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1.
Cancer Epidemiol Biomarkers Prev ; 28(11): 1802-1808, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31395589

RESUMO

BACKGROUND: Type II diabetes and certain diabetes treatments have been observed to impact breast cancer risk. However, their associations with different breast cancer molecular subtype defined by estrogen receptor (ER)/progesterone receptor (PR)/HER2 status are unclear. METHODS: We conducted a retrospective multi-center population-based case-case study consisting of 4,557 breast cancer cases to evaluate the impact of type II diabetes and diabetes medications on the risk of different breast cancer molecular subtypes [ER+/HER2-, ER+/HER2+, triple negative (ER-/PR-/HER2-), and HER2 overexpressing (H2E, ER-/PR-/HER2+)]. Using ER+/HER2- cases as the reference group, we estimated ORs and corresponding 95% confidence intervals (CI) for each subtype using polytomous logistic regression. RESULTS: Compared with those without a diabetes history, women with type II diabetes had a 38% (95% CI, 1.01-1.89) increased odds of triple-negative breast cancer (TNBC). Current and longer term recent metformin use (13-24 months of treatment within the 24-month period prior to breast cancer diagnosis) was associated with elevated odds of TNBC (OR = 1.54; 95% CI, 1.07-2.22 and OR = 1.80; 95% CI, 1.13-2.85, respectively). CONCLUSIONS: The odds of having a triple-negative rather than ER+/HER2- breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin. This finding is supported by some preclinical data suggesting that diabetes may be more strongly associated with risk of triple-negative disease. IMPACT: Our study provides novel evidence regarding potential differential effects of type II diabetes and metformin use on risk of different molecular subtypes of breast cancer.

3.
Am J Prev Med ; 56(5): e143-e152, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31003603

RESUMO

INTRODUCTION: The purpose of this study was to test the hypothesis that patients with Medicaid insurance or Medicaid-like coverage would have longer times to follow-up and be less likely to complete colonoscopy compared with patients with commercial insurance within the same healthcare systems. METHODS: A total of 35,009 patients aged 50-64years with a positive fecal immunochemical test were evaluated in Northern and Southern California Kaiser Permanente systems and in a North Texas safety-net system between 2011 and 2012. Kaplan-Meier estimation was used between 2016 and 2017 to calculate the probability of having follow-up colonoscopy by coverage type. Among Kaiser Permanente patients, Cox regression was used to estimate hazard ratios and 95% CIs for the association between coverage type and receipt of follow-up, adjusting for sociodemographics and health status. RESULTS: Even within the same integrated system with organized follow-up, patients with Medicaid were 24% less likely to complete follow-up as those with commercial insurance. Percentage receiving colonoscopy within 3 months after a positive fecal immunochemical test was 74.6% for commercial insurance, 63.10% for Medicaid only, and 37.5% for patients served by the integrated safety-net system. CONCLUSIONS: This study found that patients with Medicaid were less likely than those with commercial insurance to complete follow-up colonoscopy after a positive fecal immunochemical test and had longer average times to follow-up. With the future of coverage mechanisms uncertain, it is important and timely to assess influences of health insurance coverage on likelihood of follow-up colonoscopy and identify potential disparities in screening completion.

4.
Horm Cancer ; 10(2-3): 71-76, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30989580

RESUMO

Oral contraceptive use is a well-established risk factor for breast cancer and is common among reproductive-aged women in the USA. Its relationship with less common, more aggressive, molecular subtypes is less clear. A population-based case-case analysis was conducted comparing three less common molecular subtypes to luminal A breast cancer among 1701 premenopausal cases aged 21-49 diagnosed with a first primary invasive breast cancer between 2004 and 2015. Medical record reviews and structured interviewer-administered questionnaires were used to collect data on oral contraceptive use. Multinomial logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for recency of oral contraceptive use for each subtype of breast cancer. Current use of oral contraceptives and use within 5 years before diagnosis was associated with lower odds of H2E tumors compared with luminal A tumors [OR = 0.5, 95% CI: 0.3, 0.9 and OR = 0.5, 95% CI: 0.4, 0.8, respectively] with increasing duration associated with decreasing odds (p for trend < 0.05). Oral contraceptive use was not associated with risks of TN or luminal B breast cancer. Oral contraceptive use may be more strongly positively associated with risks of luminal A, luminal B, and TN breast cancer than with risk of H2E tumors. These findings contribute to the etiological understanding of different molecular subtypes of breast cancer.

5.
Cancer Causes Control ; 30(6): 651-661, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30976958

RESUMO

PURPOSE: One in 1,000 pregnancies is complicated by malignancies. Prevalence is greater for benign neoplasms. Adverse outcomes among women with malignancies have been reported. Less is known of postpartum outcomes for infants, or outcomes among women with benign neoplasms. METHODS: We conducted a population-based cohort study using Washington State-linked vital-hospital discharge records. Women with neoplasms (707 malignant; 13,156 benign) with deliveries in 1987-2012 were identified, and a randomly selected comparison cohort. Obstetrical/infant outcomes and rehospitalization < 2 years post-delivery were compared separately for each group by multivariable regressions to estimate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Women with either condition had increased anemia, cesarean, and preterm delivery; their infants were more often < 2,500 g or jaundiced. Women with benign conditions had increased gestational diabetes (RR = 1.20; 95% CI 1.12-1.28) and preeclampsia (RR = 1.27; 95% CI 1.18-1.36); their infants had increased malformations (RR = 1.29; 95% CI 1.19-1.38). Women with neoplasms more often were hospitalized seven or more days or rehospitalized; their infants' hospitalizations were also longer. CONCLUSION: Malignant and benign neoplasms were associated with several adverse outcomes. Reasons for relationships of benign neoplasms with gestational diabetes, preeclampsia, and congenital malformations merit further study.


Assuntos
Diabetes Gestacional/epidemiologia , Pré-Eclâmpsia/epidemiologia , Complicações Neoplásicas na Gravidez/epidemiologia , Resultado da Gravidez , Adolescente , Adulto , Cesárea/estatística & dados numéricos , Estudos de Coortes , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Retrospectivos , Washington , Adulto Jovem
6.
JAMA Oncol ; 5(5): 635-642, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30816931

RESUMO

Importance: Breast cancer screening examinations using digital breast tomosynthesis (DBT) has been shown to be associated with decreased false-positive test results and increased breast cancer detection compared with digital mammography (DM). Little is known regarding the size and stage of breast cancer types detected and their association with age and breast density. Objective: To determine whether screening examinations using DBT detect breast cancers that are associated with an improved prognosis and to compare the detection rates by patient age and breast density. Design, Setting, and Participants: This retrospective analysis of prospective cohort data from 3 research centers in the Population-based Research Optimizing Screening Through Personalized Regimens (PROSPR) consortium included data of women aged 40 to 74 years who underwent screening examinations using DM and DBT from January 1, 2011, through September 30, 2014. Statistical analysis was performed from November 8, 2017, to August 14, 2018. Exposures: Use of DBT as a supplement to DM at breast cancer screening examination. Main Outcomes and Measures: Recall rate, cancer detection rate, positive predictive value, biopsy rate, and distribution of invasive cancer subtypes. Results: Among 96 269 women (mean [SD] patient age for all examinations, 55.9 [9.0] years), patient age was 56.4 (9.0) years for DM and 54.6 (8.9) years for DBT. Of 180 340 breast cancer screening examinations, 129 369 examinations (71.7%) used DM and 50 971 examinations (28.3%) used DBT. Screening examination with DBT (73 of 99 women [73.7%]) was associated with the detection of smaller, more often node-negative, HER2-negative, invasive cancers compared with DM (276 of 422 women [65.4%]). Screening examination with DBT was also associated with lower recall (odds ratio, 0.64; 95% CI, 0.57-0.72; P < .001) and higher cancer detection (odds ratio, 1.41; 95% CI, 1.05-1.89; P = .02) compared with DM for all age groups even when stratified by breast density. The largest increase in cancer detection rate and the greatest shift toward smaller, node-negative invasive cancers detected with DBT was for women aged 40 to 49 years. For women aged 40 to 49 years with nondense breasts, the cancer detection rate for examinations using DBT was 1.70 per 1000 women higher compared with the rate using DM; for women with dense breasts, the cancer detection rate was 2.27 per 1000 women higher for DBT. For these younger women, screening with DBT was associated with only 7 of 28 breast cancers (25.0%) categorized as poor prognosis compared with 19 of 47 breast cancers (40.4%) when screening with DM. Conclusions and Relevance: The findings suggest that screening with DBT is associated with increased specificity and an increased proportion of breast cancers detected with better prognosis compared with DM. In the subgroup of women aged 40 to 49 years, routine DBT screening may have a favorable risk-benefit ratio.

