Latin America and the Caribbean Code Against Cancer 1st Edition: Medical interventions including hormone replacement therapy and cancer screening.

Prostate, breast, colorectal, cervical, and lung cancers are the leading cause of cancer in Latin America and the Caribbean (LAC) accounting for nearly 50% of cancer cases and cancer deaths in the region. Following the IARC Code Against Cancer methodology, a group of Latin American experts evaluated the evidence on several medical interventions to reduce cancer incidence and mortality considering the cancer burden in the region. A recommendation to limit the use of HRT was issued based on the risk associated to develop breast, endometrial, and ovarian cancer and on growing concerns related to the over-the-counter and without prescription sales, which in turn bias estimations on current use in LAC. In alignment with WHO breast and cervical cancer initiatives, biennial screening by clinical breast examination (performed by trained health professionals) from the age of 40 years and biennial screening by mammography from the age of 50 years to 74, as well as cervical screening by HPV testing (either self-sampling or provider-sampling) every 5-10 years for women aged 30-64 years, were recommended. The steadily increasing rates of colorectal cancer in LAC also led to recommend colorectal screening by occult blood testing every two years or by endoscopic examination of the colorectum every 10 years for both men and women aged 50-74 years. After evaluating the evidence, the experts decided not to issue recommendations for prostate and lung cancer screening; while there was insufficient evidence on prostate cancer mortality reduction by prostate-specific antigen (PSA) testing, there was evidence of mortality reduction by low-dose computed tomography (LDCT) targeting high-risk individuals (mainly heavy and/or long-term smokers) but not individuals with average risk to whom recommendations of this Code are directed. Finally, the group of experts adapted the gathered evidence to develop a competency-based online microlearning program for building cancer prevention capacity of primary care health professionals.

Repercusión de la pandemia COVID-19 en el diagnóstico y tratamiento del cáncer de mama en pacientes asistidas en la Unidad de Mastología del Hospital de Clínicas

Introducción: la crisis sanitaria por COVID-19 impactó en la atención de diversas patologías, entre ellas, el cáncer. Con el fin de disminuir el riesgo de contraer SARS-CoV-2 se redujo el número de consultas, lo que determinó un aumento en la tasa de morbilidad y mortalidad para otras patologías, lo que se ha denominado la "segunda pandemia". Objetivo: describir la actividad asistencial de la Unidad de Mastología (UM) en el período marzo 2020 - marzo 2022 y compararla con la del período marzo 2019 - marzo 2021. Objetivo: describir la actividad asistencial de la Unidad de Mastología (UM) en el período marzo 2020 - marzo 2022 y compararla con la del período marzo 2019 - marzo 2021. Material y método: estudio observacional retrospectivo que incluyó a pacientes asistidas por cáncer de mama (CM) en el período marzo 2019 - marzo 2022. Resultados: durante el año previo a la pandemia se asistieron 30 nuevas pacientes. En cuanto al tiempo entre el diagnóstico anatomopatológico y el primer tratamiento, en 73,3% fue ≤ 2 meses, 16,6% > 2 meses y ≤ 4 meses y en 10% fue > 4 meses. Durante la pandemia se asistieron 50 pacientes nuevas, lo que se traduce en un descenso de 16,6%. En cuanto al tiempo entre el diagnóstico anatomopatológico y el primer tratamiento: en 41% fue ≤ 2 meses, 33% > 2 meses y ≤ 4 meses y en 25% fue > 4 meses. Conclusiones: si bien se logró mantener la actividad asistencial y dar continuidad a la mayoría de los tratamientos, durante la pandemia COVID-19 se redujo el número de pacientes derivadas al servicio en aproximadamente 16,6% y se produjo un aumento en el tiempo transcurrido entre el diagnóstico y el primer tratamiento.

Introduction: the COVID-19 health crisis had a significant impact on the management of various pathologies, including cancer. To reduce the risk of contracting SARS-CoV-2, the number of consultations was reduced, leading to increased morbidity and mortality rates for other pathologies, which has been referred to as the "second pandemic." Objective: The aim of this study is to describe the clinical activity of the Breast Unit (BU) during the period March 2020-2022 and compare it with the activity during the period March 2019-2021. Objective: the aim of this study is to describe the clinical activity of the Breast Unit (BU) during the period March 2020-2022 and compare it with the activity during the period March 2019-2021. Method: retrospective observational study including patients attending the BU during the period March 2019-2022. Results: in the year before the pandemic, 30 new patients were assisted. Regarding the time between anatomopathological diagnosis and the initiation of the first treatment: in 73.3% of cases, it was ≤ 2 months, 16.6% > 2 months and ≤ 4 months, and in 10%, it was > 4 months. During the pandemic, 50 new patients were assisted, representing a decrease of approximately 16.6% in the number of new patients attended. Regarding the time between anatomopathological diagnosis and the initiation of the first treatment: in 41% of cases, it was ≤ 2 months, 33% > 2 months and ≤ 4 months, and in 25%, it was > 4 months. Conclusion: although the BU managed to maintain its clinical activity and continuity of most treatments during the COVID pandemic, there was a reduction in the number of patients referred to the service by approximately 16.6% and an increase in the time elapsed between diagnosis and the initiation of the first treatment.

Introdução: a crise sanitária causada pela COVID-19 impactou o atendimento de diversas patologias, inclusive o câncer. Para diminuir o risco de contrair SARS-CoV-2, reduziu-se o número de consultas, o que determinou um aumento da taxa de morbimortalidade por outras patologias, o que tem sido chamado de "segunda pandemia". Objetivo: descrever a atividade assistencial da Unidade de Mastologia (UM) no período março de 2020 - março de 2022 e compará-la com a do período março de 2019 - março de 2020. Material e método: estudo observacional retrospectivo que incluiu pacientes atendidos pelo CM no período março de 2019 - março de 2022. Resultados: no ano anterior à pandemia foram atendidos 30 novos pacientes. Em relação ao tempo entre o diagnóstico patológico e o primeiro tratamento: em 73,3% foi ≤2 meses, 16,6% >2 meses e ≤4 meses e em 10% foi >4 meses. Durante a pandemia, foram atendidos 50 novos pacientes, o que se traduz em uma queda de 16,6%no número de novos pacientes atendidos. Quanto ao tempo entre o diagnóstico patológico e o primeiro tratamento: em 41% foi ≤2 meses, 33% >2 meses e ≤4 meses e em 25% foi >4 meses. Conclusão: embora tenha conseguido manter a atividade assistencial e dar continuidade à maioria dos tratamentos, durante a pandemia de COVID-19 o número de pacientes encaminhados para o Serviço diminuiu cerca de 16,6% e houve um aumento do tempo decorrido entre o diagnóstico e o primeiro tratamento.

Trastuzumab-induced cardiotoxicity in early breast cancer over a 10-year period in Uruguay.

This srudy aimed to estimate the prevalence of trastuzumab-induced cardiotoxicity in Uruguayan women diagnosed with human epidermal growth factor receptor 2 (HER2)-positive breast cancer over a 10-year period, who were treated under the financial coverage of the National Resources Fund (Fondo Nacional de Recursos). This was an observational, descriptive study based on the analysis of an anonymized database of Uruguayan women diagnosed with HER2-positive breast cancer who received adjuvant trastuzumab treatment from to 2006 to 2016, provided by the Fondo Nacional de Recursos. Statistical analysis was performed using SPSS Statistics version 25, and variables were assessed using measures of central tendency, dispersion, contingency tables, and proportions. The chi-square test was used to analyze the association between the different variables. The study included 1401 patients diagnosed with stage I to III HER2-positive breast cancer. The mean age at diagnosis was 52 years. The prevalence of cardiotoxicity was 20.3%. Most patients who discontinued treatment owing to cardiotoxicity eventually resumed treatment (92.6%). Moreover, the prevalence of cardiotoxicity was similar among patients who received regimens with and without anthracyclines. No association was observed between prior cardiovascular events or trastuzumab administration (concurrent vs sequential) and the development of cardiotoxicity. In the present study, the prevalence of cardiotoxicity was similar to that reported nationally and internationally. Most patients did not develop cardiotoxicity, while the ones who developed it remained asymptomatic and cardiotoxicity was reversible.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

Population-based screening of Uruguayan Ashkenazi Jews for recurrent BRCA1 and BRCA2 pathogenic sequence variants.

In Ashkenazi Jews (AJ) three recurring pathogenic sequence variants (PSVs) are detected in ~2.5% of the general population in the BRCA1 (c.68_69del = 185delAG, c.5266dup = 5382insC), and BRCA2 (c.5946del = 6174delT). Population-based screening for these PSVs in AJ women is part of the health basket in Israel. To assess the feasibility and outcome of BRCA genotyping in the Jewish population of Uruguay, AJ in the greater Montevideo area were recruited using ethically approved protocol and without pretest counseling were genotyped for the three predominant AJ PSVs in the BRCA genes. Independently confirmed PSV carriers were counseled, and genetic testing was offered to additional family members. Overall, 327 participants were enrolled: 312 (95%) female, 261 (80%) had all four grandparents AJ, and 14 (4%) women were breast cancer survivors with a mean age ± standard deviation (SD) 50 ± 11.5 years. The BRCA1 c.68_69del PSV was detected in three cancer free participants (0.92%, CI 95% 0.31-2.6), all with a suggestive family history. No carriers of the other two recurrent PSVs were detected. Online oncogenetic counseling was provided for all carriers. In conclusion, the rate of the BRCA1 c.68_69del PSV was similar with the rate in other AJ communities. AJ population BRCA genotyping screens in Uruguay seem feasible and should be promoted.

