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INTRODUCTION: Reserve Officers' Training Corps (ROTC) trainees are college students who complete military courses and participate in physical and tactical training under the direction of military Service Members assigned to ROTC programs to serve as faculty and staff at US colleges. ROTC trainees report musculoskeletal injuries (MSKIs) attributable to ROTC training in line with MSKI incidence in other training environments. However, concealment is prevalent, as 66% of MSKIs in ROTC go unreported. The current study investigated if a brief, online educational video could increase ROTC trainees' reporting intentions. In addition, we investigated if the message's source (i.e., peer or authority figure) affected reporting intentions. MATERIALS AND METHODS: A repeated measures design was used to evaluate the impact of 2 MSKI educational interventions, one delivered by a high-achieving Army ROTC trainee (peer-led) and the other delivered by an Army ROTC battalion commander (authority-led), on MSKI reporting intentions, as compared to each other and a control intervention. Other than their personal introductions, both individuals had the same script addressing 4 areas: (1) MSKI prevalence in ROTC, (2) evidence of improved outcomes with early treatment, (3) encouraging injury reporting, and (4) addressing specific barriers and stigma beliefs previously identified in ROTC. The control condition consisted of a video demonstrating exercise technique with voiceover. A survey was developed to measure stigma regarding MSKI reporting and intentions to seek help for MSKI. ROTC trainees at 23 universities were invited to participate via an anonymous survey link. Participants completed the following using an online survey platform: (1) pre-intervention MSKI intentions scale, (2) randomly assigned intervention video, and (3) repeat MSKI intentions scale post-intervention. A two-way mixed, ANOVA was performed to assess interaction effects and main effects pre- and post-intervention. RESULTS: One-hundred ROTC trainees (39% female; age = 21 ± 2 years, ROTC experience = 2 ± 1 years) completed the study. Participants were primarily from Army ROTC programs (72 Army, 14 Air Force, and 14 Naval). Pre-intervention survey scores (possible score range 8-56 with lower scores indicating greater intention to seek help): authority-led (n = 31) 20.3 ± 9.4, peer-led (n = 32) 21.8 ± 8.7, control (n = 37) 19.1 ± 10.1, total 20.3 ± 9.4. Post-intervention scores: authority-led 20.9 ± 11.2, peer-led 20.2 ± 10.0, control 17.3 ± 7.7, total 19.7 ± 9.3. There was no significant group*time interaction (F2,97 = 0.92, P = .403, η2partial = 0.02). There were no significant main effects for time (F1,97 = 1.461, P = .230, η2partial =0.015) or group (F2,97 = 1.08, P = .342, η2partial = 0.02). CONCLUSIONS: Findings did not support the use of a single educational intervention video to influence MSKI help-seeking intentions of ROTC trainees. Intentions may already be ingrained such that a single intervention could not influence change. Previous research on concussion reporting indicates that concealment cultures may be systematic and indoctrination of concealment can influence one's reporting intentions. Our sample had already participated in ROTC for 2 years. Future research should evaluate if MSKI help-seeking intentions change over the course of ROTC participation, or even over a military career.
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Intenção , Militares , Humanos , Masculino , Feminino , Militares/psicologia , Militares/estatística & dados numéricos , Grupo Associado , Inquéritos e Questionários , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Adulto , Adulto Jovem , Gravação em Vídeo/métodos , Doenças Musculoesqueléticas/psicologia , Doenças Musculoesqueléticas/terapia , Sistema Musculoesquelético/lesões , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologiaRESUMO
Although detrimental changes in mitochondrial morphology and function are widely described symptoms of fetal alcohol exposure, no studies have followed these mitochondrial deficits into adult life or determined if they predispose individuals with fetal alcohol spectrum disorders (FASDs) to accelerated biological aging. Here, we used a multiplex preclinical mouse model to compare markers of cellular senescence and age-related outcomes induced by maternal, paternal, and dual-parental alcohol exposures. We find that even in middle life (postnatal day 300), the adult offspring of alcohol-exposed parents exhibited significant increases in markers of stress-induced premature cellular senescence in the brain and liver, including an upregulation of cell cycle inhibitory proteins and increased senescence-associated ß-galactosidase activity. Strikingly, in the male offspring, we observe an interaction between maternal and paternal alcohol use, with histological indicators of accelerated age-related liver disease in the dual-parental offspring exceeding those induced by either maternal or paternal alcohol use alone. Our studies indicate that chronic parental alcohol use causes enduring mitochondrial dysfunction in offspring, resulting in a reduced NAD+/NAHD ratio and altered expression of the NAD+-dependent deacetylases SIRT1 and SIRT3. These observations suggest that some aspects of FASDs may be linked to accelerated aging due to programmed changes in the regulation of mitochondrial function and cellular bioenergetics.
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Although dose-response analyses are a fundamental tool in developmental toxicology, few studies have examined the impacts of toxicant dose on the non-genetic paternal inheritance of offspring disease and dysgenesis. In this study, we used geometric morphometric analyses to examine the impacts of different levels of preconception paternal alcohol exposure on offspring craniofacial shape and symmetry in a mouse model. Procrustes ANOVA followed by canonical variant analysis of geometric facial relationships revealed that Low-, Medium-, and High-dose treatments each induced distinct changes in craniofacial shape and symmetry. Our analyses identified a dose threshold between 1.543 and 2.321 g/kg/day. Below this threshold, preconception paternal alcohol exposure induced changes in facial shape, including a right shift in facial features. In contrast, above this threshold, paternal exposures caused shifts in both shape and center, disrupting facial symmetry. Consistent with previous clinical studies, changes in craniofacial shape predominantly mapped to regions in the lower portion of the face, including the mandible (lower jaw) and maxilla (upper jaw). Notably, high-dose exposures also impacted the positioning of the right eye. Our studies reveal that paternal alcohol use may be an unrecognized factor contributing to the incidence and severity of alcohol-related craniofacial defects, complicating diagnostics of fetal alcohol spectrum disorders.
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Importance: Half of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals. Germline variants in BRCA1 and BRCA2 (also known as pathogenic or likely pathogenic variants, referred to here as BRCA1/2 PVs) are well known to significantly increase the risk of breast and ovarian cancers in female carriers, and knowledge of BRCA1/2 PVs informs established cancer screening and options for risk reduction. While risks to male carriers of BRCA1/2 PVs are less characterized, there is convincing evidence of increased risk for prostate cancer, pancreatic cancer, and breast cancer in males. There has also been a rapid expansion of US Food and Drug Administration-approved targeted cancer therapies, including poly ADP ribose polymerase (PARP) inhibitors, for breast, pancreatic, and prostate cancers associated with BRCA1/2 PVs. Observations: This narrative review summarized the data that inform cancer risks, targeted cancer therapy options, and guidelines for early cancer detection. It also highlighted areas of emerging research and clinical trial opportunities for male BRCA1/2 PV carriers. These developments, along with the continued relevance to family cancer risk and reproductive options, have informed changes to guideline recommendations for genetic testing and strengthened the case for increased genetic testing for males. Conclusions and Relevance: Despite increasing clinical actionability for male carriers of BRCA1/2 PVs, far fewer males than female individuals undergo cancer genetic testing. Oncologists, internists, and primary care clinicians should be vigilant about offering appropriate genetic testing to males. Identifying more male carriers of BRCA1/2 PVs will maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer.
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BACKGROUND: TP53 alterations are common in certain pediatric cancers, making identification of putative germline variants through tumor genomic profiling crucial for disease management. METHODS: We analyzed TP53 alterations in 3123 tumors from 2788 pediatric patients sequenced using tumor-only or tumor-normal paired panels. Germline confirmatory testing was performed when indicated. Somatic and germline variants were classified based on published guidelines. RESULTS: In 248 tumors from 222 patients, 284 tier 1/2 TP53 sequence and small copy number variants were detected. Following germline classification, 86.6% of 142 unique variants were pathogenic or likely pathogenic. Confirmatory testing on 118 patients revealed germline TP53 variants in 28 of them (23 pathogenic or likely pathogenic and 5 of uncertain significance), suggesting a minimum Li-Fraumeni syndrome incidence of 0.8% (23/2788) in this cohort, 10.4% (23/222) in patients with TP53 variant-carrying tumors, and 19.5% (23/118) with available normal samples. About 25% (7/28) of patients with germline TP53 variants did not meet Li-Fraumeni syndrome diagnostic or testing criteria, while 20.9% (28/134) with confirmed or inferred somatic origins did. TP53 biallelic inactivation occurred in 75% of germline carrier tumors and was also prevalent in other groups, causing an elevated tumor-observed variant allelic fraction. Somatic evidence, however, including low variant allele fraction correctly identified only 27.8% (25/90) of patients with confirmed somatic TP53 variants. CONCLUSION: The high incidence and variable phenotype of Li-Fraumeni syndrome in this cohort highlights the importance of assessing germline status of TP53 variants identified in all pediatric tumors. Without clear somatic evidence, distinguishing somatic from germline origins is challenging. Classifying germline and somatic variants should follow appropriate guidelines.
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Mutação em Linhagem Germinativa , Síndrome de Li-Fraumeni , Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Criança , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/epidemiologia , Neoplasias/genética , Neoplasias/epidemiologia , Masculino , Feminino , Pré-Escolar , Adolescente , Predisposição Genética para Doença , Variações do Número de Cópias de DNA , Testes Genéticos/métodos , Prevalência , LactenteRESUMO
Pathogenic germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer is the most common cancer in LFS females. We performed first of its kind multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC. Nearly all LFS-BC underwent biallelic loss of TP53 with no recurrent oncogenic variants except ERBB2 (HER2) amplification. Compared to sporadic BC, in situ and invasive LFS-BC exhibited a high burden of short amplified aneuploid segments (SAAS). Pro-apoptotic p53 target genes BAX and TP53I3 failed to be up-regulated in LFS-BC as was seen in sporadic BC compared to normal breast tissue. LFS-BC had lower CD8+ T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression from in situ to invasive BC was marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue.
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Study question: Are the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of reproductively adult oocyte donors? Summary answer: The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors. What is known already: Adolescents experience a period of subfecundity following menarche. Recent evidence suggests that this may be at least partially due to increased oocyte aneuploidy. Reproductive juvenescence in mammals is associated with suboptimal oocyte quality. Study design size duration: This was a prospective cohort study. Adolescents (10-19 years old, N=23) and oocyte donors (22-30 years old, N=31) undergoing ovarian stimulation and oocyte retrieval at the Northwestern Fertility and Reproductive Medicine Center between November 1, 2020 and May 1, 2023 were enrolled in this study. Participants/materials setting methods: Patient demographics, ovarian stimulation, and oocyte retrieval outcomes were collected for all participants. The transcriptome of CCs associated with mature oocytes was compared between adolescents (10-19 years old, n=19), and oocyte donors (22-30 years old, n=19) using bulk RNA-sequencing. FF cytokine profiles (10-19 years old, n=18 vs. 25-30 years old, n=16) were compared using cytokine arrays. Main results and the role of chance: RNA-seq analysis revealed 581 differentially expressed genes (DEGs) in cumulus cells of adolescents relative to oocyte donors, with 361 genes downregulated and 220 upregulated. Genes enriched in pathways involved in cell cycle and cell division (e.g., GO:1903047, p= 3.5 × 10-43; GO:0051983, p= 4.1 × 10-30; GO:0000281, p= 7.7 × 10-15; GO:0044839, p= 5.3 × 10-13) were significantly downregulated, while genes enriched in several pathways involved in cellular and vesicle organization (e.g., GO:0010256, p= 1.2 × 10-8; GO:0051129, p= 6.8 × 10-7; GO:0016050, p= 7.4 × 10-7; GO:0051640, p= 8.1 × 10-7) were upregulated in CCs of adolescents compared to oocyte donors. The levels of 9 cytokines were significantly increased in FF of adolescents compared to oocyte donors: IL-1 alpha (2-fold), IL-1 beta (1.7-fold), I-309 (2-fold), IL-15 (1.6-fold), TARC (1.9-fold), TPO (2.1-fold), IGFBP-4 (2-fold), IL-12-p40 (1.7-fold) and ENA-78 (1.4-fold). Interestingly, 7 of these cytokines have known pro-inflammatory roles. Importantly, neither the CC transcriptomes or FF cytokine profiles were different in adolescents with or without cancer. Large scale data: Original high-throughput sequencing data will be deposited in Gene Expression Omnibus (GEO) before publication, and the GEO accession number will be provided here. Limitations reasons for caution: This study aims to gain insights into the associated gamete quality by studying the immediate oocyte microenvironment. The direct study of oocytes is more challenging due to sample scarcity, as they are cryopreserved for future use, but will provide a more accurate assessment of oocyte reproductive potential. Wider implications of the findings: Understanding the underpinnings of altered immediate oocyte microenvironment of adolescent patients may provide insights into the reproductive potential of the associated gametes in the younger end of the age spectrum. This has implications for the fertility preservation cycles for very young patients. Study funding/competing interests: This project was supported by Friends of Prentice organization SP0061324 (M.M.L and E.B.), Gesualdo Family Foundation (Research Scholar: M.M.L.), and NIH/NICHD K12 HD050121 (E.B.). The authors have declared that no conflict of interest exists.
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Patients with cancer considering immune checkpoint inhibitor (ICI) therapy often look for health information and peer support through online communities. The authors used social media content analysis to obtain the perspectives of patients receiving ICI treatment about immune-related adverse events (irAEs), with particular focus on rheumatological symptoms. The most reported rheumatic symptom was joint pain. Other commonly reported symptoms included muscle pain, joint stiffness, arthritis, myositis, bone pain, back pain, and tendon/ligament pain. A few users reported development of rheumatic diseases. The authors' analyses allowed for cataloging and assessment of patient and caregiver experiences with ICI therapy and rheumatic irAEs.
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Inibidores de Checkpoint Imunológico , Neoplasias , Doenças Reumáticas , Humanos , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Mídias SociaisRESUMO
BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer; however, the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of gastric cancer risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of gastric cancer in this population. A total of 100 unselected BRCA1/2 carriers who underwent endoscopic ultrasound from March 2022 to March 2023 underwent concomitant upper endoscopy with nontargeted gastric antrum and body biopsies. The study population (70% women; mean age 60.1 years) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no gastric cancers were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to that in the general population; however, identification of H. pylori or GIM may help inform future gastric cancer risk management strategies in BRCA1/2 carriers. Prevention Relevance: Evaluating the burden of H. pylori infection and GIM among BRCA1/2 carriers is warranted to better understand the mechanisms of gastric carcinogenesis and to help inform risk management strategies for gastric cancer among this at-risk population.
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Proteína BRCA1 , Proteína BRCA2 , Infecções por Helicobacter , Helicobacter pylori , Metaplasia , Neoplasias Gástricas , Humanos , Feminino , Metaplasia/microbiologia , Metaplasia/patologia , Metaplasia/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Pessoa de Meia-Idade , Prevalência , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Masculino , Proteína BRCA2/genética , Idoso , Proteína BRCA1/genética , Adulto , Heterozigoto , Fatores de Risco , Mucosa Gástrica/patologia , Mucosa Gástrica/microbiologiaRESUMO
INTRODUCTION: The 2023 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, themed "Disrupting Prostate Cancer Research: Challenge Accepted," was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023. METHODS: The 2023 marked the 10th Annual CHPCA Meeting, a discussion-oriented scientific think-tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care. The 2023 CHPCA Meeting was attended by 81 academic investigators and included 40 talks across 8 sessions. RESULTS: The central topic areas covered at the meeting included: targeting transcription factor neo-enhancesomes in cancer, AR as a pro-differentiation and oncogenic transcription factor, why few are cured with androgen deprivation therapy and how to change dogma to cure metastatic prostate cancer without castration, reducing prostate cancer morbidity and mortality with genetics, opportunities for radiation to enhance therapeutic benefit in oligometastatic prostate cancer, novel immunotherapeutic approaches, and the new era of artificial intelligence-driven precision medicine. DISCUSSION: This article provides an overview of the scientific presentations delivered at the 2023 CHPCA Meeting, such that this knowledge can help in facilitating the advancement of prostate cancer research worldwide.
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Pesquisa Biomédica , Neoplasias da Próstata , Humanos , Masculino , Pesquisa Biomédica/tendências , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Germline heterozygous TP53 pathogenic variants (PVs) cause Li Fraumeni Syndrome (LFS, OMIM#151623). TP53 PVs at lower-than-expected variant allele frequencies (VAF) may reflect postzygotic mosaicism (PZM) or clonal hematopoiesis (CH); however, no guidelines exist for workup and clinical management. PATIENTS AND METHODS: Retrospective analysis of probands who presented to an academic cancer genetics program with a TP53 PV result on germline genetic testing. RESULTS: Twenty-one of 125 unrelated probands (17 %) were found to harbor a TP53 PV with VAF<30 % or a designation of "mosaic". A diagnosis of PZM was made in nine (43 %) due to a clinical phenotype consistent with LFS with (n = 8) or without (n = 1) positive ancillary tissue testing. Twelve patients (57 %) were diagnosed with presumed CH (pCH) due to a diagnosis of a myeloproliferative neoplasm, negative ancillary tissue testing, clinical phenotype not meeting LFS criteria, no cancer, and/or no first cancer age<50. Of the 19 patients with biological offspring, nine had either partial or complete offspring testing, all negative. CONCLUSIONS: Determining the etiology of low VAF TP53 PVs requires ancillary tissue testing and incorporation of clinical phenotype. Discerning PZM versus CH is important to provide optimal care and follow-up.
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Testes Genéticos , Mutação em Linhagem Germinativa , Síndrome de Li-Fraumeni , Mosaicismo , Proteína Supressora de Tumor p53 , Humanos , Testes Genéticos/métodos , Proteína Supressora de Tumor p53/genética , Feminino , Masculino , Síndrome de Li-Fraumeni/genética , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Germline genetic testing is a vital component of guideline-recommended cancer care for males with pancreatic, breast, or metastatic prostate cancers. We sought to determine whether there were racial disparities in germline genetic testing completion in this population. PATIENTS AND METHODS: This retrospective cohort study included non-Hispanic White and Black males with incident pancreatic, breast, or metastatic prostate cancers between January 1, 2019, and September 30, 2021. Two nationwide cohorts were examined: (1) commercially insured individuals in an administrative claims database, and (2) Veterans receiving care in the Veterans Health Administration. One-year germline genetic testing rates were estimated by using Kaplan-Meier methods. Cox proportional hazards regression was used to test the association between race and genetic testing completion. Causal mediation analyses were performed to investigate whether socioeconomic variables contributed to associations between race and germline testing. RESULTS: Our cohort consisted of 7,894 males (5,142 commercially insured; 2,752 Veterans). One-year testing rates were 18.0% (95% CI, 16.8%-19.2%) in commercially insured individuals and 14.2% (95% CI, 11.5%-15.0%) in Veterans. Black race was associated with a lower hazard of testing among commercially insured individuals (adjusted hazard ratio [aHR], 0.73; 95% CI, 0.58-0.91; P=.005) but not among Veterans (aHR, 0.99; 95% CI, 0.75-1.32; P=.960). In commercially insured individuals, income (aHR, 0.90; 95% CI, 0.86-0.96) and net worth (aHR, 0.92; 95% CI, 0.86-0.98) mediated racial disparities, whereas education (aHR, 0.98; 95% CI, 0.94-1.01) did not. CONCLUSIONS: Overall rates of guideline-recommended genetic testing are low in males with pancreatic, breast, or metastatic prostate cancers. Racial disparities in genetic testing among males exist in a commercially insured population, mediated by net worth and household income; these disparities are not seen in the equal-access Veterans Health Administration. Alleviating financial and access barriers may mitigate racial disparities in genetic testing.
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Testes Genéticos , Neoplasias Pancreáticas , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico , Testes Genéticos/estatística & dados numéricos , Testes Genéticos/métodos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Disparidades em Assistência à Saúde/estatística & dados numéricos , Mutação em Linhagem Germinativa , Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/patologia , Estados Unidos , Adulto , Predisposição Genética para Doença , Negro ou Afro-Americano/estatística & dados numéricos , Negro ou Afro-Americano/genéticaRESUMO
BACKGROUND: A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features. METHODS: This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology. RESULTS: Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor-positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. CONCLUSION: We observed high rates of ductal carcinoma in situ, hormone receptor-positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor-positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.
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Neoplasias da Mama , Proteína Supressora de Tumor p53 , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Pessoa de Meia-Idade , Adulto , Idoso , Proteína Supressora de Tumor p53/genética , Adulto Jovem , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/epidemiologia , Síndrome de Li-Fraumeni/complicações , Mutação em Linhagem Germinativa , Estudos de Coortes , Mastectomia , Estadiamento de NeoplasiasRESUMO
Importance: Non-Hispanic Black (hereafter, Black) individuals experience worse prostate cancer outcomes due to socioeconomic and racial inequities of access to care. Few studies have empirically evaluated these disparities across different health care systems. Objective: To describe the racial and ethnic and neighborhood socioeconomic status (nSES) disparities among residents of the same communities who receive prostate cancer care in the US Department of Veterans Affairs (VA) health care system vs other settings. Design, Setting, and Participants: This cohort study obtained data from the VA Central Cancer Registry for veterans with prostate cancer who received care within the VA Greater Los Angeles Healthcare System (VA cohort) and from the California Cancer Registry (CCR) for nonveterans who received care outside the VA setting (CCR cohort). The cohorts consisted of all males with incident prostate cancer who were living within the same US Census tracts. These individuals received care between 2000 and 2018 and were followed up until death from any cause or censoring on December 31, 2018. Data analyses were conducted between September 2022 and December 2023. Exposures: Health care setting, self-identified race and ethnicity (SIRE), and nSES. Main Outcomes and Measures: The primary outcome was all-cause mortality (ACM). Cox proportional hazards regression models were used to estimate hazard ratios for associations of SIRE and nSES with prostate cancer outcomes in the VA and CCR cohorts. Results: Included in the analysis were 49â¯461 males with prostate cancer. Of these, 1881 males were in the VA cohort (mean [SD] age, 65.3 [7.7] years; 833 Black individuals [44.3%], 694 non-Hispanic White [hereafter, White] individuals [36.9%], and 354 individuals [18.8%] of other or unknown race). A total of 47â¯580 individuals were in the CCR cohort (mean [SD] age, 67.0 [9.6] years; 8183 Black individuals [17.2%], 26 206 White individuals [55.1%], and 13 191 individuals [27.8%] of other or unknown race). In the VA cohort, there were no racial disparities observed for metastasis, ACM, or prostate cancer-specific mortality (PCSM). However, in the CCR cohort, the racial disparities were observed for metastasis (adjusted odds ratio [AOR], 1.36; 95% CI, 1.22-1.52), ACM (adjusted hazard ratio [AHR], 1.13; 95% CI, 1.04-1.24), and PCSM (AHR, 1.15; 95% CI, 1.05-1.25). Heterogeneity was observed for the racial disparity in ACM in the VA vs CCR cohorts (AHR, 0.90 [95% CI, 0.76-1.06] vs 1.13 [95% CI, 1.04-1.24]; P = .01). No evidence of nSES disparities was observed for any prostate cancer outcomes in the VA cohort. However, in the CCR cohort, heterogeneity was observed for nSES disparities with ACM (AHR, 0.82; 95% CI, 0.80-0.84; P = .002) and PCSM (AHR, 0.86; 95% CI, 0.82-0.89; P = .007). Conclusions and Relevance: Results of this study suggest that racial and nSES disparities were wider among patients seeking care outside of the VA health care system. Health systems-related interventions that address access barriers may mitigate racial and socioeconomic disparities in prostate cancer.
