Measuring β-tubulin III, Bcl-2, and ERCC1 improves pathological complete remission predictive accuracy in breast cancer.

Abstract

Weekly PCb (paclitaxel + carboplatin) in neoadjuvant chemotherapy (NCT) for breast cancer has a high pathological complete remission (pCR) rate. The present study was to identify pCR predictive biomarkers and to test whether integrating candidate molecular biomarkers can improve the pCR predictive accuracy. Ninety-one breast cancer patients treated with weekly PCb NCT were retrospectively analyzed. Eleven candidate molecular biomarkers (Tau, β-tubulin III, PTEN, MAP4, thioredoxin, multidrug resistance-1, Ki67, p53, Bcl-2, BAX, and ERCC1) were detected by immunohistochemistry in pre-NCT core needle biopsy specimens. We analyzed the relationship between these biomarkers and pCR. Univariate analysis showed that estrogen receptor, progesterone receptor, molecular classification (clinicopathological markers), and Tau, β-tubulin III, p53, Bcl-2, ERCC1 (candidate molecular biomarkers) expression were associated with pCR rate; however, multivariate analysis revealed that only β-tubulin III, Bcl-2, and ERCC1 were independent pCR predictive factors. Patients with β-tubulin III negative, Bcl-2 negative, or ERCC1 negative tumors were associated with higher pCR rate, with OR (odds ratios) 6.03 (95% confidence interval [CI], 1.44-25.24, P = 0.014), 7.54 (95% CI, 1.52-37.40, P = 0.013), and 4.09 (95% CI, 1.17-14.30, P = 0.028), respectively. To compare different logistic regression models, built with different combinations of these variables, we found that the model integrating routine clinical and pathological variables, as well as the β-tubulin III, Bcl-2, ERCC1 molecular biomarkers had the highest pCR predictive power. The area under the ROC curve for this model was 0.900 (95% CI, 0.831-0.968), indicating that it deserves further investigation. Trial name: Weekly Paclitaxel Plus Carboplatin in Preoperative Treatment of Breast Cancer.

• Authors: Xiaosong Chen, Jiayi Wu, Hongfen Lu, Ou Huang, Kunwei Shen
• Journal: Cancer science (Cancer Sci) Vol. 103 Issue 2 Pg. 262-8 (Feb 2012) ISSN: 1349-7006 [Electronic] England
• PMID: 22035021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Estrogen
• Receptors, Progesterone
• Tubulin
• Tumor Suppressor Protein p53
• Carboplatin
• ERCC1 protein, human
• Endonucleases
• Paclitaxel

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor
• Biopsy, Needle
• Breast Neoplasms (drug therapy, metabolism, mortality, pathology)
• Carboplatin (therapeutic use)
• DNA-Binding Proteins (analysis)
• Disease-Free Survival
• Endonucleases (analysis)
• Female
• Humans
• Middle Aged
• Paclitaxel (therapeutic use)
• Prognosis
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• Receptors, Estrogen (biosynthesis)
• Receptors, Progesterone (biosynthesis)
• Retrospective Studies
• Tubulin (biosynthesis)
• Tumor Suppressor Protein p53 (biosynthesis)