BAG-1: a novel biomarker predicting long-term survival in early-stage breast cancer.

Abstract

PURPOSE:

Among women with early-stage breast cancer treated with lumpectomy and radiation therapy, 30% to 40% will develop metastatic disease, which is often fatal. A need exists therefore for biomarkers that distinguish patients at high risk of relapse. We performed a retrospective correlative analysis of BAG-1 protein expression in breast tumors derived from a cohort of early-stage breast cancer patients.

PATIENTS AND METHODS:

Archival paraffin blocks from 122 women with stages I to II breast cancer treated with lumpectomy and radiation therapy (median follow-up, 12.1 years) were analyzed by immunohistochemical methods using monoclonal antibodies recognizing BAG-1 and other biomarkers, including Bcl-2, estrogen receptor, progesterone receptor, p53, and HER2/Neu. Immunostaining data were correlated with distant metastasis-free survival (DMFS) and overall survival (OS).

RESULTS:

Cytosolic immunostaining for BAG-1 was upregulated in 79 (65%) of 122 invasive breast cancers (P <.001) compared with normal breast. Elevated BAG-1 was significantly associated with longer DMFS and OS, overall (stages 1 and II) and in node-negative (stage I only) patients, on the basis of univariate and multivariate analyses (DMFS, P =.005; OS, P =.01, in multivariate analysis of all patients; DMFS, P =.005; OS, P =.001, in multivariate analysis of node-negative patients). All other biomarkers failed to reach statistical significance in multivariate analysis. Clinical stage was an independent predictor of OS (P =.04) and DMFS (P =.02).

CONCLUSION:

These findings provide preliminary evidence that BAG-1 represents a potential marker of improved survival in early-stage breast cancer patients, independent of the status of axillary lymph nodes.

• Authors: B C Turner, S Krajewski, M Krajewska, S Takayama, A A Gumbs, D Carter, T R Rebbeck, B G Haffty, J C Reed
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 4 Pg. 992-1000 (Feb 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11181661 (Publication Type: Evaluation Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• BCL2-associated athanogene 1 protein
• Biomarkers, Tumor
• Carrier Proteins
• DNA-Binding Proteins
• Transcription Factors

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (diagnosis, drug therapy, mortality, radiotherapy)
• Carrier Proteins (analysis)
• Combined Modality Therapy
• DNA-Binding Proteins
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Lymphatic Metastasis
• Mastectomy, Segmental
• Middle Aged
• Retrospective Studies
• Transcription Factors