Measuring β-tubulin III, Bcl-2, and ERCC1 improves pathological complete remission predictive accuracy in breast cancer.
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.
Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaosong
X
Chen
Jiayi
J
Wu
Hongfen
H
Lu
Ou
O
Huang
Kunwei
K
Shen
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016190:Carboplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000032:analysis*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000032:analysis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D012189:Retrospective Studies; D014404:Tubulin / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel