Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

Disparities on prostate cancer survival in Mexico: a retrospective cohort study.

OBJECTIVE: To estimate prostate cancer (PC) survival in Mexico and explore survival disparities according to the marginalization level of residence place. MATERIALS AND METHODS: A nationwide administrative claims database (4 110 men) whose PC treatment was financed by Seguro Popular between 2012-2016, was cross-linked to the National Mortality Registry up to December 2019. Patients were classified according to their oncological risk at diagnosis and the marginalization level of the residence municipality. Cox proportional hazards regression was used to estimate multivariable survival functions. RESULTS: Five-years PC survival (69%; 95%CI: 68,71%) ranged from 72% to 54% at very low and very high marginalization, respectively (p for trend<0.001). The lowest PC survival was observed in men with high-risk PC (47%; 95%CI: 33,66%) residents in very high marginalization municipalities. CONCLUSIONS: Overall, PC survival was lower than that reported in other Latin American countries. The distribution of oncologic risk and survival differences across marginalization levels suggests limited early detection and cancer health disparities.

Implementation of a population-based cancer registry network in Mexico 2017-2020.

The growing cancer burden particularly among less developed countries requires local data to plan and evaluate cancer control measures. This article describes the development of a population-based cancer registry network (PBCRN) in Mexico that took place between 2017 and 2020 and present related data. The PBCRN, led by the National Cancer Institute (Incan), included nine registries representing 11.3% of the Mexican population. Definitions, coding, and operative processes were based on international standards. All cities were visited to set up local structure; personnel were hired by Incan and trained in basic cancer registration in Merida. A specific software was developed. Regular virtual meetings took place for data verification and quality control. Data collection included institutions of the public and private health system. Personnel included 34 registrars, nine local leaders, and 12 staff members at the Incan. A total of 13 517 cases were recorded between 2017-2020, 64% percent of them were among females. Breast cancer was the more frequent malignancy (23.3%), followed by digestive organs with (18.4%) and female genital cancers (13.5%). Childhood (0-14 years) and adolescents cancer represented 4.4% of the total new cancer cases. The network was suspended in 2020. The present effort lacked sustainability and data were only partial. However, the experience provides valuable insights to be considered for the renewed cancer registration efforts that are currently ongoing in Mexico.

Latin America and the Caribbean Code Against Cancer 1st Edition: 17 cancer prevention recommendations to the public and to policy-makers (World Code Against Cancer Framework).

Preventable risk factors are responsible of at least 40% of cases and almost 45% of all cancer deaths worldwide. Cancer is already the leading cause of death in almost half of the Latin American and the Caribbean countries constituting a public health problem. Cost-effective measures to reduce exposures through primary prevention and screening of certain types of cancers are critical in the fight against cancer but need to be tailored to the local needs and scenarios. The Latin America and the Caribbean (LAC) Code Against Cancer, 1st edition, consists of 17 evidence-based recommendations for the general public, based on the most recent solid evidence on lifestyle, environmental, occupational, and infectious risk factors, and medical interventions. Each recommendation is accompanied by recommendations for policymakers to guide governments establishing the infrastructure needed to enable the public adopting the recommendations. The LAC Code Against Cancer has been developed in a collaborative effort by a large number of experts from the region, under the umbrella strategy and authoritative methodology of the World Code Against Cancer Framework. The Code is a structured instrument ideal for cancer prevention and control that aims to raise awareness and educate the public, while building capacity and competencies to policymakers, health professionals, stakeholders, to contribute to reduce the burden of cancer in LAC.

Mortality Prognosis Factors in Patients with Active Cancer Under Treatment, and Severe COVID-19.

BACKGROUND: COVID-19 is associated with systemic inflammation. This inflammatory response is further deregulated by oncological treatments increasing mortality in this population. However, there is conflicting information regarding the clinical factors that increase mortality in patients with severe COVID-19. OBJECTIVE: The aim of this study was to identify prognostic factors associated with mortality during severe COVID-19 in patients with active cancer. In addition, the correlation between oncologic codes and mortality related to severe COVID-19 was evaluated. PATIENTS AND METHODS: We analyzed a cohort of Mexican patients with active cancer and severe COVID-19 between March 2020 and February 2021. We collected information on patient demographic characteristics, COVID-19 symptoms, clinical and laboratory data, and treatments. Patients were classified according to oncologic code. We defined the oncological code based on clinical stage, treatment intention, performance status before COVID-19, and median overall survival with palliative treatment. A log-rank test was performed to determine survival. A multivariate logistic regression model was used to adjust for potential confounders. RESULTS: One hundred fifty-two patients with severe COVID-19 were analyzed. The red oncologic code was associated with an increased risk of mortality OR 22.8 (CI 95% 5.0-105.1, p <0.001), low oxygen saturation OR 5.4 (CI 95% 1.7-17.4, p = 0.005), chronic corticosteriod use OR 4.3 (CI 95% 1.0-18.1, p = 0.050) and high D-dimer level OR 3.2 (CI 95% 1.2-8.2, p = 0.019). CONCLUSIONS: The survival of patients with active cancer and severe COVID-19 was possible to identify, at the time of admission, specific oncological characteristics. Based on this code, decreased oxygen saturation, increased D-dimer levels, and chronic corticosteroid use were the main predictive factors related to mortality.

Breast cancer survival in Mexico between 2007 and 2016 in women without social security: a retrospective cohort study.

Background: Essential indicators of health system performance for breast cancer are lacking in Mexico. We estimated survival and clinical stage distribution for women without social insurance who were treated under a health financing scheme that covered 60% of the Mexican population. Methods: We conducted a retrospective cohort study cross-linking reimbursement claims for 56,847 women treated for breast cancer between 2007 and 2016 to a mortality registry. We estimated overall- and clinical stage-specific survival and breast cancer survival according to patient age, state of residence, marginalization, type of treatment facility, and patient volume of the treatment facility. We also explored the distribution of clinical stage according to age, year of treatment initiation, and state where the woman was treated. We used log-rank tests and estimated 95% CIs to compare differences between patient groups. Findings: Median age was 52 years (interquartile range [IQR] 45, 61) (Sixty five percent patients (36,731/56,847) had advanced disease at treatment initiation. Five-year overall survival was 72.2% (95% CI 71.7, 72.6). For early disease (excluding stage 0), 5-year overall survival was 89.0% (95% CI 88.4, 89.5), for locally advanced disease 69.9% (95% CI 69.0, 70.2) and for metastatic 36.9% (95% CI 35.4, 38.4). Clinical stage at treatment initiation and breast cancer survival remained unchanged in the period analyzed. Clinical stage and survival differed across age groups, state of residence, and type of facility where women received treatment. Interpretation: In the absence of population-based cancer registries, medical claims data may be efficiently leveraged to estimate essential cancer-related performance indicators. Funding: The authors received no financial support for this research.

Time intervals to care and health service use experiences of uninsured cancer patients treated under public financing in Mexico City.

BACKGROUND: The present study assesses the time intervals from symptom discovery to treatment start and describes the health service use experiences of uninsured patients with cancer of the breast, cervix uteri, testicle, and prostate before their arrival to the cancer hospital. METHODS: This cross-sectional study included 1468 patients who were diagnosed between June 2016 and May 2017 and received treatment for the selected cancers in two of the largest public cancer hospitals in Mexico City, financed through Seguro Popular. Data was collected through a survey administered via face-to-face interviews with patients and a review of their medical files. RESULTS: The median time between detection (symptom discovery or first abnormal screening test) and treatment start was 6.6 months. For all types of cancer, the longest interval was the diagnostic interval -between the first use of healthcare services and the confirmation of cancer. Less than 20% cancer patients were diagnosed in the earliest stages that are associated with the best chances of long-term survival. The participants described a high use of private services for their first consultation, the use of several different types of health services and multiple consultations before arrival to the cancer centers, and 35% perceived being misdiagnosed by the first doctor they consulted. CONCLUSIONS: Most cancer patients treated in the two largest public institutions available for the uninsured faced long delays to get diagnosed and started treatment at advanced stages. Strengthening quality and access for effective early cancer diagnosis and treatment is key to improve patient outcomes in low and middle-income settings.

Reduction in the Treatment Gap for Breast Cancer in Mexico under Seguro Popular, 2007 to 2016.

As Mexico's government restructures the health system, a comprehensive assessment of Seguro Popular's Fund for Protection against Catastrophic Expenses (FPGC) can help inform decision makers to improve breast cancer outcomes and health system performance. This study aimed to estimate the treatment gap for breast cancer patients treated under FPGC and assess changes in this gap between 2007 (when coverage started for breast cancer treatment) and 2016. We used a nationwide administrative claims database for patients whose breast cancer treatment was financed by FPGC in this period (56,847 women), Global Burden of Disease breast cancer incidence estimates, and other databases to estimate the population not covered by social security. We compared the observed number of patients who received treatment under FPGC to the expected number of breast cancer cases among women not covered by social security to estimate the treatment gap. Nationwide, the treatment gap was reduced by more than half: from 0.71, 95% CI (0.69, 0.73) in 2007 to 0.15, 95%CI (0.09, 0.22) in 2016. Reductions were observed across all states . This is the first study to assess the treatment gap for breast cancer patients covered under Seguro Popular. Expanded financing through FPGC sharply increased access to treatment for breast cancer. This was an important step toward improving breast cancer care, but high mortality remains a problem in Mexico. Increased access to treatment needs to be coupled with effective interventions to assure earlier cancer diagnosis and earlier initiation of high-quality treatment.

Germline Variants in Cancer Genes from Young Breast Cancer Mexican Patients.

Breast cancer (BC) is one of the most frequent cancer types in women worldwide. About 7% is diagnosed in young women (YBC) less than 40 years old. In Mexico, however, YBC reaches 15% suggesting a higher genetic susceptibility. There have been some reports of germline variants in YBC across the world. However, there is only one report from a Mexican population, which is not restricted by age and limited to a panel of 143 genes resulting in 15% of patients carrying putatively pathogenic variants. Nevertheless, expanding the analysis to whole exome involves using more complex tools to determine which genes and variants could be pathogenic. We used germline whole exome sequencing combined with the PeCanPie tool to analyze exome variants in 115 YBC patients. Our results showed that we were able to identify 49 high likely pathogenic variants involving 40 genes on 34% of patients. We noted many genes already reported in BC and YBC worldwide, such as BRCA1, BRCA2, ATM, CHEK2, PALB2, and POLQ, but also others not commonly reported in YBC in Latin America, such as CLTCL1, DDX3X, ERCC6, FANCE, and NFKBIE. We show further supporting and controversial evidence for some of these genes. We conclude that exome sequencing combined with robust annotation tools and further analysis, can identify more genes and more patients affected by germline mutations in cancer.

Presentación.

No disponible.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico.

OBJECTIVE: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. MATERIALS AND METHODS: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. RESULTS: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. CONCLUSION: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Infraestructura oncológica en el Sistema de Salud Mexicano.

No disponible.

Germline pathogenic variants in Mexican patients with hereditary triple-negative breast cancer.

OBJECTIVE: Describe the prevalence of breast cancer (BC)- associated germline pathogenic variants (PVs) among Mexican patients with triple-negative BC (TNBC). MATERIALS AND METHODS: The spectrum of PVs identified among patients with TNBC who were enrolled in a prospective registry and underwent genetic testing was analyzed. RESULTS: Of 387 patients with invasive TNBC and a median age at diagnosis of 39 years (range 21-72), 113 (29%) were carriers of PVs in BC-susceptibility genes: BRCA1 (79%), BRCA2 (15%), and other (6%: ATM, BRIP1, PALB2, PTEN, RAD51C, and TP53). PV carriers were younger at BC diagnosis (37 vs. 40 years, p=0.004) than non-carriers. CONCLUSION: A large proportion of TNBC in Mexican patients is associated with germline PVs, the vast majority in BRCA. The incremental yield of PVs in other BC-susceptibility genes was modest, and a stepwise approach starting with BRCA testing may be justified if it is more cost-effective than multigene panel testing.

Developing a collaborative international partnership for cancer control in Mexico.

In 2014, a partnership was established between the Univer-sity of California and Mexico, which subsequently catalyzed formation of collaborations between cancer researchers at University of California, San Francisco and in Mexico. Over the past two decades cancer burden has dramatically increased in Mexicans on both sides of the California - Mexico border. Together, we face a growing burden of cancer in the context of globalized economies, diverse migration patterns, and dynamic immigration policies. Our partnership aims to: (1) understand the life course impact of cancer risk factors and interactions with changing environments; (2) address cancer disparities within Mexico, in Mexican migrants to the United States, and in naturalized Mexican-Americans; and (3) identify effective cancer screening strategies and cancer control policies that are tailored to existing healthcare systems and social and cultural factors. Herein, we describe the principles of partner-ship and early successes and challenges of this collaboration.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico / Niveles de aflatoxina y prevalencia de mutaciones del gen TP53 por aflatoxina en carcinoma hepatocelular en México

Abstract: Objective: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. Materials and methods: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. Results: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. Conclusion: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Resumen: Objetivo: Determinar la exposición a aflatoxina_B1 (AFB1) en el sur de México y la presencia de la mutación característica de AFB1 en tejido de carcinoma hepatocelular (CHC) de pacientes de un centro oncológico. Material y métodos: Se estimó la prevalencia y distribución de AFB1 en una muestra representativa de 100 mujeres y hombres de Chiapas a partir de la Encuesta Nacional de Salud y Nutrición 2018-19. También se observó la presencia de la mutación característica de AFB1 en el codón 249 (R249S), y otras mutaciones relevantes del gen TP53 en bloques de tejido de CHC de 24 mujeres y 26 hombres estudiados en un centro de referencia nacional de oncología. Resultados: La prevalencia de AFB1 en las muestras de suero fue de 85.5% (IC95% 72.1-93.1) y la mediana de la concentración 0.117 pg/µL (IQR, 0.050-0.350). Se detectó TP53 R249S en tres de 50 casos de CHC (6.0%) y se observaron cuatro transversiones G>T potencialmente inducidas por AFB1. Conclusión: El presente análisis proporciona evidencia de que la AFB1 puede tener un papel relevante en la etiología del CHC en México.

Germline pathogenic variants in Mexican patients with hereditary triple-negative breast cancer / Variantes patóge nas de línea germinal en mexicanas con cáncer de mama triple negativo hereditario

Abstract: Objective: Describe the prevalence of breast cancer (BC)-associated germline pathogenic variants (PVs) among Mexican patients with triple-negative BC (TNBC). Materials and methods: The spectrum of PVs identified among patients with TNBC who were enrolled in a prospective registry and underwent genetic testing was analyzed. Results: Of 387 patients with invasive TNBC and a median age at diagnosis of 39 years (range 21-72), 113 (29%) were carriers of PVs in BC-susceptibility genes: BRCA1 (79%), BRCA2 (15%), and other (6%: ATM, BRIP1, PALB2, PTEN, RAD51C, and TP53). PV carriers were younger at BC diagnosis (37 vs. 40 years, p=0.004) than non-carriers. Conclusion: A large proportion of TNBC in Mexican patients is associated with germline PVs, the vast majority in BRCA. The incremental yield of PVs in other BC-susceptibility genes was modest, and a stepwise approach starting with BRCA testing may be justified if it is more cost-effective than multigene panel testing.

