WIN-MTB-2024017 - WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers.

Copyright: © 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Multiple primary cancers (MPC), the occurrence of two or more distinct malignancies in the same patient, pose significant clinical challenges due to their complexity and the need for individualized treatment strategies. This case, discussed at the WIN Consortium International Molecular Tumor Board, illustrates the clinical journey of a 48-year-old female with a BRCA1 germline mutation who developed multiple primary cancers: breast, skin, high-grade serous carcinoma of the ovary, colon and small bowel cancers. Her treatment history included doxorubicin and cyclophosphamide for breast cancer, Mohs surgery for basal cell carcinoma, and carboplatin and paclitaxel for ovarian cancer. After participating in the PRIMA trial with niraparib, she was diagnosed with PIK3CA-mutated colon cancer, leading to resection and CAPOX chemotherapy. A subsequent diagnosis of small bowel adenocarcinoma, molecularly resembling her colon cancer, along with a unique BRCA1-STARD3 fusion in inguinal lymph nodes prompted a comprehensive MTB review. The panel discussed several precision strategies, including combinations of cetuximab, niraparib, and temsirolimus; FOLFIRI with anti-EGFR inhibitors; anti-CTLA-4 and anti-PD-1 (botensilimab and balstilimab); regorafenib with anti-CTLA-4 and anti-PD-1 (ipilimumab and nivolumab); trifluridine/tipiracil with bevacizumab; regorafenib alone; aspirin for potential benefits in patients with PIK3CA mutations; therapies targeting PIK3CA and EGFR alterations; regular imaging and liquid biopsies assessments for monitoring disease progression and guide future treatment decisions; and vaccines targeting PIK3CA, STARD3 and TP53. This case underscores the complexity of managing MPC and highlights the essential role of international molecular tumor boards in generating innovative, tailored treatment recommendations for patients with rare and multifaceted disease courses.