Centromere protein-A, an essential centromere protein, is a prognostic marker for relapse in estrogen receptor-positive breast cancer.

Abstract

INTRODUCTION:

Centromere protein A (CENP-A), an essential centromere protein, has been associated with high grade cancers. This study was undertaken to determine if CENP-A is a prognostic factor for breast cancer patients not receiving systemic therapy or predictive of response to tamoxifen or neoadjuvant chemotherapy.

METHODS:

mRNA levels of CENP-A and CENP-B, a centromere protein that binds independently of CENP-A, were measured in breast cancer specimens from 484 patients receiving no systemic therapy, 276 patients receiving tamoxifen, and 233 patients treated with neoadjuvant chemotherapy. Associations between CENP-A, CENP-B, Ki-67, relapse, and chemotherapy response were determined.

RESULTS:

CENP-A but not CENP-B was higher in estrogen receptor (ER)-negative tumors than ER-positive tumors and positively correlated with Ki-67 expression. Among patients with ER-positive disease who received no systemic therapy or tamoxifen, higher levels of CENP-A were associated with lower rates of 5-year distant relapse free survival (DRFS). On multivariate analyses including Ki-67, high CENP-A expression had a hazard ratio of 10.9 for relapse in patients with ER-positive disease not receiving systemic therapy (95% CI, 2.86 to 41.78; P = 0.00047) and 1.64 for patients with ER-positive disease receiving tamoxifen (95% CI, 0.99 to 2.71; P = 0.054). CENP-A was not an independent prognostic marker in ER-negative tumors. For both ER-positive and ER-negative tumors, CENP-A was not a significant independent predictor of chemotherapy response.

CONCLUSIONS:

CENP-A was a significant independent prognostic marker for patients with ER-positive breast cancer not treated with systemic therapy but had limited predictive value in tamoxifen treated patients and was not predictive of response to neoadjuvant chemotherapy.

• Authors: Susan L McGovern, Yuan Qi, Lajos Pusztai, William F Symmans, Thomas A Buchholz
• Journal: Breast cancer research : BCR (Breast Cancer Res) Vol. 14 Issue 3 Pg. R72 (May 04 2012) ISSN: 1465-542X [Electronic] England
• PMID: 22559056 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Hormonal
• Autoantigens
• Biomarkers, Tumor
• CENPA protein, human
• Centromere Protein A
• Centromere Protein B
• Chromosomal Proteins, Non-Histone
• Ki-67 Antigen
• RNA, Messenger
• Receptors, Estrogen
• Tamoxifen

Topics

• Adult
• Aged
• Antineoplastic Agents, Hormonal (therapeutic use)
• Autoantigens (genetics, metabolism)
• Biomarkers, Tumor (analysis, genetics)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Centromere Protein A
• Centromere Protein B (genetics, metabolism)
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Ki-67 Antigen (metabolism)
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (genetics)
• RNA, Messenger (biosynthesis)
• Receptors, Estrogen (genetics, metabolism)
• Tamoxifen (therapeutic use)