Use of Olaparib in the Management of Metastatic Parathyroid Carcinoma With BRCA1 Mutation.

Abstract

Parathyroid carcinoma (PC) is a rare cause of primary hyperparathyroidism with a highly variable clinical course. We report the case of a man with metastatic PC who presented with severe hypercalcemia, discovered incidentally after a fall. He underwent left upper parathyroidectomy with left thyroid lobectomy, and pathology confirmed PC. After a year of absence from follow-up, he developed recurrence with bilateral pulmonary metastases. Cinacalcet and denosumab were initiated due to persistent, severe hypercalcemia, followed by wedge resection and palliative radiotherapy of pulmonary metastases. Genetic analysis revealed no actionable pathogenic variants, but a BRCA1 mutation classified as a variant of unknown significance (VUS) was identified. He was started on olaparib, a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, 3 years after initial diagnosis. Following this, his PTH level declined by approximately 40% within 7 months. Subsequently, his PTH levels began increasing despite continuation of olaparib and, after 20 months, rose to his original PTH level prior to the initiation of therapy. This is a unique case of a patient with metastatic PC who had a BRCA1 VUS mutation, with initial partial reduction in PTH and calcium levels after PARP inhibitor treatment.