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1.
Breast Cancer Res Treat ; 170(1): 203, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29644560

RESUMO

The third category for extent of involution in Table 4 was published incorrectly in the original publication. The correct classification is ≥ 75% and the corrected Table 4 is given in the Correction article.

2.
PLoS One ; 13(2): e0191814, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29432432

RESUMO

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC.


Assuntos
Neoplasias da Mama/genética , Mama/metabolismo , MicroRNAs/metabolismo , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco
3.
J Clin Oncol ; 36(6): 581-590, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29185869

RESUMO

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

4.
Breast Cancer Res Treat ; 165(3): 623-631, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28643020

RESUMO

PURPOSE: Women with benign breast disease (BBD) have an increased risk of subsequent breast cancer. However, whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD is unclear. In this study, we investigated the associations of lifestyle, menstrual/reproductive, and histological factors with risk of breast cancer among women biopsied for BBD. METHODS: We conducted a case-control study, nested within a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest between 1971 and 2006. Cases were women who developed a subsequent invasive breast cancer during follow-up; controls were individually matched to cases on age at BBD diagnosis. A total of 526 case-control pairs were included in the study. We calculated crude and multivariable OR and 95% CI for the associations between lifestyle, menstrual/reproductive, and histological factors and breast cancer risk using conditional logistic regression. RESULTS: Compared to premenopausal women, postmenopausal women had reduced risk of subsequent breast cancer (OR 0.60; 95% CI 0.39-0.94), whereas women who ever used hormone replacement therapy (HRT) had increased risk (OR 3.61; 95% CI 1.68-7.75), as did women whose BBD lesion showed atypical hyperplasia (OR 5.56; 95% CI 2.05-15.06). Smoking, BMI, early menarche, multiparity (≥4), history of oophorectomy, and extent of lobular involution were not associated with risk of breast cancer. CONCLUSION: This study suggests that use of HRT and having atypical hyperplasia are associated with increased risk of breast cancer among women with BBD, while postmenopausal women with BBD have a reduced risk.


Assuntos
Doenças Mamárias/epidemiologia , Doenças Mamárias/patologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estilo de Vida , Ciclo Menstrual , História Reprodutiva , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Doenças Mamárias/complicações , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Gravidez , Medição de Risco , Fatores de Risco , Adulto Jovem
5.
J Clin Oncol ; 35(18): 1991-1998, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28358655

RESUMO

Purpose To perform the first meta-analysis of the performance of the genomic classifier test, Decipher, in men with prostate cancer postprostatectomy. Methods MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports between 2011 and 2016 of men treated by prostatectomy that assessed the benefit of the Decipher test. Multivariable Cox proportional hazards models fit to individual patient data were performed; meta-analyses were conducted by pooling the study-specific hazard ratios (HRs) using random-effects modeling. Extent of heterogeneity between studies was determined with the I2 test. Results Five studies (975 total patients, and 855 patients with individual patient-level data) were eligible for analysis, with a median follow-up of 8 years. Of the total cohort, 60.9%, 22.6%, and 16.5% of patients were classified by Decipher as low, intermediate, and high risk, respectively. The 10-year cumulative incidence metastases rates were 5.5%, 15.0%, and 26.7% ( P < .001), respectively, for the three risk classifications. Pooling the study-specific Decipher HRs across the five studies resulted in an HR of 1.52 (95% CI, 1.39 to 1.67; I2 = 0%) per 0.1 unit. In multivariable analysis of individual patient data, adjusting for clinicopathologic variables, Decipher remained a statistically significant predictor of metastasis (HR, 1.30; 95% CI, 1.14 to 1.47; P < .001) per 0.1 unit. The C-index for 10-year distant metastasis of the clinical model alone was 0.76; this increased to 0.81 with inclusion of Decipher. Conclusion The genomic classifier test, Decipher, can independently improve prognostication of patients postprostatectomy, as well as within nearly all clinicopathologic, demographic, and treatment subgroups. Future study of how to best incorporate genomic testing in clinical decision-making and subsequent treatment recommendations is warranted.


Assuntos
Biomarcadores Tumorais/genética , Nomogramas , Neoplasias da Próstata/genética , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Metástase Neoplásica , Prognóstico , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Medição de Risco , Fatores de Risco
6.
JAMA Oncol ; 3(2): 186-193, 2017 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-27711920

RESUMO

Importance: Within 10 years after breast cancer diagnosis, roughly 5% of patients develop contralateral breast cancer (CBC). Randomized trials have found that therapy including tamoxifen citrate and aromatase inhibitors (AIs) reduces CBC risk. But little is known about the magnitude and duration of protective associations within the context of real-world clinical management settings, where varying durations of and gaps in treatment are common. Objective: To determine the association between adjuvant tamoxifen and AI therapy and CBC risk within a general community setting. Design, Setting, and Participants: A retrospective cohort study of CBC risk among 7541 patients diagnosed with a first primary unilateral invasive breast cancer at Kaiser Permanente Institute for Health Research (Colorado) or Kaiser Permanente Northwest Center for Health Research (Oregon) between January 1, 1990, and December 31, 2008. Data were analyzed from 1 year after diagnosis of the first breast cancer through the earliest of the following events: CBC diagnosis, other second cancer diagnosis, death, last tumor registry follow-up, exit from the Kaiser Permanente health care plan, or end of study follow-up (December 31, 2010, for Oregon and December 31, 2011, for Colorado). Exposures: Adjuvant tamoxifen use and AI therapy were treated as time-dependent exposures, assessed using electronic prescription records. Main Outcomes and Measures: Incident CBC based on long-term systematic follow-up. Results: Among 7541 women with invasive breast cancer, median age at initial breast cancer diagnosis was 60.6 years (age range, 24.9-84.9 years). Women were predominantly (92.9% [7009 of 7541]) of white race. During a median of 6.3 years (range, 1-20.9 years) of follow-up, 248 women developed CBC (45 in situ and 203 invasive). Contralateral breast cancer risk decreased significantly with increasing tamoxifen therapy duration. In current users, the relative risk (RR) per year of tamoxifen use was 0.76 (95% CI, 0.64-0.89), with an estimated 66% (RR, 0.34; 95% CI, 0.29-0.40) RR reduction for 4 years of use compared with nonusers. Risk reductions were slightly smaller for past users but were still significant at least 5 years after stopping tamoxifen therapy (RR per year of use, 0.85; 95% CI, 0.71-0.995). In addition, AI use without tamoxifen therapy was associated with reduced CBC risk (RR for AI users compared with nonusers, 0.48; 95% CI, 0.22-0.97). Risk reductions were most apparent among women whose primary and CBCs were estrogen receptor positive. Conclusions and Relevance: Tamoxifen therapy was associated with reduced CBC risk during treatment and after its cessation, with risk progressively decreasing as tamoxifen therapy duration increased. Among those surviving at least 5 years, tamoxifen use for at least 4 years was estimated to prevent 3 CBCs per 100 women by 10 years after an estrogen receptor-positive first breast cancer, an absolute risk reduction that is consistent with findings from clinical trials. If adjuvant endocrine therapy is indicated for breast cancer treatment, these findings in concert with trial data suggest that women should be encouraged to complete the full course.

7.
J Urol ; 195(6): 1748-53, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26626216

RESUMO

PURPOSE: We determined the value of Decipher®, a genomic classifier, to predict prostate cancer outcomes among patients after prostatectomy in a community health care setting. MATERIALS AND METHODS: We examined the experience of 224 men treated with radical prostatectomy from 1997 to 2009 at Kaiser Permanente Northwest, a large prepaid health plan in Portland, Oregon. Study subjects had aggressive prostate cancer with at least 1 of several criteria such as preoperative prostate specific antigen 20 ng/ml or greater, pathological Gleason score 8 or greater, stage pT3 disease or positive surgical margins at prostatectomy. The primary end point was clinical recurrence or metastasis after surgery evaluated using a time dependent c-index. Secondary end points were biochemical recurrence and salvage treatment failure. We compared the performance of Decipher alone to the widely used CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical) score, and assessed the independent contributions of Decipher, CAPRA-S and their combination for the prediction of recurrence and treatment failure. RESULTS: Of the 224 patients treated 12 experienced clinical recurrence, 68 had biochemical recurrence and 34 experienced salvage treatment failure. At 10 years after prostatectomy the recurrence rate was 2.6% among patients with low Decipher scores but 13.6% among those with high Decipher scores (p=0.02). When CAPRA-S and Decipher scores were considered together, the discrimination accuracy of the ROC curve was increased by 0.11 compared to the CAPRA-S score alone (combined c-index 0.84 at 10 years after radical prostatectomy) for clinical recurrence. CONCLUSIONS: Decipher improves our ability to predict clinical recurrence in prostate cancer and adds precision to conventional pathological prognostic measures.


Assuntos
Biomarcadores Tumorais/metabolismo , Recidiva Local de Neoplasia/genética , Prostatectomia/efeitos adversos , Neoplasias da Próstata/patologia , Idoso , Centros Comunitários de Saúde , Genômica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Oregon , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia , Curva ROC , Sistema de Registros , Estudos Retrospectivos , Medição de Risco/métodos , Terapia de Salvação/efeitos adversos , Falha de Tratamento
8.
J Natl Cancer Inst ; 106(8)2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24895374

RESUMO

BACKGROUND: Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer. We prospectively examined the association between TMEM score and risk of distant metastasis and compared risk associated with TMEM score with that associated with IHC4. METHODS: We conducted a case-control study nested within a cohort of 3760 patients with invasive ductal breast carcinoma diagnosed between 1980 and 2000 and followed through 2010. Case patients were women who developed a subsequent distant metastasis; control subjects were matched (1:1) on age at and calendar year of primary diagnosis. TMEM was assessed by triple immunostain and IHC4 by standard methods; slides were read by pathologists blinded to outcome. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for clinical variables. A Receiver Operating Characteristic analysis was performed, and the area under the curve was estimated. All statistical tests were two-sided. RESULTS: TMEM score was associated with increased risk of distant metastasis in estrogen receptor (ER)(+)/human epidermal growth factor receptor (HER2)(-) tumors (multivariable OR high vs low tertile = 2.70; 95% CI = 1.39 to 5.26; P trend = .004), whereas IHC4 score had a borderline positive association (OR10 unit increase = 1.06; 95% CI = 1.00 to 1.13); the association for TMEM score persisted after adjustment for IHC4 score. The area under the curve for TMEM, adjusted for clinical variables, was 0.78. Neither TMEM score nor IHC4 score was independently associated with metastatic risk overall or in the triple negative or HER2(+) subgroups. CONCLUSIONS: TMEM score predicted risk of distant metastasis in ER(+)/HER2(-) breast cancer independently of IHC4 score and classical clinicopathologic features.


Assuntos
Neoplasias da Mama/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/fisiopatologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade
9.
BMC Health Serv Res ; 14: 189, 2014 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-24767095

RESUMO

BACKGROUND: To examine duration of daily filgrastim prophylaxis, and risk and consequences of chemotherapy-induced neutropenic complications (CINC) requiring inpatient care. METHODS: Using a retrospective cohort design and US healthcare claims data (2001-2010), we identified all cancer patients who initiated ≥1 course of myelosuppressive chemotherapy and received daily filgrastim prophylactically in ≥1 cycle. Cycles with daily filgrastim prophylaxis were pooled for analyses. CINC was identified based on hospital admissions with a diagnosis of neutropenia, fever, or infection; consequences were characterized in terms of hospital mortality, hospital length of stay (LOS), and CINC-related healthcare expenditures. RESULTS: Risk of CINC requiring inpatient care-adjusted for patient characteristics-was 2.4 (95% CI: 1.6-3.4) and 1.9 (1.3-2.8) times higher with 1-3 (N = 8371) and 4-6 (N = 3691) days of filgrastim prophylaxis, respectively, versus ≥7 days (N = 2226). Among subjects who developed CINC, consequences with 1-3 and 4-6 (vs. ≥7) days of filgrastim prophylaxis were: mortality (8.4% [n/N = 10/119] and 4.0% [3/75] vs. 0% [0/34]); LOS (means: 7.4 [N = 243] and 7.1 [N = 99] vs. 6.5 [N = 40]); and expenditures (means: $18,912 [N = 225] and $14,907 [N = 94] vs. $13,165 [N = 39]). CONCLUSIONS: In this retrospective evaluation, shorter courses of daily filgrastim prophylaxis were found to be associated with an increased risk of CINC as well as poorer outcomes among those developing this condition. Because of the limitations inherent in healthcare claims databases specifically and retrospective evaluations generally, additional research addressing these limitations is needed to confirm the findings of this study.


Assuntos
Neutropenia Febril/etiologia , Neutropenia Febril/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/complicações , Idoso , Feminino , Filgrastim , Hospitalização , Humanos , Revisão da Utilização de Seguros , Masculino , Pessoa de Meia-Idade , Profilaxia Pós-Exposição , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Medição de Risco/métodos , Estados Unidos
10.
Support Care Cancer ; 22(5): 1363-73, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24389827

RESUMO

PURPOSE: The purpose of this paper is to document the use of intravenous (IV) bisphosphonates for prevention of skeletal-related events (SREs) in patients with bone metastases (BM) due to breast cancer (BC), lung cancer (LC), or prostate cancer (PC). METHODS: Using data from two large US health systems, we identified all patients aged ≥ 18 years with primary BC, LC, or PC and newly diagnosed BM between 1/1/1995 and 12/31/2009. Starting with the diagnosis of BM, we reviewed medical and administrative records for evidence of receipt of IV bisphosphonates (zoledronic acid or pamidronate) and occurrence of SREs. Initiation of IV bisphosphonates prior to occurrence of an SRE was designated "primary prophylaxis"; use following an SRE was designated "secondary prophylaxis". RESULTS: We identified a total of 1,193 patients with newly diagnosed BM, including 400 with BC, 332 with LC, and 461 with PC. Use of IV bisphosphonates was substantially higher in BC (55.8 % of all patients) than in LC (14.8 %) or PC (20.2 %). Use of IV bisphosphonates was fairly evenly split between primary and secondary prophylaxis in BC (26.3 vs. 29.5 %, respectively) and PC (10.6 vs 9.5 %); in LC, however, primary prophylaxis was much less common than secondary prophylaxis (4.8 vs 9.9 %). CONCLUSIONS: Almost one half of all patients with BM due to BC, and substantially more with LC and PC, do not receive IV bisphosphonates. Among patients receiving such therapy, treatment often is not initiated until after the occurrence of an SRE. Our study suggests that IV bisphosphonates may be substantially underutilized in patients with BM due to these common cancers.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pamidronato , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Ácido Zoledrônico
11.
Support Care Cancer ; 21(12): 3279-86, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23884473

