The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation.

Objective: To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis. Methods: We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil. Results: Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery. Conclusion: Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973.

Socioeconomic Impact of Cancer in Latin America and The Caribbean.

The incidence of cancer in Latin America and the Caribbean (LAC) is increasing yearly and is expected to reach 2.4 million new cases by 2040, with a more pronounced effect in Central America and South America. In addition, cancer is already the most frequent cause of premature death for most countries in LAC, and the second cause of death independent of country socioeconomic status, clearly demonstrating that the cancer burden in LAC should be addressed now rather than considered as an issue to be dealt with in the future. LAC countries performed in a mid-range zone in terms of income and mortality-to-incidence ratio compared to other countries globally. The LAC continent has, in general, a median income per capita and a median availability of radiotherapy (RDT) machines per capita. Patients that have private health coverage are more likely to receive preventive care such as pap smears and mammography in many countries of the LAC. The human development index was negatively related to mortality from oral cancer in the LAC countries with medium and low Human Development Index (HDI). Cancer treatment adverse events can negatively affect survivors' workability compromising their return to work after diagnosis. In conclusion, the cancer burden can be a major public health issue with a considerable socioeconomic impact in LAC countries. It is demonstrated in several studies that unequal access to optimal care is frequent in LAC and that health insurance type may impact patients' diagnosis and outcome.

Cost-effectiveness of breast, lung, colon, prostate and cervical cancer outcomes in Brazil: a worldwide comparison.

INTRODUCTION: Cancer is the second leading cause of death in the world, and it is expected to be the main cause by the year 2030. Current trends of higher incidence and the introduction of new treatments lead to the challenge of treating more people with increasing costs per capita. In Brazil, current and future challenges are even more significant because of the limited resources destined for healthcare. METHODS: We propose a methodology to compare cost-effectiveness performance with a regression of cancer lethality against the resources available for different nations, using the gross domestic product and the mortality-to-incidence ratio. Our objective is to evaluate and compare outcomes observed in Brazil. RESULTS: According to our methodology, Brazil is performing well in breast and prostate cancer (observed lethality 9% and 15% lower than expected, respectively). It performs close to expected in colon (0.8% higher) and cervix (2% higher). However, lung cancer had a higher lethality than expected (6.5% higher). We also found that breast, prostate and cervical cancers are the primary sites more related to income. Lung cancer had the weakest relationship with resources. CONCLUSION: Brazil has different cost-effectiveness results in the management of cancer depending on the primary site. Also, national income has a significant and heterogeneous effect on the lethality of different tumour types. This economic analysis is important for low- to middle-income countries seeking to evaluate cancer outcomes in limited-resource settings.

Skeletochronology and Paleohistology of Hyposaurus rogersii (Crocodyliformes, Dyrosauridae) from the Early Paleogene of New Jersey, USA.

The paleohistology of dyrosaurids is known from a small sample, despite being common fossils and representing a rare lineage of crocodylomorphs that survived the Cretaceous-Paleogene extinction. Their lifestyle has been inferred only from sections of the snout, vertebrae, partial femur, and tibia. To improve this, we conducted a skeletochronological and paleohistological study of midshaft cross-sections of both femora and humeri of a nearly complete Hyposaurus rogersii skeleton. We found lamellar-zonal bone that underwent remodeling, evidenced by resorption cavities and abundant secondary osteons within the primary periosteal cortex. The osteons, mostly longitudinally oriented and arranged in circular rows, often anastomose radially along a linear path, resembling radial rows. The medullary cavity is completely open, lacking trabeculae: endosteal deposition is limited to thin lamellae surrounding the cavity. Analysis of cyclical growth marks and the presence of an external fundamental system indicate the specimen was a fully mature adult 17-18 years of age. Comparison of the skeleton to others suggests sexual dimorphism and that it was female. The open medullary cavity, and no evidence for pachyosteosclerosis, osteosclerosis, osteoporosis, or pachyostosis indicate H. rogersii was not a deep diver or a fast swimmer in the open ocean but a near-shore marine ambush predator.

Lack of access to CDK4/6 inhibitors for premenopausal patients with metastatic breast cancer in Brazil: estimation of the number of premature deaths.

PURPOSE: A CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy is the standard of care for patients with hormone receptor-positive (HR+) and HER2-negative (HER2-) metastatic breast cancer (MBC). However, the incorporation of these agents into clinical practice remains challenging. This study aims to estimate the impact of the lack of access to ribociclib on mortality of premenopausal patients with MBC in Brazil. METHODS: Based on published epidemiological studies and national cancer registries, we estimated the number of premenopausal patients with potential indication of ribociclib as first-line treatment for MBC. Efficacy estimates were based on results from the Monaleesa-7 trial. Our analysis is made under the unrealistic assumption that all premenopausal MBC patients would be candidates for the treatment. To estimate the number of yearly premature deaths that could be prevented, we considered the largest absolute effect on mortality when sequentially applying the observed hazard ratio. RESULTS: We estimated an annual incidence of 4,294 premenopausal HR+, HER2- MBC patients in Brazil. Considering these patients, at 12, 24 and 60 months, the number of surviving subjects would be 3,504, 2,859 and 1,553 for endocrine therapy (ET) alone; and 3,717, 3,217 and 2,086 for ET plus ribociclib. The largest difference between both groups was observed at the end of the sixth year when the use of ribociclib would prevent 538 premature deaths (survival of 1,805 versus 1,267 patients by the 72nd month). CONCLUSION: We estimate that lack of access to CDK4/6i for patients with HR+, HER2-, MBC will cause the premature death of a significant number of premenopausal women with MBC. The unavailability of effective therapies has measurable consequences. Progress in this area demands a concerted effort to prevent further loss of lives.

Estimation of the Number of Brazilian Women Living With Metastatic Breast Cancer.

PURPOSE: Breast cancer is the most common cancer and the leading cause of cancer-related death in women worldwide. The number of women living with metastatic breast cancer (MBC) in Brazil is unknown. The objective of this article was to use population-based data to estimate the prevalence of MBC in Brazil. METHODS: Using 4 different sources and cancer registries (DataSUS, Registro Hospitalar de Câncer, the Brazilian National Health Agency, and the National Geography and Statistics Institute) with data from 2008 to 2018, we built a database that represents Brazilian MBC cases. The current number of women in the model living with MBC was considered the prevalence (recurrent or de novo), and new cases in the year 2018 represented the incidence. In each of these outcomes, we were able to separate our population on the basis of cancer subtype, age, and time from diagnosis. RESULTS: We estimate that 44,642 women currently live with MBC in Brazil. This accounts for one in every 2,409 Brazilian women and approximately 41 women per 100,000. A total of 58% have hormone receptor-positive/human epidermal growth factor receptor 2-negative tumors, 25% are human epidermal growth factor receptor 2-positive, and 16% have triple-negative breast cancer. According to our methodology, the estimated median overall survival of Brazilian women after diagnosis of MBC is 26.2 months. CONCLUSION: The significant number of patients living with MBC should inform and raise the interest of the many stakeholders involved. This collaborative effort is a clear requirement to improve the lives of these patients as well as to prepare for future challenges related to the trend of a progressive increase in MBC prevalence.

The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation

Abstract Objective To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis. Methods We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil. Results Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery. Conclusion Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973.

Impacto na Sobrevida Livre de Progressão pela Falta de Acesso a Inibidores de EGFR em Carcinoma de Pulmão de Células não Pequenas no Sistema de Saúde Público Brasileiro / Impact that Lack of Access to EGFR Inhibitors has on Progression-Free Survival in Non-Small Cell Lung Cancer treated via the Public Health Care System in Brazil / Impacto en la Sobrevida Libre de Progresión por la Falta de Acceso a los Inhibidores de EGFR en el Carcinoma de Pulmón de Células no Pequeñas en el Sistema de Salud Pública Brasileña

Introdução: O advento de terapias-alvo antirreceptor do fator de crescimento epidérmico (anti-EGFR) impactou na sobrevida dos pacientes com câncer de pulmão de células não pequenas avançado e portadores de mutação no EGFR, que são tratados no Sistema Único de Saúde Brasileiro (SUS). Objetivo: Estimar o impacto da falta de acesso a terapias anti-EGFR na sobrevida livre de progressão (SLP) desses pacientes. Método: Por meio da base de dados do Instituto Nacional de Câncer José Alencar Gomes da Silva e de estudos que descrevem a prevalência de mutação em EGFR na população brasileira, foi estimado o número de pacientes com adenocarcinoma de pulmão avançado, portadores de mutação EGFR, candidatos à terapia-alvo no ano de 2017. Para a estimativa de efetividade, quatro diferentes esquemas de tratamentos foram considerados: quimioterapia, erlotinib, afatinib e gefitinib. O número de pacientes livres de progressão de doença, após dois anos, foi estimado com base nos resultados para SLP em ensaios clínicos randomizados. Resultados: Foram estimados 1.735 pacientes com adenocarcinoma de pulmão metastático portadores de mutações ativadoras de EGFR no Brasil para o ano de 2017. Projetou-se que, caso fossem tratados com quimioterapia, apenas 71 estariam livres de progressão após 24 meses do início do tratamento. Em contrapartida, com o uso de inibidores de tirosina-quinase anti-EGFR, a expectativa seria de 312 pacientes livres de doença para erlotinib, 377 para gefitinib e 388 para afatinib. Conclusão: Apesar de recomendadas internacionalmente, as terapias anti-EGFR não são disponibilizadas no SUS, sendo oferecida aos pacientes apenas a quimioterapia. Isso problematiza a situação de falta de acesso no âmbito do SUS e embasa, localmente, a discussão acerca da incorporação dessas terapias no âmbito público.

