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J Clin Oncol. 2008 Nov 1;26(31):5027-35. doi: 10.1200/JCO.2007.14.6597. Epub 2008 Sep 2.

Type 1 receptor tyrosine kinase profiles identify patients with enhanced benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial.

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  • 1Endocrine Cancer Research Group, Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh, UK. John.Bartlett@ed.ac.uk

Abstract

PURPOSE:

Patients with early breast cancer who receive anthracycline-containing chemotherapy experience improved relapse-free (RFS) and overall survival (OS) compared with those who receive non-anthracycline-containing chemotherapy. Such benefit, however, may be restricted to women whose tumors have specific molecular characteristics. We tested the hypothesis that HER2, epidermal growth factor receptor (EGFr)/HER1, HER3, Ki67, and topoisomerase IIalpha expression are predictive of outcome after anthracycline-based chemotherapy.

METHODS:

Tissue microarrays from 322 of 374 women in the BR9601 trial, which compared cyclophosphamide, methotrexate, and fluorouracil (CMF) with epirubicin followed by CMF (epi-CMF), were analyzed for HER1, 2, 3, 4; Ki67; and topoisomerase IIalpha protein expression and for HER2/topoisomerase IIalpha gene amplification. Their relationships to RFS and OS were investigated, and multiple regression analysis was used to identify interactions.

RESULTS:

A significant interaction was seen between tumors with normal HER1, HER2 fluorescent in situ hybridization (FISH), or HER3 levels and the enhanced benefit from epi-CMF versus CMF for RFS (hazard ratio [HR], 0.36; HR for overexpressed HER1 or HER2 FISH or HER3, 0.92; P = .035) and for OS (HR, 0.30; HR for overexpressed HER1 or HER2 FISH or HER3), 0.98; P = .023). Neither Ki67 nor TIIalpha expressions or gene alterations showed clear predictive value for benefit from the addition of the anthracycline.

CONCLUSION:

Patients with HER2 amplified and those with HER1, HER2 FISH, or HER3-positive tumors did not benefit from the addition of epirubicin to CMF. Conversely, patients with HER2 nonamplified and HER1 through HER3-negative tumors showed significantly increased RFS and OS rates when treated with epi-CMF compared with CMF.

PMID:
18768436
DOI:
10.1200/JCO.2007.14.6597
[PubMed - indexed for MEDLINE]

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