Germline Mutations Associated with Triple Negative Breast Cancer in US Hispanic and Guatemalan Women using Hospital and Community-Based Recruitment Strategies

Purpose Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer. We evaluated hospital and community-based recruitment strategies. Methods We used targeted gene sequencing to identify mutations in DNA from unselected Hispanic breast cancer cases from community and hospital-based recruitment in the US and Guatemala. Results We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2 , and ATM . In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic mutations (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (P<0.001). Conclusions Guatemalan and US Hispanic women have rates of hereditary breast cancer mutations similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under NCI Contract No. 75N910D00024. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of the National Cancer Institute approved the study. [ClinicalTrials.gov][1] Identifier: [NCT01251900][2]) and the research committees of the Instituto de Cancerologia and the Guatemalan Ministry of Health. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01251900&atom=%2Fmedrxiv%2Fearly%2F2023%2F07%2F03%2F2023.07.01.23292051.atom