Dataset Information

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach.

ABSTRACT: Purpose: 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.

SUBMITTER: Oliver J

PROVIDER: S-EPMC6933010 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Latin American Study of Hereditary Breast and Ovarian Cancer <i>LACAM</i>: A Genomic Epidemiology Approach.

Oliver Javier J Quezada Urban Rosalía R Franco Cortés Claudia Alejandra CA Díaz Velásquez Clara Estela CE Montealegre Paez Ana Lorena AL Pacheco-Orozco Rafael Adrián RA Castro Rojas Carlos C García-Robles Reggie R López Rivera Juan Javier JJ Gaitán Chaparro Sandra S Gómez Ana Milena AM Suarez Obando Fernando F Giraldo Gustavo G Maya Maria Isabel MI Hurtado-Villa Paula P Sanchez Ana Isabel AI Serrano Norma N Orduz Galvis Ana Isabel AI Aruachan Sandra S Nuñez Castillo Johanna J Frecha Cecilia C Riggi Cecilia C Jauk Federico F Gómez García Eva María EM Carranza Claudia Lorena CL Zamora Vanessa V Torres Mejía Gabriela G Romieu Isabelle I Castañeda Carlos Arturo CA Castillo Miluska M Gitler Rina R Antoniano Adriana A Rojas Jiménez Ernesto E Romero Cruz Luis Enrique LE Vallejo Lecuona Fernando F Delgado Enciso Iván I Martínez Rizo Abril Bernardette AB Flores Carranza Alejandro A Benites Godinez Verónica V Méndez Catalá Claudia Fabiola CF Herrera Luis Alonso LA Chirino Yolanda Irasema YI Terrazas Luis Ignacio LI Perdomo Sandra S Vaca Paniagua Felipe F

Frontiers in oncology 20191220

<b>Purpose:</b> 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 countr ...[more]

PMID: 31921681

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Project description:ImportanceGenomic screening for hereditary breast and ovarian cancer (HBOC) in unselected women offers an opportunity to prevent cancer morbidity and mortality, but the potential clinical impact and cost-effectiveness of such screening have not been well studied.ObjectiveTo estimate the lifetime incremental incidence of HBOC and the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of HBOC genomic screening in an unselected population vs family history-based testing.Design, setting, and participantsIn this study conducted from October 27, 2017, to May 3, 2020, a decision analytic Markov model was developed that included health states for precancer, for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), for earlier- and later-stage HBOC, after cancer, and for death. A complimentary cascade testing module was also developed to estimate outcomes in first-degree relatives. Age-specific RRM and RRSO uptake probabilities were estimated from the Geisinger MyCode Community Health Initiative and published sources. Parameters including RRM and RRSO effectiveness, variant-specific cancer risk, costs, and utilities were derived from published sources. Sensitivity and scenario analyses were conducted to evaluate model assumptions and uncertainty.Main outcomes and measuresLifetime cancer incidence, QALYs, life-years, and direct medical costs for genomic screening in an unselected population vs family history-based testing only were calculated. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in cost between strategies divided by the difference in QALYs between strategies. Earlier-stage and later-stage cancer cases prevented and total cancer cases prevented were also calculated.ResultsThe model found that population screening of 30-year-old women was associated with 75 (95% credible range [CR], 60-90) fewer overall cancer cases and 288 QALYs (95% CR, 212-373 QALYs) gained per 100 000 women screened, at an incremental cost of $25 million (95% CR, $21 millon to $30 million) vs family history-based testing; the ICER was $87 700 (78% probability of being cost-effective at a threshold of $100 000 per QALY). In contrast, population screening of 45-year-old women was associated with 24 (95% CR, 18-29) fewer cancer cases and 97 QALYs (95% CR, 66-130 QALYs) gained per 100 000 women screened, at an incremental cost of $26 million (95% CR, $22 million to $30 million); the ICER was $268 200 (0% probability of being cost-effective at a threshold of $100 000 per QALY). A scenario analysis without cascade testing increased the ICER to $92 600 for 30-year-old women and $354 500 for 45-year-old women. A scenario analysis assuming a 5% absolute decrease in mammography screening in women without a variant was associated with the potential for net harm (-90 QALYs per 100 000 women screened; 95% CR, -180 to 10 QALYs).Conclusions and relevanceThe results of this study suggest that population HBOC screening may be cost-effective among younger women but not among older women. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value. The potential for harm conferred by inappropriate reduction in mammography among noncarriers should be quantified.

Dataset Information

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach.

Publications

Latin American Study of Hereditary Breast and Ovarian Cancer <i>LACAM</i>: A Genomic Epidemiology Approach.

Similar Datasets

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