Abstract IA23: Steps to address the profound disparity in access to genetic cancer risk assessment in Mexico: Documenting hereditary breast and ovarian cancer and the beginning of a prevention program
Authors: Villarreal-Garza Cynthia 
Published: October 2015

Abstract
Despite a broad base of evidence documenting the effectiveness of screening and risk reduction procedures among BRCA carriers, in Mexico, a middle-income country, BRCA testing is not broadly available and genetic cancer risk assessment (GCRA) services are not routinely provided. Barriers to implement GCRA strategies among Mexican patients include: elevated costs and lack of coverage for genetic testing within the public health system, limited awareness among providers and patients concerning target population for testing and GCRA benefits, as well as a restricted number of clinicians with GCRA expertise.
These limitations have resulted in scarce data regarding the prevalence of BRCA mutations among Mexican breast cancer patients, information that is absolutely relevant due to the reported earlier age at onset1-3 and the high prevalence of triple negative breast cancer1, which suggests a high proportion of hereditary breast cancer cases. This is supported by previous studies among high-risk Hispanics in the United States that have reported an extremely high prevalence of deleterious BRCA mutations (25%)4, and the discovery of a founder Mexican mutation, BRCA1 ex9-12del, that accounts for a significant proportion of BRCA-associated breast and ovarian cancer cases5.
Efforts should be directed to implement and maintain a program of GCRA in Mexico that will enable a shift in public health policy to provide coverage for preventive services, including genetic testing, as well as screening and therapeutic interventions for patients and their families. The first steps for the beginning of a successful prevention program in Mexico have taken place at the Instituto Nacional de Cancerologia (INCan), which serves as the main referral center for patients from Central and South Mexico, with approximately 800 new breast cancer patients diagnosed and treated each year. The main purpose of this abstract is to describe the initiation process of this program, preliminary findings, current achievements of the established GCRA program, challenges for its implementation and future plans to disseminate its adoption and sustainability.
First steps and achievements:
Although the hereditary clinic at the INCan has been delivering clinical service for a significant period of time, clinical practice was notably limited as genetic testing was not readily accessible for routinely use.
The initiation in the shift of clinical practice began with the establishment of critical collaborations between INCan and two leading international institutions with particular interest in high-risk/familial cancer among Hispanics, the City of Hope Clinical Cancer Genetics Community Research Network (CCGCRN) consortium and the Women's College Research Institute, over the past three years, which have accelerated our progress in the establishment of a GCRA program. The productivity of these nascent collaborations has already been exemplified by joint presentations at international meetings, as well as a joint publication between INCan and City of Hope. Overall, the results of the first study showed a remarkably high prevalence of BRCA mutations among 92 ovarian and 96 breast cancer cases not selected for family history (28% and 15%, respectively). Additionally, the BRCA1 ex9-12del mutation accounted for 33% of the identified mutations.6, 7 The prevalence of detected mutations was found to be 23% in a subsequent cohort of 190 young unselected triple-negative breast cancer cases.8 These findings suggest an extremely high prevalence of BRCA mutations and a high frequency of the large Mexican founder rearrangement mutation, which might represent a potential public health threat.
The assay that has been used for the detection of BRCA mutations in the previous and current projects is the HISPANEL, a novel inexpensive genomic panel assay for the identification of 114 recurrent Hispanic mutations developed by the CCGCRN consortium. At a 2% of the sequencing and MLPA cost, the HISPANEL detected 68% of all BRCA mutations.7 Although this level of sensitivity is less than optimal for a screening tool, it is far better than not having access at all to genetic sequencing in Mexico, and thus is likely to have clinical utility, while dramatically reducing overall genotyping cost among underserved women in Mexico. Its use presents an opportunity for cost-effective genetic testing strategies with full clinical translation, while also catalyzing the integration of GCRA in clinical practice in this country.
Another key piece for the consolidation of our program was the training of six of our team members through the participation in the Intensive Course and Clinical Cancer Genetics Community of Practice, which was facilitated by our collaboration with the CCGCRN team, which has been crucial to guarantee the follow-up and execution of required patient interventions. Scheduled monitoring sessions from our expert collaborators from CCGCRN, have resulted in refinement of processes for high quality GCRA implementation. Also, we have been prospectively accruing patients in the common CCGCRN registry platform that enables us to maintain data harmonization with the data-coordinating center at City of Hope, and this will speed the pace of research.
