Development and Pilot Implementation of the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) Intervention in Mexico.

PURPOSE: Genomic cancer risk assessment (GCRA) is standard-of-care practice that uses genomic tools to identify individuals with increased cancer risk, enabling screening for early detection and cancer prevention interventions. GCRA is not available in most of Mexico, where breast cancer (BC) is the leading cause of cancer death and ovarian cancer has a high mortality rate. METHODS: Guided by an implementation science framework, we piloted the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) intervention, combining GCRA training, practice support, and low-cost BRCA1/2 (BRCA) gene testing at four centers in Mexico. The RE-AIM model was adapted to evaluate GRACIAS intervention outcomes, including reach, the proportion of new patients meeting adapted National Comprehensive Cancer Network criteria who participated in GCRA. Barriers to GCRA were identified through roundtable sessions and semistructured interviews. RESULTS: Eleven clinicians were trained across four sites. Mean pre-post knowledge score increased from 60% to 67.2% (range 53%-86%). GCRA self-efficacy scores increased by 31% (95% CI, 6.47 to 55.54; P = .02). Participant feedback recommended Spanish content to improve learning. GRACIAS promoted reach at all sites: 77% in Universidad de Guadalajara, 86% in Instituto Nacional de Cancerología, 90% in Tecnológico de Monterrey, and 77% in Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Overall, a pathogenic BRCA variant was identified in 15.6% (195 of 1,253) of patients. All trainees continue to provide GCRA and address barriers to care. CONCLUSION: We describe the first project to use implementation science methods to develop and deliver an innovative multicomponent implementation intervention, combining low-cost BRCA testing, comprehensive GCRA training, and practice support in Mexico. Scale-up of the GRACIAS intervention will promote risk-appropriate care, cancer prevention, and reduction in related mortality.

The Burden of Breast Cancer Predisposition Variants Across The Age Spectrum Among 10 000 Patients.

BACKGROUND/OBJECTIVES: Women diagnosed with breast cancer (BC) at an older age are less likely to undergo genetic cancer risk assessment and genetic testing since the guidelines and referrals are biased toward earlier age at diagnosis. Thus, we determined the prevalence and type of pathogenic cancer predisposition variants among women with a history of BC diagnosed at the age of 65 years or older vs younger than 65 years. DESIGN: Prospective registration cohort. SETTING: The Clinical Cancer Genomics Community Research Network, including 40 community-based clinics in the United States and 5 in Latin America. PARTICIPANTS: Women with BC and genetic testing results. MEASUREMENTS: Sociodemographic characteristics, clinical variables, and genetic profiles were compared between women aged 65 years and older and those younger than 65 years at BC diagnosis. RESULTS: Among 588 women diagnosed with BC and aged 65 years and older and 9412 diagnosed at younger than 65 years, BC-associated pathogenic variants (PVs) were detected in 5.6% of those aged 65 years and older (n = 33) and 14.2% of those younger than 65 years (n = 1340) (P < .01). PVs in high-risk genes (eg, BRCA1 and BRCA2) represented 81.1% of carriers among women aged 65 years and older (n = 27) and 93.1% of those younger than 65 years (n = 1248) (P = .01). BRCA2 PVs represented 42.4% of high-risk gene findings for those aged 65 years and older, whereas BRCA1 PVs were most common among carriers younger than 65 years (49.7%). PVs (n = 7) in moderate-risk genes represented 21.2% for carriers aged 65 years and older and 7.3% of those younger than 65 years (n = 98; P < .01). CHEK2 PVs were the most common moderate-risk gene finding in both groups. CONCLUSION: Clinically actionable BC susceptibility PVs, particularly in BRCA2 and CHEK2, were relatively prevalent among older women undergoing genetic testing. The significant burden of PVs for older women with BC provides a critical reminder to recognize the full spectrum of eligibility and provide genetic testing for older women, rather than exclusion based on chronological age alone. J Am Geriatr Soc 67:884-888, 2019.

Genetic Cancer Risk Assessment for Breast Cancer in Latin America.

In Latin America, breast cancer is the most common malignancy in women, and limited available data suggest that up to 15% of all breast cancer cases in the region are hereditary. Genetic cancer risk assessment and counseling is a critical component of the appropriate clinical care of patients with hereditary breast cancer and their families. Unfortunately, genetic services are underdeveloped across Latin America, and access to genetic testing and counseling is very scarce in the region. Barriers contributing to the access to genetic care are high cost and lack of insurance coverage for genetic tests, insufficient oncogenetics training or expertise, nonexistence of genetic counseling as a clinical discipline, and lack of supportive healthcare policies. In this review, we highlight relevant initiatives undertaken in several Latin American countries aimed at creating genetic cancer risk assessment programs. Additionally, we present a review of the scientific literature on the current status of breast cancer genomics in Latin America, with specific emphasis on demographic indicators, access to cancer genetic care, training and strategies to improve outcomes, and international collaborations.

Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico.

BACKGROUND: Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico. METHODS: In a multistage approach, 188 patients with cancer who were unselected for family cancer history (92 with ovarian cancer and 96 with breast cancer) were screened for BRCA mutations using a Hispanic mutation panel (HISPANEL) of 115 recurrent mutations in a multiplex assay (114 were screened on a mass spectroscopy platform, and a polymerase chain reaction assay was used to screen for the BRCA1 ex9-12del mutation). This was followed by sequencing of all BRCA exons and adjacent intronic regions and a BRCA1 multiplex ligation-dependent probe amplification assay (MLPA) for HISPANEL-negative patients. BRCA mutation prevalence was calculated and correlated with histology and tumor receptor status, and HISPANEL sensitivity was estimated. RESULTS: BRCA mutations were detected in 26 of 92 patients (28%) with ovarian cancer, in 14 of 96 patients (15%) with breast cancer overall, and in 9 of 33 patients (27%) who had tumors that were negative for estrogen receptor, progesterone receptor, and human epithelial growth factor 2 (triple-negative breast cancer). Most patients with breast cancer were diagnosed with locally advanced disease. The Mexican founder mutation (BRCA1 ex9-12del) accounted for 35% of BRCA-associated ovarian cancers and 29% of BRCA-associated breast cancers. At 2% of the sequencing and MLPA cost, HISPANEL detected 68% of all BRCA mutations. CONCLUSIONS: In this study, a remarkably high prevalence of BRCA mutations was observed among patients with ovarian cancer and breast cancer who were not selected for family history, and the BRCA1 ex9-12del mutation explained 33% of the total. The remarkable frequency of BRCA1 ex9-12del in Mexico City supports a nearby origin of this Mexican founder mutation and may constitute a regional public health problem. The HISPANEL mutation panel presents a translational opportunity for cost-effective genetic testing to enable breast and ovarian cancer prevention.