Impact of Expression Levels of Platinum-uptake Transporters Copper Transporter 1 and Organic Cation Transporter 2 on Resistance to Anthracycline/Taxane-based Chemotherapy in Triple-negative Breast Cancer

Breast Cancer: Basic and Clinical Research

Original Research

Satoru Shimizu¹  Kae Kawachi²  Naoki Ogane³  Yoichi Kameda⁴  Ayano Naka⁵  Risa Takeda⁵  Shingo Kamoshida⁵ 

[1] Department of Breast and Endocrine Surgery, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Japan.;Department of Pathology, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Japan.;Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Ashigarakami-gun, Kanagawa, Japan.;Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Ashigarakami-gun, Kanagawa, Japan.;Department of Pathology, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Japan.;Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan.;

关键词: copper transporter 1;    organic cation transporter 2;    platinum drug;    neoadjuvant chemotherapy;    triple-negative breast cancer;    immunohistochemistry;   

DOI  :  10.4137/BCBCR.S27534

 received in 2015-04-14, accepted in 2015-06-11,  发布年份 2015

来源: Sage Journals

【 摘 要 】

Adding platinum drugs to anthracycline/taxane (ANC-Tax)-based neoadjuvant chemotherapy (NAC) improves pathological complete response (pCR) rates in triple-negative breast cancer (TNBC). Copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2) critically affect the uptake and cytotoxicity of platinum drugs. We immunohistochemically determined CTR1 and OCT2 levels in pre-chemotherapy biopsies from 105 patients with HER2-negative breast cancer treated with ANC-Tax-based NAC. In the TNBC group, Ki-67high [pathological good response (pGR), P = 0.04] was associated with response, whereas CTR1high (non-pGR, P = 0.03), OCT2high (non-pGR, P = 0.01; non-pCR, P = 0.03), and combined CTR1high and/or OCT2high (non-pGR, P = 0.005; non-pCR, P = 0.003) were associated with non-response. In multivariate analysis, Ki-67high was an independent factor for pGR and CTR1 for non-pGR. Combined CTR1/OCT2 was a strong independent factor for non-pGR. However, no variables were associated with response in luminal BC. These results indicate that platinum uptake transporters are predominantly expressed in ANC-Tax-resistant TNBCs, which implies that advantage associated with adding platinum drugs may depend on high drug uptake.

【 授权许可】

CC BY-NC   
© 2015 SAGE Publications.

【 图 表 】

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