Adjuvant Docetaxel in Node-Negative Breast Cancer Patients: A Randomized Trial of AGO-Breast Study Group, German Breast Group, and EORTC-Pathobiology Group

Simple Summary The NNBC-3 Europe trial was designed to study the risk assessment in node-negative breast cancer and to test whether taxanes as substitute in an adjuvant anthracycline-containing combination chemotherapy may improve disease-free survival in patients with a high risk of recurrence. We assessed 4146 node-negative breast cancer patients by clinico-pathological or tumor-biological prognostic factors (uPA/PAI-1), and 2541 of these were classified as high-risk and, therefore, treated with six courses of a standard anthracycline combination (FEC) or, by randomization, three courses of the same combination followed by three courses of docetaxel. After a median follow-up of 45 months, we observed only few recurrences without difference between the chemotherapy regimens. With docetaxel, more toxicity was observed. In conclusion, patients with high-risk node-negative breast cancer have an excellent prognosis in the first years after diagnosis independent from the type of chemotherapy. To date, we did not observe sufficient events to evaluate the type of prognostic assessment. Background: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy. Methods: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers. Risk assessment was performed by clinico-pathological factors (43%) or biomarkers (uPA/PAI-1, urokinase-type plasminogen activator/its inhibitor PAI-1). High-risk patients received six courses 5-fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), cyclophosphamide (500 mg/m(2)) (FEC), or three courses FEC followed by three courses docetaxel 100 mg/m(2) (FEC-Doc). Primary endpoint was disease-free survival (DFS). Results: In the intent-to-treat population, 1286 patients had received FEC-Doc, and 1255 received FEC. Median follow-up was 45 months. Tumor characteristics were equally distributed; 90.6% of tested tumors had high uPA/PAI-1-concentrations. Planned courses were given in 84.4% (FEC-Doc) and 91.5% (FEC). Five-year-DFS was 93.2% (95% C.I. 91.1-94.8) with FEC-Doc and 93.7% (91.7-95.3) with FEC. Five-year-overall survival was 97.0% (95.4-98.0) for FEC-Doc and 96.6% % (94.9-97.8) for FEC. Conclusions: With adequate adjuvant chemotherapy, even high-risk node-negative breast cancer patients have an excellent prognosis. Docetaxel did not further reduce the rate of early recurrences and led to significantly more treatment discontinuations.

Automated summary

The NNBC-3 Europe trial aimed to assess the risk of recurrence in node-negative breast cancer patients and to determine whether taxanes can improve disease-free survival in high-risk patients. The study found that patients with high-risk node-negative breast cancer have a favorable prognosis in the first few years after diagnosis regardless of the type of chemotherapy.