Safety and efficacy trial of preoperative sequential chemo-radiation therapy for the nonsurgical treatment (NST) in early breast cancer (EBC): Japan Clinical Oncology Group trial (JCOG0306)

Abstract

601 Background: The combination of preoperative anthracycline-containing regimen and taxane can obtain a good pathologic complete response (pCR) rate for patients (pts) with EBC. To pursue higher pCR rate with maintaining good systemic control may lead to the NST in the future. The objective of this trial is to determine whether the addition of radiation therapy (RT) to chemotherapy (CT) can surpass the pCR rate of 50% as the first step of turning the NST into reality. Methods: We conducted a safety and efficacy trial of CT (4 courses of doxorubicin and cyclophosphamide [60/600mg/m2] followed by 12 courses of weekly paclitaxel [80mg/m2]) and RT (whole breast 45Gy + boost 10Gy) sequentially as a primary therapy in pts with stage I- IIIA (5.0cm > tumor size > 2.0cm) breast cancer (BC). All pts received mastectomy or lumpectomy 12–16 weeks after completion of RT to maximize the effect of RT. Primary endpoint was %pCR. pCR was assessed by the central pathological review board. Results: Between June 2004 and April 2005, 108 pts were enrolled in this trial. Median age was 50 years (range 23–69). 60%(65/108) were ER+, and 31%(34/108) had HER2 overexpression. The planned interim analysis after completion of accrual was carried out in Nov 2005. None of pCR was observed in first 7pts and study was terminated. In case of the pts had not undergone RT at the time, surgery without preoperative RT was recommended. A clinical response rate was 76%. 39(36%) had pCR+DCIS and 27(25%) had pCR. The rate of breast conserving surgery was 89%. 1 pt received debridement for radiation associated necrosis 3 months after lumpectomy and 3 pts needed antibiotics for postoperative wound infection. Other toxicities were mild to moderate. Conclusions: Preoperative sequential chemo-radiation therapy didn't increase the risk of operative complications and could achieve high rate of breast conserving surgery, even though expected % pCR was not achieved. Further therapeutic development is needed to realize NST for BC. No significant financial relationships to disclose.