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Candidate biomarkers predictive of anthracycline and taxane efficacy against breast cancer


1 Department of Thoracic, Breast and Endocrine Surgery, Kagawa University, Faculty of Medicine, Kita-gun; Department of Surgery, Takamatsu Red Cross Hospital, Takamatsu, Japan
2 Department of Thoracic, Breast and Endocrine Surgery, Kagawa University, Faculty of Medicine, Kita-gun, Japan
3 Department of Surgery, Takamatsu Red Cross Hospital, Takamatsu, Japan
4 Department of Surgery, Ito Breast Surgical Clinic, Kouchi, Japan
5 Department of Surgery, Kumegawa Hospital, Higashimurayama, Japan
6 Department of Thoracic and Endocrine Surgery and Oncology, Faculty of Medicine, University of Tokushima, Tokushima, Japan

Correspondence Address:
Keiichi Kontani,
Department of Thoracic, Breast and Endocrine Surgery, Kagawa University Faculty of Medicine, Kita-gun
Japan
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Source of Support: None, Conflict of Interest: None

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.


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    -  Norimura S
    -  Kontani K
    -  Kubo T
    -  Hashimoto Si
    -  Murazawa C
    -  Kenzaki K
    -  Liu D
    -  Tamaki M
    -  Aki F
    -  Miura K
    -  Yoshizawa K
    -  Tangoku A
    -  Yokomise H
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