RESUMO

PURPOSE: To document the risk of skeletal complications in patients with bone metastases from breast cancer (BC), lung cancer (LC), or prostate cancer (PC) in routine clinical practice. METHODS: We used data from two large US health systems to identify patients aged ≥18 years with primary BC, LC, or PC and newly diagnosed bone metastases between January 1, 1995 and December 31, 2009. Beginning with the date of diagnosis of bone metastasis, we estimated the cumulative incidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, radiation to bone, bone surgery), based on review of medical records, accounting for death as a competing risk. RESULTS: We identified a total of 621 BC, 477 LC, and 721 PC patients with newly diagnosed bone metastases. SREs were present at diagnosis of bone metastasis in 22.4, 22.4, and 10.0 % of BC, LC, and PC patients, respectively. Relatively few LC or PC patients received intravenous bisphosphonates (14.8 and 20.2 %, respectively); use was higher in patients with BC, however (55.8 %). In BC, cumulative incidence of SREs during follow-up was 38.7 % at 6 months, 45.4 % at 12 months, and 54.2 % at 24 months; in LC, it was 41.0, 45.4, and 47.7 %; and in PC, it was 21.5, 30.4, and 41.9 %. More than one half of patients with bone metastases had evidence of SREs (BC: 62.6 %; LC: 58.7 %; PC: 51.7 %), either at diagnosis of bone metastases or subsequently. CONCLUSIONS: SREs are a frequent complication in patients with solid tumors and bone metastases, and are much more common than previously recognized in women with BC.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Neoplasias Pulmonares/patologia , Neoplasias da Próstata/patologia , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Difosfonatos/administração & dosagem , Feminino , Fraturas Espontâneas/patologia , Humanos , Incidência , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologia , Estudos Retrospectivos , Compressão da Medula Espinal/epidemiologia , Compressão da Medula Espinal/patologia , Estados Unidos/epidemiologia
12.
Cancer Causes Control ; 24(9): 1653-60, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23744043

RESUMO

BACKGROUND: Although the effectiveness of cervical cancer screening has been firmly established in reproductive-age women, its usefulness in older women is unclear. We sought to evaluate the efficacy of cervical cancer screening in older women. METHODS: We conducted a case-control study within two integrated health care systems in the northwestern United States. Cases (n = 69) were women aged 55-79 years who were diagnosed with invasive cervical cancer during 1980-1999. Controls (n = 208) were women with an intact uterus and no diagnosis of cervical cancer, but otherwise similar to cases in terms of age and length of enrollment in the health plan. We reviewed medical records to ascertain screening history during the 7 years prior to reference date. RESULTS: Compared to cases, controls were more likely to have received a Pap test. After adjustment for age and current smoking status, screening prior to an estimated 1-year duration of the occult invasive phase of cervical cancer was associated with a substantial reduction in risk [odds ratio (OR) 0.23; 95% CI 0.11-0.44]. Similar results were obtained using different estimates of the duration of the occult invasive phase. Analysis of the relative incidence of invasive cervical cancer in relation to the time following a negative screening test suggested a large reduction during the first year (OR 0.09; 95% CI 0.03-0.24). The incidence remained low for several years thereafter, returning to the incidence among unscreened women after 5-7 years. CONCLUSIONS: Cervical cancer screening by means of cytology is highly efficacious in older women. Our findings also suggest that five-yearly screening is approximately as efficacious as more frequent screening.


Assuntos
Neoplasias do Colo do Útero/prevenção & controle , Fatores Etários , Idoso , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Noroeste dos Estados Unidos/epidemiologia , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
13.
J Clin Oncol ; 30(25): 3044-50, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22851570

RESUMO

PURPOSE: To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction. METHODS: Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated. RESULTS: A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap. CONCLUSION: HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasia Intraepitelial Cervical/virologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Fatores Etários , Idoso , Algoritmos , Carcinoma de Células Escamosas/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , DNA Viral/isolamento & purificação , Feminino , Seguimentos , Sistemas Pré-Pagos de Saúde , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Incidência , Estimativa de Kaplan-Meier , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Oregon/epidemiologia , Teste de Papanicolaou , Infecções por Papillomavirus/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Irrigação Terapêutica , Fatores de Tempo , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal
14.
Prostate ; 72(15): 1678-87, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22473923

