title: [Correlation of metastasis-free survival in patients with breast cancer and changes in the direction of expression of multidrug resistance genes during neoadjuvant chemotherapy].
abstract: Previously, we showed the association of neoadjuvant chemotherapy (NAC) response with changing the expression vector (increase or decrease) of multidrug resistance genes (MDR) in breast tumors during chemotherapy. The aim of the present study was to evaluate the relation between changes in the expression vector of MDR genes and distant metastasis-free survival. Patients (n = 120) with breast cancer (T1-4N0-3M0) treated by 2-4 cycles of NAC (CAX, FAC, and taxane regimes) and 4 cycles of adjuvant chemotherapy (FAC) were included. TaqMan-based quantitative reverse transcriptase PCR (qRT-PCR) was used to estimate the expression of the following MDR genes: ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2, GSTP1, and MVP--in biopsies before NAC and in tumor samples after chemotherapy. Comparing the corresponding expression levels allowed us to identify the vector of expression change during NAC. The results showed that 5-year distant metastasis-free survival was 73-78% in patients with a decrease in ABCB1, ABCC2, and ABCG1 expression. The up-regulation of these genes during NAC was related to a significant decrease (up to 50-55%) in metastasis-free survival (Kaplan-Meier analysis: log-rank p value = 0.006-0.03). The association of changing the expression vector of MDR genes with metastasis-free survival did not depend on tumor size, lymph node involvement, histological form, receptor status, molecular subtype, and others clinicopathological parameters of breast cancer. The obtained data suggest that changing the expression vector of MDR genes in breast tumors during NAC may be used as a new potential prognostic marker of breast cancer. An increase in tumor expression of ABCB1, ABCC2, and ABCG1 during chemotherapy is a factor of poor prognosis, whereas down-regulation of these genes--a favorable prognostic marker.
authors.forename: N V
authors.initials: NV
authors.lastname: Litviakov
authors.forename: E Iu
authors.initials: EIu
authors.lastname: Garbukov
authors.forename: E M
authors.initials: EM
authors.lastname: Slonimskaia
authors.forename: M M
authors.initials: MM
authors.lastname: Tsyganov
authors.forename: E V
authors.initials: EV
authors.lastname: Denisov
authors.forename: S V
authors.initials: SV
authors.lastname: Vtorushin
authors.forename: K Iu
authors.initials: KIu
authors.lastname: Khristenko
authors.forename: M V
authors.initials: MV
authors.lastname: Zav'ialova
authors.forename: N V
authors.initials: NV
authors.lastname: Cherdyntseva
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015536:Down-Regulation; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D015854:Up-Regulation
chemical_list: C000715087:ABCC2 protein, human; D014408:Biomarkers, Tumor; D000089762:Multidrug Resistance-Associated Protein 2; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil