Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients

Abstract

Purpose: Although dose-dense (dd) chemotherapy plays a fundamental role in the treatment of breast cancer (BC), a variety of trials have presented divergent survival results. Here, we present data of patients with more than 3 positive axillary lymph nodes (+aLN) receiving dd chemotherapy after a median follow-up period of 12.3 years. Methods: In the years 1996-2000, 231 patients with invasive BC, ≥pN2a and no evidence of distant metastases were recruited to receive treatment A, i.e. dd 3 × epirubicin (E, 90 mg/m2) + paclitaxel (P, 175 mg/m2) every 2 weeks (q2w) followed by 3 × cyclophosphamide (C)/methotrexate/5-fluorouracil (CMF, 600/40/600 mg/m2, q2w), or treatment B, i.e. 4 × E + C (C, 600 mg/m2) q3w followed by 3 × CMF q3w. Results: 113 patients in arm A and 113 patients in arm B were analysed after an updated median follow-up of 12.3 years. The median age was 55 years, with a median number of 6 +aLN, 50.4% had a T2 and 79.2% hormone receptor-positive BC. The disease-free survival (DFS) rate was 53.1% in arm A and 42.5% in arm B (adjusted p = 0.027). The overall survival (OS) rate was 54.9% in arm A and 48.7% in arm B (adjusted p = 0.058). In the multivariable analysis, the tumour burden was a significant predictor for DFS and OS. Conclusion: The adjuvant use of dd chemotherapy led to a statistically significant improvement of DFS after a follow-up of 12.3 years.

Prognostic and predictive impact of gene expression in node‐positive early breast cancer patients receiving dose‐dense versus standard‐dose adjuvant chemotherapy

“…We conducted a transcriptomic analysis of primary tumors collected from patients enrolled in a randomized, open‐label, multicenter, phase 3 trial, which has been reported previously [ 10 , 11 ]. Briefly, patients with nonmetastatic, resected, primary breast cancer, ≥ 4 involved axillary nodes, and no prior chemotherapy or radiotherapy were randomized to either ddCTX (four cycles of epirubicin plus paclitaxel followed by three cycles of cyclophosphamide, methotrexate, and 5‐fluorouracil [CMF], every 2 weeks) or stCTX (four cycles of epirubicin plus cyclophosphamide, followed by three cycles of CMF, every 3 weeks).…”

“…The clinical trial was conducted in accordance with the Declaration of Helsinki and had approval from independent ethics committees (IECs) at the study sites as well as written informed consent from patients [ 10 , 11 ]. The principal site, Charité Mitte Hospital, Berlin, Germany, acted as the repository for tumor samples and the use of these for prospective exploratory analysis was approved by the IEC (Ethikkommission der Charité – Universitaetsmedizin Berlin, Berlin, Germany; Approval Number: 57/97).…”

“…This treatment effect is better demonstrated through a Kaplan-Meier plot; OS was significantly longer with ddCTX in Table 1. Patient characteristics from the per-protocol population (N = 226) enrolled in the clinical trial [11,12] and from sub-cohort of patients (N = 141) whose tumors were analyzed using the BC360 TM comparison with stCTX in the HER2-E subtype (Fig. 3C).…”

“…In order to answer this question, we attempted to identify whether there was an association between treatment/survival outcomes and the expression of genes and gene signatures relevant to breast cancer in tumor samples collected during the course of a randomized phase 3 trial for which long-term follow-up was available [10,11]. We also explored prognostic/predictive associations within the intrinsic group subtypes who, due to the period of enrolment (1996)(1997)(1998)(1999)(2000), did not receive HER2-targeted therapy or platinum agents.…”

The impact of age group in breast cancer survival outcome according to neoadjuvant treatment response: A matched case–control study

“…Chemotherapy is an effective therapeutic option for invasive breast cancer. In the past, chemotherapy was considered as an effective adjuvant therapy after surgery 5 . Recently, neoadjuvant chemotherapy has been recommended as a treatment for patients with advanced breast cancer and greater tumor size 6,7 .…”