Single Nucleotide Polymorphism Directed Antiemetic Treatment in Women With Breast Cancer Treated With Neo- or Adjuvant Chemotherapy: A Randomised Multicentre Phase II Study. (EudraCT: 2015–000658-39)

Abstract

Background/Aim: The role of single nucleotide polymorphisms (SNPs) in the frequency and intensity of chemotherapy-induced nausea and vomiting (CINV) in women with breast cancer (BC) is unclear. The primary purpose of this study was to compare/evaluate the effect of SNP-guided antiemetic treatment versus standard CINV treatment. Patients and Methods: A randomised, factorial, phase II multicentre study design was used. Women planned for neoadjuvant or adjuvant chemotherapy with epirubicin, cyclophosphamide and fluorouracil (FEC /EC, with or without fluorouracil) for BC were randomised to SNP-guided antiemetic treatment (based on the results of SNP analyses) versus standard CINV treatment. Blood samples were taken before the treatment was initiated. Patient-reported data on CINV (during 10 days from onset of cancer treatment) and health-related quality of life (HRQoL), were collected before and after the first cancer treatment. Results: A total of 188 women were included. Overall, nausea was reported by 86% (n=129) of the patients during the ten-day period from the start of cancer treatment. The SNP genotype studied varied. In FAS-CD95, the genotypes AG and GG were overrepresented; in RB1-LPAR6, GG was overrepresented, and in CCL2, both AA and GG were overrepresented. We found no statistically significant difference in CINV between SNP-guided antiemetic treatment versus standard CINV treatment. Conclusion: SNP-guided antiemetic treatment could be as effective as standard treatment. SNPguided antiemetic treatment of CINV is possibly useful in detecting patients with a higher or lower risk for CINV and thus may help in avoiding over-treatment with toxic components. CINV negatively affects the HRQL.Chemotherapy-induced nausea and vomiting (CINV) varies in both incidence and intensity between individuals. The development of antiemetic drugs has been significant over the past 30 years. The most common drug combination for CINV is a combination of NH1 receptor antagonist, 5-HT3 receptor antagonist, and some form of corticosteroids (1). Even though treatment has improved significantly with these treatment protocols, CINV remains a clinical problem (2), negatively affecting many cancer patients' daily lives.

Causal effects and metabolites mediators between immune cell and risk of breast cancer: a Mendelian randomization study

“…Moreover, SNPs may influence the response of patients with BC to treatment. Some SNPs could affect the activity of drug-metabolizing enzymes, thus impacting drug concentrations and efficacy in vivo, ultimately affecting treatment effects and prognosis for patients with BC Frontiers in Genetics frontiersin.org (Noguchi et al, 2009;Duong et al, 2023;Oliva et al, 2023). These genes as mentioned, which could be influenced by SNPs and had an impact on the pathogenesis and treatment of BC, include noncoding genes and genes encoding protein, such as those in our research.…”