Abstract P6-08-19: Germline mutation prevalence among US and non-US Hispanic patients undergoing genetic testing for breast and ovarian cancer predisposition
Authors: Lincoln Stephen E , Pineda-Alvarez Daniel , Michalski Scott T , Yang Shan , Esplin Edward D 
Published: March 2020

Background: A variety of studies have examined the prevalence of germline mutations in patients undergoing genetic testing for a wide variety of breast cancer predisposition genes. Many of these studies have focused on patients of Northern European descent, leaving variant prevalence and clinical presentations of patients from underrepresented, and often underserved, populations much less well understood. Our study aimed to examine the prevalence of germline mutations among referred patients from Mexico, Central and South America, as well as a comparative population of Hispanic patients from the United States. Methods: We analyzed a de-identified laboratory-based cohort of patients who had received physician-ordered germline multigene panel test results between December 2014 and June 2019. Inclusion criteria for this study were a personal or family history of breast or ovarian cancer, and either (a) an ordering physician based in Mexico, Central America, or South America, or (b) a Hispanic self-reported ethnicity and a US based ordering physician. For this analysis, Mexican patients were combined with Central Americans. Panel size was per physician discretion, and most (&gt;70%) physicians chose large (at least 20 gene) panels of high- and moderate-risk genes including BRCA1, BRCA2, PALB2, CHEK2, ATM, and TP53, among others. Full gene sequencing and deletion/duplication analysis were performed as described previously [PMID: 26207792] and variants were classified using a framework based on the ACMG/AMP guidelines for variant interpretation [PMID: 28492532]. Results: Of the 25,249 participants who met criteria, 18,513 were self-identified Hispanic-Amercians and 6,736 were non-US participants. Of the non-US group, 6,398 were from South America (including 1200 from Chile and 3781 from Brazil) while 273 were from Mexico and 65 from Central America. Pathogenic or Likely Pathogenic variants were uncovered in 14.4% of all participants, with 1864 findings (representing 7.4% of participants) in BRCA1 or BRCA2, and 1769 (7.0% of participants) in other cancer risk genes. Stratified by location, mutation positive rates were highest among Central (26.9%) and South Americans (19.2%), and lowest among the US Hispanics (12.5%). Based on NCCN guidelines, many of these findings would warrant consideration of a change in care for the patient and/or reflex testing of family members.

Conclusions: Cancer patients in Mexico, Central, and South America may have less access to germline genetic testing than patients in (for example) the United States, although our study suggests that Latin American patients and their families can benefit from genetic testing at least at the same rate as Hispanic patients in the US. The higher positive rate among Central and South Americans in this study compared to Hispanic-Americans may be due to referral patterns and cost impact, although this question requires further study. The relative VUS rates between populations, mutation rates for specific clinical presentations, and relevant psychosocial issues also need further study to help maximize the utility of germline genetic testing in Latin America.

Citation Format: Stephen E Lincoln, Daniel Pineda-Alvarez, Scott T Michalski, Shan Yang, Edward D Esplin. Germline mutation prevalence among US and non-US Hispanic patients undergoing genetic testing for breast and ovarian cancer predisposition [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-19.