Candidate biomarkers predictive of anthracycline and taxane efficacy against breast cancer

• Published in: Journal of cancer research and therapeutics Vol. 14; no. 2; pp. 409 - 415
• Main Authors: Norimura, Shoko, Kontani, Keiichi, Kubo, Takako, Hashimoto, Shin-ichiro, Murazawa, Chisa, Kenzaki, Koichiro, Liu, Dage, Tamaki, Masafumi, Aki, Fuminori, Miura, Kazumasa, Yoshizawa, Kiyoshi, Tangoku, Akira, Yokomise, Hiroyasu
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.01.2018; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd
• Subjects: Adult; Aged; Anthracyclines; Anthracyclines - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological markers; Biomarkers; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Bridged-Ring Compounds - administration & dosage; Cancer therapies; Chemotherapy; Disease; DNA Topoisomerases, Type II - metabolism; Dosage and administration; Drug therapy; Female; Health aspects; Hospitals; Humans; Immunoglobulins; Immunohistochemistry; Laboratories; Medical prognosis; Medicine; Metastasis; Methods; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Patient outcomes; Patients; Poly-ADP-Ribose Binding Proteins - metabolism; Prognosis; Receptor, ErbB-2 - metabolism; Surgery; Taxoids - administration & dosage; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Treatment Outcome; Tumors; Japan; Anthracycline; topoisomerase-II alpha; breast cancer; beta-tubulin; predictive biomarker; taxane; tissue inhibitor of metalloprotease-1
• ISSN: 0973-1482; 1998-4138
• DOI: 10.4103/jcrt.jcrt_1053_16

Background: Since breast cancer shows diversity in clinical behaviors, a standard therapy does not always lead to favorable outcomes. Materials and Methods: The expression statuses of candidate markers, including topoisomerase-II alpha (TOP2A), beta-tubulin (B-tub), and tissue inhibitor of metalloprotease-1 (TIMP-1), were immunohistochemically evaluated in 70 breast cancer tissues from 68 patients with advanced breast cancers receiving chemotherapy. Results: The response rates to anthracycline and taxane were 70.5% and 67.2%, respectively. Overall, 25.1% ± 29.7%, 8.32% ± 10.1%, and 16.37% ±17.5% of cancer cells in the tumors studied were positive for B-tub, TOP2A, and TIMP-1 expressions, respectively. However, positive molecule expression did not differ between patients who did and did not exhibit clinical responses to treatment. The proportion of TOP2A-positive cancer cells was significantly higher among anthracycline responders than among nonresponders in HR-negative cancer (15.4% ±17.5% vs. 2.0% ± 2.4%, respectively, P = 0.048), whereas TOP2A and TIMP-1 expression statuses did not differ in HR-positive cancer. When patients were stratified according to B-tub, TOP2A, or TIMP-1 expression statuses (B-tub ≥10% vs. <10%, TOP2A ≥5% vs. <5%, TIMP-1 ≤20% vs. >20%, respectively), the proportion of patients with ≥10% B-tub-positive cancer cells was significantly higher in taxane responders than in nonresponders (72.4% vs. 37.5%, respectively, P = 0.016). Anthracycline responders showed a trend to have a higher proportion of patients with either ≥5% TOP2A-positive cancer cells or ≤20% TIMP-1-positive cancer cells compared to nonresponders (86.7% vs. 61.5%, respectively, P = 0.066). Conclusion: Immunohistochemical TOP2A, TIMP-1, and B-tub expression analyses are expected to be useful for predicting tumor responses to chemotherapy.