Survival and Time to Initiation of Adjuvant Chemotherapy Among Breast Cancer Patients in Uruguay.

INTRODUCTION: Increases in disease-free survival and overall survival (OS) with the use of adjuvant chemotherapy in early breast cancer (BC) are widely known; however, the optimal time to initiate treatment with adjuvant chemotherapy remains controversial. OBJECTIVE: To evaluate the time elapsed between surgery and the initiation of adjuvant chemotherapy and its possible impact on OS in patients diagnosed with BC stages I-III. MATERIALS AND METHODS: This retrospective study included 112 patients diagnosed with BC stages I-III who received adjuvant chemotherapy at the Mastology Unit of the Hospital de Clínicas in Uruguay from 2009 to 2019. OS was estimated using the Kaplan-Meier method, and a Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals. RESULTS: No statistically significant association was found between the time from surgery to the initiation of chemotherapy and the described variables. OS was worse for patients initiating chemotherapy more than 90 days after breast surgery (n = 19) (HR 7.63; p = 0.004) and between 61 and 90 days after surgery (n = 46) (HR 4.58; p = 0.040) compared to those who started before 30 days (n = 23). Controlling by type of surgery and stage, the prognosis of patients who started chemotherapy between 61 and 90 days after surgery was similar to that of patients who underwent chemotherapy within the first 30 days, controlling for surgery (HR 4.10; p = 0.056) and controlling for stage (HR 3.76; p = 0.075). Prognosis was worse for patients with stage III disease (p = 0.022) who underwent a mastectomy and/or axillary lymph node dissection (p = 0.025). CONCLUSION: Patients who started chemotherapy more than 90 days following surgery and those with stage III disease or underwent mastectomy and/or axillary lymph node dissection who initiated it between 61 and 90 days had a worse OS. Multiple factors are involved in the time between surgery and the initiation of chemotherapy, and further studies are needed to evaluate which of these factors influence the delay of chemotherapy in order to design strategies to avoid such delays and their negative impact on survival.

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.

Impact of the COVID-19 pandemic on health care activities at a Uruguayan mastology unit.

PURPOSE: Health emergency due to COVID-19 started in Uruguay on March 13, 2020; our mastology unit tried to ensure adequate oncological care, and protect patients from the virus infection and complications. OBJECTIVE: To assess the health care activities in the "peak" of the pandemic during 3 months. MATERIALS AND METHODS: we collected data from the electronic health record. RESULTS: There were a total of 293 medical appointments from 131 patients (221 face-to-face), that decreased by 16.7% compared to the same period in 2019 (352 appointments). The medical appointments were scheduled to evaluate the continuity of systemic treatment or modifications (95 patients; 72.5%), follow-up (17; 12.9%), first-time consultation (12; 9.1%), and assess paraclinical studies (7; 5.3%). The patients were on hormone therapy (81 patients; 74%), chemotherapy (CT) (21; 19%), and anti-HER2 therapies (9; 8%). New twenty treatments were initiated. Of the 14 patients that were on adjuvant/neoadjuvant CT, 9 (64.3%) continued with the same regimen with the addition of prophylactic granulocyte-colony-stimulating factors (G-CSF), and 5 (35.7%), who were receiving weekly paclitaxel, continued the treatment with no changes. Of the seven patients that were on palliative CT, 2 (28.5%) continued the treatment with the addition of G-CSF, 3 (42.8%) continued with weekly capecitabine or paclitaxel with no treatment changes, and 2 (28.5%) changed their treatment regimen (a less myelosuppressive regimen was selected for one and due to progression of the disease in the other patient). The ninety patients who were receiving adjuvant, neoadjuvant, or palliative criteria hormone therapy and/or anti-HER2 therapies, continued the treatment with no changes. CONCLUSIONS: The evidence suggests that, although medical appointments decreased by approximately 17%, we could maintain healthcare activities, continued most of the treatments while the most modified was CT with G-CSF to avoid myelosuppression.

Social Distancing and Economic Crisis During COVID-19 Pandemic Reduced Cancer Control in Latin America and Will Result in Increased Late-Stage Diagnoses and Expense.

Since December 2019, the world has been mired in an infectious pandemic that has displaced other health priorities for 21st century populations. Concerned about this situation, Latin American experts on cancer decided to evaluate the impact of the pandemic on cancer control in the region. The analysis was based on information obtained from public sources and scientific publications and included the characteristics of the health care and cancer control prior to the pandemic, the COVID-19 pandemic and measures implemented by the governments of the region, and the regional impact of the pandemic on cancer control together with the costs of cancer care and possible impact of the pandemic on cancer expense. We compared 2019 and 2020 data corresponding to the period March 16-June 30 and found a significant reduction in the number of first-time visits to oncology services (variable depending on the country between -28% and -38%) and a corresponding reduction in pathology (between -6% and -50%), cancer surgery (between -28% and -70%), and chemotherapy (between -2% and -54%). Furthermore, a significant reduction in cancer screening tests was found (PAP smear test studies: between -46% and -100%, mammography: between -32% and -100%, and fecal occult blood test: -73%). If this situation becomes a trend, the health and economic impact will be compounded in the postpandemic period, with an overload of demand on health services to ensure diagnostic tests and consequent treatments. On the basis of this information, a set of prevention and mitigation measures to be immediately implemented and also actions to progressively strengthen health systems are proposed.

