Human Microbiota and Breast Cancer—Is There Any Relevant Link?—A Literature Review and New Horizons Toward Personalised Medicine

Breast cancer; Personalized medicine; PharmacomicrobiomicsCáncer de mama; Medicina personalizada; FarmacomicrobiómicaCàncer de mama; Medicina personalitzada; FarmacomicrobiòmicaBreast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Recently, gut microbiota dysbiosis emerged as a key player that may directly and/or indirectly influence development, treatment, and prognosis of BC through diverse biological processes: host cell proliferation and death, immune system function, chronic inflammation, oncogenic signalling, hormonal and detoxification pathways. Gut colonisation occurs during the prenatal period and is later diversified over distinct phases throughout life. In newly diagnosed postmenopausal BC patients, an altered faecal microbiota composition has been observed compared with healthy controls. Particularly, β-glucuronidase bacteria seem to modulate the enterohepatic circulation of oestrogens and their resorption, increasing the risk of hormone-dependent BC. Moreover, active phytoestrogens, short-chain fatty acids, lithocholic acid, and cadaverine have been identified as bacterial metabolites influencing the risk and prognosis of BC. As in gut, links are also being made with local microbiota of tumoural and healthy breast tissues. In breast microbiota, different microbial signatures have been reported, with distinct patterns per stage and biological subtype. Total bacterial DNA load was lower in tumour tissue and advanced-stage BC when compared with healthy tissue and early stage BC, respectively. Hypothetically, these findings reflect local dysbiosis, potentially creating an environment that favours breast tumour carcinogenesis (oncogenic trigger), or the natural selection of microorganisms adapted to a specific microenvironment. In this review, we discuss the origin, composition, and dynamic evolution of human microbiota, the links between gut/breast microbiota and BC, and explore the potential implications of metabolomics and pharmacomicrobiomics that might impact BC development and treatment choices toward a more personalised medicine. Finally, we put in perspective the potential limitations and biases regarding the current microbiota research and provide new horizons for stronger accurate translational and clinical studies that are needed to better elucidate the complex network of interactions between host, microorganisms, and drugs in the field of BC

Human microbiota and breast cancer : is there any relevant link? A literature review and new horizons toward personalised medicine

Copyright © 2021 Alpuim Costa, Nobre, Batista, Ribeiro, Calle, Cortes, Marhold, Negreiros, Borralho, Brito, Cortes, Braga and Costa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Recently, gut microbiota dysbiosis emerged as a key player that may directly and/or indirectly influence development, treatment, and prognosis of BC through diverse biological processes: host cell proliferation and death, immune system function, chronic inflammation, oncogenic signalling, hormonal and detoxification pathways. Gut colonisation occurs during the prenatal period and is later diversified over distinct phases throughout life. In newly diagnosed postmenopausal BC patients, an altered faecal microbiota composition has been observed compared with healthy controls. Particularly, β-glucuronidase bacteria seem to modulate the enterohepatic circulation of oestrogens and their resorption, increasing the risk of hormone-dependent BC. Moreover, active phytoestrogens, short-chain fatty acids, lithocholic acid, and cadaverine have been identified as bacterial metabolites influencing the risk and prognosis of BC. As in gut, links are also being made with local microbiota of tumoural and healthy breast tissues. In breast microbiota, different microbial signatures have been reported, with distinct patterns per stage and biological subtype. Total bacterial DNA load was lower in tumour tissue and advanced-stage BC when compared with healthy tissue and early stage BC, respectively. Hypothetically, these findings reflect local dysbiosis, potentially creating an environment that favours breast tumour carcinogenesis (oncogenic trigger), or the natural selection of microorganisms adapted to a specific microenvironment. In this review, we discuss the origin, composition, and dynamic evolution of human microbiota, the links between gut/breast microbiota and BC, and explore the potential implications of metabolomics and pharmacomicrobiomics that might impact BC development and treatment choices toward a more personalised medicine. Finally, we put in perspective the potential limitations and biases regarding the current microbiota research and provide new horizons for stronger accurate translational and clinical studies that are needed to better elucidate the complex network of interactions between host, microorganisms, and drugs in the field of BC.info:eu-repo/semantics/publishedVersio

A Cross-Sectional Survey-Based Study of Medical Oncologists

Funding Information: We would like to thank Andrea Bothwell who wrote the manuscript outline and first draft on behalf of Springer Healthcare Communications. We also thank Prof. Carina Silva (ESTEsL – Escola Superior de Tecnologias de Saúde de Lisboa) who performed the preliminary statistical analysis of this study. This medical writing assistance and statistical analysis was funded by CUF Oncologia. Funding Information: Diogo Alpuim Costa has received honoraria from the Portuguese Navy, CUF Oncologia, and NTT DATA, and has served as a speaker, advisory board member, or has received research or education funding from CUF Oncologia, AstraZeneca, Hoffmann-La Roche, Merck KGaA, Novartis, Pfizer, Uriage, Daiichi Sankyo, Gilead, Merck Sharp & Dohme, Nanobiotix, Puma Biotechnology Inc., Sanofi, and Seagen Inc. Margarida Brito has participated as advisory board member for Roche, Novartis, Merck Sharp & Dohme, and Pfizer. Mário Fontes-Sousa has served as a speaker or advisory board member for Bristol Myers Squibb, Daiichi Sankyo, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Servier. Diogo Martins-Branco received honoraria and advisory board fees from Janssen, Pfizer, Merck Sharp & Dohme, Angelini, AstraZeneca, and Novartis, meeting and travel grants from LEO Farmacêuticos, Merck Sharp & Dohme, Ipsen, Janssen, and Roche, and institutional grants from F. Hoffmann-La Roche Ltd. José Guilherme Gonçalves Nobre, João Paulo Fernandes, Marta Vaz Batista, Ana Simas, Carolina Sales, Helena Gouveia, Leonor Abreu Ribeiro, Andreia Coelho, Mariana Inácio, André Cruz, Mónica Mariano, Joana Savva-Bordalo, Ricardo Fernandes, André Oliveira, Andreia Chaves, Mafalda Sampaio-Alves, and Noémia Afonso have nothing to declare. Publisher Copyright: © 2022, The Author(s).Introduction: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer. Methods: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents’ regions, case volumes, and practice type were explored. Results: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents’ region and case volume were noted. Conclusion: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.publishersversionepub_ahead_of_prin

Lesões Ósseas de Novo: Quando a Origem Não é a Mais Evidente

É apresentado o caso de uma doente de 50 anos com diagnóstico concomitante de esclerose sistémica e neoplasia da mama em estádio precoce. Em exames complementares são detetadas lesões ósseas no esqueleto axial. Surge a dúvida diagnóstica de qual a doença primária que está na base destas alterações. Conclui-se tratar-se de envolvimento ósseo da esclerose sistémica que, apesar de raro na localização onde surgiu, se encontra descrito na literatura. Recebido: 12/07/2017 - Aceite: 05/09/201

Lesões Ósseas de Novo: Quando a Origem Não é a Mais Evidente

É apresentado o caso de uma doente de 50 anos com diagnóstico concomitante de esclerose sistémica e neoplasia da mama em estádio precoce. Em exames complementares são detetadas lesões ósseas no esqueleto axial. Surge a dúvida diagnóstica de qual a doença primária que está na base destas alterações. Conclui-se tratar-se de envolvimento ósseo da esclerose sistémica que, apesar de raro na localização onde surgiu, se encontra descrito na literatura. Recebido: 12/07/2017 - Aceite: 05/09/201

Ansiedade e medos face ao COVID-19 em estudantes do ensino superior

info:eu-repo/semantics/publishedVersio

Building significant, pleasant and autonomous mathematical learning using a virtual scale model: related experience / Construindo aprendizagem matemática significativa, prazerosa e com autonomia utilizando uma maquete virtual: relato de experiência

Mathematics is a very important subject in every citizen's life and is found in all the curricular matrix, however, it is verified that there is difficulty in learning this content in a pleasant and effective way. In order to understand mathematics, it is necessary to have knowledge of logic and plenty of attention, although in many cases only memorization is stimulated, with an exaggerated load of lectures. This research proposed the accomplishment of a virtual model with the Minecraft software in order to verify if it can promote significant, pleasant and autonomous mathematical learning. The research had a qualitative approach, with an exploratory study and participant observation, with six subjects from an elementary school. The data was collected in 16 meetings of one hour in the Friends of Gaby Association. It verified that this software can be used as a pedagogical tool and it was concluded that the carrying out of the virtual scale model promoted interdisciplinary learning that surpassed the proposal of the research. The feeling of joy in carrying out the activity was highlighted at all times, the way of learning was autonomous and most do not understand the game as a way of learning, only as entertainment. The inability of the researchers to follow the pedagogical possibilities of the proposed digital game was also verified

Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial

[AHEAD] Data de publicació electrónica: 26-05-2022Background: trastuzumab deruxtecan (T-DXd) has shown durable antitumor activity in pretreated patients with HER2-positive advanced breast cancer (ABC), but its efficacy has not yet been evaluated in patients with active brain metastases (BMs). DEBBRAH aims to assess T-DXd in patients with HER2-positive or HER2-low ABC and central nervous system involvement. Methods: this ongoing, five-cohort, phase II study (NCT04420598) enrolled patients with pretreated HER2-positive or HER2-low ABC with stable, untreated, or progressing BMs and/or leptomeningeal carcinomatosis. Here, we report findings from HER2-positive ABC patients with non-progressing BMs after local therapy (n=8; cohort 1), asymptomatic untreated BMs (n=4; cohort 2), or progressing BMs after local therapy (n=9; cohort 3). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was 16-week progression-free survival (PFS) for cohort 1 and intracranial overall response rate (ORR-IC) for cohorts 2 and 3. Results: as of October 20, 2021, 21 patients received T-DXd. In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3-99.7; P<.001). ORR-IC was 50.0% (95%CI, 6.7-93.2) in cohort 2 and 44.4% (95%CI, 13.7-78.8; P<.001) in cohort 3. Overall, the ORR-IC in patients with active BMs was 46.2% (95%CI, 19.2-74.9). Among patients with measurable intracranial or extracranial lesions at baseline, the ORR was 66.7% (12 out of 18 patients; 95%CI, 41.0-86.7), 80.0% (95%CI, 28.4-99.5) in cohort 1, 50.0% (95%CI, 6.7-93.2) in cohort 2, and 66.7% (95%CI, 29.9-92.5) in cohort 3. All responders had partial responses. The most common adverse events included fatigue (52.4%; 4.8% grade≥3), nausea (42.9%; 0% grade≥3), neutropenia (28.6%; 19% grade≥3), and constipation (28.6%; 0% grade≥3). Two (9.5%) patients suffered grade 1 interstitial lung disease/pneumonitis. Conclusions: T-DXd showed intracranial activity with manageable toxicity and maintained quality of life in pretreated HER2-positive ABC patients with stable, untreated, or progressing BMs. Further studies are needed to validate these results in larger cohorts

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved