How a gBRCA2 Mutation and Targeted Therapies Prolonged Life Beyond Expectations

A 74-year-old woman was initially diagnosed with Stage IVB (FIGO 2014) high-grade serous carcinoma (HGSC), featuring multiple brain metastases, lung metastases, lymph node involvement, and rectal invasion. Genetic testing revealed a germline BRCA2 (gBRCA2) mutation, providing a critical target for personalized therapy. Early in her treatment, she underwent gamma knife irradiation to address the brain lesions and completed nine cycles of paclitaxel plus carboplatin (TC) chemotherapy.

Unfortunately, two years after this aggressive initial approach, the cancer recurred in the peritoneum. Her care team proceeded with six cycles of TC again, effectively shrinking the new tumors. Recognizing the importance of targeted maintenance therapy, they introduced the PARP inhibitor olaparib, capitalizing on her BRCA2 mutation. She remained on olaparib for seven months before discontinuing.

Forty-five months post-diagnosis, the disease resurfaced with additional peritoneal spread and multiple new lymph node metastases. At this point, she received four cycles of liposomal doxorubicin plus carboplatin (PLD-C) and progressed to a single cycle of gemcitabine. Despite these efforts, the patient passed away at 57 months post-diagnosis due to respiratory failure—yet throughout her extended survival, there was no evidence of brain metastasis recurrence.

Her case underscores the complexity of managing advanced ovarian cancer when it has spread to the brain. It also highlights how targeted approaches—including gamma knife radiotherapy, chemotherapy regimens, and PARP inhibitors—can significantly prolong survival and control CNS disease in patients with germline BRCA2 mutations. Although she ultimately succumbed to respiratory complications, her 57-month survival from initial diagnosis (and consistent absence of brain lesion recurrence) demonstrates the value of aggressive, personalized treatment strategies for advanced gynecologic cancers.