Prevalence of Known Risk Factors in Uruguayan Women Treated for Breast Cancer at a University Hospital.

INTRODUCTION: In Uruguay, breast cancer has the highest incidence and mortality of all cancer in women. Knowledge of the distribution of risk factors related to disease development supports the implementation of prevention strategies in routine clinical practice. This study aimed to determine the epidemiological profile for breast cancer and the frequency of mammographic surveillance in the surveyed population. MATERIALS AND METHODS: A survey was conducted among Uruguayan women diagnosed with breast cancer who were assisted in the mastology unit of the oncology service of the Hospital de Clínicas in Montevideo, Uruguay, from September 1, 2018, to March 1, 2020. RESULTS: This study included 398 respondents, with a median (SD) age at diagnosis of 61 (34-86) years. A total of 310 respondents (78.0%) had 1 or more risk factors. Most women aged over 50 years (264 out of a total of 338 [78.1%]) underwent mammographic surveillance at least biennially. CONCLUSIONS: Consistent with international reports, most respondents had a risk factor. Among the group of respondents aged over 50 years, most underwent mammographic and clinical surveillance at least biennially. Although it is only possible to formulate conclusions about the surveyed women because of the study design, the obtained data further our understanding of the epidemiological profile of the Uruguayan population, which can contribute to prevention practices.

Evaluación de la eficacia de la consulta telefónica y el nivel de satisfacción de las pacientes asistidas en la Unidad Docente Asistencial de Mastología durante la alerta sanitaria por COVID 19 / Evaluation of the effectiveness of telephone consultations and the level of satisfaction of patients assisted at the Mastology Teacher Assistance Department with this modality during the COVID health emergency / Avaliação da eficácia da consulta telefônica e do nível de satisfação das pacientes atendidas na Unidade de Docência Assistencial de Mastologia durante o alerta de saúde para o COVID 19

Resumen: Introducción: en marzo de 2020 se decretó la emergencia sanitaria por COVID-19, lo que produjo cambios en la organización de los servicios de la salud. Uno de los objetivos de la reorganización fue minimizar las consultas presenciales (CP) y promocionar las telefónicas (CT). Objetivo: evaluar la eficacia de la CT y el nivel de satisfacción de las pacientes asistidas en la Unidad de Mastología con la misma durante la alerta sanitaria por COVID. Material y métodos: se aplicó una encuesta para valorar la eficacia de la CT y el nivel de satisfacción con la misma. Resultados: se encuestaron 42 pacientes, 69% se encontraba recibiendo tratamiento adyuvante y 14,2% paliativo. En cuanto a la eficacia de la CT, 76,1% fueron resueltas en forma telefónica; 78,6% de las pacientes prefirió realizar la consulta en forma telefónica; 97,6% creyó que el tiempo empleado fue suficiente y que el horario en que se la contactó fue adecuado. Las respuestas mostraron un alto grado de satisfacción con la asistencia. La atención médica cumplió con las expectativas de todas las pacientes, 83,3% creyó que una vez recuperada la normalidad, la CT es una opción para su situación. Conclusión: la CT fue valorada con un alto grado de satisfacción y permitió mantener la asistencia durante la emergencia. Si bien es pronto para evaluar el impacto asistencial de la CT y su capacidad resolutiva, resultados preliminares muestran que es una herramienta útil y valiosa en la práctica clínica durante periodos de emergencia sanitaria.

Summary: Introduction: in March 2020, a national health emergency was declared due to the COVID-19, what resulted in changes in the organization of health services. One of the objectives of this restructure was to minimize in person consultations and to promote telephone consultations. that took place was a reduction in face-to-face consultations (FTFC), and the promotion of telephone consultations (TC). Objective: to evaluate the effectiveness of telephone consultations and the level of satisfaction of patients assisted at Mastology Department with this modality during the COVID 19 health emergency. Materials and methods: a survey was used to assess the effectiveness of telephone consultations and the level of satisfaction with this modality. Results: forty-two patients were surveyed, 69% of which were receiving adjuvant treatment and 14.2% of which were receiving palliative treatment. With regard to the effectiveness of telephone consultations, 76.1% of those surveyed had their need solved by telephone; 78.6% of patients preferred to do the consultation by telephone; 97.6% believed that sufficient time was spent and that the timing of the appointment was appropriate. The responses showed a high level of satisfaction with the care received. The medical care met the expectations of all patients, and 83.3% believed that once the situation went back to normal, telephone consultations would be an option for their requirements. Conclusion: the telephone consultation method was evaluated with a high level of satisfaction and it allowed health care services to be maintained during the emergency. Although it is early to assess the healthcare impact of telephone consultations and the modality's capacity to resolve issues, preliminary results show that it is a useful and valuable tool in clinical practice during periods of healthcare emergency.

