Latin American study of hereditary breast and ovarian cancer LACAM : a genomic epidemiology approach

Q2Q1Artículo original1-13Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5–10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations

Analysis of the cost-effectiveness of liquid biopsy to determine treatment change in patients with her2-positive advanced breast cancer in Colombia

Background: Breast cancer is highly prevalent worldwide and leads to high health-care costs. HER2-positive subtype represents 30% of all breast cancers and is associated with a poor prognosis. Patients treated with anti-HER2 therapies frequently develop resistance and require pharmacological treatment change. Liquid biopsy is a minimally invasive and an easily accessible technique, with high sensitivity and specificity, to detect molecular treatment resistance even before the onset of clinical manifestations and can thus be used to reduce unnecessary anti-HER2 treatment costs. Objective: To evaluate the cost-effectiveness of using liquid biopsy (ctDNA detection) to determine treatment change in women with HER2-positive advanced breast cancer in Colombia. Methodology: We performed an economic evaluation using decision tree modeling and deterministic analyses based on literature search for first and second lines of treatment (trastuzumab, pertuzumab, docetaxel, and TDM1); resistance; outcomes; and sensitivity and specificity of tests detecting molecular resistance. The effectiveness was measured using quality-adjusted life year (QALY) score, and costs were obtained from databases with national validity, suppliers, the Colombian Drug Price Information System (SISMED), and local studies. Results: The use of liquid biopsy (ctDNA detection) with conventional treatment was more expensive and less effective than conventional treatment without liquid biopsy (US $177,985.35 and 0.533889206 QALY, respectively). The incremental cost with liquid biopsy was US$7,333.17 and the incremental effectiveness was 0.00042256 QALY relative to the conventional method. Conclusion: Including liquid biopsy in the treatment of HER2-positive advanced breast cancer was considered currently inapplicable in Colombia because it was not cost effective. Our results open a window of opportunity to improve the development and implementation of ctDNA testing in Colombia, potentially reducing current costs. More evidence is required on the utility of this test, depending on the financial capacity of Colombia and other countries

Cancer genomic resources and present needs in the latin american region

In Latin America (LA), cancer is the second leading cause of death, and little is known about the capacities and needs for the development of research in the field of cancer genomics. In order to evaluate the current capacity for and development of cancer genomics in LA, we collected the available information on genomics, including the number of next-generation sequencing (NGS) platforms, the number of cancer research institutions and research groups, publications in the last 10 years, educational programs, and related national cancer control policies. Currently, there are 221 NGS platforms and 118 research groups in LA developing cancer genomics projects. A total of 272 articles in the field of cancer genetics/genomics were published by authors affiliated to Latin American institutions. Educational programs in genomics are scarce, almost exclusive of graduate programs, and only few are concerning cancer. Only 14 countries have national cancer control plans, but all of them consider secondary prevention strategies for early diagnosis, opportune treatment, and decreasing mortality, where genomic analyses could be implemented. Despite recent advances in introducing knowledge about cancer genomics and its application to LA, the region lacks development of integrated genomic research projects, improved use of NGS platforms, implementation of associated educational programs, and health policies that could have an impact on cancer care

AR-V7 as a biomarker for resistance to treatment with abiraterone/enzalutamide in three Latin American countries: a hypothetical cost-saving analysis

Background Prostate cancer is the most incident and one of the deadliest male cancers in Latin America. Treatment for patients with metastatic castration‐resistant prostate cancer (mCRPC) includes androgen receptor signaling inhibitors such as abiraterone and enzalutamide, for which androgen receptor splice variant 7 (AR‐V7) has emerged as a biomarker for primary resistance. Our study sought to analyze the potential economic impact of the use of AR‐V7 detection as a treatment indicator in patients with mCRPC in three Latin American countries. Materials and Methods A hypothetical cost prediction model for the use of noninvasive circulating tumor cell–based AR‐V7 testing as a treatment indicator for patients eligible for treatment with abiraterone/enzalutamide was conducted using available information on treatment and testing costs from Mexico, Argentina, and Colombia. Results At an estimated prevalence of AR‐V7 positivity of 20%, the use of upfront AR‐V7 genetic testing resulted in annual net savings of $9,801,669.97,$6,390,055.75, and $3,096,780.91 in Mexico, Argentina, and Colombia, respectively. A direct relationship between AR‐V7 positivity prevalence and net savings was found. Conclusion The use of a noninvasive AR‐V7 detection assay as a treatment indicator tool in patients eligible for treatment with abiraterone or enzalutamide in Latin America could be a cost‐effective approach for the management of these patients. Additional efforts are needed to accurately determine the incidence of castration‐resistant prostate cancer cases and the prevalence of AR‐V7 positivity in Latin America in order to predict the potential economic benefit of its clinical use. Implications for Practice In Latin America, prostate cancer is the most frequently diagnosed cancer in men, and the burden of this disease is expected to double in this region by 2030. Noninvasive detection of androgen receptor splice variant 7 (AR‐V7) is being currently validated as a predictive biomarker for benefit with androgen receptor signaling inhibitor therapy in patients with metastatic castration‐resistant prostate cancer (mCRPC). This hypothetical cost‐saving analysis shows that AR‐V7 testing in peripheral blood of patients with CRPC eligible for treatment with abiraterone or enzalutamide might represent a cost‐effective strategy to select patients who will benefit from AR‐axis–directed treatment in three Latin American countries