Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Arthralgia and myalgia associated with aromatase inhibitors: frequency and characterization in real-life patients.

Introduction: Adjuvant treatment with aromatase inhibitors (AI) in oestrogen receptor-positive and/or progesterone receptor-positive breast cancer (BC) has been shown to increase overall survival. However, arthralgias and myalgias are common adverse effects in patients treated with AI. Objective: To evaluate the frequency and characteristics of arthralgias and myalgias in patients with early BC-treated adjuvantly with AI in the Mastology Unit of the Oncology Service of the Hospital de Clínicas and the Departmental Hospital of Soriano. Materials and methods: A prospective, cross-sectional and descriptive study was performed. A questionnaire was administered to patients to assess the presence and characteristics of arthralgias and myalgias associated with AI. Statistical analysis: 'Age' was described with measures of central tendency and dispersion. Qualitative variables were presented in absolute and relative frequencies. Logistic models were used to evaluate the association between patient characteristics, tumour characteristics, treatment characteristics and the presence of pain. Results were presented by odds ratio and p-value, using R software (version 4.1.2) with a significance threshold of 5%. Results: 83 patients were included, with a median age of 69 years. 75.9% presented arthralgias and/or myalgias related to treatment, with an average intensity of 5-7. 80.9% received non-steroidal anti-inflammatory drugs (NSAIDs), achieving satisfactory analgesia. The presence of arthralgias and myalgias was significantly associated with age and time since the last menstrual period (LMP), being more frequent in patients older than 50 years and those with more than 5 years since the LMP. Conclusion: Approximately 70% of the patients presented arthralgias or myalgias. These findings suggest a possible role of oestrogen withdrawal in its mechanism of development. Multidisciplinary and translational research is crucial to evaluate the ethology and therapeutic options for patients with AI-related arthralgia.

Efficacy of First-Line Treatment With Pertuzumab and Trastuzumab in Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in Routine Clinical Practice.

Background: The first-line treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) involves a combination of trastuzumab, pertuzumab, and a taxane (TPH). This study assessed the efficacy of trastuzumab and pertuzumab (PH) in routine practice, following the treatment protocols of Uruguay's National Resources Fund (FNR), akin to clinical trials. Methods: Patients with advanced MBC treated with PH between 2008 and 2022 per FNR protocols were evaluated. The Kaplan-Meyer method and log-rank test were utilized for analyzing overall survival (OS). Demographic and clinical variables, including age, menopausal status, and hormone receptors (HR), were analyzed. Results: The study included 318 PH-treated patients. The median age was 56 years, with 63.2% being postmenopausal and 60.4% HR and HER-2 positive. With a median follow-up of 17.2 months, the median OS was 29 months. OS varied based on HR status and the presence of metastases at different sites, significantly lower in patients with brain, cutaneous/subcutaneous, and pulmonary metastases. Additionally, OS was higher in patients treated at private institutions compared to public ones. Conclusions: This study demonstrates the disparity in oncological treatment efficacy between clinical trials and clinical reality in Uruguay, emphasizing the importance of authentic environment research for more representative and effective medicine in Latin America.

Características clínico- patológicas y evolución del cáncer de mama en pacientes asistidas en la Unidad de Mastología del Hospital de Clínicas

