Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial.

Abstract

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 E(90)C(600) followed by three cycles of C(600)M(40)F(600) every 2 weeks (DD) or a rapidly cycled tandem high-dose regimen with two cycles of E(90)C(600) every 2 weeks followed by two cycles of E(90)C(3000)Thiotepa(400) 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.

• Authors: O Gluz, U A Nitz, N Harbeck, E Ting, R Kates, A Herr, W Lindemann, C Jackisch, W E Berdel, H Kirchner, B Metzner, F Werner, G Schütt, M Frick, C Poremba, R Diallo-Danebrock, S Mohrmann, West German Study Group
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 19 Issue 5 Pg. 861-70 (May 2008) ISSN: 1569-8041 [Electronic] England
• PMID: 18174609 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Biomarkers, Tumor
• Estrogens
• Neoplasm Proteins
• Tamoxifen
• Granulocyte Colony-Stimulating Factor
• Epirubicin
• Cyclophosphamide
• Fluorouracil
• Methotrexate

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (chemistry, drug therapy, pathology, radiotherapy)
• Carcinoma (chemistry, drug therapy, pathology, radiotherapy)
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage)
• Dose-Response Relationship, Drug
• Epirubicin (administration & dosage)
• Estrogens
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Kaplan-Meier Estimate
• Methotrexate (administration & dosage)
• Middle Aged
• Neoplasm Proteins (analysis)
• Neoplasms, Hormone-Dependent (drug therapy, radiotherapy)
• Proportional Hazards Models
• Retrospective Studies
• Single-Blind Method
• Survival Analysis
• Tamoxifen (administration & dosage)
• Treatment Outcome