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


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).


CONCLUSIONS
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.
Turner
B C
BC
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
Krajewski
S
S
Krajewska
M
M
Takayama
S
S
Gumbs
A A
AA
Carter
D
D
Rebbeck
T R
TR
Haffty
B G
BG
Reed
J C
JC
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy; D002352:Carrier Proteins / Q000032:analysis*; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D012189:Retrospective Studies; D014157:Transcription Factors
C091732:BCL2-associated athanogene 1 protein; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors