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1.
JAMA Netw Open ; 5(4): e224361, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35416993

RESUMO

Importance: Hormone receptor-positive, ERBB2 (formerly HER2/neu)-negative metastatic breast cancer (HR-positive, ERBB2-negative MBC) is treated with targeted therapy, endocrine therapy, chemotherapy, or combinations of these modalities; however, evaluating the increasing number of treatment options is challenging because few regimens have been directly compared in randomized clinical trials (RCTs), and evidence has evolved over decades. Information theoretic network meta-analysis (IT-NMA) is a graph theory-based approach for regimen ranking that takes effect sizes and temporality of evidence into account. Objective: To examine the performance of an IT-NMA approach to rank HR-positive, ERBB2-negative MBC treatment regimens. Data Sources: HemOnc.org, a freely available medical online resource of interventions, regimens, and general information relevant to the fields of hematology and oncology, was used to identify relevant RCTs. Study Selection: All primary and subsequent reports of RCTs of first-line systemic treatments for HR-positive, ERBB2-negative MBC that were referenced on HemOnc.org and published between 1974 and 2019 were included. Additional RCTs that were evaluated by a prior traditional network meta-analysis on HR-positive, ERBB2-negative MBC were also included. Data Extraction and Synthesis: RCTs were independently extracted from HemOnc.org and a traditional NMA by separate observers. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for NMA with several exceptions: the risk of bias within individual studies and inconsistency in the treatment network were not assessed. Main Outcomes and Measures: Regimen rankings generated by IT-NMA based on clinical trial variables, including primary end point, enrollment number per trial arm, P value, effect size, years of enrollment, and year of publication. Results: A total of 203 RCTs with 63 629 patients encompassing 252 distinct regimens were compared by IT-NMA, which resulted in 151 rankings as of 2019. Combinations of targeted and endocrine therapy were highly ranked, especially the combination of endocrine therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. For example, letrozole plus palbociclib was ranked first and letrozole plus ribociclib, third. Older monotherapies that continue to be used in RCTs in comparator groups, such as anastrozole (251 of 252) and letrozole (252), fell to the bottom of the rankings. Many regimens gravitated toward indeterminacy by 2019. Conclusions and Relevance: In this network meta-analysis study, combination therapies appeared to be associated with better outcomes than monotherapies in the treatment of HR-positive, ERBB2-negative MBC. These findings suggest that IT-NMA is a promising method for longitudinal ranking of anticancer regimens from RCTs with different end points, sparse interconnectivity, and decades-long timeframes.


Assuntos
Neoplasias da Mama , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Letrozol/uso terapêutico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2
2.
Blood Cancer Discov ; 3(3): 181-193, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35262738

RESUMO

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non-B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non-recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19. SIGNIFICANCE: Our study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies. This article is highlighted in the In This Issue feature, p. 171.


Assuntos
COVID-19 , Doenças Linfáticas , Neoplasias , COVID-19/epidemiologia , Teste para COVID-19 , Humanos , Neoplasias/epidemiologia , Fatores de Risco , SARS-CoV-2
4.
JAMA Dermatol ; 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35338704

RESUMO

Importance: Hematopoietic cell transplantation (HCT) is a potential cure for hematologic cancer but is associated with a risk of relapse and death. Dynamic biomarkers to predict relapse and inform treatment decisions after HCT are a major unmet clinical need. Objective: To identify a quantitative characteristic of leukocyte-endothelial interactions after HCT and test its associations with patient outcomes. Design, Setting, and Participants: In this prospective single-center cohort study from June 2017 to January 2020, patients of any age, sex, race, and ethnicity who had HCT for hematologic cancer were referred by health care professionals as either suspected of having symptoms or not having symptoms of acute graft-vs-host disease between 25 and 161 days after HCT. Patients underwent noninvasive skin videomicroscopy. Videos of dermal microvascular flow were recorded with a reflectance confocal microscope. Two blinded observers (J.R.P. and Z.Z.) counted leukocytes adherent to and rolling along the vessel wall per hour (A&R). Of 57 enrolled patients, 1 relapsed before imaging and was excluded, resulting in 56 patients included in analyses. Main Outcomes and Measures: Relapse of cancer, relapse-free survival, and overall survival. Results: Among the 56 patients (median age, 59 years; 38 [68%] male) who underwent imaging a median of 40 days after HCT, 21 had high A&R and 35 had low A&R. After correcting for the revised Disease Risk Index, patients with high A&R had higher rates of relapse (hazard ratio [HR], 4.24; 95% CI, 1.32-13.58; P = .02), reduced relapse-free survival (HR, 3.29; 95% CI, 1.26-8.55; P = .02), and reduced overall survival (HR, 3.06, 95% CI, 1.02-9.19; P = .05). These associations were preserved after correcting for possible confounders, steroid treatment, and acute graft-vs-host disease status. In the prognostic adequacy calculation by using Cox models, the new imaging biomarker (A&R) accounted for 82% to 95% of the prognostic information to predict each outcome. By contrast, the best existing clinical predictor routinely available, the revised Disease Risk Index, accounted for 10% to 28% of the prognostic information in the same model. Conclusions and Relevance: In this cohort study, leukocyte-endothelial interactions, visualized directly in skin after HCT, were associated with the patient outcomes of relapse, relapse-free survival, and overall survival. Assessing this dynamic marker could help patients at high risk for relapse who may benefit from interventions, such as early withdrawal of immunosuppression.

5.
Eur J Hum Genet ; 30(3): 349-362, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35027648

RESUMO

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Teorema de Bayes , Carcinoma Epitelial do Ovário/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco
6.
Cancer Causes Control ; 33(4): 515-524, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35088206

RESUMO

PURPOSE: To evaluate the association between obesity and the relative prevalence of tumor subtypes among Black women with breast cancer (BC). METHODS: We conducted a pooled case-only analysis of 1,793 Black women with invasive BC recruited through three existing studies in the southeastern US. Multivariable case-only polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between obesity, measured by pre-diagnostic body mass index (BMI), and human epidermal growth factor receptor 2 + (HER2 +) and triple negative BC (TNBC) subtype relative to hormone receptor (HR) + /HER2- status (referent). RESULTS: Among 359 premenopausal women, 55.4% of cases were HR + /HER2 -, 20.1% were HER2 + , and 24.5% were TNBC; corresponding percentages among 1,434 postmenopausal women were 59.3%, 17.0%, and 23.6%. Approximately, 50-60% of both pre- and postmenopausal women were obese (BMI > 30 kg/m2), regardless of BC subtype. We did not observe a significant association between obesity and BC subtype. Among postmenopausal women, class I obesity (BMI 35 + kg/m2) was not associated with the development of HER2 + BC (OR 0.69; 95% CI 0.42-1.14) or TNBC (OR 0.93; 95% CI 0.60-1.45) relative to HR + /HER2- tumors. Corresponding estimates among premenopausal women were 1.03 (95% CI 0.43-2.48) and 1.13 (95% CI 0.48-2.64). CONCLUSION: In this large study of Black women with BC, there was no evidence of heterogeneity of BMI by BC subtype.


Assuntos
Afro-Americanos , Neoplasias da Mama , Obesidade , Neoplasias de Mama Triplo Negativas , Afro-Americanos/estatística & dados numéricos , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pré-Menopausa , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Fatores de Risco , Sudeste dos Estados Unidos/epidemiologia , Neoplasias de Mama Triplo Negativas/epidemiologia
7.
Am J Prev Med ; 62(3): 395-403, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34756753

RESUMO

INTRODUCTION: Demonstrating human papillomavirus vaccine impact is critical for informing guidelines to increase vaccination and decrease human papillomavirus‒related outcomes, particularly in states with suboptimal vaccination coverage, such as Tennessee. This study examines the trends in high-grade cervical lesion incidence among Tennessee Medicaid-enrolled women aged 18-39 years and the subset of women who were screened for cervical cancer. METHODS: Using a validated claims-based model to identify incident cervical intraepithelial neoplasia Grades 2 or 3 or adenocarcinoma in situ events, annual age group‒specific incidence rates from Tennessee Medicaid billing data, 2008-2018, were calculated. Significant trends were determined by Joinpoint. Analyses were conducted in 2020. RESULTS: From 2008 to 2018, high-grade cervical lesion incidence significantly declined in women aged 18-20 years (average annual percentage change= -31.9, 95% CI= -38.6, -24.6), 21-24 years (average annual percentage change= -12.9, 95% CI= -22.3, -2.4), and 25-29 years (average annual percentage change= -6.4, 95% CI= -8.1, -4.6). Among screened women, rates significantly declined for ages 18-20 years (average annual percentage change= -20.3, 95% CI= -25.3, -15.0), 21-24 years (average annual percentage change= -10.2, 95% CI= -12.6, -7.8), and 25-29 years (average annual percentage change= -2.6, 95% CI= -3.9, -1.2). Trends from 2008 to 2018 were stable for older age groups (30-34 and 35-39 years). CONCLUSIONS: Results show reductions in high-grade cervical lesion incidence among ages most likely to have benefited from the human papillomavirus vaccine. Declines among young, screened women suggest causes other than reduction in screening. Evidence of vaccine impact in populations with low-vaccination coverage, such as Tennessee, is promising.


Assuntos
Adenocarcinoma in Situ , Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Adenocarcinoma in Situ/epidemiologia , Adenocarcinoma in Situ/prevenção & controle , Adolescente , Adulto , Idoso , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Feminino , Humanos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adulto Jovem
8.
Cancer Discov ; 12(2): 303-330, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34893494

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic has left patients with current or past history of cancer facing disparate consequences at every stage of the cancer trajectory. This comprehensive review offers a landscape analysis of the current state of the literature on COVID-19 and cancer, including the immune response to COVID-19, risk factors for severe disease, and impact of anticancer therapies. We also review the latest data on treatment of COVID-19 and vaccination safety and efficacy in patients with cancer, as well as the impact of the pandemic on cancer care, including the urgent need for rapid evidence generation and real-world study designs. SIGNIFICANCE: Patients with cancer have faced severe consequences at every stage of the cancer journey due to the COVID-19 pandemic. This comprehensive review offers a landscape analysis of the current state of the field regarding COVID-19 and cancer. We cover the immune response, risk factors for severe disease, and implications for vaccination in patients with cancer, as well as the impact of the COVID-19 pandemic on cancer care delivery. Overall, this review provides an in-depth summary of the key issues facing patients with cancer during this unprecedented health crisis.


Assuntos
COVID-19/epidemiologia , Neoplasias/complicações , COVID-19/complicações , COVID-19/terapia , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Pandemias
9.
Cancers (Basel) ; 13(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34638514

RESUMO

Obesity contributes to ovarian cancer (OC) progression via tumorigenic chemokines. Adipocytes and OC cells highly express CXCR2, and its ligands CXCL1/8, respectively, indicating that the CXCL1/8-CXCR2 axis is a molecular link between obesity and OC. Here, we investigated how the adipocyte-specific CXCR2 conditional knockout (cKO) affected the peritoneal tumor microenvironment of OC in a high-fat diet (HFD)-induced obese mouse model. We first generated adipocyte-specific CXCR2 cKO in mice: adipose tissues were not different in crown-like structures and adipocyte size between the wild-type (WT) and cKO mice but expressed lower levels of CCL2/6 compared to the obese WT mice. HFD-induced obese mice had a shorter survival time than lean mice. Particularly, obese WT and cKO mice developed higher tumors and ascites burdens, respectively. The ascites from the obese cKO mice showed increased vacuole clumps but decreased the floating tumor burden, tumor-attached macrophages, triglyceride, free fatty acid, CCL2, and TNF levels compared to obese WT mice. A tumor analysis revealed that obese cKO mice attenuated inflammatory areas, PCNA, and F4/80 compared to obese WT mice, indicating a reduced tumor burden, and there were positive relationships between the ascites and tumor parameters. Taken together, the adipocyte-specific CXCR2 cKO was associated with obesity-induced ascites despite a reduced tumor burden, likely altering the peritoneal tumor microenvironment of OC.

10.
Cancer Epidemiol ; 74: 102013, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34438316

RESUMO

INTRODUCTION: While individual-level measures of socioeconomic status have been well-studied in relation to ovarian cancer survival, no studies to date have examined both state and national-level Area Deprivation Indices (ADIs), which incorporate neighborhood affluence and resources. METHODS: We abstracted clinical data from medical records for ovarian cancer cases from the Vanderbilt University Medical Center and obtained ADIs from the Neighborhood Atlas®. Associations with clinical characteristics were assessed with Spearman correlations and Kruskal-Wallis tests; associations with progression-free survival (PFS) and overall survival (OS) were assessed with Cox proportional-hazards regression. RESULTS: Among 184 cases, state and national ADIs were highly correlated, but not related to any cancer characteristics. In multivariable adjusted regression models, both were significantly associated with OS; each decile increase in state or national ADI corresponded to a 9 % or 10 % greater risk of death, respectively. CONCLUSIONS: Increasing area-level deprivation may negatively impact ovarian cancer survival.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/epidemiologia , Feminino , Humanos , Neoplasias Ovarianas/epidemiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Características de Residência , Classe Social
11.
Cancers (Basel) ; 13(16)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34439369