Resumo: Introdução: em março de 2020, foi decretada a emergência sanitária decorrente do COVID-19, o que produziu mudanças na organização dos serviços de saúde. Um dos objetivos da reorganização era minimizar as consultas presenciais (CP) e promover as consultas telefônicas (CT). Objetivo: avaliar a eficácia da CT e o nível de satisfação das pacientes atendidas na Unidade de Docência Assistencial de Mastologia com a prestada previamente durante o alerta de saúde para o COVID. Material e métodos: foi realizada uma pesquisa telefônica para avaliar a eficácia da TC e o nível de satisfação com a mesma. Resultados: foram entrevistadas 42 pacientes, 69% estavam recebendo tratamento adjuvante e 14,2% paliativo. Em relação à eficácia da CT, 76,1% foram resolvidas por telefone; 78,6% das pacientes preferiram fazer a consulta por telefone; 97,6% consideraram que o tempo despendido foi suficiente e que o momento em que foram contatados foi adequado. As respostas mostraram alto grau de satisfação com o atendimento. O atendimento médico atendeu às expectativas de todos os pacientes, 83,3% acreditam que, uma vez restaurada a normalidade, a CT é uma opção para sua situação. Conclusão: a CT foi avaliada com alto grau de satisfação e permitiu manter o atendimento durante a emergência. Embora seja muito cedo para avaliar o impacto da CT na saúde e sua capacidade de resolução, resultados preliminares mostram que é uma ferramenta útil e valiosa na prática clínica durante períodos de emergência de saúde.

Expresión tumoral de BRCA1 y resultados clínicos en pacientes uruguayas diagnosticadas de cáncer de mama antes de los 40 años / BRCA1 tumor expression and clinical results in uruguayan patients diagnosed with breast cancer before the age of 40 years old / Expressão tumoral de BRCA1 e resultados clínicos em pacientes uruguaias com diagnóstico de câncer de mama antes dos 40 anos

Resumen: Las mutaciones de BRCA1 son raras en el cáncer de mama (CM) esporádico; sin embargo, su expresión a nivel tumoral se encuentra disminuida o ausente en 30%-50% de los casos. Objetivo: valorar la expresión tumoral de BRCA1 por inmunohistoquímica (IHQ) en mujeres uruguayas diagnosticadas de CM antes de los 40 años. Material y método: se incluyeron pacientes diagnosticadas de CM antes de los 40 años. Se utilizaron los anticuerpos monoclonales anti-BRCA1 MS110 contra el extremo N-terminal y GLK-2 contra el extremo C-terminal. Se calculó la sobrevida global (SVG) y la sobrevida libre de enfermedad (SVLE), para la construcción de las curvas se utilizó el método de Kaplan-Meier y la diferencia de sobrevida se evaluó mediante el test de log rank. Resultados: se incluyeron 40 pacientes, la SVG y la SVLE a cinco años fueron de 73% y 60% respectivamente. La expresión de BRCA1 mediante GLK-2 fue <10% en 16 de las 40 pacientes (40%). La SVG y la SVLE a cinco años para las pacientes con expresión <10% fue de 56% vs 85% para las pacientes con expresión >10% (p=0,015) y de 40% vs 72% (p=0,034) respectivamente. La expresión de BRCA1 mediante MS110 fue <10% en 11 de las 40 pacientes (27,5%). No se encontraron diferencias en la SVG ni en la SVLE a cinco años con este marcador. Conclusión: la pérdida de la expresión tumoral de BRCA1 determinada mediante GLK-2 se encontró en el 40% de las pacientes incluidas y se asoció a una menor SVG y SVLE, por lo que podría tener un valor pronóstico desfavorable en estas pacientes.