Introducción: En Uruguay el cáncer de mama (CM) ocupa el primer lugar en incidencia y mortalidad por cáncer en la mujer, se trata de una enfermedad multifactorial que guarda relación con la herencia genética, historial hormonal estrogénico, estilo de vida, factores ambientales y culturales. Objetivos: investigar las características clínico-patológicas de pacientes con CM diagnosticadas en el Hospital de Clínicas y evaluar la sobrevida global total (SVG) y de acuerdo al subtipo biológico. Metodología: se recolectaron datos relacionados con las características clínico-patológicas y la evolución de pacientes tratadas por CM en el período comprendido entre el 1º de enero del 2011 y 31 de diciembre de 2020 asistidas en la Unidad de Mastología del Hospital de Clínicas. Se calculó la SVG para todas las pacientes, globalmente, y según el subtipo biológico. Resultados: se incluyeron 390 pacientes. Las características clínico-patológicas fueron: carcinoma ductal: 83%, estadio: in situ (1.8 %), I (27.7 %), II (29.7 %), III (23.6%), IV (12.6 %). Con respecto al perfil biológico: 235 tumores (60.3%) fueron RRHH+ HER 2−, 88 tumores (22.6%) fueron HER2 +, mientras que otros 41 tumores (10.5%) fueron clasificados como triple negativos (TN). La SVG para la totalidad de las pacientes tuvo una mediana de 92 meses. Las tasas de SVG a 2 y 5 años fueron para las luminales de 92% y 64%; en las TN la tasa de SVG a 24 meses fue de 69%, siendo a 5 años de 53.3% y en las HER2 + 76.6% y 67.3% respectivamente. Conclusiones: La mayoría de los tumores fueron diagnosticados en estadios precoces, siendo estos datos son concordantes con los reportados en estudios realizados a nivel nacional. La frecuencia de tumores RE/RP+ algo inferior a la reportada en estudios previos (70%) a nivel nacional, mientras que la de tumores HER 2 + TN fue similar a la reportada en estudios europeos, norteamericanos y en Latinoamérica donde se la prevalencia encontrada es del 20%

Introduction: In Uruguay, breast cancer (BC) ranks first in incidence and mortality from cancer in women. It is a multifactorial disease that is related to genetic inheritance, estrogenic hormonal history, lifestyle, environmental and cultural factors. Objectives: to investigate the clinicopathological characteristics of patients with BC diagnosed at the Hospital de Clínicas and to evaluate the overall overall survival (SVG) and according to the biological subtype. Metodology: data related to the clinicopathological characteristics and the evolution of patients treated for BC in the period between January 1, 2011 and December 31, 2020 assisted in the Mastology Unit of the Hospital de Clínicas were collected. Overall survival (SVG) was calculated for all patients, globally, and according to biological subtype. Results: 390 patients were included. The clinicopathological characteristics were: ductal carcinoma: 83%, stage: in situ (1.8%), I (27.7%), II (29.7%), III (23.6%), IV (12.6%). Regarding the biological profile: 235 tumors (60.3%) were HR+ HER 2−, 88 tumors (22.6%) were HER2 +, while another 41 tumors (10.5%) were classified as triple negative (TN). The SVG for all the patients had a median of 92 months. SVG rates at 2 and 5 years were 92% and 64% for luminals; in TN the 24-month survival rate was 69%, being 53.3% at 5 years and in HER2 + 76.6% and 67.3% respectively. Conclusions: Most of the tumors were diagnosed in early stages, these data being consistent with those reported in studies carried out at the national level. The frequency of ER/RP+ tumors was somewhat lower than that reported in previous studies (70%) at the national level, while that of HER 2 + TN tumors was similar to that reported in European, North American and Latin American studies where the prevalence found is 20%

Introdução: No Uruguai, o câncer de mama (CM) ocupa o primeiro lugar em incidência e mortalidade por câncer em mulheres. É uma doença multifatorial que está relacionada à herança genética, história hormonal estrogênica, estilo de vida, fatores ambientais e culturais. Objetivos: investigar as características clinicopatológicas dos pacientes com CM diagnosticados no Hospital de Clínicas e avaliar a sobrevida global (OSV) e segundo o subtipo biológico. Material e método: foram coletados dados referentes às características clínico-patológicas e à evolução dos pacientes atendidos por CM no período de 1º de janeiro de 2011 a 31 de dezembro de 2020 atendidos na Unidade de Mastologia do Hospital de Clínicas. A sobrevida global (SVG) foi calculada para todos os pacientes, globalmente e de acordo com o subtipo biológico. Resultados: 390 pacientes foram incluídos. As características clínico-patológicas foram: carcinoma ductal: 83%, estádio: in situ (1,8%), I (27,7%), II (29,7%), III (23,6%), IV (12,6%). Quanto ao perfil biológico: 235 tumores (60,3%) eram HR+ HER 2−, 88 tumores (22,6%) eram HER2+, enquanto outros 41 tumores (10,5%) foram classificados como triplo negativo (TN). O SVG para todos os pacientes teve uma mediana de 92 meses. As taxas de SVG aos 2 e 5 anos foram de 92% e 64% para luminais; em TN a sobrevida em 24 meses foi de 69%, sendo 53,3% em 5 anos e em HER2 + 76,6% e 67,3%, respectivamente. Conclusões: A maioria dos tumores foi diagnosticada em estágios iniciais, sendo esses dados consistentes com os relatados em estudos realizados em nível nacional. A frequência de tumores ER/RP+ foi um pouco menor do que a relatada em estudos anteriores (70%) em nível nacional, enquanto a de tumores HER 2 + TN foi semelhante à relatada em estudos europeus, norte-americanos e latino-americanos, onde a prevalência encontrado é 20%

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.

Assessing Adherence to Adjuvant Hormone Therapy in Breast Cancer Patients in Routine Clinical Practice.

Background: Adjuvant hormone therapy (HT) in patients with hormone receptor-positive breast cancer (BC) increases overall survival (OS). A lack of adherence to adjuvant endocrine therapy is common, 31.0-73.0% of women discontinue endocrine treatment before 5 years. The aim of the study was to assess adherence to HT in routine clinical practice in patients assisted at the Clinical Oncology Department of the Hospital de Clinicas - Universidad de la Republica, Uruguay. Methods: Patients treated with HT for stage 0-III BC between 2017 and 2019 were included. The medication possession (MPR) rate was calculated using pharmacy records, and the Morisky-Green Scale was applied to assess adherence. Adherent patients were those with MPR ≥ 0.80 and who correctly answered the Morisky-Green treatment adherence questionnaire. The association of adherence with polypharmacy, treatment, and patient characteristics was assessed using simple logistic models. The associations between qualitative variables and adherence were assessed using simple logistic regression model or Fisher's exact test. The association between quantitative variables and adherence was assessed using the Student's t-test. The odds ratio (OR) for non-adherence to treatment and its 95% confidence interval were estimated. Results: Totally, 118 patients were included; 65.2% were treated with aromatase inhibitors (AIs), 36.0% presenting polypharmacy. The adherence rate at the end of 2 years was 81.0 %; and it was associated with age (P = 0.03, OR = 0.96 for non-adherence), with adherent and non-adherent patients having a mean age of 65.0 and 60.3 years, respectively; however, adherence was not associated with polypharmacy, territory of origin, marital status, living alone, level of education, occupation, or stage. The adherence profile was similar for both drugs, but homemakers and retired women showed greater adherence to AI. Conclusions: Adherence to HT was assessed in real life, with 19.0% of the patients not adhering to the treatment, despite the known benefit for OS, being a well-tolerated treatment, and being provided free of charge. Older patients were associated with being more adherent. The results show the need of the Pharmacy Service and Department of Clinical Oncology Medical Oncology combining efforts to develop coordinated strategies and interventions to increase adherence, given the impact that this may have on patients' OS.

Impact of breast cancer treatments on fertility and the importance of timing for a fertility preservation intervention / Impacto en la fertilidad de los tratamientos oncológicos para el cáncer de mama e importancia del momento oportuno para una intervención de preservación

The increased survival achieved with surgery and cancer treatments for breast cancer has led to a growing concern about fertility in young women, adversely affecting quality of life outcomes. Th e potential loss of fertility not only has a psychological but can also affect patients' treatment adherence or decisions, such as selection of treatments associated with a lower risk of infertility despite inferior outcomes. Our objective is to provide an overview of current knowledge about how systemic cancer treatments could impact the future fertility of breast cancer survivors The main hypothesis of how chemotherapy produce damage to the ovaries is a direct damage to the DNA of the oocytes, resulting in the activation of apoptosis and / or autophagy-related pathways. Alkylating agents as cyclophosphamide are the chemotherapeutic agents that are associated with the highest risk of gonadotoxicity; however, breast cancer patients are usually given combinations of chemotherapy drugs. Conversely, endocrine therapy, such as tamoxifen, does not appear to have a permanent effect on fertility but long-term use could lower oocyte quality due to patient aging. There is still not enough evidence about the effect on ovarian reserve for many biological therapies and for new drugs being used in the non-metastatic setting, and further research in this area is needed. Members of multidisciplinary teams in breast cancer should understand the impact on fertility of cancer treatments and the importance of an early referral of premenopausal patients to specialists in reproductive medicine to discuss all possible fertility preservation strategies. (AU)

La mayor sobrevida alcanzada con la cirugía y los tratamientos del cáncer de mama ha generado una creciente preocupación por la afectación de la fertilidad en mujeres jóvenes, lo cual puede impactar negativamente en su calidad de vida. La posible afectación de la fertilidad no solo tiene repercusión psicológica, sino que también puede afectar la adherencia al tratamiento o su selección, pudiendo incluso las pacientes optar por tratamientos asociados con un menor riesgo de infertilidad aún con resultados inferiores. Nuestro objetivo es brindar una visión general del conocimiento actual sobre cómo los tratamientos sistémicos oncológicos pueden impactar en la fertilidad futura de pacientes sobrevivientes al cáncer de mama. La principal hipótesis de cómo la quimioterapia produce daño en los ovarios es el daño directo al ADN de los ovocitos, lo que resulta en la activación de vías relacionadas con la apoptosis y / o autofagia. Los agentes alquilantes como la ciclofosfamida son los agentes quimioterapéuticos que se asocian a mayor riesgo de gonadotoxicidad, si bien habitualmente las pacientes con cáncer de mama reciben combinaciones de varios agentes de quimioterapia. Por el contrario, la terapia endocrina, como el tamoxifeno, no parece tener un efecto permanente sobre la fertilidad, pero su uso prolongado podría reducir la calidad de los ovocitos debido al envejecimiento. Se están utilizando nuevas terapias biológicas en la enfermedad localizada para las cuales aún es desconocido su efecto sobre la reserva ovárica, necesitándose un mayor desarrollo de la investigación en esta área. Los integrantes de equipos multidisciplinarios deben comprender el potencial impacto en la fertilidad de los tratamientos oncológicos y la importancia de una derivación temprana de las pacientes premenopáusicas a especialistas en medicina reproductiva con el objetivo de discutir todas las posibles estrategias para la preservación de la fertilidad. (AU)

Conocimiento y uso de las distintas herramientas de tamizaje del cáncer de mama entre médicos del primer nivel de atención: un estudio transversal / Knowledge and use of different breast cancer screening tools among primary care physicians: a cross-sectional study / Conhecimento e uso de diferentes ferramentas de rastreamento do câncer de mama entre médicos da atenção primária: um estudo transversal

Resumen: Introducción: en Uruguay el cáncer de mama (CM) ocupa el primer lugar en incidencia y mortalidad por cáncer en la mujer. Objetivo: conocer la implementación del tamizaje del CM en la práctica clínica habitual y el grado de adhesión a las recomendaciones planteadas en el año 2015 por el Ministerio de Salud Pública (MSP) para la detección temprana del CM entre los médicos del primer nivel de atención. Material y métodos: se trata de un estudio observacional descriptivo y transversal. Se aplicó una encuesta dirigida a médicos del primer nivel de atención, de carácter anónimo. Resultados: se incluyeron 169 médicos, 89,4% (151) considera que el uso de la mamografía de tamizaje disminuye la mortalidad por CM, 54,4% (92) indica la mamografía a partir de los 40 años de edad y 38,5% (65) a partir de los 50 años. El 56,8% (96) indica la mamografía cada 2 años en la población de mujeres que se encuentran entre 50 y 69 años. El 65,7% de los encuestados (111) conoce la guía nacional y 47,9% (81) la utiliza, mientras que el 18,9% (32) utiliza recomendaciones de otras sociedades científicas. Conclusión: el presente estudio evidenció que los médicos del primer nivel de atención hacen un uso correcto de las distintas herramientas de tamizaje del CM. Se necesitan medidas activas para desarrollar programas educativos para el personal de salud, que podrían permitirles difundir conocimientos e influir positivamente en las actitudes de los pacientes.

