Shoko Norimura1, Keiichi Kontani2, Takako Kubo3, Shin-Ichiro Hashimoto2, Chisa Murazawa2, Koichiro Kenzaki3, Dage Liu2, Masafumi Tamaki3, Fuminori Aki4, Kazumasa Miura3, Kiyoshi Yoshizawa5, Akira Tangoku6, Hiroyasu Yokomise2. 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.
Abstract
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.
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.
Entities:
Keywords:
Anthracycline; beta-tubulin; breast cancer; predictive biomarker; taxane; tissue inhibitor of metalloprotease-1; topoisomerase-II alpha
Authors: Carlos A Barrón-Gallardo; Mariel Garcia-Chagollán; Andres J Morán-Mendoza; Raul Delgadillo-Cristerna; María G Martínez-Silva; Adriana Aguilar-Lemarroy; Luis F Jave-Suárez Journal: Technol Cancer Res Treat Date: 2022 Jan-Dec