The study describes a relationship between the 3′UTR variants, clinicopathological parameters and response to chemotherapy. We analyzed 33 germline polymorphisms in 3′UTRs of ADME genes in 305 breast cancer women treated with FAC regime. Clinical endpoints of this study were: overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS) and overall response defined as treatment failure-free survival (TFFS). The shortened OS was connected with the presence of NR1/2 rs3732359 AA, SLC22A16 rs7756222 CC, as well as SLC22A16 rs9487402 allele G and clinical factors belonging to TNM classification: tumor size >1 cm, nodal involvement and presence of metastases. PFS was related to two polymorphisms PGR rs1824125 GG, PGR rs12224560 CC and SLC22A16 rs7756222 CC as well as preexisting metastases. The RFS was shortened due to the DPYD rs291593 CC, AKR1C3 rs3209896 AG and negative expression of PGR. The presence of ALDH5A1 rs1054899 allele A, lack of pre-chemotherapy surgery and negative status of PGR correlated with worse treatment response. The germline variants commonly present in the population are important factors determining the response to treatment. We observed the effect of the accumulation of genetic and clinical factors on poor survival prognosis and overall treatment response. Breast cancer usually affects women in postmenopausal period, although it is diagnosed increasingly in younger patients often in advanced clinical stages 1. The 5-year survival is around 80% in developed countries 2. Therapeutic strategies for breast cancer include targeted therapy, hormone therapy, radiotherapy, surgery and chemotherapy 1,3. Toxicity and resistance to chemotherapeutic drugs are common problems observed in patients during and after treatment. Lack of sensitivity to chemotherapy is most often associated with dysfunction of protein transporters that remove chemotherapeutic agents from the cells or DNA repair processes 4. The response to systemic treatment is different in patients with the same type of cancer, similar stage of disease and treated with the same medications. Lack of chemotherapy response is observed as cancer-related mortality, disease progression or recurrence 5,6. Metabolism, absorption, distribution and excretion (ADME processes) of drugs are regulated by genes and proteins responsible for biotransformation and metabolic elimination of drugs (enzymes cytochrome P450). Also, proteins belonging to ATP binding cassette (ABC) and solute carrier (SLC) control influx or efflux of toxin and medicines and their cellular distribution 7,8. The expression of ADME genes is regulated at the transcriptional and translational levels. In addition, they undergo posttranslational modifications. ADME dysfunction may lead to reduced drug efficacy or to an adverse drug reaction in pharmacotherapy 9,10. Genetic and epigenetic transformations of ADME genes can modulate the activity and therapeutic effects of chemotherapy and underline interpatient differences in response to therapy 5,11-13 .