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1.
Emerg Infect Dis ; 29(4): 761-770, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36918377

RESUMO

SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021-March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19-0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40-0.49) and death (RR 0.45, 95% CI 0.34-0.59) than primary vaccine-only residents.


Assuntos
COVID-19 , Estados Unidos/epidemiologia , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Casas de Saúde , Surtos de Doenças
2.
PLoS One ; 18(3): e0282422, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36862756

RESUMO

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), is spread primarily through exposure to respiratory droplets from close contact with an infected person. To inform prevention measures, we conducted a case-control study among Colorado adults to assess the risk of SARS-CoV-2 infection from community exposures. METHODS: Cases were symptomatic Colorado adults (aged ≥18 years) with a positive SARS-CoV-2 test by reverse transcription-polymerase chain reaction (RT-PCR) reported to Colorado's COVID-19 surveillance system. From March 16 to December 23, 2021, cases were randomly selected from surveillance data ≤12 days after their specimen collection date. Cases were matched on age, zip code (urban areas) or region (rural/frontier areas), and specimen collection date with controls randomly selected among persons with a reported negative SARS-CoV-2 test result. Data on close contact and community exposures were obtained from surveillance and a survey administered online. RESULTS: The most common exposure locations among all cases and controls were place of employment, social events, or gatherings and the most frequently reported exposure relationship was co-worker or friend. Cases were more likely than controls to work outside the home (adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI): 1.09-1.28) in industries and occupations related to accommodation and food services, retail sales, and construction. Cases were also more likely than controls to report contact with a non-household member with confirmed or suspected COVID-19 (aOR 1.16, 95% CI: 1.06-1.27). CONCLUSIONS: Understanding the settings and activities associated with a higher risk of SARS-CoV-2 infection is essential for informing prevention measures aimed at reducing the transmission of SARS-CoV-2 and other respiratory diseases. These findings emphasize the risk of community exposure to infected persons and the need for workplace precautions in preventing ongoing transmission.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Adolescente , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos de Casos e Controles , Colorado/epidemiologia , Acomodação Ocular
3.
Infect Control Hosp Epidemiol ; 44(6): 1005-1009, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36645205

RESUMO

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.


Assuntos
COVID-19 , Viroses , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Casas de Saúde , Surtos de Doenças/prevenção & controle
4.
Public Health Rep ; 138(4): 619-624, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35856418

RESUMO

OBJECTIVES: Although many people who are incarcerated have risk factors for hepatitis A virus (HAV) infection, the proportion of hepatitis A cases among people with a recent incarceration is unknown. We examined the relationship between recent incarceration and HAV infection during community-based, person-to-person outbreaks to inform public health recommendations. METHODS: The Centers for Disease Control and Prevention surveyed health departments in 33 jurisdictions reporting person-to-person HAV outbreaks during 2016-2020 on the number of outbreak-associated cases, HAV-infected people recently incarcerated, and HAV-associated hospitalizations and deaths. RESULTS: Twenty-five health departments reported 18 327 outbreak-associated hepatitis A cases during January 11, 2016-January 24, 2020. In total, 2093 (11.4%) HAV-infected people had been recently incarcerated. Of those with complete data, 1402 of 1462 (95.9%) had been held in a local jail, and 1513 of 1896 (79.8.%) disclosed hepatitis A risk factors. Eighteen jurisdictions reported incarceration timing relative to the exposure period. Of 9707 cases in these jurisdictions, 991 (10.2%) were among recently incarcerated people; 451 of 688 (65.6%) people with complete data had been incarcerated during all (n = 55) or part (n = 396) of their exposure period. CONCLUSIONS: Correctional facilities are important settings for reaching people with risk factors for HAV infection and can also be venues where transmission occurs. Providing HAV vaccination to incarcerated people, particularly people housed in jails, can be an effective component of community-wide outbreak response.


Assuntos
Vírus da Hepatite A , Hepatite A , Humanos , Estados Unidos/epidemiologia , Hepatite A/epidemiologia , Vacinação , Surtos de Doenças , Estabelecimentos Correcionais
5.
PLoS One ; 17(10): e0274946, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36215247

RESUMO

While risk of fomite transmission of SARS-CoV-2 is considered low, there is limited environmental data within households. This January-April 2021 investigation describes frequency and types of surfaces positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) among residences with ≥1 SARS-CoV-2 infection, and associations of household characteristics with surface RT-PCR and viable virus positivity. Of 1232 samples from 124 households, 27.8% (n = 342) were RT-PCR positive with nightstands (44.1%) and pillows (40.9%) most frequently positive. SARS-CoV-2 lineage, documented household transmission, greater number of infected persons, shorter interval between illness onset and sampling, total household symptoms, proportion of infected persons ≤12 years old, and persons exhibiting upper respiratory symptoms or diarrhea were associated with more positive surfaces. Viable virus was isolated from 0.2% (n = 3 samples from one household) of all samples. This investigation suggests that while SARS-CoV-2 on surfaces is common, fomite transmission risk in households is low.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Teste para COVID-19 , Criança , Colorado , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética
6.
Vaccine ; 40(33): 4845-4855, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35803846

RESUMO

BACKGROUND: COVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts. METHODS: We conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts. RESULTS: We enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40-51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45-57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11-42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%). CONCLUSIONS: Although SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , California/epidemiologia , Colorado/epidemiologia , Humanos
7.
Emerg Infect Dis ; 28(8): 1551-1558, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35705189

RESUMO

A COVID-19 outbreak occurred among Cameron Peak Fire responders in Colorado, USA, during August 2020-January 2021. The Cameron Peak Fire was the largest recorded wildfire in Colorado history, lasting August-December 2020. At least 6,123 responders were involved, including 1,260 firefighters in 63 crews who mobilized to the fire camps. A total of 79 COVID-19 cases were identified among responders, and 273 close contacts were quarantined. State and local public health investigated the outbreak and coordinated with wildfire management teams to prevent disease spread. We performed whole-genome sequencing and applied social network analysis to visualize clusters and transmission dynamics. Phylogenetic analysis identified 8 lineages among sequenced specimens, implying multiple introductions. Social network analysis identified spread between and within crews. Strategies such as implementing symptom screening and testing of arriving responders, educating responders about overlapping symptoms of smoke inhalation and COVID-19, improving physical distancing of crews, and encouraging vaccinations are recommended.


Assuntos
COVID-19 , Bombeiros , Incêndios Florestais , COVID-19/epidemiologia , Colorado/epidemiologia , Surtos de Doenças , Humanos , Filogenia
8.
J Pediatr ; 247: 29-37.e7, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35447121

RESUMO

OBJECTIVE: To assess the household secondary infection risk (SIR) of B.1.1.7 (Alpha) and non-Alpha lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. STUDY DESIGN: During January to April 2021, we prospectively followed households with a SARS-CoV-2 infection. We collected questionnaires, serial nasopharyngeal swabs for reverse transcription polymerase chain reaction testing and whole genome sequencing, and serial blood samples for serology testing. We calculated SIRs by primary case age (pediatric vs adult), household contact age, and viral lineage. We evaluated risk factors associated with transmission and described symptom profiles among children. RESULTS: Among 36 households with pediatric primary cases, 21 (58%) had secondary infections. Among 91 households with adult primary cases, 51 (56%) had secondary infections. SIRs among pediatric and adult primary cases were 45% and 54%, respectively (OR, 0.79; 95% CI, 0.41-1.54). SIRs among pediatric primary cases with Alpha and non-Alpha lineage were 55% and 46%, respectively (OR, 1.52; 95% CI, 0.51-4.53). SIRs among pediatric and adult household contacts were 55% and 49%, respectively (OR, 1.01; 95% CI, 0.68-1.50). Among pediatric contacts, no significant differences in the odds of acquiring infection by demographic or household characteristics were observed. CONCLUSIONS: Household transmission of SARS-CoV-2 from children and adult primary cases to household members was frequent. The risk of secondary infection was similar among child and adult household contacts. Among children, household transmission of SARS-CoV-2 and the risk of secondary infection was not influenced by lineage. Continued mitigation strategies (eg, masking, physical distancing, vaccination) are needed to protect at-risk groups regardless of virus lineage circulating in communities.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , COVID-19/epidemiologia , California , Criança , Colorado/epidemiologia , Humanos
9.
JAMA Intern Med ; 182(7): 701-709, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35486394

RESUMO

Importance: As self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed. Objective: To evaluate the diagnostic performance of home antigen tests compared with reverse transcription-polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability. Design, Setting, and Participants: This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR-confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR-confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants. Results: This study enrolled 225 persons with RT-PCR-confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145 [64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter. Conclusions and Relevance: The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.


Assuntos
COVID-19 , Adulto , COVID-19/diagnóstico , Criança , Estudos de Coortes , Feminino , Humanos , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Sensibilidade e Especificidade
10.
Clin Infect Dis ; 75(1): e122-e132, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35147176

RESUMO

BACKGROUND: In Spring 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) became the predominant variant in the United States. Research suggests that Alpha has increased transmissibility compared with non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections. METHODS: We followed households with SARS-CoV-2 infection for 2 weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, reverse transcription-polymerase chain reaction (RT-PCR), and whole-genome sequencing. We stratified SIR and symptoms by lineage and identified characteristics associated with transmission using generalized estimating equations. RESULTS: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval, 52.4-69.0%]) than non-Alpha (55.6% [44.7-65.9%], P = .49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = .01 and .03, respectively). Close contact (eg, kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs 76.8%, P = .05). CONCLUSIONS: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households due to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Características da Família , Humanos , SARS-CoV-2/genética , Estados Unidos/epidemiologia
11.
MMWR Morb Mortal Wkly Rep ; 70(32): 1084-1087, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34383734

RESUMO

On May 5, 2021, the Colorado Department of Public Health and Environment (CDPHE) identified the first five COVID-19 cases caused by the SARS-CoV-2 B.1.617.2 (Delta) variant in Mesa County in western Colorado (population 154,933, <3% of the state population). All five initial cases were associated with school settings. Through early June, Mesa County experienced a marked increase in the proportion of Delta variant cases identified through sequencing: the 7-day proportion of sequenced specimens identified as B.1.617.2 in Mesa County more than doubled, from 43% for the week ending May 1 to 88% for the week ending June 5. As of June 6, more than one half (51%) of sequenced B.1.617.2 specimens in Colorado were from Mesa County. CDPHE assessed data from surveillance, vaccination, laboratory, and hospital sources to describe the preliminary epidemiology of the Delta variant and calculate crude vaccine effectiveness (VE). Vaccination coverage in early May in Mesa County was lower (36% of eligible residents fully vaccinated) than that in the rest of the state (44%). Compared with that in all other Colorado counties, incidence, intensive care unit (ICU) admissions, and COVID-19 case fatality ratios were significantly higher in Mesa County during the analysis period, April 27-June 6, 2021. In addition, during the same time period, the proportion of COVID-19 cases in persons who were fully vaccinated (vaccine breakthrough cases) was significantly higher in Mesa County compared with that in all other Colorado counties. Estimated crude VE against reported symptomatic infection for a 2-week period ending June 5 was 78% (95% confidence interval [CI] = 71%-84%) for Mesa County and 89% (95% CI = 88%-91%) for other Colorado counties. Vaccination is a critical strategy for preventing infection, serious illness, and death from COVID-19. Enhanced mitigation strategies, including masking in indoor settings irrespective of vaccination status, should be considered in areas with substantial or high case rates.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Idoso , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Criança , Pré-Escolar , Colorado/epidemiologia , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Adulto Jovem
12.
MMWR Morb Mortal Wkly Rep ; 70(19): 717-718, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33988184

RESUMO

The B.1.427 and B.1.429 variants of SARS-CoV-2, the virus that causes COVID-19, were first described in Southern California on January 20, 2021 (1); on March 16 they were designated variants of concern* (2). Data on these variants are limited, but initial reports suggest that, compared with other lineages, they might be more infectious (1,2), cause more severe illness (2), and be less susceptible to neutralizing monoclonal antibody products such as bamlanivimab, an investigational treatment for mild-to-moderate COVID-19 (1-3). On January 24, the Colorado Department of Public Health and Environment (CDPHE) identified the first Colorado case of COVID-19 attributed to these variants. B.1.427 and B.1.429 were considered a single variant described as CAL.20C or B.1.427/B.1.429 in the 20C clade (1,3); in this report "B.1.427/B.1.429" refers to B.1.427 or B.1.429 lineage, including those reported as B.1.427/B.1.429 without further differentiation.


Assuntos
COVID-19/virologia , Vigilância em Saúde Pública , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Criança , Pré-Escolar , Colorado/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
MMWR Morb Mortal Wkly Rep ; 69(33): 1139-1143, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32817597

RESUMO

Preventing coronavirus disease 2019 (COVID-19) in correctional and detention facilities* can be challenging because of population-dense housing, varied access to hygiene facilities and supplies, and limited space for isolation and quarantine (1). Incarcerated and detained populations have a high prevalence of chronic diseases, increasing their risk for severe COVID-19-associated illness and making early detection critical (2,3). Correctional and detention facilities are not closed systems; SARS-CoV-2, the virus that causes COVID-19, can be transmitted to and from the surrounding community through staff member and visitor movements as well as entry, transfer, and release of incarcerated and detained persons (1). To better understand SARS-CoV-2 prevalence in these settings, CDC requested data from 15 jurisdictions describing results of mass testing events among incarcerated and detained persons and cases identified through earlier symptom-based testing. Six jurisdictions reported SARS-CoV-2 prevalence of 0%-86.8% (median = 29.3%) from mass testing events in 16 adult facilities. Before mass testing, 15 of the 16 facilities had identified at least one COVID-19 case among incarcerated or detained persons using symptom-based testing, and mass testing increased the total number of known cases from 642 to 8,239. Case surveillance from symptom-based testing has likely underestimated SARS-CoV-2 prevalence in correctional and detention facilities. Broad-based testing can provide a more accurate assessment of prevalence and generate data to help control transmission (4).


Assuntos
Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Surtos de Doenças/prevenção & controle , Programas de Rastreamento , Pneumonia Viral/epidemiologia , Prisões , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Habitação/estatística & dados numéricos , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Prevalência , Estados Unidos/epidemiologia
14.
Breast Cancer Res ; 14(5): R130, 2012 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-23036105

RESUMO

INTRODUCTION: Signal transducer and activator of transcripton-5a (Stat5a) and its close homologue, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome. METHODS: Stat5a and Stat5b protein levels were quantified in situ in breast-cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data by using multivariate models. RESULTS: Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared with normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a- and Stat5b-modulated genes was found. In two cohorts of therapy-naïve, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with a more than fourfold risk of unfavorable outcome. CONCLUSIONS: Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Fator de Transcrição STAT5/metabolismo , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Núcleo Celular/metabolismo , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Fosforilação , Prognóstico , Transporte Proteico , Resultado do Tratamento , Carga Tumoral
15.
J Clin Oncol ; 29(18): 2448-58, 2011 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-21576635

RESUMO

PURPOSE: To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. PATIENTS AND METHODS: Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. RESULTS: Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). CONCLUSION Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Proteínas de Neoplasias/fisiologia , Proteínas Nucleares/fisiologia , Fator de Transcrição STAT5/fisiologia , Proteínas Supressoras de Tumor/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/patologia , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Moduladores de Receptor Estrogênico/farmacologia , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Proteínas de Neoplasias/química , Proteínas Nucleares/química , Fosforilação , Fosfotirosina/química , Prognóstico , Processamento de Proteína Pós-Traducional , Fator de Transcrição STAT5/química , Análise de Sobrevida , Falha de Tratamento , Proteínas Supressoras de Tumor/química , Adulto Jovem
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