BRCA mutation as a predictor of systemic therapy response in a patient with synchronous multiple primary cancer (breast, ovarian, and gastric cancer)

Synchronous multiple primary malignancies (MPM) represent an increasingly relevant challenge in oncology due to rising the incidence and complexity of selecting optimal therapy. Germline mutations in BRCA1/2 genes are associated with a higher risk of breast and ovarian cancers and may serve as predictors of sensitivity to systemic therapies, including platinum-based chemotherapy and PARP inhibitors. We present a case of a 63-year-old female patient with MPM, including stage IV serous ovarian carcinoma with metastases in mediastinal lymph nodes, stage IIA breast carcinoma, and signet-ring cell gastric carcinoma stage IIB. Next-generation sequencing (NGS) identified a germline BRCA1 mutation (c.5382_5383insC). The patient received six cycles of paclitaxel plus carboplatin chemotherapy, resulting in a significant reduction of ovarian and breast tumor lesions by more than threefold and stabilization of the gastric tumor as assessed by imaging. Following partial response, radical surgical treatment was performed, including distal subtotal gastrectomy with D2 lymphadenectomy, hysterectomy with bilateral salpingo-oophorectomy, and right mastectomy. Considering the detected BRCA1 mutation, maintenance therapy with the PARP inhibitor olaparib was administered for 24 months in combination with aromatase inhibitors. During two years of follow-up, no disease progression was observed, the therapy was well tolerated, and adverse effects were limited to grade 1 anemia. This case highlights the clinical value of molecular genetic testing and a multidisciplinary approach in patients with MPM. Identification of a germline BRCA1 mutation allowed for selection of an effective systemic therapy, including platinum-based agents and a PARP inhibitor, achieving durable remission in the context of multiple synchronous primary tumors. The report underscores the importance of personalized treatment strategies for patients with synchronous multiple malignancies.

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