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

Risa Takeda; Ayano Naka; Naoki Ogane; Yoichi Kameda; Kae Kawachi; Satoru Shimizu; Shingo Kamoshida

doi:10.4137/BCBCR.S27534

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 (Auckl). 2015 Aug 4:9:49-57. doi: 10.4137/BCBCR.S27534. eCollection 2015.

Authors

Risa Takeda¹, Ayano Naka¹, Naoki Ogane², Yoichi Kameda³, Kae Kawachi⁴, Satoru Shimizu⁵, Shingo Kamoshida¹

Affiliations

¹ Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan.
² Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Ashigarakami-gun, Kanagawa, Japan.
³ Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Ashigarakami-gun, Kanagawa, Japan. ; Department of Pathology, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Japan.
⁴ Department of Pathology, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Japan.
⁵ Department of Breast and Endocrine Surgery, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Japan.

Abstract

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-67(high) [pathological good response (pGR), P = 0.04] was associated with response, whereas CTR1(high) (non-pGR, P = 0.03), OCT2(high) (non-pGR, P = 0.01; non-pCR, P = 0.03), and combined CTR1(high) and/or OCT2(high) (non-pGR, P = 0.005; non-pCR, P = 0.003) were associated with non-response. In multivariate analysis, Ki-67(high) 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.

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