Miyoshi Yasuo, Kurosumi Masafumi, Kurebayashi Junichi, Matsuura Nariaki, Takahashi Masato, Tokunaga Eriko, Egawa Chiyomi, Masuda Norikazu, Kim Seung Jin, Okishiro Masatsugu, Yanagisawa Tetsu, Ueda Satsuki, Taguchi Tetsuya, Tamaki Yasuhiro, Noguchi Shinzaburo
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Cancer Lett. 2008 Jun 8;264(1):44-53. doi: 10.1016/j.canlet.2008.01.015. Epub 2008 Feb 15.
Epirubicin exerts its anti-tumor effect through binding to topoisomerase IIalpha (TOP2A) and inducing DNA double-strand breaks. BRCA1 is involved in the repair of these breaks. We investigated the relationship between TOP2A or BRCA1 immunohistochemical expression and pathological response in 108 primary breast cancers treated with epirubicin-based regimens. The pCR (pathological complete response) rate for TOP2A-positive (17%) was significantly (P < 0.005) higher than for TOP2A-negative (2%), while the pCR rate for BRCA1-negative (11%) was non-significantly higher than for BRCA1-positive (5%). The pCR rate of TOP2A-positive and BRCA1-negative (30%) was significantly higher than for TOP2A-negative and BRCA1-positive (3%; P < 0.05), or TOP2A-negative and BRCA1-negative (0%; P < 0.005). The TOP2A-positive and BRCA1-negative phenotype associates with a favorable response to epirubicin-based regimens.
表柔比星通过与拓扑异构酶IIα（TOP2A）结合并诱导DNA双链断裂发挥其抗肿瘤作用。BRCA1参与这些断裂的修复。我们研究了108例接受以表柔比星为基础方案治疗的原发性乳腺癌中TOP2A或BRCA1免疫组化表达与病理反应之间的关系。TOP2A阳性患者的病理完全缓解（pCR）率（17%）显著高于TOP2A阴性患者（2%）（P<0.005），而BRCA1阴性患者的pCR率（11%）略高于BRCA1阳性患者（5%），差异无统计学意义。TOP2A阳性且BRCA1阴性患者的pCR率（30%）显著高于TOP2A阴性且BRCA1阳性患者（3%；P<0.05），或TOP2A阴性且BRCA1阴性患者（0%；P<0.005）。TOP2A阳性且BRCA1阴性表型与对以表柔比星为基础方案的良好反应相关。