RESUMO

BACKGROUND: We recently established the rationale that NRBP1 (nuclear receptor binding protein 1) has a potential growth-promoting role in cell biology. NRBP1 interacts directly with TSC-22, a potential tumor suppressor gene that is differently expressed in prostate cancer. Consequently, we analyzed the role of NRBP1 expression in prostate cancer cell lines and its expression on prostate cancer tissue microarrays (TMA). METHODS: The effect of NRBP1 expression on tumor cell growth was analyzed by using RNAi. NRBP1 protein expression was evaluated on two TMAs containing prostate samples from more than 1,000 patients. Associations with clinico-pathological features, the proliferation marker Ki67 and survival data were analyzed. RESULTS: RNAi mediated silencing of NRBP1 expression in prostate cancer cell lines resulted in reduced cell growth (P < 0.05). TMA analysis revealed NRBP1 protein expression in benign prostate hyperplasia in 6% as compared to 60% in both, high-grade intraepithelial neoplasia and prostate cancer samples. Strong NRBP1 protein expression was restricted to prostate cancer and correlated with higher expression of the proliferation marker Ki67 (P < 0.05). Further, patients with strong NRBP1 protein expression showed poor clinical outcomes (P < 0.05). Analysis of matched localized cancer tissues before and after castration revealed that post-therapy-related repression of NRBP1 expression was significantly associated with better overall survival. CONCLUSIONS: We demonstrate that expression of NRBP1 is up-regulated during the progression of prostate cancer and that high NRBP1 expression is linked with poor prognosis and enhanced tumor cell growth.


Assuntos
Adenocarcinoma/patologia , Expressão Gênica , Neoplasias da Próstata/patologia , Receptores Citoplasmáticos e Nucleares/genética , Proteínas de Transporte Vesicular/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Finlândia/epidemiologia , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Prostatectomia , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Taxa de Sobrevida , Suíça/epidemiologia , Análise Serial de Tecidos , Proteínas de Transporte Vesicular/metabolismo
15.
Int J Cancer ; 131(8): 1921-9, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22290745

RESUMO

Obesity strongly increases the risk of endometrial cancer and is projected to increase current and future endometrial cancer incidence. In order to fully understand endometrial cancer incidence, one should also examine both hysterectomy, which eliminates future risk of endometrial cancer, and endometrial hyperplasia (EH), a precursor that prompts treatment (including hysterectomy). Hysterectomy and EH are more common than endometrial cancer, but data on simultaneous temporal trends of EH, hysterectomy and endometrial cancer are lacking. We used linked pathology, tumor registry, surgery and administrative datasets at the Kaiser Permanente Northwest Health Plan to calculate age-adjusted and age-specific rates, 1980-2003, of EH only (N = 5,990), EH plus hysterectomy (N = 904), hysterectomy without a diagnosis of EH or cancer (N = 14,926) and endometrial cancer (N = 1,208). Joinpoint regression identified inflection points and quantified annual percentage changes (APCs). The EH APCs were -5.3% (95% confidence interval [CI] = -7.4% to -3.2%) for 1980-1990, -12.9% (95% CI = -15.6% to -10.1%) for 1990-1999 and 2.4% (95% CI = -6.6% to 12.2%) for 1999-2003. The EH-plus-hysterectomy APCs were -8.6% (95% CI = -10.6% to -6.5%) for 1980-2000 and 24.5% (95% CI = -16.5% to 85.7%) for 2000-2003. Hysterectomy rates did not significantly change over time. The endometrial cancer APCs were -6.5% (95% CI = -10.3% to -2.6%) for 1980-1988 and 1.4% (95% CI = -0.2% to 3.0%) for 1988-2003. Hysterectomy rates were unchanged, but increased endometrial cancer incidence after 1988 and the reversal, in 1999, of the longstanding decline in EH incidence could reflect the influence of obesity on endometrial neoplasia.


