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[Background]In adjuvant settings of HER2 positive cancer, trastuzumab has been shown to be effective in combination with anthracycline- based chemotherapy followed by taxane-based chemotherapy. However, the role of anthracyclines for the treatment of breast cancer has remained in controversy,due to the increased risk of cardiotoxicity and secondary carcinogenesis. Recently, additional anthracycline-free treatment regimens have also been reported. In a single-arm multicenter trial of 406 patients treated with paclitaxel plus trastuzumab for Citation Format: Watanuki R, Hayashida T, Yuko K, Kikuchi M, Nakashoji A, Yokoe T, Toyota T, Seki T, Takahashi M, Kitagawa Y. Optimal omission of anthracycline in adjuvant chemotherapy of HER2 positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-11.

Background Azathioprine (AZA) is an immunosuppressant with indications for use including inflammatory bowel disease (IBD), organ transplantation and systemic lupus erythematosus (SLE). Following oral administration, AZA is converted into its active form, 6-thioguanine nucleotides (6-TGNs), inside red blood cells. One enzyme in this pathway is thiopurine S-methyltransferase (TPMT). IBD and SLE patients with low TPMT activity show an increased intracellular concentration of 6-TGNs and thus tend to respond well to low dose AZA therapy. Moreover, in a previous study of SLE patients received low dose AZA therapy, we found that the group with the 94C >A mutation in inosine triphosphatase (ITPA) showed greater improvement in their disease activity index. Purpose AZA is increasingly being prescribed to rheumatoid arthritis (RA) patients who cannot take methotrexate, but it is not yet clear how genotypes relate to responsiveness to RA treatment. This clinical study was conducted to determine whether genetic polymorphism of AZA metabolising enzymes affects response to RA treatment. Material and methods PCR-RFLP analysis of 22 RA patients was performed to determine whether they had the mutations TPMT*3C and ITPA 94C >A. The relationship between these genotypes and response to AZA therapy was evaluated on the basis of pre- and post-treatment disease activity measured by the DAS28 scale and various other types of medical information. This study was conducted with research ethics committee approval. Results Of the 22 patients, none had the TPMT*3C mutation, 15 had the ITPA 94C/C genotype (wild type; WT group) and 7 had the ITPA 94C/A genotype (mutant type; MT group). The groups showed a similar change in DAS28 score at 6 months after the start of treatment (−1.6 ± 2.1 vs −1.9 ± 2.2; p = 0.39). However, the AZA dose during the treatment period was significantly lower in the MT group at 0.85 ± 0.30 mg/kg/day compared with the WT group at 1.2 ± 0.46 mg/kg/day (p = 0.043). Conclusion We found the MT group of patients showed the same response to treatment as the WT group but at a lower dose. This demonstrates that RA patients with the ITPA 94C >A mutation are also more responsive to AZA. References and/or Acknowledgements This study was supported by JSPS KAKNHI, grant No 15K18933 No conflict of interest.