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Takeda R, Naka A, Ogane N, et al. 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;9:49-57doi: 10.4137/BCBCR.S27534.
Takeda, R., Naka, A., Ogane, N., Kameda, Y., Kawachi, K., Shimizu, S., & Kamoshida, S. (2015). 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, 949-57. https://doi.org/10.4137/BCBCR.S27534
Takeda, Risa, et al. "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 vol. 9 (2015): 49-57. doi: https://doi.org/10.4137/BCBCR.S27534
Takeda R, Naka A, Ogane N, Kameda Y, Kawachi K, Shimizu S, Kamoshida S. 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 04;9:49-57. doi: 10.4137/BCBCR.S27534. eCollection 2015. PMID: 26309405; PMCID: PMC4527352.
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Breast Cancer (Auckl). 2015 Aug 04;9:49-57. doi: 10.4137/BCBCR.S27534. eCollection 2015.

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

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

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.

PMID: 26309405 PMCID: PMC4527352 DOI: 10.4137/BCBCR.S27534

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

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