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Case Reports
. 2021 Nov 27:14:5353-5360.
doi: 10.2147/OTT.S334847. eCollection 2021.

Favorable Response to Olaparib in a Patient with Cancer of Unknown Primary Carrying a Germline BRCA1 R71K Mutation

Xiaomeng Jia #  1 , Shanshan Zhao #  1 , Xiang Li #  2 , Li Lv #  3 , Xin Chen  4 , Evenki Pan  4 , Qiuxiang Ou  4 , Chen Song  1 , Siwen Sun  1 , Jinbo Zhao  1 , Lingzhi Xu  1 , Man Li  1
Affiliations
Case Reports

Favorable Response to Olaparib in a Patient with Cancer of Unknown Primary Carrying a Germline BRCA1 R71K Mutation

Xiaomeng Jia et al. Onco Targets Ther. .

Abstract

The treatment options for cancer of unknown primary (CUP) are challenging due to the lack of knowledge about the primary sites, often resulting in a poor prognosis. The emerging next-generation sequencing (NGS) technique has provided a reliable approach to facilitate tumor primary site prediction and targetable gene alteration identification for CUP patients. In this report, we described a 63-year-old female patient who experienced recurrent CUP. NGS-based genetic profiling results revealed a pathogenic germline BRCA1 R71K mutation. Accordingly, the patient received the poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib treatment and demonstrated a favorable response to this treatment. Our case suggests that NGS holds great promise for providing improved diagnosis and treatment options to patients with CUP, warranting further clinical investigation.

Keywords: BRCA1 germline mutation; cancer of unknown primary; next-generation sequencing; olaparib.

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Conflict of interest statement

Xin Chen, Evenki Pan, and Qiuxiang Ou are employees of Nanjing Geneseeq Technology Inc., China. The remaining authors have no competing interests to declare.

Figures

Figure 1
Figure 1
Timeline of treatment with radiography of responses and CA125 concentration. (A) Timeline of treatment and corresponding MRI. (B) Timeline of treatment and corresponding CA125 concentration.
Figure 2
Figure 2
Imaging examinations during the treatment. (A) MRI and PET-CT evaluation at the time of the patient’s initial admission in October 2012. (B) H&E and IHC staining in October 2012. The p40-positive cells are pointed by the red triangles. (C) MRI evaluation in July 2017 and PET-CT evaluation in May 2019. (D) H&E and IHC staining in November 2019. Scale bars represent 200 µm.
Figure 3
Figure 3
Diagrams of mutations identified in NGS testing. (A) Schematic diagram of the R71K mutation in full-length BRCA1 (adopted from cBioPortal MutationMapper https://www.cbioportal.org/mutation_mapper, retrieved on Nov. 3, 2021). (B) Abundance change of TP53 S241C in the time course of olaparib treatment. The ctDNA abundance measured by each NGS test is represented by the dot.
See this image and copyright information in PMC

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