s / The Breast 22 S3 (2013) S19–S63 S61 rs1801133 Methylenetetrahydrofolate reductase (MTHFR) is a relatively common well-known single nucleotide polymorphism (SNP) of methylenetetrahydrofolate reductase (MTHFR) gene. This gene encodes an enzyme that takes part in folate metabolism. Homozygous rs1801133 (T:T) individuals have approximately 35% MTHFR enzyme activity. Heterozygous (C:T) have 65% enzyme activity. However the most common genotype is (C:C). Reduced MTHFR activity has been linked to several diseases such as coronary artery disease, depression, migraine, cleft palate, hyperhomocysteinemia, and neural tube defects. In addition, several studies reported a relationship between MTHFR polymorphism and several types of cancer including gastric, bladder, breast, head and neck and ovarian. However, the clinical relevance of these results is debated. In this study we studied the role of rs1801133 SNP in metastatic and relapsed breast cancer patients. It is well-known that one of the major prognostic and predictive indicators in breast cancer is lymph node metastasis, and relapses in cancers are stemmed from micrometastasis. Actually the aim of adjuvant treatment is to eradicate these micrometastatic cancer cells. If there are micrometastases and the treatment we give does not eradicate these cells, relapses occur. However, adjuvant treatments do not show the same effect in all cases because of several reasons. The possible reasons are host-related factors, cancer type and histology, and drug resistance. Drug-resistance may be the only compatible factor that we can deal with different treatment strategies. Based on this background we retrospectively analyzed the metastatic patients of whom that we had their genetic profile. We compared the breast cancer patients who were metastatic at diagnosis and node-positive patients who had relapsed after adjuvant treatment, to node-positive patients who were relapse-free at least for 3 years. All node-positive patients we included in this study received chemotherapy (AC, EC, AC-T, EC-T), and trastuzumab and hormonal treatments according to their tumor immunochemistry. We found significantly different relapse ratios between the patients with different MTHFR SNPs. Among node-positive patients (101) who received AC-T or EC-T the differences were significant (p=0.01). The relapse ratio is 32% (26/54) in (C:C) profile, 32% (20/41) in (C:T) profile, and 68% (13/6) in (T:T) profile. However, in patients who were metastatic at the time of the diagnosis the ratios were insignificant, which were 15.1 in (C:C) profile, 13.6 in (C:T) profile and 12.6 in (T:T) profile. Our results showed no SNP difference among the patients who were metastatic at the time of the diagnosis, and showed significant difference among the patients who relapsed after adjuvant chemotherapy. The results noted a significantly high relapse ratios in (T:T) profile which has the lowest MTHFR enzyme activity. We believe that this difference may occur from drug resistance or from reduced drug effect with reduced MTHFR enzyme activity.