7.
Hum Genet ; 138(4): 307-326, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30820706

RESUMO

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
8.
Am J Perinatol ; 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30726999

RESUMO

OBJECTIVE: To describe obstetric outcomes in a large cohort of young women with breast cancer, considering the chronological relationship of pregnancies with breast cancer diagnosis. STUDY DESIGN: From a population-based cohort study of young women with breast cancer from 2004 to 2010, we conducted secondary interviews to obtain detailed obstetric histories. Pregnancies were categorized based on timing of breast cancer diagnosis: prior, postpartum, and subsequent pregnancies after breast cancer diagnosis. A generalized estimated equation model was used to account for correlated data. RESULTS: In this cohort (n = 366), median age at breast cancer diagnosis was 40.1 years, and 84.7% were Caucasian. Tumor type was notable for 25.1% triple negative, and 56.1% had Stage I disease. There were 922 prior pregnancies, 21 with postpartum diagnosis of breast cancer, and 24 pregnancies subsequent to breast cancer diagnosis. Non-live birth outcomes occurred significantly more often in the postpartum group (p-value: 0.001) compared with the other groups, which had higher live birth rates, after adjustment for maternal age, parity, body mass index, and race. CONCLUSION: Overall, pregnancy outcomes before and after breast cancer diagnosis are reassuring.

9.
Cancer Causes Control ; 30(1): 113-120, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30539315

RESUMO

PURPOSE: In situ breast cancer patients have a higher risk of developing a second primary breast cancer than women in the general population have of developing breast cancer. We have limited understanding of why some women with a previous in situ breast cancer develop second primary breast cancers while others do not. METHODS: In this population-based nested case-control study, we evaluated the association between reproductive and menopausal factors and risk of developing a second primary breast cancer among women with a previous in situ breast cancer. Using conditional logistic regression, these associations were evaluated in 552 cases and 1032 individually matched controls. RESULTS: Older age at menarche was associated with risk of second primary breast cancer among women with a previous in situ breast cancer (compared to age < 12, age 13: OR 0.60 (0.42, 0.85); age ≥ 14: OR 0.69 (0.47, 1.00); Ptrend = 0.07). Breastfeeding for > 12 months was associated with a decreased risk of developing a second primary breast cancer (OR 0.62 (0.39, 0.98)). No associations were observed for other reproductive or menopausal factors evaluated. CONCLUSIONS: Results from this study suggest that reproductive factors may play a role in development of a second primary breast cancer after diagnosis of in situ breast carcinoma.


Assuntos
Neoplasias da Mama/patologia , Menopausa , Segunda Neoplasia Primária/patologia , Idoso , Aleitamento Materno , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Menarca , Pessoa de Meia-Idade , Reprodução , História Reprodutiva , Fatores de Risco
10.
Artigo em Inglês | MEDLINE | ID: mdl-30523039

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death. Biomarkers to predict treatment outcomes are needed, as is evidence whether post-diagnosis diet and lifestyle can affect well-being and clinical outcomes. The international ColoCare Consortium aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with short-term and long-term patient-reported and clinical outcomes among CRC patients. METHODS/RESULTS: ColoCare is recruiting newly diagnosed CRC patients across six sites in the U.S. and one in Germany. As of April 2018 we have recruited >2,000 patients across all sites. Our projected enrollment is >4,000 multiethnic CRC patients. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. Our initial studies demonstrated metabolic differences in adipose tissue types. We further reported on associations of biological factors (e.g., inflammation, DNA methylation, metabolomics) with lifestyle factors (e.g., adiposity, smoking, physical activity, dietary supplement use) or joint associations with clinical outcomes. CONCLUSION: ColoCare is a consortium for the investigation of multi-level factors relevant to CRC survivorship. IMPACT: The combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource that facilitates wide-ranging, innovative, and impactful research on CRC.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30481098

RESUMO

BACKGROUND: U.S. women of ages 50-74 years are recommended to receive screening mammography at least biennially. Our objective was to evaluate multilevel predictors of nonadherence among screened women, as these are not well known. MATERIALS AND METHODS: A cohort study was conducted among women of ages 50-74 years with a screening mammogram in 2011 with a negative finding (Breast Imaging-Reporting and Data System 1 or 2) within Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium research centers. We evaluated the association between woman-level factors, radiology facility, and PROSPR research center, and nonadherence to breast cancer screening guidelines, defined as not receiving breast imaging within 27 months of an index screening mammogram. Multilevel mixed-effects logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS: Nonadherence to guideline-recommended screening interval was 15.5% among 51,241 women with a screening mammogram. Non-Hispanic Asian/Pacific Islander women, women of other races, heavier women, and women of ages 50-59 years had a greater odds of nonadherence. There was no association with ZIP code median income. Nonadherence varied by research center and radiology facility (variance = 0.10, standard error = 0.03). Adjusted radiology facility nonadherence rates ranged from 10.0% to 26.5%. One research center evaluated radiology facility communication practices for screening reminders and scheduling, but these were not associated with nonadherence. CONCLUSIONS: Breast cancer screening interval nonadherence rates in screened women varied across radiology facilities even after adjustment for woman-level characteristics and research center. Future studies should investigate other characteristics of facilities, practices, and health systems to determine factors integral to increasing continued adherence to breast cancer screening.

12.
Cancer Res ; 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30291105

RESUMO

Many normal tissues undergo age-related drift in DNA methylation, providing a quantitative measure of tissue age. Here we identify and validate 781 CpG-islands (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues and show that these CGI continue to drift in neoplasia while retaining significant correlations across samples. However, compared with normal colon, this drift advanced (~3-4 fold) faster in neoplasia, consistent with increased cell proliferation during neoplastic progression. The observed drift patterns were broadly consistent with modeled adenoma-carcinoma sojourn time distributions from colorectal cancer (CRC) incidence data. These results support the hypothesis that, beginning with the founder premalignant cell, cancer precursors frequently sojourn for decades before turning into cancer, implying that the founder cell typically arises early in life. At least 77-89% of the observed drift variance in distal and rectal tumors was explained by stochastic variability associated with neoplastic progression, while only 55% of the variance was explained for proximal tumors. However, gene-CGI pairs in the proximal colon that underwent drift were significantly and primarily negatively correlated with cancer gene expression, suggesting that methylomic drift participates in the clonal evolution of CRC. Methylomic drift advanced in colorectal neoplasia consistent with extended sojourn time distributions, which accounts for a significant fraction of epigenetic heterogeneity in CRC. Importantly, these estimated long-duration premalignant sojourn times suggest that early dietary and lifestyle interventions may be more effective than later changes in reducing CRC incidence.

13.
Cancer Epidemiol ; 56: 83-89, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30099328

RESUMO

BACKGROUND: Biomarker candidates are often ranked using P-values. Standard P-value calculations use normal or logit-normal approximations, which may not be correct for small P-values and small sample sizes common in discovery research. METHODS: We compared exact P-values, correct by definition, with logit-normal approximations in a simulated study of 40 cases and 160 controls. The key measure of biomarker performance was sensitivity at 90% specificity. Data for 3000 uninformative false markers and 30 informative true markers were generated randomly. We also analyzed real data for 2371 plasma protein markers measured in 121 breast cancer cases and 121 controls. RESULTS: In our simulation, using the same discovery criterion, exact P-values led to discovery of 24 true and 82 false biomarkers, while logit-normal approximate P-values yielded 20 true and 106 false biomarkers. The estimated true discovery rate was substantially off for approximate P-values: logit-normal estimated 42 but found 20. The exact method estimated 22, very close to 24, which was the actual number of true discoveries. Although these results are based on one specific simulation, qualitatively similar results were obtained from 10 random repetitions. With real data, ranking candidate biomarkers by exact P-values, versus approximate P-values, resulted in a very different ordering of these markers. CONCLUSIONS: Exact P-values, which correspond to permutation tests with non-parametric rank statistics such as empirical ROC statistics, are preferred over approximate P-values. Approximate P-values can lead to inappropriate biomarker selection rules and incorrect conclusions. IMPACT: Exact P-values in place of approximate P-values in discovery research may improve the yield of biomarkers that validate clinically.