RESUMO

Disparities in human papillomavirus (HPV) vaccination exist between urban (metropolitan statistical areas (MSAs)) and rural (non-MSAs) regions. To address whether the HPV vaccine's impact differs by urbanicity, we examined trends in cervical intraepithelial neoplasia grades 2 or 3 and adenocarcinoma in situ (collectively, CIN2+) incidence in MSAs and non-MSAs among Tennessee Medicaid (TennCare)-enrolled women aged 18-39 years and among the subset screened for cervical cancer in Tennessee, United States. Using TennCare claims data, we identified annual age-group-specific (18-20, 21-24, 25-29, 30-34, and 35-39 years) CIN2+ incidence (2008-2018). Joinpoint regression was used to identify trends over time. Age-period-cohort Poisson regression models were used to evaluate age, period, and cohort effects. All analyses were stratified by urbanicity (MSA versus non-MSA). From 2008-2018, 11,243 incident CIN2+ events (7956 in MSAs; 3287 in non-MSAs) were identified among TennCare-enrolled women aged 18-39 years. CIN2+ incident trends (2008-2018) were similar between women in MSAs and non-MSAs, with largest declines among ages 18-20 (MSA average annual percent change (AAPC): -30.4, 95% confidence interval (95%CI): -35.4, -25.0; non-MSA AAPC: -30.9, 95%CI: -36.8, -24.5) and 21-24 years (MSA AAPC: -14.8, 95%CI: -18.1, -11.3; non-MSA AAPC: -15.1, 95%CI: -17.9, -12.2). Significant declines for ages 18-20 years began in 2008 in MSAs compared to 2010 in non-MSAs. Trends were largely driven by age and cohort effects. These patterns were consistent among screened women. Despite evidence of HPV vaccine impact on reducing CIN2+ incidence regardless of urbanicity, significant declines in CIN2+ incidence were delayed in non-MSAs versus MSAs.

12.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1669-1680, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34162658

RESUMO

BACKGROUND: Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance. METHODS: We carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy. RESULTS: We found seven SNPs at 12q24.33 associated with PFS (P < 5 × 10-8), the top SNP being rs10794418 (HR = 1.24; 95% CI, 1.15-1.34; P = 1.47 × 10-8). High expression of a nearby gene, ULK1, is associated with shorter PFS in EOC, and with poor prognosis in other cancers. SNP rs10794418 is also associated with expression of ULK1 in ovarian tumors, with the allele associated with shorter PFS being associated with higher expression, and chromatin interactions were detected between the ULK1 promoter and associated SNPs in serous and endometrioid EOC cell lines. ULK1 knockout ovarian cancer cell lines showed significantly increased sensitivity to carboplatin in vitro. CONCLUSIONS: The locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. ULK1 is a plausible candidate for the target of this association. IMPACT: This finding provides insight into genetic markers associated with EOC outcome and potential treatment options.See related commentary by Peres and Monteiro, p. 1604.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Carcinoma Epitelial do Ovário/genética , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/mortalidade , Feminino , Técnicas de Inativação de Genes , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Ovarianas/mortalidade , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão
13.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1660-1668, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34155063

RESUMO

BACKGROUND: Genital powder use is more common among African-American women; however, studies of genital powder use and ovarian cancer risk have been conducted predominantly in White populations, and histotype-specific analyses among African-American populations are limited. METHODS: We used data from five studies in the Ovarian Cancer in Women of African Ancestry consortium. Participants included 620 African-American cases, 1,146 African-American controls, 2,800 White cases, and 6,735 White controls who answered questions on genital powder use prior to 2014. The association between genital powder use and ovarian cancer risk by race was estimated using logistic regression. RESULTS: The prevalence of ever genital powder use for cases was 35.8% among African-American women and 29.5% among White women. Ever use of genital powder was associated with higher odds of ovarian cancer among African-American women [OR = 1.22; 95% confidence interval (CI) = 0.97-1.53] and White women (OR = 1.36; 95% CI = 1.19-1.57). In African-American women, the positive association with risk was more pronounced among high-grade serous tumors (OR = 1.31; 95% CI = 1.01-1.71) than with all other histotypes (OR = 1.05; 95% CI = 0.75-1.47). In White women, a significant association was observed irrespective of histotype (OR = 1.33; 95% CI = 1.12-1.56 and OR = 1.38; 95% CI = 1.15-1.66, respectively). CONCLUSIONS: While genital powder use was more prevalent among African-American women, the associations between genital powder use and ovarian cancer risk were similar across race and did not materially vary by histotype. IMPACT: This is one of the largest studies to date to compare the associations between genital powder use and ovarian cancer risk, overall and by histotype, between African-American and White women.