Summary: BRCA1 mutations are rare in sporadic breast cancer (CM), however their expression at the tumor level is diminished or absent in 30-50% of cases. Objective: to assess the tumor expression of BRCA1 using immunohistochemistry (IHC) in Uruguayan women diagnosed with BC before the age of 40 years. Material and methods: patients diagnosed with BC before the age of 40 between. The antibodies used were anti BRCA1 MS110 monoclonal antibodies against the N-terminal end and GLK-2 against the C-terminal. Overall survival (OS) and disease free survival (DFS) were calculated; the curves were developed using the Kaplan-Meier method and the difference in survival was evaluated through the log rank test. Results: the average age of the 40 patients included was 36 years. The 5-year OS and DFS were 73% and 60% respectively. The expression of BRCA1 with GLK-2 was <10% in 16 of the 40 patients included (40%). The 5-year OS and DFS for patients with <10% expression was 56% vs. 85% for patients with >10% (p=0.015) and 40% vs. 72% (p = 0.034) respectively. The expression of BRCA1 by MS110 was <10% in 11 of the 40 patients included (27.5%). No differences were found in the 5-year OS or DFS based on the expression of this marker. Conclusion: The loss of BRCA1 expression using GLK-2, which suggests the presence of a truncated protein, was associated with a statistically significantly lower OS and DFS, that the decrease in the BRCA1 protein as determined by GLK2 has an unfavorable prognostic value for young patients with BC.

Resumo: As mutações de BRCA1 são raras no câncer de mama (CM) esporádico; no entanto sua expressão no nível tumoral está diminuída ou ausente em 30-50% dos casos. Objetivo: avaliar a expressão tumoral de BRCA1 por imuno-histoquímica (IHQ) em mulheres uruguaias com diagnóstico de CM antes dos 40 anos. Material e métodos: foram incluídas pacientes com diagnóstico de CM antes dos 40 anos. Foram utilizados anticorpos monoclonais anti BRCA1 MS110 contra o extremo N-terminal e GLK-2 contra o extremo C-terminal. A sobrevida global (SVG) e a sobrevida livre de enfermidade (SVLE) foram calculadas; o método de Kaplan-Meier foi utilizado para a construção das curvas e a diferença de sobrevida foi avaliada usando o teste de log-rank. Resultados: foram incluídas 40 pacientes; a SVG e a SVLE aos 5 anos foram 73% e 60% respectivamente. A expressão de BRCA1 mediante GLK-2 foi <10% em 16 das 40 pacientes (40 %). A SVG e a SVLE aos 5 anos para as pacientes com expressão £10% foi 56% vs. 85% para as pacientes com expressão >10% (p=0,015) e 40% vs. 72% (p=0,034) respectivamente. A expressão de BRCA1 mediante MS110 foi =10% em 11 das 40 pacientes (27,5%). Não foram encontradas diferenças na SVG nem na SVLE aos 5 anos com este marcador. Conclusão: foi encontrada perda da expressão tumoral de BRCA1 determinada por GLK-2 em 40% das pacientes incluídas e foi associada a uma menor SVG e SVLE, o que poderia ter um valor prognóstico desfavorável nestas pacientes.

Effectiveness of Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in a Real-Life Setting: One Decade of Experience Under National Treatment Coverage Regulations.

PURPOSE: Trastuzumab has shown an overall survival (OS) benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), in both the adjuvant and the metastatic setting. We assessed the effectiveness of trastuzumab in patients treated in daily practice according to national treatment coverage protocols and compared our results with those reported by randomized clinical trials. These coverage protocols included patient selection criteria similar to those of those clinical trials and were developed by the Uruguayan National Resource Fund (FNR), the agency that has funded these prescriptions for more than a decade. PATIENTS AND METHODS: We included all patients with HER2-positive BC treated with trastuzumab under FNR coverage approved between January 1, 2006, and December 31, 2016. The source of data was the FNR database, and primary outcome was OS, analyzed through Cox proportional hazards regression analysis. RESULTS: A total of 1,944 women were included: 1,085 women (55.8%) were postmenopausal and 1,240 (63.7%) had HER2 and hormone receptor-positive BC. Trastuzumab was administered as adjuvant therapy to 1,233 patients (63.5%), of whom 154 also received it as a neoadjuvant treatment. Three hundred nineteen patients (16.4%) received trastuzumab for advanced disease. Five-year OS in the adjuvant setting was 86.4% (95% CI, 84.0% to 88.7%). The median survival of patients with advanced BC was 25.1 months (95% CI, 10.1 to 42.5 months). CONCLUSION: Our survival results are not inferior to those reported in clinical trials, in both adjuvant and advanced settings. Importantly, these results support the relevance and the feasibility of treating patients in routine practice, following coverage protocols based on patient selection criteria and methods supported by positive clinical trials. In addition, these results favor quality and appropriate access to BC treatment in our country.

Personalizing Precision Oncology Clinical Trials in Latin America: An Expert Panel on Challenges and Opportunities.

