Mutation Patterns in Portuguese Families with Hereditary Breast and Ovarian Cancer Syndrome

Funding Information: The authors R.V., M.V., A.D.M. and C.S. declare no conflict of interest. D.A.C. 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 AstraZeneca, CUF Oncologia, Daiichi Sankyo, Gilead, Hoffmann-La Roche, Merck KGaA, Merck Sharp & Dohme, Nestlé, Novartis, Pfizer, Nanobiotix, Puma Biotechnology Inc., Sanofi, Seagen Inc., and Uriage. MFS is a consultant/speaker for Astellas, Daiichi-Sankyo, Bristol Myers Squibb, Gilead, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Pierre-Fabre Ipsen, Roche and Server. Publisher Copyright: © 2022 by the authors.Germline pathogenic variants in the Breast Cancer Genes 1 (BRCA1) and 2 (BRCA2) are responsible for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Genetic susceptibility to breast cancer accounts for 5–10% of all cases, phenotypically presenting with characteristics such as an autosomal dominant inheritance pattern, earlier age of onset, bilateral tumours, male breast cancer, and ovarian tumours, among others. BRCA2 pathogenic variant is usually associated with other cancers such as melanoma, prostate, and pancreatic cancers. Many rearrangements of different mutations were found in both genes, with some ethnic groups having higher frequencies of specific mutations due to founder effects. Despite the heterogeneity of germline BRCA1/BRCA2 mutations in Portuguese breast or/and ovarian cancer families, the first described founder mutation in the BRCA2 gene (c.156_157insAlu) and two other variants in the BRCA1 gene (c.3331_3334del and c.2037delinsCC) contribute to about 50% of all pathogenic mutations. Furthermore, the families with the BRCA1 c.3331_3334del or the c.2037delinsCC mutations share a common haplotype, suggesting that these may also be founder mutations in the Portuguese population. Identifying specific and recurrent/founder mutations plays an important role in increasing the efficiency of genetic testing since it allows the use of more specific, cheaper and faster strategies to screen HBOC families. Therefore, this review aims to describe the mutational rearrangements of founder mutations and evaluate their impact on the genetic testing criteria for HBOC families of Portuguese ancestry.publishersversionpublishe

mTOR signaling pathway regulates sperm quality in older men

Understanding how age affects fertility becomes increasingly relevant as couples delay childbearing toward later stages of their lives. While the influence of maternal age on fertility is well established, the impact of paternal age is poorly characterized. Thus, this study aimed to understand the molecular mechanisms responsible for age-dependent decline in spermatozoa quality. To attain it, we evaluated the impact of male age on the activity of signaling proteins in two distinct spermatozoa populations: total spermatozoa fraction and highly motile/viable fraction. In older men, we observed an inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) in the highly viable spermatozoa population. On the contrary, when considering the entire spermatozoa population (including defective/immotile/apoptotic cells) our findings support an active mTORC1 signaling pathway in older men. Additionally, total spermatozoa fractions of older men presented increased levels of apoptotic/stress markers (e.g., cellular tumor antigen p53-TP53) and mitogen-activated protein kinases (MAPKs) activity. Moreover, we established that the levels of most signaling proteins analyzed were consistently and significantly altered in men more than 27 years of age. This study was the first to associate the mTOR signaling pathway with the age impact on spermatozoa quality. Additionally, we constructed a network of the sperm proteins associated with male aging, identifying TP53 as a central player in spermatozoa aging.publishe

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

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies

Gastric cancer (GC) remains a public health problem, being the fifth most common cancer worldwide. In the western countries, the majority of patients present with advanced disease. Additionally, 65 to 75% of patients treated with curative intent will relapse and develop systemic disease. In metastatic disease, systemic treatment still represents the state of the art, with less than a year of median overall survival. The new molecular classification of GC was published in 2014, identifying four distinct major subtypes of gastric cancer, and has encouraged the investigation of new and more personalized treatment strategies. This paper will review the current evidence of immunotherapy in advanced gastric cancer

Pancreatic neuroendocrine tumor liver metastasis in a patient with previously diagnosed pancreatic adenocarcinoma: an unexpected diagnosis

Locally advanced pancreatic carcinoma has an usually poor prognosis despite multimodal approaches and sequential chemotherapy. The authors present a case of a long-term survivor with stage III pancreatic adenocarcinoma achieving partial response after a multimodal approach including local and systemic treatments. However, three years after diagnosis and amidst several episodes of cholangitis, hepatic metastasis were suspected. Despite pancreatic adenocarcinoma being the obvious culprit for metastization, a hepatic biopsy was considered at that time given a stable primary disease and presenting three years since the initial diagnosis. At this point, a biopsy could have specific diagnostic, prognostic and therapeutic implications and after it was performed, an unexpected diagnosis of pancreatic neuroendocrine tumor was made. Therefore, we urge clinicians to consider hepatic biopsy in similar cases - generally when it may change prognosis and treatment strategies - and perform histological confirmation of metastatic disease whenever feasible, even if the answer may seem obvious at first impression

Electrocardiographic Reference Values in Clinically Healthy Lusitano Horses

The Lusitano horse is gaining popularity in the equestrian world, and as a result, the significance of applied sports medicine for this breed is growing. As cardiology plays a crucial role in this field, numerous studies have been conducted to establish electrocardiographic reference values in various breeds to ensure a more accurate evaluation. However, studies regarding healthy Lusitano horses are lacking. So, this study aimed to establish electrocardiographic reference values for Lusitano horses, utilizing a sample of 82 clinically healthy animals. The evaluation involved lead II and base–apex lead measurements, with a median heart rate of 39 beats per minute being recorded. The P wave demonstrated a predominantly bifid configuration, while the QRS complex exhibited various forms. The most common QRS configurations were QR and R in lead II, and RS in the base–apex lead. Additionally, most T waves displayed a biphasic shape in both methods. Furthermore, statistically significant differences were noted based on age and gender. Some of the electrocardiographic values obtained differed from those previously published for other breeds. Given the relevance of electrocardiogram in cardiovascular evaluation, these findings bring valuable insights regarding the specific parameters for Lusitano horse and emphasize the importance of obtaining breed-specific electrocardiographic reference values

Primary CDK4/6 inhibitor and endocrine therapy in locally advanced breast cancer and its effect on gut and intratumoral microbiota : case report

Copyright © 2024 Vilhais, Alpuim Costa, Fontes-Sousa, Ribeiro, Martinho, Botelho de Sousa, Santos, Negreiros, Canastra, Borralho, Guia Pereira, Marçal, Germano Sousa, Chaleira, Rocha, Calhau and Faria. 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.Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient's gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.info:eu-repo/semantics/publishedVersio