Predictive factors for anthracycline-based chemotherapy for human breast cancer |
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Authors: | Yasuo Miyoshi Masafumi Kurosumi Junichi Kurebayashi Nariaki Matsuura Masato Takahashi Eriko Tokunaga Chiyomi Egawa Norikazu Masuda Seishi Kono Koji Morimoto Seung Jin Kim Masatsugu Okishiro Tetsu Yanagisawa Satsuki Ueda Tetsuya Taguchi Yasuhiro Tamaki Shinzaburo Noguchi |
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Affiliation: | 1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan 2. Department of Pathology, Saitama Cancer Center, Saitama, Japan 3. Department of Breast and Thyroid Surgery, Kawasaki Medical School, Matsushima, Kurashiki, Okayama, Japan 4. Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University, Osaka, Japan 5. First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan 6. Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan 7. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan 8. Department of Surgery, Osaka National Hospital, Osaka, Japan
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Abstract: | Predictive factors for anthracycline-based chemotherapy have yet to be incorporated into daily practice. Meta-analyses of studies using anthracycline-based treatment regimens have shown an improved prognosis for human epidermal growth factor receptor type 2 (HER2)-positive tumors, but not for HER2-negative tumors compared with results of non-anthracycline regimens. Currently it is believed that the positive association between HER2 status and anthracycline sensitivity is indirect, that is, their association may be mediated through topoisomerase II alpha (TOP2A), a target molecule of anthracyclines, since TOP2A is near HER-2 and co-amplification of the TOP2A gene frequently occurs in HER2-amplified tumors. This strongly suggests that TOP2A gene amplification is a predictive factor for anthracyline-based regimens. The Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society has demonstrated that TOP2A-positive and BRCA1-negative subsets evaluated by immunohistochemical staining show a significantly higher pathological complete response when treated with preoperative epirubicin-containing regimens. Combining these findings with the observation that triple-negative tumors and basal-like tumors respond to anthracycline treatment suggests that not only HER2-positive tumors but also a distinct subset of HER2-negative tumors may be sensitive to anthracycline-based regimens. |
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