Syed N, Chintakuntlawar AV, Vilasini D, Al Salami AM, Al Hasan R, Afrooz I, Uttam Chandani K, Chandani AU, Chehal A. Low testing rates and high BRCA prevalence: Poly (ADP-ribose) polymerase inhibitor use in Middle East BRCA/homologous recombination deficiency-positive cancer patients. World J Clin Oncol 2024; 15(7): 848-858 [PMID: 39071455 DOI: 10.5306/wjco.v15.i7.848]
Corresponding Author of This Article
Naveed Syed, DNB, Doctor, MBBS, Attending Doctor, Department of Hematology and Oncology, Sheikh Shakbout Medical City, Mafraq Area, Abu Dhabi 11001, United Arab Emirates. naveed3642003@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Jul 24, 2024; 15(7): 848-858 Published online Jul 24, 2024. doi: 10.5306/wjco.v15.i7.848
Low testing rates and high BRCA prevalence: Poly (ADP-ribose) polymerase inhibitor use in Middle East BRCA/homologous recombination deficiency-positive cancer patients
Naveed Syed, Department of Hematology and Oncology, Sheikh Shakbout Medical City, Abu Dhabi 11001, United Arab Emirates
Ashish Vittalrao Chintakuntlawar, Department of Oncology, Mayo Clinic, Rochester, NY 790339, United States
Deepti Vilasini, Aisha Mohamed Al Salami, Riad Al Hasan, Ashok Uttam Chandani, Aref Chehal, Department of Oncology, Sheikh Shakbout Medical City, Abu Dhabi 11001, United Arab Emirates
Imrana Afrooz, Clinical Research, Sheikh Shakbout Medical City, Abu Dhabi 11001, United Arab Emirates
Kanishka Uttam Chandani, Department of Internal Medicine, Landmark Medical Center, Rhode Island, RI 02895, United States
Author contributions: Syed N contributed to the conceptualization of the study, design of the methodology, formal analysis of the data, and original drafting of the manuscript as well as review and editing of the successive versions; Chintakuntlawar AV contributed to the design of the methodology, formal analysis of the data, review and editing of the successive versions of the manuscript, and supervision of the overall project; Vilasini D provided resources for the study and contributed to the review and editing of the successive versions of the manuscript; Al Salami AM, Al Hasan R, Uttam Chandani K and Chandani AU provided resources for the study; Afrooz I contributed to the original drafting of the manuscript as well as review and editing of the successive versions, provided resources for the study, and performed supervision of the overall project; Chehal A contributed to the conceptualization of the study and design of the methodology, provided resources for the study, and participated in the review and editing of the successive versions and to the supervision of the overall project.
Institutional review board statement: This study was approval by the Ethics Committee of Sheikh Shakhbout Medical City (No. SSMCREC-384).
Informed consent statement: The Informed consent statement was waived by the Ethics Committee of Sheikh Shakhbout Medical City.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The data used in this retrospective study are deposited and available in the Mendley Data platform, accessible at the following DOI: 10.17632/pd4n24wh7t.1. All patient data were anonymized prior to deposit in the Mendeley Data platform.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Naveed Syed, DNB, Doctor, MBBS, Attending Doctor, Department of Hematology and Oncology, Sheikh Shakbout Medical City, Mafraq Area, Abu Dhabi 11001, United Arab Emirates. naveed3642003@gmail.com
Received: March 23, 2024 Revised: May 14, 2024 Accepted: June 14, 2024 Published online: July 24, 2024 Processing time: 114 Days and 16.6 Hours
Abstract
BACKGROUND
Poly (ADP-ribose) polymerase inhibitors (PARPis) are approved as first-line therapies for breast cancer gene (BRCA)-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. They are also effective for new and recurrent ovarian cancers that are BRCA- or homologous recombination deficiency (HRD)-positive. However, data on these mutations and PARPi use in the Middle East are limited.
AIM
To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.
METHODS
This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations, and 25 of 65 ovarian cancer patients tested for HRD. These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023. Data were summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.
RESULTS
Among the 472 breast cancer patients, 12.1% underwent BRCA testing, and 38.5% of 65 ovarian cancer patients received HRD testing. Pathogenic mutations were found in 25.6% of the tested patients: 26.3% breast cancers had germline BRCA (gBRCA) mutations and 24.0% ovarian cancers showed HRD. Notably, 40.0% of gBRCA-positive breast cancers and 66.0% of HRD-positive ovarian cancers were Middle Eastern and Asian patients, respectively. PARPi treatment was used in 5 (33.3%) gBRCA-positive breast cancer patients as first-line therapy (n = 1; 7-months progression-free), for maintenance (n = 2; > 15-months progression-free), or at later stages due to compliance issues (n = 2). Four patients (66.6%) with HRD-positive ovarian cancer received PARPi and all remained progression-free.
CONCLUSION
Lower testing rates but higher BRCA mutations in breast cancer were found. Ethnicity reflected United Arab Emirates demographics, with breast cancer in Middle Eastern and ovarian cancer in Asian patients.
Core Tip: Following National Comprehensive Cancer Network guidelines, breast cancer patients were tested for BRCA1/2 mutations, while ovarian cancer patients underwent homologous recombination defect testing. These mutations can be targeted with poly (ADP-ribose) polymerase inhibitor (PARPi) therapy, a form of precision medicine. In this single-center study, we analyzed the proportion of breast and ovarian cancer patients tested for mutations, demographics and disease characteristics of tested patients, and PARPi therapy outcomes. This first-of-its-kind study in the Middle East offers insights into targeted therapy use, contributing to knowledge on PARPis for breast and ovarian cancers.