Abstract
Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic cancer that disproportionately affects patients with advanced breast cancer. Moreover, those with BRCA1/2-mutated disease more often experience leptomeningeal metastasis. Treatment options for LC are limited and often include significant toxicities. PARP inhibitors offer an important potential treatment for patients with BRCA1/2-mutated breast and ovarian cancers, but clinical studies excluded patients with central nervous system (CNS) metastases, including LC. Efficacy data in this area are therefore limited, although a phase I study of olaparib in glioblastoma did show CNS penetration. Here we report a case of a patient with BRCA2-mutated breast cancer and solitary recurrence in the leptomeninges with ongoing complete response to treatment with the PARP inhibitor olaparib. PARP inhibitors may be an important treatment option for patients with BRCA-mutated disease and LC, and warrant further study.
Highlights
Leptomeningeal carcinomatosis (LC) is a complication of advanced cancer that carries a poor prognosis and most commonly affects patients with breast cancer.[1,2] in a retrospective case series of 103 consecutive unselected patients with LC from breast cancer, median overall survival was only 3.8 months, less than even the already poor estimates reported among selected patients enrolled in prospective randomized trials.[3]
human epidermal growth factor receptor 2 (HER2) amplification followed by trastuzumab treatment, and good initial performance status has been associated with a better prognosis in patients with breast cancer LC
Data suggest that patients with BRCA1/2 mutations and metastatic breast cancer develop central nervous system (CNS) involvement, and that BRCA2 mutation carriers develop CNS metastases at a higher frequency than non-carriers when controlling for subtype.[16]
Summary
Leptomeningeal carcinomatosis (LC) is a complication of advanced cancer that carries a poor prognosis and most commonly affects patients with breast cancer.[1,2] in a retrospective case series of 103 consecutive unselected patients with LC from breast cancer, median overall survival was only 3.8 months, less than even the already poor estimates reported among selected patients enrolled in prospective randomized trials.[3]. Some studies have demonstrated that cytologic and clinical response are both associated with improvement in survival.[15] Data suggest that patients with BRCA1/2 mutations and metastatic breast cancer develop CNS involvement, and that BRCA2 mutation carriers develop CNS metastases at a higher frequency than non-carriers when controlling for subtype.[16]
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