Germline and Somatic mutations in postmenopausal breast cancer patients.

OBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Germline and Somatic mutations in postmenopausal breast cancer patients

OBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Cancer and Cardiovascular Diseases during the COVID-19 Pandemic. / Câncer e Doenças Cardiovasculares na Pandemia de COVID-19.

The challenges that the COVID-19 pandemic cretead to the healthcare system have made it necessary to adapt routines and services, with the objectives of controlling the spread of the virus and preserving health. Safe and correct management of patients in risks groups, such as elderly patients, patients with cardiovascular diseases, and patients with cancer, has become even more important. Thus, cardio-oncology has gained a new dimension, with the aim of adapting to patients' needs during the pandemic by restructuring the system of care in a manner that offers quality and safety in healthcare.

O desafio imposto ao sistema de saúde pela pandemia da COVID-19 faz com que haja uma necessidade de readequações de rotinas e serviços de saúde, com os objetivos de controlar a disseminação do vírus e preservar a saúde. Torna-se ainda mais importante o manejo seguro e correto dos pacientes dos grupos de risco, como os pacientes idosos, os portadores de doenças cardiovasculares e os pacientes com câncer. Dessa forma, a cardio-oncologia ganha novo dimensionamento, no intuito de se adequar às necessidades dos pacientes diante de uma pandemia, reestruturando o sistema de atendimento de forma a oferecer qualidade e segurança na assistência à saúde.

Câncer e Doenças Cardiovasculares na Pandemia de COVID-19 / Cancer and Cardiovascular Diseases during the COVID-19 Pandemic

Resumo O desafio imposto ao sistema de saúde pela pandemia da COVID-19 faz com que haja uma necessidade de readequações de rotinas e serviços de saúde, com os objetivos de controlar a disseminação do vírus e preservar a saúde. Torna-se ainda mais importante o manejo seguro e correto dos pacientes dos grupos de risco, como os pacientes idosos, os portadores de doenças cardiovasculares e os pacientes com câncer. Dessa forma, a cardio-oncologia ganha novo dimensionamento, no intuito de se adequar às necessidades dos pacientes diante de uma pandemia, reestruturando o sistema de atendimento de forma a oferecer qualidade e segurança na assistência à saúde.

Abstract The challenges that the COVID-19 pandemic cretead to the healthcare system have made it necessary to adapt routines and services, with the objectives of controlling the spread of the virus and preserving health. Safe and correct management of patients in risks groups, such as elderly patients, patients with cardiovascular diseases, and patients with cancer, has become even more important. Thus, cardio-oncology has gained a new dimension, with the aim of adapting to patients' needs during the pandemic by restructuring the system of care in a manner that offers quality and safety in healthcare.

Clinical spectrum of Li-Fraumeni syndrome/Li-Fraumeni-like syndrome in Brazilian individuals with the TP53 p.R337H mutation.

BACKGROUND: The TP53 p.R337H germline mutation is highly prevalent among children with adrenocortical tumors (ACTs) from South and Southeast Brazil. However, the prevalence of other tumors of the Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL) spectrum, the clinical outcomes and the potential tumor occurrence in relatives carrying this distinct TP53 mutation were not fully investigated. PATIENTS AND METHODS: We investigated tumor profile data and outcomes of individuals and their close relatives with the TP53 p.R337H germline mutation. A questionnaire and the Toronto protocol were used for evaluation of asymptomatic carriers of this TP53 mutation. RESULTS: The cohort of this study comprised 51 patients from 46 different families; 67% were female. All but one harbored the TP53 p.R337H mutation in heterozygous state; only one child was homozygous for this variant. Maternal allele inheritance occurred in 72% of the cases (p= 0,002). In pediatric group, ACT was the most common primary tumor at the diagnosis (55%; median age= 2 years). No patient of the pediatric group who initially presented with ACT developed a second primary tumor and 11% (n= 3) died due to complications related to the primary tumor (median follow-up time of 81.5 months, range= 3-378 months). In adult group, the main tumors at diagnosis were: adrenocortical carcinoma (ACC) (23%; median age= 29.5 years), breast cancer (12%; median age= 38.5 years), soft tissue sarcoma (8%; median age= 50.3 years) and choroid plexus carcinoma (CPC) (2%; median age= 18 years). Among adult patients who were diagnosed with ACC as the first primary tumor, all presented with aggressive disease as per histologic and clinical criteria at diagnosis, and 75% of patients died (median follow-up time of 19 months, range= 1-69 months). Five adult patients (22%) had a second primary tumor, including bronchoalveolar lung cancer (2 cases), ACC, uterine cervical carcinoma and fibrosarcoma. The diagnosis of these tumors was established from 8 to 36 months after the first primary tumor. Three families presented more than one case of ACT. Nine malignant neoplasms were diagnosed in asymptomatic carriers using Toronto protocol. CONCLUSIONS: This study confirms a high frequency of TP53 p.R337H mutation in pediatric group with ACT. In addition, we observed the occurrence of other tumors of LFS/LFL spectrum and a difference in the aggressiveness of ACTs depending on the age group in which they were diagnosed. The predominance of maternal mutated allele inheritance was first demonstrated in the affected Brazilian's families.

Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric cancer patients in Brazil.

INTRODUCTION: The contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil. We aimed to evaluate the frequency of CDH1 germline variants and the diet/lifestyle habits in early age onset gastric cancer (EOGC, ≤ 55 years old) patients. METHODOLOGY: From 2013 to 2015, a total of 88 unrelated and consecutive patients diagnosed with EOGC were enrolled. All CDH1 exons and intronic boundaries were sequenced, and large genomic rearrangements were screened by MLPA. CDH1 transcription analysis was performed for variants that could potentially induce an effect on splicing. The diet and lifestyle habits of EOGC patients were compared to Brazilian population diet and lifestyle, obtained from governmental databases. RESULTS: Of 88 patients, the mean age at EOGC diagnosis was 39 years and 55% fulfilled the criteria for hereditary diffuse gastric cancer. The majority of the tumors were diffuse (74%) and poorly differentiated (80%). In total, 4 novel missense variants of uncertain significance (VUS) were identified: c.313T>A, c.387G>T, c.1676G>A, and c.1806C>A. The MLPA results revealed no rearrangements and CDH1 transcription analysis for variants of interest were inconclusive. EOGC patients had a higher red (OR:2.6, 95%CI:1.4-4.9) and processed (OR:3.1, 95%CI:1.6-6.0) meat intake and higher fruit consumption (OR:0.4, 95%IC:0.3-0.7) compared to eating habits of the Brazilian population. CONCLUSIONS: No unequivocal pathogenic germline CDH1 variants were identified in Brazilian EOGC patients. Dietary habits may be associated with the EOGC development.

Integrated care pathway for rectal cancer treatment: cross-sectional post-implementation study using a logic model framework.

BACKGROUND: Management of rectal cancer has become more complex with multimodality therapy (neoadjuvant chemoradiotherapy and surgery) and this has led to the need to organize multidisciplinary teams. The aim of this study was to report on the planning, implementation and evaluation of an integrated care pathway for neoadjuvant treatment of middle and lower rectal cancer. DESIGN AND SETTING: This was a cross-sectional post-implementation study that was carried out at a public university cancer center. METHODS: The Framework for Program Evaluation in Public Health of the Centers for Disease Control and Prevention (CDC) was used to identify resources and activities; link results from activities and outcomes with expected goals; and originate indicators and outcome measurements. RESULTS: The logic model identified four activities: stakeholders' engagement, clinical pathway development, information technology improvements and training programs; and three categories of outcomes: access to care, effectiveness and organizational outcomes. The measurements involved 218 patients, among whom 66.3% had their first consultation within 15 days after admission; 75.2% underwent surgery < 14 weeks after the end of neoadjuvant treatment and 72.7% completed the treatment in < 189 days. There was 100% adherence to the protocol for the regimen of 5-fluorouracil and leucovorin. CONCLUSIONS: The logic model was useful for evaluating the implementation of the integrated care pathways and for identifying measurements to be made in future outcome studies.

Cost effectiveness of the cancer prevention program for carriers of the BRCA1/2 mutation.

OBJECTIVE: To analyze the cost effectiveness of the diagnostic program for the germline mutation in BRCA1/2 genes and of preventative strategies for the relatives of patients diagnosed with ovarian cancer associated with this mutation. METHODS: The study analyzed the cost effectiveness by developing an analysis of the Markov decision process from the perspective of the National Health System. The strategies compared reflect upon the adoption of genetic testing and preventative strategies for relatives or the usual care currently proposed. The incremental cost-effectiveness ratio was expressed in terms of cost per case avoided. The sensitivity analysis was performed in a univariate and deterministic manner. RESULTS: The study showed increments for effectiveness and for costs when performing genetic testing and adopting prophylactic measures for family members. The incremental cost-effectiveness ratio was estimated at R$908.58 per case of cancer avoided, a figure considered lower than the study's cost-effectiveness threshold (R$7,543.50). CONCLUSIONS: The program analyzed should be considered a cost-effective strategy for the national situation. Studies in various other countries have reached similar conclusions. One possible ramification of this research might the need to perform a budgetary-impact analysis of making the program one of the country's health policies.

Health Economic Evaluations of Cancer in Brazil: A Systematic Review.

Background: A large number of health economic evaluation (HEE) studies have been published in developed countries. However, Brazilian HEE literature in oncology has not been studied. OBJECTIVE: To investigate whether the scientific literature has provided a set of HEE in oncology capable of supporting decision making in the Brazilian context. Methods: A systematic review was conducted to identify and characterize studies in this field. We searched multiple databases selecting partial and full HEE studies in oncology (1998-2013). Results: Fifty-five articles were reviewed, of these, 33 (60%) were full health economic evaluations. Type of cancers most frequently studied were: breast (38.2%), cervical (14.6%), lung (10.9%) and colorectal (9.1%). Procedures (47.3%) were the technologies most frequently evaluated. In terms of the intended purposes of the technologies, most (63.6%) were treatments. The majority of the incremental cost-effectiveness ratios (ICERs) reported have been below the cost-effectiveness threshold suggested by the World Health Organization (WHO). Conclusions: There has been an increase in the number of HEEs related to cancer in Brazil. These studies may support decision-making processes regarding the coverage of and reimbursement of healthcare technologies for cancer treatment in Brazil.

Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management.

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.

Guidelines for early detection of breast cancer in Brazil. II - New national recommendations, main evidence, and controversies. / Diretrizes para detecção precoce do câncer de mama no Brasil. II - Novas recomendações nacionais, principais evidências e controvérsias.

Breast cancer is the leading cause of cancer mortality in Brazilian women. The new Brazilian guidelines for early detection of breast cancer were drafted on the basis of systematic literature reviews on the possible harms and benefits of various early detection strategies. This article aims to present the recommendations and update the summary of evidence, discussing the main controversies. Breast cancer screening recommendations (in asymptomatic women) were: (i) strong recommendation against mammogram screening in women under 50 years of age; (ii) weak recommendation for mammogram screening in women 50 to 69 years of age; (iii) weak recommendation against mammogram screening in women 70 to 74 years of age; (iv) strong recommendation against mammogram screening in women 75 years or older; (v) strong recommendation that screening in the recommended age brackets should be every two years as opposed to shorter intervals; (vi) weak recommendation against teaching breast self-examination as screening; (vii) absence of recommendation for or against screening with clinical breast examination; and (viii) strong recommendation against screening with magnetic resonance imaging, ultrasonography, thermography, or tomosynthesis alone or as a complement to mammography. The recommendations for early diagnosis of breast cancer (in women with suspicious signs or symptoms) were: (i) weak recommendation for the implementation of awareness-raising strategies for early diagnosis of breast cancer; (ii) weak recommendation for use of selected signs and symptoms in the current guidelines as the criterion for urgent referral to specialized breast diagnosis services; and (iii) weak recommendation that every breast cancer diagnostic workup after the identification of suspicious signs and symptoms in primary care should be done in the same referral center.

O câncer de mama é a principal causa de morte por câncer em mulheres no Brasil. As novas diretrizes para detecção precoce no Brasil foram elaboradas com base em revisões sistemáticas da literatura sobre riscos e possíveis benefícios de diversas estratégias de detecção precoce. O objetivo do presente artigo é apresentar as recomendações e atualizar a síntese de evidências, discutindo as principais controvérsias existentes. As recomendações para o rastreamento do câncer de mama (mulheres assintomáticas) foram: (i) recomendação contrária forte ao rastreamento com mamografia em mulheres com menos de 50 anos; (ii) recomendação favorável fraca ao rastreamento com mamografia em mulheres com idades entre 50 e 69 anos; (iii) recomendação contrária fraca ao rastreamento com mamografia em mulheres com idades entre 70 e 74 anos; (iv) recomendação contrária forte ao rastreamento com mamografia em mulheres com 75 anos ou mais; (v) recomendação favorável forte de que o rastreamento nas faixas etárias recomendadas seja bienal, quando comparada às periodicidades menores do que a bienal; (vi) recomendação contrária fraca ao ensino do autoexame das mamas para rastreamento; (vii) ausência de recomendação favorável ou contrária ao rastreamento com exame clínico das mamas; e (viii) recomendação contrária forte ao rastreamento com ressonância nuclear magnética, ultrassonografia, termografia ou tomossíntese, seja isoladamente, seja como complemento à mamografia. As recomendações para o diagnóstico precoce do câncer de mama (mulheres com sinais ou sintomas suspeitos) foram: (i) recomendação favorável fraca à implementação de estratégias de conscientização para o diagnóstico precoce do câncer de mama; (ii) recomendação favorável fraca ao uso de sinais e sintomas selecionados nas presentes diretrizes como critério de referência urgente para serviços de diagnóstico mamário; e (iii) recomendação favorável fraca de que toda a avaliação diagnóstica do câncer de mama, após a identificação de sinais e sintomas suspeitos na atenção primária, seja feita em um mesmo centro de referência.

El cáncer de mama es la principal causa de muerte por cáncer en mujeres en Brasil. Las nuevas directrices para la detección precoz en Brasil fueron elaboradas basándose en revisiones sistemáticas de la literatura sobre riesgos y posibles beneficios de diversas estrategias de detección precoz. El objetivo del presente artículo es presentar las recomendaciones y actualizar la síntesis de evidencias, discutiendo las principales controversias existentes. Las recomendaciones para el tamizaje del cáncer de mama (mujeres asintomáticas) fueron: (i) fuerte recomendación contraria al tamizaje con mamografía en mujeres con menos de 50 años; (ii) baja recomendación favorable al tamizaje con mamografía en mujeres con edades entre 50 y 69 años; (iii) baja recomendación contraria al tamizaje con mamografía en mujeres con edades entre 70 y 74 años; (iv) fuerte recomendación contraria al tamizaje con mamografía en mujeres con 75 años o más; (v) fuerte recomendación favorable de que el tamizaje en las franjas etarias recomendadas sea bienal, cuando se compara con periodicidades menores a la bienal; (vi) baja recomendación contraria a la enseñanza del autoexamen de las mamas para tamizaje; (vii) ausencia de recomendación favorable o contraria al tamizaje con examen clínico de las mamas; y (viii) fuerte recomendación contraria al tamizaje con resonancia magnética nuclear, ultrasonografía, termografía o tomosíntesis, bien sea aisladamente, bien sea como complemento a la mamografía. Las recomendaciones para el diagnóstico precoz del cáncer de mama (mujeres con señales o síntomas sospechosos): (i) baja recomendación favorable a la implementación de estrategias de concienciación para el diagnóstico precoz del cáncer de mama; (ii) baja recomendación favorable al uso de señales y síntomas seleccionados en las presentes directrices como criterio de referencia urgente para servicios de diagnóstico mamario; y (iii) baja recomendación favorable de que toda la evaluación diagnóstica del cáncer de mama, tras la identificación de señales y síntomas sospechosos en la atención primaria, sea realizada en un mismo centro de referencia.

Stafne's bone defect in a metastatic prostate cancer patient: A diagnostic conundrum.

Stafne's bone defect (SBD) is an uncommon bone alteration that affects the mandible and usually presents as an asymptomatic radiolucency located in the posterior region of body or angle of the mandible, below the alveolar canal. Although clinical and radiographic features are more often sufficient for the diagnosis, other lesions and bone alterations have been described in the differential diagnosis and may lead to a misinterpretation and an incorrect diagnosis. Herein, we report a case of an 89-yearold man with metastatic prostate cancer to multiple bones, presenting an asymptomatic solitary well-defined radiolucent image on the right side of the posterior body of the mandible, in close contact with its inferior border. A bone depression was confirmed by computed tomography scans of the mandible and a metastatic inclusion was ruled out by bone scintigraphy with a final diagnosis of SBD. The aim of this report was to highlight the importance of differentiating SBD from metastases in cancer patients and to reinforce the usefulness of multiple imaging modalities in the differential diagnosis of SBD. Key words:Stafne's bone defect, Mandible, Depression, Metastases, Imaging modalities.

Diretrizes para detecção precoce do câncer de mama no Brasil. II - Novas recomendações nacionais, principais evidências e controvérsias / Directrices para la detección precoz del cáncer de mama en Brasil. II - Nuevas recomendaciones nacionales, principales evidencias y controversias / Guidelines for early detection of breast cancer in Brazil. II - New national recommendations, main evidence, and controversies

Resumo: O câncer de mama é a principal causa de morte por câncer em mulheres no Brasil. As novas diretrizes para detecção precoce no Brasil foram elaboradas com base em revisões sistemáticas da literatura sobre riscos e possíveis benefícios de diversas estratégias de detecção precoce. O objetivo do presente artigo é apresentar as recomendações e atualizar a síntese de evidências, discutindo as principais controvérsias existentes. As recomendações para o rastreamento do câncer de mama (mulheres assintomáticas) foram: (i) recomendação contrária forte ao rastreamento com mamografia em mulheres com menos de 50 anos; (ii) recomendação favorável fraca ao rastreamento com mamografia em mulheres com idades entre 50 e 69 anos; (iii) recomendação contrária fraca ao rastreamento com mamografia em mulheres com idades entre 70 e 74 anos; (iv) recomendação contrária forte ao rastreamento com mamografia em mulheres com 75 anos ou mais; (v) recomendação favorável forte de que o rastreamento nas faixas etárias recomendadas seja bienal, quando comparada às periodicidades menores do que a bienal; (vi) recomendação contrária fraca ao ensino do autoexame das mamas para rastreamento; (vii) ausência de recomendação favorável ou contrária ao rastreamento com exame clínico das mamas; e (viii) recomendação contrária forte ao rastreamento com ressonância nuclear magnética, ultrassonografia, termografia ou tomossíntese, seja isoladamente, seja como complemento à mamografia. As recomendações para o diagnóstico precoce do câncer de mama (mulheres com sinais ou sintomas suspeitos) foram: (i) recomendação favorável fraca à implementação de estratégias de conscientização para o diagnóstico precoce do câncer de mama; (ii) recomendação favorável fraca ao uso de sinais e sintomas selecionados nas presentes diretrizes como critério de referência urgente para serviços de diagnóstico mamário; e (iii) recomendação favorável fraca de que toda a avaliação diagnóstica do câncer de mama, após a identificação de sinais e sintomas suspeitos na atenção primária, seja feita em um mesmo centro de referência.

Resumen: El cáncer de mama es la principal causa de muerte por cáncer en mujeres en Brasil. Las nuevas directrices para la detección precoz en Brasil fueron elaboradas basándose en revisiones sistemáticas de la literatura sobre riesgos y posibles beneficios de diversas estrategias de detección precoz. El objetivo del presente artículo es presentar las recomendaciones y actualizar la síntesis de evidencias, discutiendo las principales controversias existentes. Las recomendaciones para el tamizaje del cáncer de mama (mujeres asintomáticas) fueron: (i) fuerte recomendación contraria al tamizaje con mamografía en mujeres con menos de 50 años; (ii) baja recomendación favorable al tamizaje con mamografía en mujeres con edades entre 50 y 69 años; (iii) baja recomendación contraria al tamizaje con mamografía en mujeres con edades entre 70 y 74 años; (iv) fuerte recomendación contraria al tamizaje con mamografía en mujeres con 75 años o más; (v) fuerte recomendación favorable de que el tamizaje en las franjas etarias recomendadas sea bienal, cuando se compara con periodicidades menores a la bienal; (vi) baja recomendación contraria a la enseñanza del autoexamen de las mamas para tamizaje; (vii) ausencia de recomendación favorable o contraria al tamizaje con examen clínico de las mamas; y (viii) fuerte recomendación contraria al tamizaje con resonancia magnética nuclear, ultrasonografía, termografía o tomosíntesis, bien sea aisladamente, bien sea como complemento a la mamografía. Las recomendaciones para el diagnóstico precoz del cáncer de mama (mujeres con señales o síntomas sospechosos): (i) baja recomendación favorable a la implementación de estrategias de concienciación para el diagnóstico precoz del cáncer de mama; (ii) baja recomendación favorable al uso de señales y síntomas seleccionados en las presentes directrices como criterio de referencia urgente para servicios de diagnóstico mamario; y (iii) baja recomendación favorable de que toda la evaluación diagnóstica del cáncer de mama, tras la identificación de señales y síntomas sospechosos en la atención primaria, sea realizada en un mismo centro de referencia.

Abstract: Breast cancer is the leading cause of cancer mortality in Brazilian women. The new Brazilian guidelines for early detection of breast cancer were drafted on the basis of systematic literature reviews on the possible harms and benefits of various early detection strategies. This article aims to present the recommendations and update the summary of evidence, discussing the main controversies. Breast cancer screening recommendations (in asymptomatic women) were: (i) strong recommendation against mammogram screening in women under 50 years of age; (ii) weak recommendation for mammogram screening in women 50 to 69 years of age; (iii) weak recommendation against mammogram screening in women 70 to 74 years of age; (iv) strong recommendation against mammogram screening in women 75 years or older; (v) strong recommendation that screening in the recommended age brackets should be every two years as opposed to shorter intervals; (vi) weak recommendation against teaching breast self-examination as screening; (vii) absence of recommendation for or against screening with clinical breast examination; and (viii) strong recommendation against screening with magnetic resonance imaging, ultrasonography, thermography, or tomosynthesis alone or as a complement to mammography. The recommendations for early diagnosis of breast cancer (in women with suspicious signs or symptoms) were: (i) weak recommendation for the implementation of awareness-raising strategies for early diagnosis of breast cancer; (ii) weak recommendation for use of selected signs and symptoms in the current guidelines as the criterion for urgent referral to specialized breast diagnosis services; and (iii) weak recommendation that every breast cancer diagnostic workup after the identification of suspicious signs and symptoms in primary care should be done in the same referral center.

Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.

Cost effectiveness of the cancer prevention program for carriers of the BRCA1/2 mutation

ABSTRACT OBJECTIVE: To analyze the cost effectiveness of the diagnostic program for the germline mutation in BRCA1/2 genes and of preventative strategies for the relatives of patients diagnosed with ovarian cancer associated with this mutation. METHODS: The study analyzed the cost effectiveness by developing an analysis of the Markov decision process from the perspective of the National Health System. The strategies compared reflect upon the adoption of genetic testing and preventative strategies for relatives or the usual care currently proposed. The incremental cost-effectiveness ratio was expressed in terms of cost per case avoided. The sensitivity analysis was performed in a univariate and deterministic manner. RESULTS: The study showed increments for effectiveness and for costs when performing genetic testing and adopting prophylactic measures for family members. The incremental cost-effectiveness ratio was estimated at R$908.58 per case of cancer avoided, a figure considered lower than the study's cost-effectiveness threshold (R$7,543.50). CONCLUSIONS: The program analyzed should be considered a cost-effective strategy for the national situation. Studies in various other countries have reached similar conclusions. One possible ramification of this research might the need to perform a budgetary-impact analysis of making the program one of the country's health policies.

Quality of life in responders after palliative radiation therapy for painful bone metastases using EORTC QLQ-C30 and EORTC QLQ-BM22: results of a Brazilian cohort.

BACKGROUND: Bone metastases cause pain, suffering and impaired quality of life (QoL). Palliative radiotherapy (RT) and/or chemotherapy are effective methods in controlling pain, reducing analgesics use and improving QoL. This study goal was to investigate the changes in QoL scores among patients who responded to palliative treatment. METHODS: A prospective study evaluating the role of radiation therapy in a public academic hospital in São Paulo-Brazil recorded patients' opioid use, pain score, Portuguese version of QLQ-BM22 and QLQ-C30 before and 2 months after radiotherapy. Analgesic use and pain score were used to calculate international pain response category. Overall response was defined as the sum of complete response (CR) and partial response (PR). CR was defined as pain score of 0 with no increase in analgesic intake whereas PR was defined as pain reduction ≥2 without analgesic increase or analgesic reduction in ≥25% without increase in pain at the treated site. RESULTS: From September 2014 to October 2015, 25 patients with bone metastases responded to RT or chemotherapy (1 CR, 24 PR). There were 8 male and 17 female patients. The median age of the 25 patients was 59 (range, 22 to 80) years old. Patient's primary cancer site was breast [11], prostate [5], lung [2], others [7]. For QLQ-BM 22, the mean scores of 4 categories at baseline were: pain site (PS) 39, pain characteristics (PC) 61, function interference (FI) 49 and psycho-social aspects (PA) 57. At 2 month follow up, the scores were PS 27, PC 37, FI 70 and PA 59. Statistical significant improvement (P<0.05) was seen in PS, PC, FI but not PA. In the QLQ-C30, the scores were not statistically different for all categories, except for pain that demonstrated a 33 point decrease in the median pain score domain (66 to 33). CONCLUSIONS: Responders to RT at 2 months presented improvement in BM22 and C30 pain domains, and also improvement in functional interference domain of the BM22 questionnaire.