BACKGROUND: Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy. METHODS: One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods. RESULTS: Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs. CONCLUSION: GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.
BACKGROUND: Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancerpatients receiving EPI/CTX chemotherapy. METHODS: One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods. RESULTS:Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs. CONCLUSION:GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.
Authors: Mohammad F Al-Harras; Maha E Houssen; Mohamed E Shaker; Kamel Farag; Omar Farouk; Rehan Monir; Rasha El-Mahdy; Ekbal M Abo-Hashem Journal: Oncol Lett Date: 2016-01-28 Impact factor: 2.967
Authors: Daniela Polessa Paula; Vanessa I do Brasil Costa; Rosane V Jorge; Flávio F Nobre Journal: Support Care Cancer Date: 2019-05-06 Impact factor: 3.603
Authors: Anubha Saxena; Varinderpal S Dhillon; Mohammad Shahid; Hesham Saleh Khalil; Madhu Rani; Trinath Prasad DAS; Suresh Hedau; Arif Hussain; Raza Ali Naqvi; S V S Deo; N K Shukla; B C DAS; Syed Akhtar Husain Journal: Exp Ther Med Date: 2012-09-17 Impact factor: 2.447