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Abstract and Introduction
Abstract
Background: We sought to determine the prognostic value of pathologic response to neoadjuvant chemotherapy with concurrent trastuzumab.
Patients and methods: Two hundred and twenty-nine women with HER2/neu (HER2)-overexpressing breast cancer were treated with neoadjuvant chemotherapy plus trastuzumab between 2001 and 2008. Patients were grouped based on pathologic complete response (pCR, n = 114) or less than pCR (<pCR, n = 115); as well as by pathologic stage. Locoregional recurrence-free (LRFS), distant metastasis-free (DMFS), recurrence-free (RFS), and overall survival (OS) rates were compared.
Results: The median follow-up was 63 (range 53–77) months. There was no difference in clinical stage between patients with pCR or <pCR. Compared with patients achieving <pCR, those with the pCR had higher 5-year rates of LRFS (100% versus 95%, P = 0.011), DMFS (96% versus 80%, P < 0.001), RFS (96% versus 79%, P < 0.001), and OS (95% versus 84%, P = 0.006). Improvements in RFS and OS were seen with decreasing post-treatment stage. Failure to achieve a pCR was the strongest independent predictor of recurrence (hazard ratio [HR] = 4.09, 95% confidence interval [CI]: 1.67–10.04, P = 0.002) and death (HR = 4.15, 95% CI: 1.39–12.38, P = 0.011).
Conclusions: pCR and lower pathologic stage after neoadjuvant chemotherapy with trastuzumab are the strongest predictors of recurrence and survival and are surrogates of the long-term outcome in patients with HER2-overexpressing disease.
Introduction
Potential benefits of neoadjuvant chemotherapy include tumor downsizing allowing appropriately selected patients to undergo breast-conserving therapy (BCT), assessment of response to therapy, and early treatment of micrometastatic disease. Response to neoadjuvant chemotherapy is an early surrogate of long-term prognosis, as pathologic complete response (pCR) has been shown to correlate with an improved outcome.
With the routine use of trastuzumab, improvements in survival among women with HER2/neu (HER2)-overexpressing tumors have been demonstrated in the metastatic and adjuvant settings. More recently, the efficacy of trastuzumab delivered in the neoadjuvant setting has been evaluated. In the first randomized trial to evaluate the addition of trastuzumab to chemotherapy in the neoadjuvant setting, Buzdar et al. reported a 66.7% pCR rate among patients receiving chemotherapy plus trastuzumab versus 25% among patients receiving chemotherapy alone (P = 0.02). After this, the GeparQuattro and NOAH (NeOAdjuvant Herceptin) trials have shown improved pCR rates among patients receiving trastuzumab, with an event-free survival benefit seen at 3 years among patients treated with trastuzumab in the NOAH trial. Long-term clinical outcomes as a function of achieving a pCR have not been reported from these studies.
In this study, we evaluated the prognostic value of achieving a pCR following neoadjuvant chemotherapy with trastuzumab. Locoregional recurrence-free, distant metastasis-free (DMFS), recurrence-free (RFS), and overall survival (OS) outcomes were evaluated to characterize the long-term benefit of a pCR.
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