Genetic risk factors for breast cancer and ovarian cancer in Latin America: Q&A with Dr Sandra Perdomo

Latin America is considered to have one of the most genetically admixed populations in the world, and its specific combinations of genetic ancestries may have impacts on the genomic determinants of various diseases, including cancer. In this region, breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women. For both incidence of and mortality from breast cancer, the proportions that occur in women younger than 44 years have been shown to be higher in Latin American countries than in high-income countries (20% vs 12% of new cases and 14% vs 7% of deaths), suggesting an important contribution of genetic and non-genetic risk factors in Latin America.

We hypothesize that additional germline alterations in cancer-related genes that have not yet been described could contribute to the development of hereditary breast cancer and ovarian cancer in admixed populations. Moreover, the effect of lifestyle modifying risk factors might differ in these cases compared with cases of European descent. Therefore, Latin America is a representative scenario in which to study hereditary breast cancer and ovarian cancer genomics, both because of the presence of admixed ethnicity and because it is a region that is currently undergoing epidemiological transition.

The Latin American Consortium for Hereditary Breast Cancer and Ovarian Cancer (LACAM) is a joint regional effort that is aimed at analysing the genetic component and modifying risk factors of inherited breast cancer in individuals in Latin America. During a 4-year period, the LACAM research team aims to recruit 3000 cases from multiple centres in six countries in Latin America, collecting biological samples and responses to epidemiological questionnaires and clinical questionnaires. This will make it the largest study of hereditary breast cancer and ovarian cancer in these populations. This population size will ensure accurate and robust findings on the role of germline pathogenic variants in cancer susceptibility genes and modifying risk factors. Currently, we have recruited 1100 individuals with complete clinical and epidemiological information, including tissue and blood samples.

The consortium is a multidisciplinary group of scientists from 16 institutions, including clinical geneticists and/or genetic counsellors, molecular biologists, epidemiologists, oncologists, pathologists, surgeons, and psychologists.

This project involves the participation of 16 institutions in six Latin American countries: Argentina, Colombia, Guatemala, Mexico, Paraguay, and Peru.

IARC is coordinating the overall recruitment of individuals in collaboration with the local investigators in each country, using standardized questionnaires and processing protocols. IARC also centralizes data curation and data analyses.

We want to characterize alterations in additional cancer-related genes that have not previously been associated with hereditary breast cancer and ovarian cancer in Latin America and to identify non-genetic modifying risk factors that could potentially be relevant for preventive interventions. Using these results, we want to improve the identification of high-risk individuals, increase diagnosis at earlier stages, and evaluate the impact of both genetic and non-genetic modifying risk factors in the clinical outcome of patients.

An additional aim is to develop knowledge translation tools for patients with hereditary breast cancer and ovarian cancer and for clinicians, to support effective communication and sharing of information.

A preliminary genomic analysis in 403 individuals who met the clinical criteria for hereditary breast cancer and ovarian cancer, recruited in five Latin American countries between October 2017 and December 2018, showed that about 20% of them had pathogenic alterations in cancer susceptibility genes, including individuals without a cancer diagnosis. Germline genetic alterations were evaluated for patients in four countries. The prevalence of pathogenic alterations found was highest in Argentina (25%), followed by Mexico (18%), Guatemala (16%), and Colombia (13%). We also found that about half (48%) of all individuals were overweight or obese at the time of recruitment. These initial results were published in Frontiers in Oncology in 2019.

We have also started developing a web-based platform on hereditary breast cancer and ovarian cancer based on the experiences and the need for information that patients with hereditary breast cancer and ovarian cancer and their family caregivers have shared with us. Patients participating in the study and their families have participated in interviews and focus groups to help us determine what type of information about the nature of the disease and care is needed.

We expect to complete recruitment of 3000 patients by the end of 2022.

The study’s findings will improve our understanding of the most important risk factors, both genetic and non-genetic, associated with breast cancer in young and high-risk women in Latin America. This will enable us to improve intervention strategies and prevention and risk management for patients affected by breast cancer and ovarian cancer. We will be able to implement a public database and biorepository of hereditary breast cancer and ovarian cancer that provides comprehensive, curated, and detailed information about genetic variants and clinical, demographic, family history, and ancestry composition variables from Latin American populations.

The LACAM study has built a network of collaborators in Latin America to investigate genetic susceptibility to breast cancer, focusing mainly on hereditary breast cancer and ovarian cancer. Exploring potential associations between the risk of hereditary breast cancer or ovarian cancer and genetic components still requires additional scientific evidence, taking into consideration ancestry, common genetic variations, and non-genetic variables such as lifestyle.