Summary: Introduction: in Uruguay, breast cancer (BC) is the leading cause of cancer incidence and mortality in women. Objective: to understand the implementation of BC screening among primary care physicians in routine clinical practice and the degree of adherence to the recommendations put forward in 2015 by the Ministry of Public Health (MPH) for the early detection of BC. Materials and methods: this was a descriptive, cross-sectional, observational study. An anonymous survey was administered to physicians working in primary care. Results: 169 physicians were included, 89.4% (151) consider the use of screening mammography decreases mortality from BC, 54.4% (92) indicate mammography from 40 years of age and 38.5% (65) from 50 years of age. The majority (56.8%, 96) indicate mammography every 2 years in the population of women aged 50-69 years. Of the respondents, 65.7% (111) were aware of the national guidelines and 47.9% (81) followed them, while 18.9% (32) followed recommendations from other scientific bodies. Conclusion: this study showed that primary care physicians make correct use of the different BC screening tools. Active measures are needed to develop educational programs for healthcare personnel, which may enable them to disseminate knowledge and positively influence patients' attitudes.

Resumo: Introdução: o câncer de mama (CM) ocupa o primeiro lugar em incidência e mortalidade por câncer em mulheres no Uruguai. Objetivo: conhecer a implementação do rastreamento do CM na prática clínica de rotina e o grau de adesão às recomendações de 2015 do Ministério da Saúde Pública para detecção precoce do CM entre os médicos do primeiro nível de atenção. Material e métodos: trata-se de um estudo observacional descritivo e transversal. Foi aplicada uma pesquisa anônima destinada aos médicos do primeiro nível de atenção. Resultados: foram incluídos 169 médicos; 89,4% (151) consideram que o uso da mamografia de rastreamento diminui a mortalidade por CM, 54,4% (92) indicam mamografia a partir dos 40 anos e 38,5% (65) a partir dos 50 anos; 56,8% (96) indicam mamografia a cada 2 anos na população de mulheres entre 50 e 69 anos. 65,7% dos respondentes (111) conhecem o guia nacional e 47,9% (81) o utilizam, enquanto 18,9% (32) utilizam recomendações de outras sociedades científicas. Conclusão: este estudo mostrou que os médicos do primeiro nível de atenção fazem uso correto das diferentes ferramentas de rastreamento do CM. São necessárias medidas ativas para desenvolver programas educacionais para os profissionais de saúde, que possam permitir que eles disseminem o conhecimento e influenciem positivamente as atitudes dos pacientes.

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.

Inclusion of information technology-based assessments of health-related quality of life in routine oncology practice in Uruguay.

BACKGROUND: Previous research has shown that the inclusion of patient-reported outcomes measures in the patient's visit to the oncologists might improve the quality of global health care. The aim of the study was to assess the feasibility, acceptance, and utility perceived by patients and oncologists of health-related quality of life (HRQL) assessments obtained prior to clinical visits, and to evaluate if this has an impact on patient's well-being in a sample of Spanish-speaking patients from Uruguay. METHODS: Patients assisted regularly in the Oncology Clinic were randomized into two groups: an intervention group that completed a set of questionnaires (European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC QLQ-C30) and Hospital Anxiety and Depression Scale using a touch screen device and a control group that did not respond to these questionnaires. At 2 months, the responses of all the participants to the Functional Assessment of Cancer Therapy-General (FACT-G) were collected over a telephone to determine whether there were differences in the HRQL between the intervention and control groups. The graphed scores of the intervention group were included in the clinical history of the patient during consultation. Patients and physicians completed the questionnaires on the usefulness of these measurements. RESULTS: In total, 58 patients participated in this study: 36 in the intervention group and 22 in the control group; 65% of the participants were female, and median age was 59 years (18-79). Regarding patients, 97% found the questionnaires easy to complete and thought that they included important questions. As for oncologists, 68.8% used the information and 87.5% found it useful for the consultation. There were no significant differences in the FACT-G scores between the intervention and control groups. CONCLUSIONS: The routine HRQL assessments using an electronic device prior to the consultations were positively valued by almost all patients and physicians. This could significantly contribute to a better understanding of the patient's overall problems during consultation. These results confirm the benefits of integrating the patient's self-reported quality of life outcomes into consultations.

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.

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.

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.

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