression analyzing patients with some response or stable disease versus patients with progression. Results: 1928 patients received NCT: 1762 (91%) had some response (minor, partial, or complete), 107 (6%) had stable disease (SD), and 59 (3%) progressed (PD) on at least one NCT regimen. Clinical factors that correlate with PD in univariate analysis include presenting T (T3 vs T1, p = 0.002) and AJCC stage (stage IIIb/IIIc vs I/II/III, p = 0.02). Predictive histopathological features were high tumor grade (p = 0.005), high Ki-67 (p = 0.002), and negative ER and PR status (p < 0.0001 and p = 0.0006). Patients with PD were more likely to be treated with a taxane (79% vs 88%, p = 0.04). In the post-NCT surgical specimens, patients with PD were more likely to have higher T stage (p < 0.0001), lymph node metastasis (p = 0.01), and lymphovascular invasion (p = 0.02). On multivariate analysis, pre-NCT T status and ER status were the most important predictors of progression. Conclusions: Pre-treatment characteristics predictive of disease progression on NCT include advanced tumors, high tumor grade, high Ki-67, and negative ER or PR status. Since high grade and negative ER/PR status have also been associated with a complete pathologic response to NCT, there is a clear need for more specific molecular predictors of response and progression in order to select appropriate treatment in these patients. No significant financial relationships to disclose.