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

[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.

[发布日期] 2015-01-01

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