Exceptional Response to Olaparib in a Patient With Recurrent Ovarian Cancer and an Entire BRCA1 Germline Gene Deletion

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  • a Department of Internal Medicine;
  • b Division of Hematology, Oncology, and Stem Cell Transplant Medicine, Department of Internal Medicine; and
  • c Department of Pathology, Rush University Medical Center, Chicago, Illinois.
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PARP inhibitors are known to be effective in patients with ovarian cancer (OC) and germline mutations in BRCA1 and BRCA2 genes (BRCA mutations). Little is known, however, about any correlation between the deletion size and location of the BRCA mutation and the response to PARP inhibitors. Women with OC commonly undergo genetic testing because the presence of a germline BRCA mutation impacts therapeutic decisions and is important for cancer surveillance in patients and their family members. This report presents a case of a rare entire germline BRCA1 gene deletion and an exceptional response to a PARP inhibitor, olaparib, in a heavily pretreated patient with OC. Her disease course was also remarkable for complete responses to platinum-based chemotherapy and long chemotherapy-free intervals. Interestingly, the deletion of the entire BRCA1 gene was found after previously negative BRCA test results and is associated with a deletion of 6 adjacent genes without known clinical significance. She has remained progression-free and asymptomatic for >3 years on olaparib, with an overall survival of >12 years. We postulate that this unusually favorable response and prolonged overall survival is related to the cancer cells’ inability to reverse the entire gene deletion to wild-type (a common mechanism of resistance to PARP inhibition). This case shows the value of genetic testing for patients with OC and highlights the utility of additional testing with previously negative results and limited genetic testing. It also provides insight into a potential mechanism of an exceptional response to PARP inhibition.

Submitted June 30, 2019; accepted for publication November 11, 2019.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Megan Randall, MD, Department of Internal Medicine, Rush University Medical Center, 1700 West Van Buren Street, Suite 500, Chicago, IL 60612. Email: megan_e_randall@rush.edu
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