Case Report: WIN-MTB-2024017 – WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers
Posted: Monday, July 27, 2026
WIN-MTB-2024017 – WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers
July 21, 2026
Oncotarget, 2026, Vol, pp: 17: 341-352
ABSTRACT
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.
INTRODUCTION
Patients who develop multiple cancers, often referred to as “multiple primary cancers” (MPC), represent a unique and challenging subset in oncology. MPC, defined as the occurrence of two or more distinct malignancies in the same patient, accounts for an estimated 2–17% of all cancers [1, 2]. Although relatively rare, MPC pose significant challenges in terms of diagnosis, treatment, and management. Patients diagnosed with one primary cancer have an elevated risk of developing additional primary malignancies, either synchronously (occurring within a short, predefined interval of the first primary tumor, commonly 2 months per SEER-criteria or 6 months per common international convention) or metachronously (occurring after that interval) [3, 4].
This phenomenon can arise from several factors, including genetic predispositions, environmental exposures, previous cancer treatments, and lifestyle factors [5, 6]. Inherited genetic mutations, such as those in the BRCA1/BRCA2 genes, significantly increase the risk of developing multiple types of cancers by impairing DNA repair mechanisms of the homologous recombination repair (HRR) pathway, leading to a higher likelihood of new, independent malignancies over time [2, 7–9]. Additionally, patients treated for one cancer, particularly with radiation or certain chemotherapies such as alkylating agents, platinum-based drugs and anthracycline topoisomerase II inhibitors, may have an elevated risk of developing a second malignancy due to induced DNA damage resulting in new cancer years later [10–13]. Continued exposure to carcinogens, such as tobacco smoke or certain occupational hazards, can also result in new primary cancers [14, 15]. Also, lifestyle factors such as diet, physical activity, and alcohol consumption may contribute to cancer development [16]. The presence of multiple malignancies complicates treatment, as therapies effective for one cancer might not be suitable for another, particularly if the cancers have differing molecular profiles [17]. This requires personalized treatment plans and close monitoring. Studies have shown that cancers in patients with MPC often present with unique molecular characteristics, and certain genetic alterations in a primary cancer may predispose patients to specific types of secondary cancers [1, 18–20].
Understanding and managing MPC is an evolving area of research, with ongoing studies aimed at personalizing treatment approaches and improving long-term outcomes for these patients, including immunotherapies and emerging strategies such as therapeutic cancer vaccines that target patient-specific tumor mutations [21–23].
We present here a case report discussed at the WIN Consortium’s International Molecular Tumor Board (MTB) with experts in precision oncology across the
world (Figure 1). This report builds on prior published WIN Consortium’s International MTB case reporting [24]. This case report presents the clinical journey of a 48-year-old female with a BRCA1 germline mutation who was initially diagnosed with breast cancer and subsequently developed skin, high grade serous carcinoma of the ovary, colon and small bowel cancers. We detail the patient’s relevant medical history, diagnostic workup and the various treatment approaches undertaken, including chemotherapy, targeted therapies and surgeries.
The international WIN MTB panel reviewed the patient’s medical history and genetic profile, discussing a range of treatment options including personalized
combination therapies and targeted therapies. The aim was to explore treatment strategies that are specifically tailored to the patient’s distinct genetic and molecular characteristics.
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