Assuntos
Carcinoma Epitelial do Ovário/etnologia , Produtos de Higiene Feminina/efeitos adversos , Neoplasias Ovarianas/etnologia , Talco/efeitos adversos , Adulto , Afro-Americanos/estatística & dados numéricos , Idoso , Carcinoma Epitelial do Ovário/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/etiologia , Pós/efeitos adversos , Fatores de Risco
14.
Cancer Epidemiol Biomarkers Prev ; 30(7): 1416-1423, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33947654

RESUMO

BACKGROUND: We investigated the association between reproductive risk factors and breast cancer subtype in Black women. On the basis of the previous literature, we hypothesized that the relative prevalence of specific breast cancer subtypes might differ according to reproductive factors. METHODS: We conducted a pooled analysis of 2,188 (591 premenopausal, 1,597 postmenopausal) Black women with a primary diagnosis of breast cancer from four studies in the southeastern United States. Breast cancers were classified by clinical subtype. Case-only polytomous logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for HER2+ and triple-negative breast cancer (TNBC) status in relation to estrogen receptor-positive (ER+)/HER2- status (referent) for reproductive risk factors. RESULTS: Relative to women who had ER+/HER2- tumors, women who were age 19-24 years at first birth (OR, 1.78; 95% CI, 1.22-2.59) were more likely to have TNBC. Parous women were less likely to be diagnosed with HER2+ breast cancer and more likely to be diagnosed with TNBC relative to ER+/HER2- breast cancer. Postmenopausal parous women who breastfed were less likely to have TNBC [OR, 0.65 (95% CI, 0.43-0.99)]. CONCLUSIONS: This large pooled study of Black women with breast cancer revealed etiologic heterogeneity among breast cancer subtypes. IMPACT: Black parous women who do not breastfeed are more likely to be diagnosed with TNBC, which has a worse prognosis, than with ER+/HER2- breast cancer.


Assuntos
Afro-Americanos/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Mama/patologia , História Reprodutiva , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Fatores de Risco , Sudeste dos Estados Unidos/epidemiologia , Adulto Jovem
15.
Int J Cancer ; 148(12): 2964-2973, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33521947

RESUMO

Family history (FH) of ovarian cancer and breast cancer are well-established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first- and second-degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high-grade serous vs others). First-degree FH of ovarian cancer was associated with high-grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First-degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high-grade serous carcinoma only in white women. Associations with second-degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high-grade serous carcinoma in both groups. First-degree FH of ovarian cancer and of breast cancer, and second-degree FH of ovarian cancer is strongly associated with high-grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high-grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.


Assuntos
Afro-Americanos/estatística & dados numéricos , Síndrome Hereditária de Câncer de Mama e Ovário/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/patologia , /estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Anamnese , Pessoa de Meia-Idade , Gradação de Tumores , Razão de Chances , Prevalência , Estados Unidos/epidemiologia , Estados Unidos/etnologia
16.
J Natl Compr Canc Netw ; 19(5): 513-520, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33524941

RESUMO

BACKGROUND: NCCN recommends evaluation and treatment of all patients with cancer who have anemia. Few studies have evaluated the prevalence of anemia among patients with gynecologic cancer and compliance with the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Growth Factors. METHODS: We performed a single-institution retrospective cohort study of patients diagnosed with primary gynecologic cancer between 2008 and 2018. We identified tumor registry-confirmed patients using ICD-O codes from the Synthetic Derivative database, a deidentified copy of Vanderbilt's electronic medical records. Patients were included if they were between ages 18 and 89 years, received initial care at Vanderbilt University Medical Center, and had a hemoglobin measurement within the first 6 months of diagnosis. Anemia was defined as a hemoglobin level ≤11 g/dL and was graded using CTCAE version 5.0. RESULTS: A total of 939 patients met inclusion criteria, with a median age of 60 years. The most common malignancy was uterine cancer. At the time of cancer diagnosis, 186 patients (20%) were noted to have anemia. Within 6 months of diagnosis, 625 patients (67%) had anemia, of whom 200 (32%) had grade 3 anemia and 209 (33%) underwent any evaluation of anemia, including 80 (38%) with iron studies performed. Of the patients with iron studies performed, 7 (9%) had absolute iron deficiency and 7 (9%) had possible functional iron deficiency. Among those with anemia within 6 months of diagnosis, 260 (42%) received treatment for anemia, including blood transfusion (n=205; 79%), oral iron (n=57; 22%), intravenous iron (n=8; 3%), vitamin B12 (n=37; 14%), and folate supplementation (n=7; 3%). Patients with ovarian cancer were significantly more likely to have anemia and undergo evaluation and treatment of anemia. CONCLUSIONS: Anemia is pervasive among patients with gynecologic cancer, but compliance with the NCCN Guidelines is low. Our data suggest that there are opportunities for improvement in the evaluation and management of anemia.


