Hashimoto Yumi, Tatsumi Shigenobu, Takeda Risa, Naka Ayano, Ogane Naoki, Kameda Yoichi, Kawachi Kae, Shimizu Satoru, Sakai Mai, Kamoshida Shingo
Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe, Hyogo, 654-0142, Japan.
Breast Cancer Res Treat. 2014 May;145(1):101-11. doi: 10.1007/s10549-014-2913-y. Epub 2014 Mar 27.
Organic anion-transporting polypeptide 1A2 (OATP1A2) and organic cation transporter 6 (OCT6) are involved in the uptake of taxanes and anthracyclines, respectively. The aim of this study was to evaluate expression levels of OATP1A2 and OCT6 as a predictor of response to neoadjuvant chemotherapy (NAC) in breast cancer. A total of 124 patients who received anthracycline/taxane-based NAC were included. Expression levels of OATP1A2 and OCT6 were immunohistochemically assessed in core needle biopsies obtained prior to NAC. A pathologic good response (pGR) and a pathologic complete response (pCR) were achieved in 24 and 10 % of patients, respectively. In univariate analysis of the entire cohort, negative hormone receptor (HR) status (pGR and pCR, P < 0.001), high Ki-67 level (pGR, P = 0.03; pCR, P = 0.02), triple negative (TN) subtype (pGR, P = 0.001; pCR, P < 0.001), and high OCT6 (pGR, P = 0.003) were associated with the response. In combined analysis, high OATP1A2/high OCT6 level was also a significant factor for pGR (P = 0.001) and pCR (P = 0.001). Two separate multivariate analyses showed that HR status, TN subtype and combined high OATP1A2/high OCT6 level were significant independent predictors. When TN and non-TN tumors were assessed separately in univariate analysis, high Ki-67 level (P = 0.04) were associated with pGR and combined high OATP1A2/high OCT6 level was associated with both pGR (P = 0.005) and pCR (P = 0.03) in the TN group. Multivariate analysis identified the combined high OATP1A2/high OCT6 level as the sole independent predictor of pGR. In the non-TN group, negative HR status (P = 0.03) and positive HER2 status (P = 0.005) were associated with pGR, but HER2 status was the sole independent predictor of pGR. These results suggest that response-associated predictors may differ between the TN and non-TN tumors. Combined high OATP1A2/high OCT6 may be a potential predictor of response to anthracycline/taxane-based chemotherapy in breast cancer, especially in TN tumors.
有机阴离子转运多肽1A2（OATP1A2）和有机阳离子转运体6（OCT6）分别参与紫杉烷类和蒽环类药物的摄取。本研究旨在评估OATP1A2和OCT6的表达水平，作为乳腺癌新辅助化疗（NAC）反应的预测指标。共纳入124例接受蒽环类/紫杉烷类为基础的NAC治疗的患者。在NAC之前获取的粗针活检组织中，通过免疫组织化学方法评估OATP1A2和OCT6的表达水平。分别有24%和10%的患者达到病理良好反应（pGR）和病理完全缓解（pCR）。在整个队列的单因素分析中，激素受体（HR）阴性状态（pGR和pCR，P<0.001）、高Ki-67水平（pGR，P = 0.03；pCR，P = 0.02）、三阴性（TN）亚型（pGR，P = 0.001；pCR，P<0.001）以及高OCT6水平（pGR，P = 0.003）与反应相关。在联合分析中，高OATP1A2/高OCT6水平也是pGR（P = 0.001）和pCR（P = 0.001）的显著因素。两项独立的多因素分析表明，HR状态、TN亚型以及高OATP1A2/高OCT6联合水平是显著的独立预测因素。在单因素分析中分别评估TN和非TN肿瘤时，高Ki-67水平（P = 0.04）与TN组的pGR相关，高OATP1A2/高OCT6联合水平与TN组的pGR（P = 0.005）和pCR（P = 0.03）均相关。多因素分析确定高OATP1A2/高OCT6联合水平是pGR的唯一独立预测因素。在非TN组中，HR阴性状态（P = 0.03）和HER2阳性状态（P = 0.005）与pGR相关，但HER2状态是pGR的唯一独立预测因素。这些结果表明，TN和非TN肿瘤之间与反应相关的预测因素可能不同。高OATP1A2/高OCT6联合水平可能是乳腺癌中蒽环类/紫杉烷类为基础化疗反应的潜在预测指标，尤其是在TN肿瘤中。
