Abstract PO1-08-08: Hereditary cancer genetic testing in Puerto Rican females
Authors: Cox Hannah , Hartzfeld Deborah , Gessy Shawn , Zaleski Christina , Machado Jerry 
Published: May 2024

Background: Puerto Rico is a Caribbean Island and unincorporated United States territory with a population of approximately 3.2 million. The incidence of breast cancer in Puerto Rico is estimated at 57.5 per 100,000 females with a mortality rate of 13.0 per 100,000 females. A recent study of hereditary breast and ovarian cancer syndrome across countries in the Caribbean reported a combined positive detection rate of 14.2% using a similar multi-gene panel to the one described here. Positive rates ranged from 5.5% to 28.3% per country, but sample sizes were limited, ranged from 61 to 298 participants per country, and did not include Puerto Rico. To provide insight into the incidence of inherited tumor predisposition syndromes in less studied populations, we analyzed the demographics and germline genetic findings for a cohort of Puerto Rican females largely ascertained based on a personal and/or family history of breast cancer. Methods: This retrospective study includes 949 consecutive female individuals who underwent genetic testing at a single clinical laboratory (PreventionGenetics LLC) using a multi-gene panel test of 29 genes associated with hereditary cancer. Clinical information was obtained from health care provider-completed test requisition forms. Next Generation Sequencing (NGS) with copy number variant (CNV) detection was performed on patient-derived DNA using the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA) and Sanger sequencing as necessary. Results: The median age at testing was 55.5 years and ranged from 19.1 to 90.0 years of age. Of the total cohort, 713 (75.1%) individuals had a personal history of breast cancer with or without additional cancer types; 43 (4.5%) individuals had non-cancerous breast findings, and 49 (5.2%) individuals had a personal history of other types of cancer(s). The remaining 144 (15.2%) individuals did not specify a personal history, but the vast majority did indicate a family history of cancer (n=133; 93.8%). Comparably, 572 (60.3%) of the individuals with a personal history of cancer or of non-cancerous breast findings reported a family history of cancer. The median age at onset for breast cancer was 53 years (n=472; range=24-89 years). A total of 90 (9.5%) individuals had a pathogenic (P) or likely pathogenic (LP) and 3 (0.3%) of individuals harbored the APC I1307K risk variant. Of the 90 individuals with positive findings, 31.1% had a P/LP variant in BRCA2, 28.0% in MUTYH, 11.8% in CHEK2, 7.5% in BRCA1, in 6.5% BRIP1, and 11.8% in ATM, CDKN2A, MSH6, NBN, PALB2, RAD51C, RAD51D, and RET. The most frequently reported pathogenic variants were MUTYH p.Gly396Asp (n=20), BRCA2 p.Glu1308* (n=16), and BRCA2 p.Asn1933Lysfs*29 (n=6). A recurrent pathogenic deletion of the upstream and exon 2 region of BRCA1 was also identified in three individuals. The indeterminate and negative rates were 36.5% (n=346) and 53.7% (n=510), respectively. Conclusion: Although the present study was limited to biological females and included individuals with broader personal and family cancer histories, the positive rate is within range of those reported for other countries in the Caribbean. Interestingly, P/LP variants have been reported to be enriched in BRCA1, BRCA2, and PALB2 across other Caribbean countries; however, this was not mirrored in the pattern of positive findings for this cohort of Puerto Rican females and may suggest a distinct background for hereditary cancer predisposition in this population. Further studies are needed to understand the landscape of germline variants in this population to ensure proper surveillance and risk mitigation is applied.

Citation Format: Hannah Cox, Deborah Hartzfeld, Shawn Gessy, Christina Zaleski, Jerry Machado. Hereditary cancer genetic testing in Puerto Rican females [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-08.