Assuntos
Hiperplasia Endometrial/epidemiologia , Neoplasias do Endométrio/epidemiologia , Histerectomia , Planos de Pré-Pagamento em Saúde , Adulto , Hiperplasia Endometrial/cirurgia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Prognóstico , Fatores de Tempo
16.
J Oncol ; 2011: 970804, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21869889

RESUMO

Mutations in the p53 tumor suppressor gene and accumulation of its protein in breast tissue are thought to play a role in breast carcinogenesis. However, few studies have prospectively investigated the association of p53 immunopositivity and/or p53 alterations in women with benign breast disease in relation to the subsequent risk of invasive breast cancer. We carried out a case-control study nested within a large cohort of women biopsied for benign breast disease in order to address this question. After exclusions, 491 breast cancer cases and 471 controls were available for analysis. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Neither p53 immunopositivity nor genetic alterations in p53 (either missense mutations or polymorphisms) was associated with altered risk of subsequent breast cancer. However, the combination of both p53 immunopositivity and any p53 nucleotide change was associated with an approximate 5-fold nonsignificant increase in risk (adjusted OR 4.79, 95% CI 0.28-82.31) but the confidence intervals were extremely wide. Our findings raise the possibility that the combination of p53 protein accumulation and the presence of genetic alterations may identify a group at increased risk of breast cancer.

17.
Cancer Epidemiol Biomarkers Prev ; 20(7): 1398-409, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21602310

RESUMO

BACKGROUND: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (≥CIN3). Adding HPV testing to cytology is recommended for women ≥30 but long-term prospective studies of HPV testing are rare. METHODS: Beginning in 1989-1990, ~20,000 women in a prepaid health maintenance organization (median age = 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan-Meier estimates of cumulative probability for ≥CIN3, up to 18 years of follow-up. RESULTS: We observed 47 cases of invasive cervical cancer during the study period, and 156 cases of CIN3. Predictive values and Kaplan-Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against ≥CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8-15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2-6.6). The risk for ≥CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7). CONCLUSION AND IMPACT: The data from this cohort study show the long-term predictive value of HPV testing, particularly in women ≥30, and a possible role for distinguishing particularly carcinogenic types like HPV16.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Adulto , DNA Viral/análise , DNA Viral/isolamento & purificação , Feminino , Humanos , Programas de Rastreamento/métodos , Oregon , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Esfregaço Vaginal
18.
Cancer Causes Control ; 21(6): 821-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20084540

RESUMO

OBJECTIVE: We used a nested case-control design within a large, multi-center cohort of women who underwent a biopsy for benign breast disease (BBD) to assess the association of broad histologic groupings and specific histologic entities with risk of breast cancer. METHODS: Cases were all women who had a biopsy for BBD and who subsequently developed breast cancer; controls were individually matched to cases and were women with a biopsy for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After exclusions, 1,239 records (615 cases and 624 controls) were available for analysis. We used conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-proliferative BBD/normal pathology, the multivariable-adjusted odds ratio for proliferative lesions without atypia was 1.45 (95% CI 1.10-1.90), and that for atypical hyperplasia was 5.27 (95% CI 2.29-12.15). The presence of multiple foci of columnar cell hyperplasia and of complex fibroadenoma without atypia was associated with a non-significantly increased risk of breast cancer, whereas sclerosing adenosis, radial scar, and papilloma showed no association with risk. CONCLUSION: Our results indicate that, compared to women with normal pathology/non-proliferative disease, women with proliferative disease without atypia have a modestly increased risk of breast cancer, whereas women with atypical hyperplasia have a substantially increased risk.


Assuntos
Doenças Mamárias , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Doença da Mama Fibrocística/patologia , Biópsia/efeitos adversos , Doenças Mamárias/complicações , Doenças Mamárias/genética , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Cicatriz/complicações , Cicatriz/genética , Cicatriz/patologia , Estudos de Coortes , Feminino , Fibroadenoma/complicações , Fibroadenoma/genética , Fibroadenoma/patologia , Doença da Mama Fibrocística/complicações , Doença da Mama Fibrocística/genética , Humanos , Hiperplasia/complicações , Modelos Logísticos , Razão de Chances , Papiloma/complicações , Papiloma/genética , Papiloma/patologia , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Fatores de Risco
19.
Cancer Epidemiol ; 34(1): 34-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20079704

