Preoperative Chemotherapy is Safe in Early Breast Cancer, Even After 10 Years of Follow-up; Clinical and Translational Results from the EORTC Trial 10902

Introduction: The Preoperative Chemotherapy in Primary Operable Breast Cancer (POCOB) study was designed to compare preoperative with postoperative chemotherapy in patients with early breast cancer concerning breast conserving therapy (BCT) procedures, disease free survival (DFS) and overall survival (OS).

Methods: Patients (n = 698) with early breast cancer were enrolled between 1991 and 1999 and randomized between preoperative versus postoperative chemotherapy (four cycles of fluorouracil, epirubicin, and cyclophosphamide). Endpoints were BCT procedures, DFS, OS, and tumor response to preoperative chemotherapy. In addition, tumor tissue was collected for translational research and the following markers were examined: ER, PgR, HER2, p21, p53, and bcl-2 expression.

Results: With a median follow-up of 10 years, there was no statistically significant difference between the two treatment arms for OS (HR = 1.09; 95%CI 0.83-1.42; P = 0.54), DFS (HR = 1.12; 95%CI 0.90-1.39; P = 0.30), or locoregional recurrences (LRR, HR = 1.16; 95%CI 0.77-1.74). Preoperative chemotherapy was associated with an increase in BCT rates. BCT in part feasible due to tumor downsizing after preoperative chemotherapy was not correlated with higher LRR or worse OS compared to BCT which was feasible without downsizing of the tumor. Using available tumor material, only tumor stage, nodal stage, and grade were independent prognostic factors for overall survival.

Conclusions: Preoperative chemotherapy does not result in a difference in OS or DFS compared to postoperative chemotherapy in patients with early breast cancer. Moreover, it increases BCT rates with no significant increase of LRR. This implies that preoperative chemotherapy is a safe procedure for patients with early breast cancer, even after a follow-up period of 10 years.