Resumen: Objetivo: Describir la prevalencia de variantes patógenas (VPs) germinales en genes asociados con cáncer de mama (CM) en pacientes mexicanos con CM triple negativo (CMTN). Material y métodos: Se analizó el espectro de VPs identificadas en pacientes con CMTN que fueron incluidos prospectivamente en un registro y se realizó un estudio genético. Resultados: Se analizó un total de 387 pacientes con una mediana de edad al diagnóstico de 39 años; 113 (29%) eran portadores de VPs en genes de susceptibilidad a CM: BRCA1 (79%), BRCA2(15%), y otros (6%: ATM, BRIP1, PALB2, PTEN, RAD51C y TP53). Los portadores de VPs eran más jóvenes al diagnóstico de CM (37 vs. 40 años, p=0.004). Conclusiones: Existe una alta prevalencia de VPs en pacientes mexicanos con CMTN y la mayoría se encuentra en genes BRCA. La realización de pruebas genéticas se puede optimizar mediante la adopción de un proceso escalonado para la detección de VPs.

Developing a collaborative international partnership for cancer control in Mexico / Desarrollo de una alianza internacional colaborativa para el control del cáncer en México

Abstract: In 2014, a partnership was established between the University of California and Mexico, which subsequently catalyzed formation of collaborations between cancer researchers at University of California, San Francisco and in Mexico. Over the past two decades cancer burden has dramatically increased in Mexicans on both sides of the California - Mexico border. Together, we face a growing burden of cancer in the context of globalized economies, diverse migration patterns, and dynamic immigration policies. Our partnership aims to: 1) understand the life course impact of cancer risk factors and interactions with changing environments; 2) address cancer disparities within Mexico, in Mexican migrants to the United States, and in naturalized Mexican-Americans; and 3) identify effective cancer screening strategies and cancer control policies that are tailored to existing healthcare systems and social and cultural factors. Herein, we describe the principles of partnership and early successes and challenges of this collaboration.

Resumen: En 2014, se estableció un convenio de colaboración colaboración entre la Universidad de California y México, que posteriormente catalizó colaboraciones específicas entre investigadores en cáncer en la Universidad de California, San Francisco y en México. En las últimas dos décadas, la carga del cáncer ha aumentado drásticamente en mexicanos de ambos lados de la frontera entre California y México. Juntos, enfrentamos una carga creciente de cáncer en un contexto de economías globalizadas y diversos patrones y políticas de migración dinámicas. Nuestra colaboración tiene como objetivo: 1) entender el impacto a lo largo de la vida de factores de riesgo de cáncer y sus interacciones en un entorno cambiante; 2) abordar disparidades del cáncer dentro de México, en os migrantes mexicanos a los Estados Unidos y en los mexicoamericanos naturalizados; y 3) identificar estrategias efectivas de detección del cáncer y políticas de control del cáncer que se adapten a sistemas de salud existentes y a factores sociales y culturales. Aquí describimos los principios de esta colaboración y los primeros éxitos y retos de la misma.

Cancer control in Latin America and the Caribbean: recent advances and opportunities to move forward.

The increasing burden of cancer represents a substantial problem for Latin America and the Caribbean. Two Lancet Oncology Commissions in 2013 and 2015 highlighted potential interventions that could advance cancer care in the region by overcoming existing challenges. Areas requiring improvement included insufficient investment in cancer control, non-universal health coverage, fragmented health systems, inequitable concentration of cancer services, inadequate registries, delays in diagnosis or treatment initiation, and insufficient palliative services. Progress has been made in key areas but remains uneven across the region. An unforeseen challenge, the COVID-19 pandemic, strained all resources, and its negative effect on cancer control is expected to continue for years. In this Series paper, we summarise progress in several aspects of cancer control since 2015, and identify persistent barriers requiring commitment of additional resources to reduce the cancer burden in Latin America and the Caribbean.