Correlation of polymorphism C3435T of the MDR-1 gene and the response of primary chemotherapy in women with locally advanced breast cancer

Abstract

ABSTRACT. Primary chemotherapy is a useful strategy for the treatment of locally advanced breast cancer and therefore allows in vivo evaluation of the action of cytotoxic drugs and the possibility of accomplishing conservative breast surgeries, as well as the early treatment of metastasis. Mechanisms of resistance to the drugs include the action of protein associated with the efflux of drugs from the intracellular environment hindering their activity; one of the most studied proteins is P-glycoprotein codified by the MDR-1 gene. The presence of polymorphisms can determine different physiological actions of these proteins, intervening with the response of the drug's action. We evaluated the presence of single nucleotide polymorphism (SNP) C3435T of the MDR-1 gene and its correlation with the response to primary chemotherapy using the RECIST criteria. Forty-one Brazilian women with stages II and III breast cancer using the PCR-RFLP analysis were evaluated. Thirtythree patients with the SNP genotype (TT and CT) and eight patients with the wild genotype (CC) were found; there was no statistically significant correlation between the diverse genotypes and the clinical and pathological responses according to the Cramer correlation coefficient (V = 0.14). The parameters: nuclear and histological degree, and estrogens, progesterone and c-erb B2 receptors did not demonstrate a statistical correlation with the SNP C3435T. Patients with complete pathological response (12.5%) showed only the polymorphic genotype and not the wild genotype. The characteristics of miscegenation in our population could explain the absence of the characterization of a sub-group of individuals where the presence of the polymorphic genotype influenced the response to the primary chemotherapy.

MDR1 C3435T polymorphism in Mexican patients with breast cancer

“…However, allele and genotype frequencies differ among diverse populations with breast cancer (Ashariati, 2008;Rodrigues et al, 2008;George et al, 2009;Henríquez-Hernández et al, 2009;Taheri et al, 2010;Fang et al, 2013). In addition, we observed that the T/T genotype appears to have a protective effect in the FCC group, whereas no association was found with IDBC.…”

“…Clinical-pathological formation can result in several cancer types (Trock et al, 1997;Tatari et al, 2009;Rao et al, 2010;Sabahi et al, 2010;Mhaidat et al, 2011). Several studies have investigated the association of the C3435T polymorphism with breast cancer development, prognosis, and treatment outcome; however, the inconsistent and contradicting evidence has led to a confused picture (Turgut et al, 2007;Huang et al, 2008;Rodrigues et al, 2008;George et al, 2009;Taheri et al, 2010;Chen et al, 2012). In the present study, we analyzed the MDR1 C3435T polymorphism in Mexican women with IDBC or FCC as compared with healthy women.…”

MDR1 (C3435T) polymorphism: relation to the risk of breast cancer and therapeutic outcome

“…In contrast, Kafka et al 28 revealed that the TT genotype at position 3435 significantly correlated (P ¼ 0.029) with clinical complete response to preoperative chemotherapy with anthracyclines alone or in combination with taxanes. Rodrigues et al 29 did not find a significant correlation with SNP C3435T and clinical response in breast cancer patients, although the complete pathological response showed only the polymorphic genotype. It should be noted that nowadays breast cancer is detected in its earlier stages.…”

Pegylated liposomal doxorubicin as first-line monotherapy in elderly women with locally advanced or metastatic breast cancer: Novel treatment predictive factors identified

“…In accordance, Turgut et al [20] showed a trend toward a shorter PFS for breast cancer patients with 3435T/T compared to heterozygous and wild-type patients. They found no correlation between ABCB1 genotype and response, as also demonstrated by Rodrigues et al [21].…”