Assuntos
Anemia , Neoplasias dos Genitais Femininos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/diagnóstico , Anemia/epidemiologia , Anemia/etiologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/epidemiologia , Fidelidade a Diretrizes , Hemoglobinas , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Adulto Jovem
17.
J Natl Cancer Inst ; 113(3): 329-337, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32359158

RESUMO

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.


Assuntos
Neoplasias da Mama/genética , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Anamnese , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de Estrogênio/metabolismo , Fatores de Risco
18.
Obes Surg ; 31(3): 1387-1391, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33104988

RESUMO

We developed a decision analysis model to evaluate risks and benefits of delaying scheduled bariatric surgery during the novel coronavirus disease (COVID-19) pandemic. Our base case was a 45-year-old female with diabetes and a body mass index of 45 kg/m2. We compared immediate with delayed surgery after 6 months to allow for COVID-19 prevalence to decrease. We found that immediate and delayed bariatric surgeries after 6 months resulted in similar 20-year overall survival. When the probability of COVID-19 infection exceeded 4%, then delayed surgery improved survival. If future COVID-19 infection rates were at least half those in the immediate scenario, then immediate surgery was favored and local infection rates had to exceed 9% before surgical delay improved survival. Surgeons should consider local disease prevalence and patient comorbidities associated with increased mortality before resuming bariatric surgery programs.


Assuntos
Cirurgia Bariátrica , COVID-19/epidemiologia , Obesidade Mórbida/cirurgia , Índice de Massa Corporal , Tomada de Decisão Clínica , Comorbidade , Bases de Dados Factuais , Técnicas de Apoio para a Decisão , Complicações do Diabetes , Diabetes Mellitus , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , SARS-CoV-2
19.
J Natl Cancer Inst ; 113(6): 710-718, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33252629

RESUMO

BACKGROUND: The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women. METHODS: We used data from 4 case-control studies and 3 case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of 10 known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were 2-sided. RESULTS: Among 3244 White EOC cases and 9638 controls and 1052 AA EOC cases and 2410 controls, AA women had a statistically significantly higher PAR (false discovery rate [FDR] P < .001) for first-degree family history of breast cancer (PAR = 10.1%, 95% confidence interval [CI] = 6.5% to 13.7%) compared with White women (PAR = 2.6%, 95% CI = 0.8% to 4.4%). After multiple test correction, AA women had a higher PAR than White women when evaluating all risk factors collectively (PAR = 61.6%, 95% CI = 48.6% to 71.3% vs PAR = 43.0%, 95% CI = 32.8% to 51.4%, respectively; FDR P = .06) and for modifiable exposures, including body mass index, oral contraceptives, aspirin, and body powder (PAR = 36.0%, 95% CI = 21.0% to 48.8% vs PAR = 13.8%, 95% CI = 4.5% to 21.8%, respectively; FDR P = .04). CONCLUSIONS: Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC.


Assuntos
Neoplasias Ovarianas , Afro-Americanos , Carcinoma Epitelial do Ovário/complicações , Carcinoma Epitelial do Ovário/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Estudos Prospectivos , Fatores Raciais , Fatores de Risco
20.
Int J Mol Sci ; 21(21)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142915

RESUMO

Platelets are critical components of a number of physiologic processes, including tissue remodeling after injury, wound healing, and maintenance of vascular integrity. Increasing evidence suggests that platelets may also play important roles in cancer. In ovarian cancer, thrombocytosis, both at the time of initial diagnosis and at recurrence, has been associated with poorer prognosis. This review describes current evidence for associations between thrombocytosis and ovarian cancer prognosis and discusses the clinical relevance of platelet count thresholds and timing of assessment. In addition, we discuss several mechanisms from in vitro, in vivo, and clinical studies that may underlie these associations and recommend potential approaches for novel therapeutic targets for this lethal disease.


Assuntos
Plaquetas/patologia , Neoplasias Ovarianas/patologia , Trombocitose/patologia , Feminino , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/etiologia , Prognóstico , Trombocitose/sangue
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