Role of ABCB1 and ABCC1 gene induction on survival in locally advanced breast cancer.
Drug resistance to chemotherapy in patients with locally advanced breast cancer results in a decrease in treatment efficacy and in patient survival. This study aimed to evaluate the impact of ABCB1 and ABCC1 gene induction during chemotherapy on disease-free and overall survival of breast cancer patients. Patients with locally advanced breast cancer were prospectively included. All patients were preoperatively treated with chemotherapy and underwent mastectomy. ABCB1 and ABCC1 gene and protein expressions were evaluated both before and after chemotherapy and investigated as molecular predictive parameters affecting diseasefree and overall survival. ABCB1 and ABCC1 gene expressions were evaluated with RTPCR following RNA isolation from tissue samples. P-glycoprotein and MRP1 in tissues were detected using immunohistochemistry. Twenty-five female patients treated with either doxorubicin or epirubicin were included. Median follow-up time was 36 months during which 11 patients (44%) had recurrence, all of whom died. Mean disease-free survival for patients with and without ABCB1 gene induction was 13 and 55 months (p=0.0004), respectively, whereas overall survival was 21 and 57 months (p=0.0025), respectively. Mean disease-free survival for patients with and without ABCC1 gene induction was 32 and 48 months (p=0.97), respectively, and overall survival was 43 and 49 months (p=0.36), respectively. ABCB1 gene induction decreases disease-free and overall survival in patients with locally advanced breast cancer due to anthracycline resistance. Detecting ABCB1 gene expression during chemotherapy helps to increase the efficacy of drug treatment by choosing the appropriate drugs resulting in prolonged survival.
Atalay
C
C
Department of General Surgery, Ankara Oncology Hospital, Ankara, Turkey. atalay_can@hotmail.com
Demirkazik
A
A
Gunduz
U
U
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008408:Mastectomy; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D015251:Epirubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1