The participation of patients in precision oncology trials needs to fulfill molecular-based selection criteria. This strongly limits accrual, and as a consequence, screening successes have decreased, costs have increased, and fewer subjects are enrolled. To achieve narrowed targets, studies have been forced to be multicenter and multinational to reach a larger pool of candidates. However, this globalization faces many challenges, as, for example, in the case of precision oncology trials. These trials have a complex structure that is dependent upon a high-tech infrastructure and knowledge in a dynamic environment. Given the movement of precision clinical cancer research to regions other than Europe and the U.S., it is important to evaluate the feasibility of performing such trials in lower-middle- and low-income countries. Here we critically discuss the advantages of conducting precision oncology clinical trials in Latin America and make suggestions on how to overcome the main challenges involved. IMPLICATIONS FOR PRACTICE: Precision clinical trials in oncology are studies that require candidates to have tumors with specific molecular alterations, which are considered the target for the trial experimental therapy. Because many molecular alterations are rare, fewer patients are enrolled. This has led to trials being forced to be multicenter and multinational, including trials in Latin America. This article discusses the challenges and opportunities to conduct precision oncology trials in Latin America, aiming to help sponsors and investigators to solve complex issues that ultimately lead to more of such trials being run in the region, potentially benefiting more Latin American patients with cancer.

Síndrome de Li Fraumeni: análisis clínico de un caso y revisión de la literatura / Li-Fraumeni syndrome: clinical case study and literature survey / Síndrome de Li Fraumeni: análise clínica de um caso e uma revisão da literatura

Resumen: El síndrome de Li-Fraumeni (SLF) es una enfermedad hereditaria autosómica dominante con elevada penetrancia, que se caracteriza por la aparición precoz de múltiples tumores en un individuo y una marcada agregación familiar. Aproximadamente el 70% de los pacientes que cumplen criterios clínicos para su diagnóstico son portadores de la mutación germinal del gen TP53 localizado en el cromosoma 17p13. El gen TP53 es un supresor tumoral que cumple una importante función en el control de la estabilidad genómica. Se estima que el riesgo de desarrollar cáncer es del 50 % para las mujeres a los 31 años de edad y para los hombres a los 46 años y cerca del 100 % para ambos sexos a los 70 años. El curso clínico de la enfermedad es similar que en pacientes sin SLF a excepción de la edad más temprana al diagnóstico. Presentamos el caso de una paciente de 31 años a la que se diagnostica un condrosarcoma pelviano tratado con cirugía y al momento de la recidiva, aproximadamente 8 meses después, un cáncer de mama localizado. En otro miembro de su familia se había identificado la mutación 375G>C en el gen TP53 mediante secuenciación Sanger, la cual fue detectada posteriormente en nuestra paciente. Se discuten aspectos particulares del manejo como la minimización de la exposición a la radioterapia (por reportes de tumores malignos en zonas irradiadas) y el especial manejo de la repercusión del diagnóstico a nivel de los otros integrantes de la familia.

Abstract: The Li-Fraumeni syndrome (SLF) is a highly penetrant condition with an autosomal dominant inheritance pattern, characterized by an early onset of multiple tumors in a subject and a marked familial occurrence. About 70 % of patients meeting clinical criteria for diagnosis of the disease carry the germline mutation of TP53 gene located in chromosome 17p13. TP53 is a tumor suppressor gene known for its major role in genome stability control. It has been estimated that risk of cancer development is 50 % for women at the age of 31 and for men at the age of 46 and nearly 100 % for both men and women at 70 years of age. Except at earlier ages of diagnosis, the clinical course of the disease for healthy patients and for patients suffering SLF shows similarities. We present the case of a 31-year-old patient diagnosed both with pelvic chondrosarcoma treated surgically and localized breast cancer during relapse, about 8 months later. By Sanger sequencing, mutation 375G>C had been identified in TP53 gene in another family member, and said mutation was later detected in our patient. We discuss particular aspects of treatment procedures, such as minimizing radiotherapy exposure (due to reports of malignancies in radiated areas) and the special management of diagnosis implications for other family members.

Resumo: A síndrome de Li-Fraumeni (SLF) é uma doença hereditária autorexistente dominante com pena de penetração, que caracteriza a aparição precoz de múltiplos tumores em um indivíduo e uma coletânea familiar. Aproximadamente o 70% dos pacientes com critérios clínicos para o diagnóstico em crianças portadores da mutação germinal do gen TP53 localizado no cromosoma 17p13. El gen TP53 é um tumor tumoral que cumple uma função importante no controle da estabilização genómica. Se estima que o riesgo do desengate faz dos 50% para as mulheres aos 31 anos de idade e para os 40 anos e cerca de 100% para ambos os sexos aos 70 anos. O curso clínico da doença é semelhante ao que ocorre com a SLF a exceção da doença mais tem sido diagnosticada. Presentamos o caso de um paciente de 31 años que diagnostica um paciente de pélvico com relato ao momento da recidiva, aproximadamente 8 meses depois, em um lugar de mama próximo. En otio miembro de la familia se habiocuident to the mutación 375G> C en el gen TP53 por secuenciación Sanger, a cual fue detectada em recente paciente. A discussão foi feita sobre os aspectos do tratamento com a minimização da exposição à radioterapia (por tumores malignos em zonas irradiadas) e o especial manejo da repercussão do diagnóstico a nível dos otros integrantes da familia

Perspectives on Strengthening Cancer Research and Control in Latin America Through Partnerships and Diplomacy: Experience of the National Cancer Institute's Center for Global Health.