Through the implementation of the genetic test tool HISPANEL, available through research projects developed at the INCan, we have identified up to 150 mutation-carriers, with a direct impact in the care of these patients and their families. Increased awareness among providers and patients has been increasingly noted and weekly clinical interdisciplinary sessions for clinical care decision-making have been established.
Challenges:
Despite the huge amount of progress achieved in a relative low amount of time, we have faced different challenges for the adoption of GCRA in our Institution.
With the current availability for genetic testing at INCan, a considerable proportion of patients have been identified as mutation carriers in a small frame of time. Some restructuring might help optimize processes, but not all team members are willing to change the established organization and procedural flow.
Additionally, concerns have been rising about the growing numbers of identified high-risk patients and mutation carriers. Soon, more support staff will be needed for the care of these patients, and at this point, this is not immediately viable. Moreover, the INCan cannot fulfill the screening strategies and risk-reduction interventions for healthy family members found to be BRCA carriers. Only some discussions have taken place to find a solution for patient overload (extra surgery day for oophorectomies or referral to second-level institutions), but no action has been taken at this moment.
Future plans and key to success:
Extension of our research studies will enable the validation of the HISPANEL and the estimation of its clinical sensitivity in our patients. A population-based study in different Mexican states will provide information regarding the prevalence of the Mexican founder mutation BRCA1 ex9-12del.
Most importantly, the next step is to ensure the implementation and dissemination of GCRA services across the Mexican health care system. For this purpose, a working group of Mexican and U.S. experts, under Dr. Jeffrey Weitzel's leadership, is developing and testing a multi-component intervention that will help identify factors influencing implementation of GCRA in Mexico and will enhance adoption and sustainment of GRCA in other health care institutions. The INCan will serve as a model for other Mexican clinical sites to reproduce the strategies that have been successful and to help understand the barriers faced through the implementation of this prevention program.
References:
1. Lara-Medina F, Perez-Sanchez V, Saavedra-Perez D, et al. Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity. Cancer. Aug 15 2011;117(16):3658-3669.
2. Rodriguez-Cuevas S, Guisa-Hohenstein F, Labastida-Almendaro S. First breast cancer mammography screening program in Mexico: initial results 2005-2006. Breast J. Nov-Dec 2009;15(6):623-631.
3. Villarreal-Garza C, Aguila C, Magallanes-Hoyos MC, et al. Breast cancer in young women in Latin America: an unmet, growing burden. Oncologist. 2013;18(12):1298-1306.
4. Weitzel JN, Clague J, Martir-Negron A, et al. Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network. J Clin Oncol. Jan 10 2013;31(2):210-216.
5. Weitzel JN, Lagos VI, Herzog JS, et al. Evidence for common ancestral origin of a recurring BRCA1 genomic rearrangement identified in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev. Aug 2007;16(8):1615-1620.
6. Villarreal-Garza C, Herrera LA, Herzog J, et al. Significant Clinical impact of recurrent BRCA1 and BRCA2 (BRCA) mutations in Mexico. Cancer Research. 2012;72(24 Supplement %U http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/72/24_MeetingAbstracts/PD08-06):PD08-06.
7. Villarreal-Garza C, Alvarez-Gomez RM, Perez-Plasencia C, et al. Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico. Cancer. Sep 18 2014.
8. Villarreal-Garza CM, Weitzel JN, Sifuentes E, et al. Founder effect and a high prevalence of BRCA1 mutations among young Mexican triple-negative breast cancer (TNBC) patients. ASCO Meeting Abstracts. 2014;32(15_suppl %U http://meeting.ascopubs.org/cgi/content/abstract/32/15_suppl/1522):1522.
Citation Format: Cynthia Villarreal-Garza. Steps to address the profound disparity in access to genetic cancer risk assessment in Mexico: Documenting hereditary breast and ovarian cancer and the beginning of a prevention program. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA23.