14.
Int J Cancer ; 143(8): 1849-1857, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29708591

RESUMO

Epidemiological evidence is limited on how alcohol consumption and smoking are associated with risk of different subtypes of breast cancer, such as triple-negative (TN) and human epidermal growth factor receptor 2-overexpressing (H2E) breast cancers, which may have different etiologies from more common luminal (estrogen receptor [ER+]) breast cancers. In this population-based case-case study, we evaluated the association between alcohol, smoking, and risk of H2E and TN breast cancer, compared with ER+ breast cancers, among women aged 20-69 years. Using polytomous regression, associations between alcohol consumption, smoking, and breast cancer risk were evaluated in 909 ER+, 1,290 TN, and 489 H2E breast cancer patients, with ER+ breast cancer patients as the reference group. Current alcohol consumption at diagnosis was associated with a lower risk of H2E breast cancer (odds ratio = 0.74, 95% confidence interval: 0.58-0.92) relative to ER+ cancers. No difference in association was observed by menopausal status. No association between alcohol consumption and TN breast cancer relative to ER+ breast cancer was observed. Women who smoked did not have an altered risk of TN or H2E breast cancer, relative to ER+ cancer. Our results suggest that alcohol is associated with lower risk of H2E breast cancer relative to ER+ breast cancer. This study adds to the body of epidemiologic evidence that breast cancer etiology differs by breast cancer subtype.

16.
Cancer Epidemiol Biomarkers Prev ; 27(3): 315-320, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29339357

RESUMO

Background: Incidence rates of in situ breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with in situ breast cancer later develop second primary breast cancers.Methods: In this population-based nested case-control study among in situ breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer.Results: First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous in situ breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05-1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status.Conclusions: Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous in situ breast cancer.Impact: Given the growing population of in situ breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. Cancer Epidemiol Biomarkers Prev; 27(3); 315-20. ©2018 AACR.

17.
Am J Clin Oncol ; 41(7): 708-715, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27893470

RESUMO

OBJECTIVE: To determine how out-of-pocket costs for adjuvant endocrine therapy (AET) medication affects adherence among newly diagnosed breast cancer survivors with private health insurance who initiate therapy. MATERIALS AND METHODS: We examined medical and pharmacy claims for the 1-year period after initiating AET using the Truven Health Analytics MarketScan database. Adherence was defined as ≥80% proportion of days covered. Mean out-of-pocket costs for AET fill were measured as the sum of copayments, coinsurance, and deductibles and adjusted to 30-day amounts. Using a multivariable logistic regression model we calculated adjusted risk ratios controlling for age, comorbidities, type of surgery, use of chemotherapy and/or radiation therapy, average out-of-pocket costs for other services, and pharmacy use characteristics. RESULTS: Of the 6863 women 64 years and younger who were diagnosed with breast cancer and initiated AET, 73.9% were adherent (proportion of days covered≥80%). A total of 19% of patients had <$5 monthly out-of-pocket costs for AET, 30% had $5 to $9.99, 17% had $10 to $14.99, 10% had $15 to $19.99, and 25% had $20 or greater. Patients with out-of-pocket costs for AET between $10 and $14.99, $15 and $19.99, and >$20 were 6% to 8% less likely to be adherent compared with patients paying <$5.00, after controlling for covariates (P<0.05). Out-of-pocket costs for inpatient, outpatient, and other pharmacy services were not associated with adherence. CONCLUSIONS: A substantial proportion of privately insured patients are nonadherent to AET and out-of-pocket costs for AET medication are significantly associated with a greater likelihood of nonadherence.

18.
Gut ; 67(3): 473-484, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-27821646

RESUMO

OBJECTIVE: To discover and confirm blood-based colon cancer early-detection markers. DESIGN: We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays. RESULTS: In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively. CONCLUSIONS: A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.


