title: Expression of organic anion-transporting polypeptide 1A2 and organic cation transporter 6 as a predictor of pathologic response to neoadjuvant chemotherapy in triple negative breast cancer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Tatsumi
authors.forename: Risa
authors.initials: R
authors.lastname: Takeda
authors.forename: Ayano
authors.initials: A
authors.lastname: Naka
authors.forename: Naoki
authors.initials: N
authors.lastname: Ogane
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.forename: Kae
authors.initials: K
authors.lastname: Kawachi
authors.forename: Satoru
authors.initials: S
authors.lastname: Shimizu
authors.forename: Mai
authors.initials: M
authors.lastname: Sakai
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D027361:Organic Anion Transporters / Q000096:biosynthesis*; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis*; D012189:Retrospective Studies; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C467737:SLC22A16 protein, human; C512988:SLCO1A2 protein, human