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Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid
Rosemary Noel Senguttuvan1, Christina Wei2, Mustafa Raoof1
1Department of Surgery, City of Hope Comprehensive Cancer Center (COH), Duarte, CA 91010, USA.
Abstract:
Treatment for endometrial cancer is rapidly evolving with the increased use and integration of somatic tumor RNA sequencing in clinical practice. There is a paucity of data regarding PARP inhibition in endometrial cancer given that mutations in homologous recombination genes are rare, and currently no FDA approval exists. A 50-year-old gravida 1 para 1 woman with a diagnosis of stage IVB poorly differentiated endometrioid endometrial adenocarcinoma presented to our comprehensive cancer center. Following surgical staging, she was placed on adjuvant chemotherapy with carboplatin/paclitaxel which was held multiple times due to poor performance status and complications. CT scan of the abdomen and pelvis following cycles 3 of adjuvant chemotherapy showed recurrent progressive disease. She received one cycle of liposomal doxorubicin but discontinued it due to severe cutaneous toxicity. Based on the BRIP1 mutation identified, the patient was placed on compassionate use of Olaparib in January 2020. Imaging during this surveillance period showed a significant decrease in hepatic, peritoneal, and extraperitoneal metastases, and eventually the patient had a clinical complete response in a year. The most recent CT A/P in December 2022 showed no sites of active recurrent or metastatic disease in the abdomen or pelvis. We present a unique case of a patient with recurrent stage IVB poorly differentiated endometrioid endometrial adenocarcinoma with multiple somatic gene mutations including BRIP1, who had a pathologic complete response following compassionate use of Olaparib for 3 years. To our knowledge, this is the first reported case of high grade endometrioid endometrial cancer that has shown a pathologic complete response to a PARP inhibitor.
Insights
This case study shows a patient with advanced endometrial cancer achieving a complete response to Olaparib, a PARP inhibitor, highlighting its potential in treating BRIP1-mutated tumors.
Area of Science:
- Oncology
- Genomics
- Cancer Therapeutics
Background:
- Endometrial cancer treatment is evolving with genomic profiling.
- PARP inhibitors have limited data in endometrial cancer due to rare homologous recombination gene mutations.
- No FDA approval currently exists for PARP inhibitors in this indication.
Observation:
- A patient with stage IVB poorly differentiated endometrioid endometrial adenocarcinoma presented with recurrent disease after standard chemotherapy.
- The patient had multiple somatic gene mutations, including BRIP1.
- Standard treatments were complicated by poor performance status and toxicity.
Findings:
- Compassionate use of Olaparib (a PARP inhibitor) was initiated based on the BRIP1 mutation.
- Significant decrease in metastases was observed on imaging.
- The patient achieved a clinical complete response within a year and maintained it for 3 years.
Implications:
- This case suggests PARP inhibition may be effective in a subset of endometrial cancers with specific mutations like BRIP1.
- It highlights the potential of targeted therapy in advanced or recurrent endometrial cancer.
- Further research is warranted to explore PARP inhibitors in endometrial cancer treatment strategies.
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