Annals of Oncology Advance Access originally published online on January 3, 2008
Annals of Oncology 2008 19(5):861-870; doi:10.1093/annonc/mdm551
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
breast cancer |
Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial
1 West German Study Group, Breast Centre, Department of Gynecology and Obstetrics
2 Department of Pathology, University Hospital, Duesseldorf
3 Department of Obstetrics and Gynecology, Technical University of Munich, Munich
4 Department of Clinical Genetics, University Hospital, Technical University, Dresden
5 Department of Hematology/Oncology, Catholic Hospital, Hagen
6 Department of Gynecology and Obstetrics, City Hospital, Offenbach
7 Department of Hematology/Oncology, University Hospital, Muenster
8 Department of Hematology/Oncology, Siloah Clinic, Hannover
9 Department of Hematology/Oncology, City Hospital, Oldenburg, Germany
* Correspondence to: Dr O. Gluz, West German Study Group, Breast Centre, University Hospital of Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany. Tel: +49-2161-5662311; Fax: +49-2161-5662319; E-mail: oleg.gluz{at}wsg-online.com
Background: This paper evaluates the prognostic and predictive impact of protein expression of various molecular markers in high-risk breast cancer (HRBC) patients with >9 involved lymph nodes, who received different chemotherapy dose-intensification strategies within a prospective randomized WSG AM-01 trial.
Materials and methods: Paraffin-embedded tumors from 236 patients, who were randomly assigned to dose-dense conventional chemotherapy with four cycles of E90C600 followed by three cycles of C600M40F600 every 2 weeks (DD) or a rapidly cycled tandem high-dose regimen with two cycles of E90C600 every 2 weeks followed by two cycles of E90C3000Thiotepa400 every 3 weeks (HD), were available for retrospective central pathological review (116 HD/120 DD). Expression of estrogen receptor (ER), progesterone receptor (PR), MIB-1, epidermal growth factor receptor, and Her-2/neu was evaluated immunohistochemically using tissue microarrays. Results were correlated with follow-up data and treatment effects by proportional hazard Cox regression models (including interaction analysis).
Results: After a median follow-up of 61.7 months, 5-year event-free survival (EFS) as well as overall survival (OS) rates for the 236 patients were significantly better in the HD arm: EFS: 62% versus 41% [hazard ratio (HR) = 0.60, 95% CI 0.43–0.85, P = 0.004]; OS: 76% versus 61% (HR = 0.58, 95% CI 0.39–0.87, P = 0.007). In multivariate analysis, HD, tumor size <3 cm, positive PR, negative MIB-1 staining, and grade 1/2 were associated with favorable outcome. Interaction analysis showed that regarding predictive effects, triple negative (ER/PR/Her-2/neu) and G3 tumors derived most benefit from HD.
Conclusion: Tandem HD improves both EFS and OS in HRBC. This therapy effect may be partly attributable to superior efficacy in the subgroup of triple-negative tumors and/or G3 with their poor prognostic marker profile.
Key words: basal-like, breast cancer, high dose chemotherapy, triple negative, breast cancer
Received for publication July 28, 2007. Accepted for publication November 2, 2007.