Introduction: The advent of targeted anti-epidermal growth factor receptor (anti-EGFR) therapies have improved survival in patients with metastatic non-small cell lung cancer that carry the EGFR mutation, including those treated via the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System). Objective: To estimate the impact that lack of access to anti-EGFR therapies has on progression-free survival (PFS) among such patients. Method: On the basis of epidemiologic data obtained from the José Alencar Gomes da Silva National Cancer Institute and from studies reporting the prevalence of the EGFR mutation in the Brazilian population, we estimated the number of patients with advanced lung adenocarcinoma and the EGFR mutation who were candidates for targeted therapy in 2017. To estimate effectiveness, we evaluated four different treatments: chemotherapy, erlotinib, afatinib, and gefitinib. The number of patients with PFS after 2 years of follow-up was estimated on the basis of the results of randomized clinical trials. Results: We evaluated 1,735 patients with EGFR mutation-positive metastatic lung adenocarcinoma in Brazil in 2017. We estimated that, if treated with chemotherapy, only 71 of those patients would be free of progression after 24 months. In contrast, if all of the patients were treated with anti-EGFR tyrosine kinase inhibitors, the expectation was that PFS would be achieved in 312 patients for erlotinib, 377 for gefitinib, and 388 for afatinib. Conclusion: Although recommended by international guidelines, anti-EGFR therapies are not available via the SUS, which offers only chemotherapy. This complicates the problem of lack of access in the SUS and promotes local discussion in the public sphere about the incorporation of these therapies.

Introducción: El advenimiento de terapias objetivo anti receptor del factor de crecimiento epidérmico (EGFR) impactó en la supervivencia de los pacientes con cáncer de pulmón de células no pequeñas avanzado y portadores de mutación en el EGFR, que son tratados en el sistema único de salud brasileño (SUS). Objetivo: Estimar el impacto de la falta de acceso a terapias anti-EGFR en la sobrevida libre de progresión (SLP) de esos pacientes. Método:A través de la base de datos del Instituto Nacional de Cáncer José Alencar Gomes da Silva y de estudios que describen la prevalencia de mutación de EGFR en la población brasileña, se estima el número de pacientes con adenocarcinoma de pulmón avanzado portadores de mutación EGFR candidatos a la terapia objetivo en el año de Para la estimación de efectividad, cuatro diferentes esquemas de tratamientos fueron considerados: quimioterapia, erlotinib, afatinib y gefitinib. El número de pacientes libres de progresión de la enfermedad después de dos años se calculó sobre la base de los resultados para SLP en los ensayos clínicos aleatorizados. Resultados: Se estimó 1.735 pacientes con adenocarcinoma de pulmón metastático, portadores de mutaciones activadoras de EGFR en Brasil para el año 2017. Se proyectó que si se tratar con quimioterapia sólo 81 estarían libres de progresión después de 24 meses. En contrapartida, con el uso de inhibidores de tirosina quinasa anti-EGFR, la expectativa sería de 312 pacientes libres de enfermedad para erlotinib, 377 para gefitinib y 388 para afatinib. Conclusión: A pesar de ser recomendadas internacionalmente, las terapias anti-EGFR no están disponibles en el SUS, siendo ofrecido a los pacientes sólo quimioterapia. Esto problematiza claramente la situación de falta de acceso en el ámbito del SUS y basan, localmente, la discusión sobre la incorporación de estas terapias en el ámbito público.

Microanatomical and histological features in the long bones of Mosasaurine mosasaurs (Reptilia, Squamata)--implications for aquatic adaptation and growth rates.

BACKGROUND: During their evolution in the Late Cretaceous, mosasauroids attained a worldwide distribution, accompanied by a marked increase in body size and open ocean adaptations. This transition from land-dwellers to highly marine-adapted forms is readily apparent not only at the gross anatomic level but also in their inner bone architecture, which underwent profound modifications. METHODOLOGY/PRINCIPAL FINDINGS: The present contribution describes, both qualitatively and quantitatively, the internal organization (microanatomy) and tissue types and characteristics (histology) of propodial and epipodial bones in one lineage of mosasauroids; i.e., the subfamily Mosasaurinae. By using microanatomical and histological data from limb bones in combination with recently acquired knowledge on the inner structure of ribs and vertebrae, and through comparisons with extant squamates and semi-aquatic to fully marine amniotes, we infer possible implications on mosasaurine evolution, aquatic adaptation, growth rates, and basal metabolic rates. Notably, we observe the occurrence of an unusual type of parallel-fibered bone, with large and randomly shaped osteocyte lacunae (otherwise typical of fibrous bone) and particular microanatomical features in Dallasaurus, which displays, rather than a spongious inner organization, bone mass increase in its humeri and a tubular organization in its femora and ribs. CONCLUSIONS/SIGNIFICANCE: The dominance of an unusual type of parallel-fibered bone suggests growth rates and, by extension, basal metabolic rates intermediate between that of the extant leatherback turtle, Dermochelys, and those suggested for plesiosaur and ichthyosaur reptiles. Moreover, the microanatomical features of the relatively primitive genus Dallasaurus differ from those of more derived mosasaurines, indicating an intermediate stage of adaptation for a marine existence. The more complete image of the various microanatomical trends observed in mosasaurine skeletal elements supports the evolutionary convergence between this lineage of secondarily aquatically adapted squamates and cetaceans in the ecological transition from a coastal to a pelagic lifestyle.