Abstract Background Solid organs recipients with subsequent cancer comprise a group of patients with unmet medical needs: they lack any clinical trials or guidelines for treatment. There are only individual case reports in literature. Meanwhile their number is growing due to achievements in transplantology and improved cancer diagnosis. Case presentation А young 34-year-old female attended our center in September 2019 with a palpable mass and peau d'orange of the left breast. A core-needle biopsy of the left breast mass revealed invasive ductal carcinoma G3, estrogen receptor 7 (Allred), progesterone receptor 6 (Allred), HER-2 (3+), Ki-67 49%. Left axillary lymph node biopsy revealed metastatic breast cancer. After a complete examination the clinical stage was cT4bN1fM0, IIIB stage. The patient had a history of Type 1 diabetes mellitus since 2003 leading to multiple complications including terminal diabetic nephropathy, which required renal replacement therapy with the use of long-term hemodialysis since July 2014. The other complications consisted of severe retinopathy with corneal transplantation on the left eye in April 2013, an episode of right eye hemophthalmia in March 2016 with consequent loss of vision in the right eye, polyneuropathy, gastropathy and enteropathy. The patient underwent a simultaneous pancreas-kidney transplantation in April, 2016 and was on permanent immunosuppressive therapy with tacrolimus 8 mg daily and methylprednisolone 8 mg daily. The function of both transplants was satisfactory. This unique case was published by Pinchuk A. et al. in Transplant Proceedings, 2017 [doi: 10.1016/j.transproceed.2017.10.005]. A multidisciplinary approach was applied to tailoring treatment plan for this patient. Initially immunosuppressive therapy was modified: the patient discontinued methylprednisolone and started everolimus with simultaneous tacrolimus dose reduction (their doses adjusted according to blood concentrations). The tumor board decision was to start neoadjuvant therapy with regimen with the mildest and the most manageable toxicity profile and to avoid anthracyclines. From October to December 2019 the patient received 12 cycles of paclitaxel 80 mg/m2 day 1 weekly and 4 cycles of anti-HER2 dual blockade: trastuzumab 8 mg/kg day 1 followed by 6 mg/kg day 1 every 21 days + pertuzumab 840 mg day 1 followed by 420 mg day 1 every 21 days. Adverse events were: stomatitis grade 1, palmar-plantar erythrodysesthesia grade 1, diarrhea grade 2. Partial response was evaluated in the end of December 2019, but due to persistent skin edema, she was not a candidate for surgical treatment. The tumor board decision was to proceed with T-DM1 + pertuzumab based on the results of the KRISTINE trial [doi:10.1016/s1470-2045(17)30716-7]. From January to March 2020 the patient received 4 cycles of trastuzumab-emtansine 3,6 mg/kg day 1 every 21 days + pertuzumab 420 mg day 1 every 21 days. The patient tolerated this treatment with mild toxicity: ALT & AST increase grade 2 and diarrhea grade 2. Considering that the edema was significantly reduced, surgical treatment was planned. The patient underwent a modified radical mastectomy for left breast cancer on 14 of April 2020. The pathological stage was ypT1аN0 R0, RCB I. The patient continued trastuzumab emtansine until November 2020 (up to 1 year of anti-HER2 targeted therapy) in the adjuvant setting. In June 2020 she underwent locoregional radiation therapy. Tamoxifen with ovarian function suppression (LHRH agonists) for 5 years was started in June 2020. Fortunately, after 3 years of follow-up after surgery there is no evidence of disease and no delayed cancer treatment complications. Conclusion: Personalized multidisciplinary team decisions for cancer patients after organ transplantation are crucial to further improve the long-term outcome of these patients. Citation Format: Lyudmila Zhukova, Natalya Polshina. Successful outcome of locally advanced HR+HER2+ breast cancer treatment in a young female after pancreas-kidney transplantation. 3-year follow-up [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-09.