RESUMO

AIM: Women with a history of benign breast disease are at increased risk of subsequent breast cancer. However, few studies have examined whether established breast cancer risk factors other than histology are associated with an altered risk of breast cancer in women with benign breast disease. We used a nested case-control design within a large, multi-center cohort of women biopsied for benign breast disease (BBD) to estimate odds ratios for breast cancer in association with exposure to a range of personal and lifestyle factors. METHODS: Cases were women biopsied for BBD who subsequently developed breast cancer; controls were individually matched to cases on center and age at diagnosis and were women biopsied for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After excluding women with prevalent breast cancer, 1357 records (661 case records and 696 records) were available for analysis. We used conditional logistic regression to obtain crude and multivariable-adjusted estimates of the association between specific factors and risk of breast cancer. RESULTS: In multivariable analyses age at first live birth, number of pregnancies, and postmenopausal status were inversely associated with risk of breast cancer. The odds ratio for women with age at first birth <25 years and >or=3 pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval 0.13-0.79, and that for postmenopausal women relative to premenopausal women was 0.60, 95% CI 0.37-0.99. CONCLUSIONS: Further study of personal factors influencing the risk of breast cancer in women with BBD may help to identify subgroups of the population at increased risk of invasive disease.


Assuntos
Doenças Mamárias/patologia , Neoplasias da Mama/epidemiologia , Adulto , Fatores Etários , Biópsia , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Menarca , Menopausa , Pessoa de Meia-Idade , Paridade , Gravidez , Fatores de Risco
20.
J Clin Oncol ; 28(5): 788-92, 2010 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-20065186

RESUMO

PURPOSE The severity of endometrial hyperplasia (EH)-simple (SH), complex (CH), or atypical (AH)-influences clinical management, but valid estimates of absolute risk of clinical progression to carcinoma are lacking. Materials and METHODS We conducted a case-control study nested in a cohort of 7,947 women diagnosed with EH (1970-2002) at one prepaid health plan who remained at risk for at least 1 year. Patient cases (N = 138) were diagnosed with carcinoma, on average, 6 years later (range, 1 to 24 years). Patient controls (N = 241) were matched to patient cases on age at EH, date of EH, and duration of follow-up, and they were counter-matched to patient cases on EH severity. After we independently reviewed original slides and medical records of patient controls and patient cases, we combined progression relative risks (AH v SH, CH, or disordered proliferative endometrium [ie, equivocal EH]) from the case-control analysis with clinical censoring information (ie, hysterectomy, death, or left the health plan) on all cohort members to estimate interval-specific (ie, 1 to 4, 5 to 9, and 10 to 19 years) and cumulative (ie, through 4, 9, and 19 years) progression risks. Results For nonatypical EH, cumulative progression risk increased from 1.2% (95% CI, 0.6% to 1.9%) through 4 years to 1.9% (95% CI, 1.2% to 2.6%) through 9 years to 4.6% (95% CI, 3.3% to 5.8%) through 19 years after EH diagnosis. For AH, cumulative risk increased from 8.2% (95% CI, 1.3% to 14.6%) through 4 years to 12.4% (95% CI, 3.0% to 20.8%) through 9 years to 27.5% (95% CI, 8.6% to 42.5%) through 19 years after AH. CONCLUSION Cumulative 20-year progression risk among women who remain at risk for at least 1 year is less than 5% for nonatypical EH but is 28% for AH.


Assuntos
Carcinoma/epidemiologia , Hiperplasia Endometrial/epidemiologia , Neoplasias do Endométrio/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Idoso , Biópsia , Carcinoma/patologia , Estudos de Casos e Controles , Progressão da Doença , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Sistemas Pré-Pagos de Saúde , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Oregon/epidemiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Sistema de Registros , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
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