Horimoto Y, Arakawa A, Harada-Shoji N, Sonoue H, Yoshida Y, Himuro T, Igari F, Tokuda E, Mamat O, Tanabe M, Hino O, Saito M
1] Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Br J Cancer. 2015 Jan 20;112(2):345-51. doi: 10.1038/bjc.2014.595. Epub 2014 Nov 25.
FOXA1 expression is a good prognostic marker for endocrine therapy in hormone-positive breast cancer. We retrospectively examined breast cancer patients with luminal human epidermal growth factor receptor 2 (HER2)-negative tumours, as defined by immunohistochemistry, who received neo-adjuvant chemotherapy (NAC) and investigated the relationship between treatment effects and FOXA1 expression.
Biopsy specimens from 103 luminal HER2-negative tumours were immunohistochemically examined. FOXA1 effects on chemo-sensitivity were also investigated employing in vitro experiments.
FOXA1 and Ki67 expressions independently predicted a pathological complete response (pCR). Knockdown of FOXA1 by siRNA boosted the chemo-effect in oestrogen receptor-positive cells. The Cox hazards model revealed a pCR to be the strongest factor predicting a good patient outcome.
Our present study showed low FOXA1 expression to be associated with a good response to NAC in luminal HER2-negative breast cancer. Improved outcomes of these patients suggest that NAC should be recommended to patients with low FOXA1 tumours.
FOXA1表达是激素阳性乳腺癌内分泌治疗的良好预后标志物。我们回顾性研究了经免疫组织化学定义为管腔型人表皮生长因子受体2（HER2）阴性肿瘤且接受新辅助化疗（NAC）的乳腺癌患者，并研究了治疗效果与FOXA1表达之间的关系。
对103例管腔型HER2阴性肿瘤的活检标本进行免疫组织化学检查。还采用体外实验研究了FOXA1对化疗敏感性的影响。
FOXA1和Ki67表达独立预测病理完全缓解（pCR）。通过小干扰RNA（siRNA）敲低FOXA1可增强雌激素受体阳性细胞的化疗效果。Cox风险模型显示pCR是预测患者良好预后的最强因素。
我们目前的研究表明，管腔型HER2阴性乳腺癌中低FOXA1表达与对NAC反应良好相关。这些患者预后的改善表明，应向FOXA1肿瘤低表达的患者推荐NAC。
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