Addressing health disparities in Hispanic breast cancer: accurate and inexpensive sequencing of BRCA1 and BRCA2

Abstract

BackgroundGermline mutations in the BRCA1 and BRCA2 genes account for 20–25 % of inherited breast cancers and about 10 % of all breast cancer cases. Detection of BRCA mutation carriers can lead to therapeutic interventions such as mastectomy, oophorectomy, hormonal prevention therapy, improved screening, and targeted therapies such as PARP-inhibition. We estimate that African Americans and Hispanics are 4–5 times less likely to receive BRCA screening, despite having similar mutation frequencies as non-Jewish Caucasians, who have higher breast cancer mortality. To begin addressing this health disparity, we initiated a nationwide trial of BRCA testing of Latin American women with breast cancer. Patients were recruited through community organizations, clinics, public events, and by mail and Internet. Subjects completed the consent process and questionnaire, and provided a saliva sample by mail or in person. DNA from 120 subjects was used to sequence the entirety of BRCA1 and BRCA2 coding regions and splice sites, and validate pathogenic mutations, with a total material cost of $85/subject. Subjects ranged in age from 23 to 81 years (mean age, 51 years), 6 % had bilateral disease, 57 % were ER/PR+, 23 % HER2+, and 17 % had triple-negative disease.ResultsA total of seven different predicted deleterious mutations were identified, one newly described and the rest rare. In addition, four variants of unknown effect were found.ConclusionsApplication of this strategy on a larger scale could lead to improved cancer care of minority and underserved populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13742-015-0088-z) contains supplementary material, which is available to authorized users.

Insights into BRCA1/2 Genetic Counseling from Ethnically Diverse Latina Breast Cancer Survivors

“…We identified facilitators and barriers to the use of BRCA genetic counseling among Latinas, none of whom reported that they had previously undergone this service, despite the fact that about 35% of the sample had undergone BRCA testing. These factors are important to consider given that there are significant disparities in the use of genetic services among this underserved group (Dean et al 2015;Gammon et al 2011;Levy et al 2011;Lynce et al 2016;Pagán et al 2009). Consistent with prior research, we found that the majority of participants demonstrated very low levels of awareness and knowledge about the benefits of genetic counseling, BRCA mutations, and increased risk associated with HBOC (Gammon et al 2011;Kinney et al 2010;Lynce et al 2016;Mai et al 2014;Sussner et al 2010Sussner et al , 2013Sussner et al , 2015Vadaparampil et al 2010a, b).…”

“…Likewise, despite the benefits of genetic counseling and testing for hereditary breast and ovarian cancer (HBOC) risk, significant disparities exist in the use of these services between women of non-Latina and Latina descent. While statistics are not available for genetic counseling alone, many studies indicate that awareness and use of genetic testing among Latinas is low (Dean et al 2015;Gammon et al 2011;Levy et al 2011;Lynce et al 2016;Mai et al 2014;Pagán et al 2009). In a recent study among at-risk Latina and non-Latina participants who had not previously undergone genetic counseling/testing, 57% of Latinas were unaware of the availability of BRCA testing, with Latina ethnicity the only notable factor associated with lack of awareness (Gammon et al 2011).…”

Assessing risk for Mendelian disorders in a Bronx population

“…Eight high risk variants in BRCA1 and BRCA2 were identified among African Americans and Puerto Ricans (Dean et al. ). Among the non‐malignant conditions identified in Puerto Ricans and African Americans were transthyretin amyloidosis ( TTR NM_000371.3:c.424G>A(p.Val142Ile)) that typically manifests after age 60 with renal amyloidosis and cardiomyopathy (Jacobson et al.…”

Food and drug administration’s regulatory shift on direct‐to‐consumer genetic tests for cancer risk

“…5 If used and interpreted appropriately, 23andMe's test could be a powerful tool for cancer prevention for this group of womennot just for one individual but for an entire family. More broadly, if developed, DTC tests for genetic variants associated with cancer risks that are common in other populations, such as African American and Hispanic women, who are 4 to 5 times less likely than women of Western European descent to undergo BRCA screening despite facing similar mutation rates, 6 could be game changers in democratizing access to such information.…”