Annals of Oncology Advance Access originally published online on May 25, 2009
Annals of Oncology 2009 20(8):1344-1351; doi:10.1093/annonc/mdp024
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breast cancer |
The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up
1 Department of Medicine, Research Unit in Medical Senology, European Institute of Oncology, Milan, Italy
2 International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, USA
3 Department of Medicine, Division of Hematology–Oncology, European Institute of Oncology, Milan, Italy
4 Centre for Developmental Cancer Therapy, The Royal Melbourne Hospital, Parkville, Australia
5 International Breast Cancer Study Group, Bern, Switzerland
6 School of Public Health, University of Sydney, Australia
7 International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Boston, MA, USA
8 Department of Hematology and Medical Oncology, The Royal Melbourne and Western Hospitals, Victoria, Australia
9 Division of Medical Oncology and Breast Unit, San Antonio Perrino Hospital, Brindisi, Italy
10 Department of Medical Oncology, University Hospital, Bern
11 Swiss Group for Clinical Cancer Research (SAKK), Berne, Switzerland
12 Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy
13 International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA
14 Department of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
* Correspondence to: Dr. M. Colleoni, Research Unit in Medical Senology, Department of Medicine, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy. Tel. +39-02-57489970 Fax. +39-02-574829212; E-mail: marco.colleoni{at}ieo.it
Background: The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established.
Patients and methods: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m2 plus cyclophosphamide 4 mg/m2 with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features.
Results: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58–1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03).
Conclusions: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.
Key words: adjuvant treatment, dose-intensive chemotherapy, early breast cancer, endocrine responsiveness
Received for publication November 20, 2008. Revision received January 9, 2009. Accepted for publication January 16, 2009.