Concurrent Neoadjuvant Chemotherapy and Radiation Therapy in Locally Advanced Breast Cancer

Abstract

Toevaluate whether concurrent neoadjuvant radiation added to standard chemotherapy could increase the pathologic complete response (pCR) to treatment for locally advanced breast cancer (LABC). This prospective phase 2 trial recruited 32 LABC patients from 2009 to 2011. Patients received neoadjuvant every-3-weekly 5-fluorouracil (500mg/m2), epirubicin (100mg/m2), and cyclophosphamide (500mg/m2) for 3 cycles, followed by weekly docetaxel (35mg/m2) for 9 cycles. Regional radiation (45Gy/25 plus 5.4Gy/5) was delivered concurrently with docetaxel, then modified radical mastectomy. Patients were matched post hoc by a blinded statistician to a concurrent cohort treated with neoadjuvant chemotherapy, modified radical mastectomy, and adjuvant regional radiation. Thirty of 32 patients completed treatment. Twenty-seven were successfully matched by propensity score to 81 control patients by age, stage, and molecular subtype. The concurrent chemoradiation produced a significant increase in pCR (14% vs 22%, P<.001) but no statistically significant difference in disease-free and overall survival at 3years (respectively, 69% vs 81%, P=.186, hazard ratio 0.51; and 74% vs 89%, P=.162, hazard ratio 0.46). Toxicity included 25% of patients with grade 3 pneumonitis and 25% of patients with dermatitis, and 1 death. Concurrent neoadjuvant radiation added to radiosensitizing chemotherapy significantly improved pCR. A prospective randomized clinical trial is warranted to exploit the improved response seen with concurrent therapy but using another radio-sensitizing taxane, to better minimize treatment-related toxicity and determine its impact on overall survival.