According to the Pan American Health Organization, noncommunicable diseases, including cancer, are the leading causes of preventable and premature death in the Americas. Governments and health care systems in Latin America face numerous challenges as a result of increasing morbidity and mortality from cancer. Multiple international organizations have recognized the need for collaborative action on and technical support for cancer research and control in Latin America. The Center for Global Health at the US National Cancer Institute (NCI-CGH) is one entity among many that are working in the region and has sought to develop a strategy for working in Latin America that draws on and expands the collaborative potential of engaged, skilled, and diverse partners. NCI-CGH has worked toward developing and implementing initiatives in collaboration with global partners that share the common objectives of building a global cancer research community and translating research results into evidence-informed policy and practice. Both objectives are complementary and synergistic and are additionally supported by an overarching strategic framework that is focused on partnerships and science diplomacy. This work highlights the overall strategy for NCI-CGH engagement in Latin America through partnerships and diplomacy, and highlights selected collaborative efforts that are aimed at improving cancer outcomes in the region.

Predictors of Postoperative Acute Kidney Injury after Coronary Artery Bypass Graft Surgery.

OBJECTIVE: The aims of this study were to identify the risk factors associated with acute kidney injury (AKI) after isolated surgical revascularization with cardiopulmonary bypass and to develop a model to predict the appearance of postoperative AKI. METHODS: A total of 435 adult patients who underwent primary isolated coronary artery bypass graft (CABG) surgery, from 2012 to 2016, in the Clinic University Hospital of Valladolid (Spain) were enrolled. AKI was defined according to the risk, injury, failure, loss, and end-stage (RIFLE) criteria. Data were collected from hospital electronic medical records. Multiple logistic regression analysis was used to identify risk factors. RESULTS: The prevalence of AKI was 12.4%. Multivariate analysis identified age (odds ratio [OR], 1.056; 95% confidence interval [CI], 1.016-1.098; P=0.005), hypertension (OR, 3.078; 95% CI, 1.151-8.230; P=0.018), low ejection fraction (EF) (OR, 6.785; 95% CI, 2.080-22.135; P=0.001), estimated glomerular filtration rate (eGFR) (OR, 1.017; 95% CI, 1.005-1.028; P=0.014), EuroSCORE II (OR, 1.049; 95% CI, 1.004-1.096; P=0.033), and no intake of calcium-channel blockers (CCB) (OR, 4.892; 95% CI, 1.496-16.025; P=0.022) as risk factors for AKI. These risk factors were included in a model to predict postoperative AKI with an area under a receiver operating characteristic curve of 0.783±0.036 (95% CI, 0.713-0.854; P<0.0001). CONCLUSION: Age, hypertension, low EF, eGFR, EuroSCORE II, and no intake of CCB were independent risk factors for postoperative AKI. These factors provide an easy and accurate model to predict postoperative AKI in patients undergoing cardiac surgery.

Predictors of postoperative acute kidney injury after coronary artery bypass graft surgery

Abstract Objective: The aims of this study were to identify the risk factors associated with acute kidney injury (AKI) after isolated surgical revascularization with cardiopulmonary bypass and to develop a model to predict the appearance of postoperative AKI. Methods: A total of 435 adult patients who underwent primary isolated coronary artery bypass graft (CABG) surgery, from 2012 to 2016, in the Clinic University Hospital of Valladolid (Spain) were enrolled. AKI was defined according to the risk, injury, failure, loss, and end-stage (RIFLE) criteria. Data were collected from hospital electronic medical records. Multiple logistic regression analysis was used to identify risk factors. Results: The prevalence of AKI was 12.4%. Multivariate analysis identified age (odds ratio [OR], 1.056; 95% confidence interval [CI], 1.016-1.098; P=0.005), hypertension (OR, 3.078; 95% CI, 1.151-8.230; P=0.018), low ejection fraction (EF) (OR, 6.785; 95% CI, 2.080-22.135; P=0.001), estimated glomerular filtration rate (eGFR) (OR, 1.017; 95% CI, 1.005-1.028; P=0.014), EuroSCORE II (OR, 1.049; 95% CI, 1.004-1.096; P=0.033), and no intake of calcium-channel blockers (CCB) (OR, 4.892; 95% CI, 1.496-16.025; P=0.022) as risk factors for AKI. These risk factors were included in a model to predict postoperative AKI with an area under a receiver operating characteristic curve of 0.783±0.036 (95% CI, 0.713-0.854; P<0.0001). Conclusion: Age, hypertension, low EF, eGFR, EuroSCORE II, and no intake of CCB were independent risk factors for postoperative AKI. These factors provide an easy and accurate model to predict postoperative AKI in patients undergoing cardiac surgery.