Assuntos
Adenoma/sangue , Adenoma/diagnóstico , Biomarcadores Tumorais/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/diagnóstico , Detecção Precoce de Câncer/métodos , Proteínas Adaptadoras de Transdução de Sinal/sangue , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Antígeno CA-19-9/metabolismo , Estudos de Casos e Controles , Neoplasias do Colo/metabolismo , Receptor gp130 de Citocina/sangue , Receptor gp130 de Citocina/metabolismo , Receptores ErbB/sangue , Receptores ErbB/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/sangue , Receptores de Hialuronatos/metabolismo , Antígenos CD15/metabolismo , Masculino , Pessoa de Meia-Idade , Oligossacarídeos/metabolismo , Análise Serial de Proteínas , Fator de von Willebrand/metabolismo
19.
Am J Epidemiol ; 186(10): 1168-1179, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29020206

RESUMO

Reports on the associations between multiple clinical and behavioral health indicators and major health outcomes among older adults are scarce. We prospectively examined concordance with guidelines from the American Cancer Society and American Heart Association for disease prevention in relation to cancer, cardiovascular disease (CVD), and mortality among Cardiovascular Health Study enrollees aged 65-98 years who, at baseline assessment in 1989-1996 (n = 3,491), were free of CVD and cancer. Total and cause-specific mortality, as well as incidence of cancer and CVD, were lower with higher guideline concordance. Independent of body mass index, blood pressure, total cholesterol, and fasting plasma glucose, better health behaviors (diet, physical activity, and alcohol consumption) were associated with lower mortality (2-sided P < 0.0001). Among individuals with ideal levels for 3-4 of these 4 cardiometabolic biomarkers, those with poor concordance with health behavior recommendations had higher mortality compared with those who had the highest concordance with these behavioral recommendations (adjusted mortality hazard ratio = 1.82, 95% confidence interval: 1.25, 2.67). Older adults who are concordant with recommendations for cancer and CVD prevention have reduced rates of chronic disease and mortality. Interventions to achieve and maintain healthy lifestyle behaviors may offer benefits both in the presence and absence of adverse traditional clinical risk factors.


Assuntos
American Cancer Society , American Heart Association , Doenças Cardiovasculares/prevenção & controle , Estilo de Vida Saudável , Neoplasias/prevenção & controle , Guias de Prática Clínica como Assunto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Dieta/normas , Dieta/estatística & dados numéricos , Exercício , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Incidência , Estudos Longitudinais , Masculino , Neoplasias/epidemiologia , Neoplasias/mortalidade , Estudos Prospectivos , Estados Unidos/epidemiologia
20.
Cancer Res ; 77(21): 6033-6041, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28935814

RESUMO

The widely prescribed diabetes medicine metformin has been reported to lower the risk of incident breast cancer, but it is unclear whether it affects malignant progression after diagnosis. In this study, we conducted a retrospective cohort study using the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Women were included in the study if they were aged 66 to 80 years, newly diagnosed with stage I or II breast cancer, and enrolled in Medicare Parts A, B, and D during 2007 to 2011. Information on dispensed diabetes-related medications was obtained from Medicare Part D claims data. Our primary outcomes were second breast cancer events (SBCE), breast cancer recurrence, and breast cancer death. Time-varying Cox proportional hazard models were used to estimate HRs and their 95% confidence intervals (CI). Among 14,766 women included in the study, 791 experienced SBCE, 627 had a recurrence, and 237 died from breast cancer. Use of metformin (n = 2,558) was associated with 28% (95% CI, 0.57-0.92), 31% (95% CI, 0.53-0.90), and 49% (95% CI, 0.33-0.78) lower risks of an SBCE, breast cancer recurrence, and breast cancer death. Use of sulfonylureas or insulin was associated with 1.49- (95% CI, 1.00-2.23) and 2.58-fold (95% CI, 1.72-3.90) higher risks of breast cancer death. Further research may be warranted to determine whether metformin is a preferred treatment for diabetes among breast cancer survivors and whether it benefits breast cancer patients without diabetes. Cancer Res; 77(21); 6033-41. ©2017 AACR.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/patologia , Feminino , Humanos , Insulina/efeitos adversos , Medicare/estatística & dados numéricos , Metformina/efeitos adversos , Estadiamento de Neoplasias , Avaliação de Resultados (Cuidados de Saúde)/métodos , Avaliação de Resultados (Cuidados de Saúde)/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Compostos de Sulfonilureia/efeitos adversos , Estados Unidos
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