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Etnicidade , Neoplasias da Próstata , Estados Unidos/epidemiologia , Masculino , Humanos , Idoso , Estudos de Coortes , Neoplasias da Próstata/terapia , Próstata , Los AngelesRESUMO
Many adults with OCD experience residual symptoms following CBT, with or without medication. A potential target for enhancing treatment effectiveness is family accommodation (FA). This study examined (1) possible sociodemographic and clinical correlates of FA in adults presenting for intensive/residential treatment, and (2) temporal relationships between FA and OCD symptom severity during acute treatment and follow-up phases. Adult patients (Nâ¯=â¯315) completed baseline measures of FA and OCD symptom severity at admission to IRT. Follow-up data were collected from a subset of participants (nâ¯=â¯111) at discharge, 1-month, and 6-month follow-up. Cross-lagged panel analysis showed that changes in OCD symptom severity from admission to discharge predicted changes in FA from discharge to 1-month follow-up. Increases in FA from discharge to 1-month follow-up predicted increases in OCD symptom severity from 1-month to 6-month follow-up. Female patients reported greater baseline FA from their family members than did males, and there were no significant differences in FA by relationship type or marital status. Contamination, Responsibility for Harm, and Symmetry/Incompleteness symptoms were each found to uniquely predict FA at admission. Results from this study provide support for the temporal precedence of FA reduction in OCD symptom improvement as adults transition home following residential treatment.
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Transtorno Obsessivo-Compulsivo , Masculino , Adulto , Humanos , Feminino , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/diagnóstico , Tratamento Domiciliar/métodos , Resultado do TratamentoAssuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Herança Multifatorial , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Feminino , Detecção Precoce de Câncer/métodos , Medição de Risco , Predisposição Genética para Doença , Fatores de Risco , Estratificação de Risco GenéticoRESUMO
Obsessive-compulsive and related disorders (OCRDs) are associated with increased risk of suicidal thoughts and behaviors (STBs), yet research characterizing suicidality in OCRDs remains limited. A major challenge in assessing STBs is the reliance on explicit self-report. This study utilized multi-method assessment to examine changes in both implicit and explicit STBs in 31 adults receiving partial/residential treatment for OCRDs. Assessments were administered at admission and weekly during treatment. Approximately three-quarters of participants reported lifetime suicidal thoughts, with 16 % reporting a prior suicide attempt. OCD severity was significantly correlated with lifetime suicidal thoughts, and was significantly higher for those with lifetime suicidal thoughts and prior attempts compared to those without. Implicit biases towards death were not associated with OCD severity, and did not predict explicitly endorsed STBs. This is the first study to measure both explicit and implicit STBs in adults with OCRDs. Limitations included small sample size and lack of racial/ethnic diversity. Given the majority had recent suicidal thoughts and one in six had a prior attempt, we emphasize the importance of STB assessment in OCD treatment settings.
Assuntos
Transtorno Obsessivo-Compulsivo , Ideação Suicida , Adulto , Humanos , Tentativa de Suicídio , Transtorno Obsessivo-Compulsivo/terapia , Pacientes , AutorrelatoRESUMO
SUMMARY: In the first prospective study evaluating circulating tumor DNA (ctDNA) for early cancer detection, Wong, Luo, and colleauges demonstrate the feasibility of liquid biopsy as an augmentation to current surveillance protocols for patients with Li-Fraumeni syndrome, an inherited cancer predisposition associated with high cancer risk in both pediatric and adult populations. Though additional clinical validation in larger cohorts is needed, this research highlights that a multimodal approach is likely necessary to improve the sensitivity of liquid biopsy assays for early cancer detection. See related article by Wong, Lou et al., p. 104 (9).