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1.
Sci Rep ; 12(1): 10825, 2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35754051

RESUMO

Racial disparities in mortality due to metastasis remain significant among breast cancer patients. Chemokine receptors contribute to breast tumors and metastatic outcome. We explored for significant differences in chemokine receptor expression in breast tumors from Black, Asian, and White patients in The Cancer Genome Atlas. We show that despite sharing the same molecular subtype, expression of the chemokine receptors ACKR1, CCR3, CCR6, CCRL1, CCRL2, CXCR1, CXCR2, CXCR4, CXCR6, and CXC3CR1 was significantly different depending on racial group. For patients with triple negative breast cancer, CCR3 was higher in Black versus White and CCRL2 was higher in Asian versus White. In luminal A tumors, ACKR1 was lower in Asian versus White, CCR3 was higher in Black versus White, and CCR6 and CXC3CR1 were lower in Black versus White. In luminal B tumors, CCRL2 was lower in Black versus White, CXCR1 and CXC3CR1 were lower in Asian versus White, and CXCR2 was lower in Black and Asian versus White. In HER2 enriched tumors, CCR3 was higher in Black versus White and CXCR4 lower in Asian versus White. CCR3, CCR6, and CXCR6 associated with worse patient survival. These findings can inform improved treatment strategies to decrease racial disparities in breast cancer burden.


Assuntos
Neoplasias da Mama , Receptores de Quimiocinas , Neoplasias de Mama Triplo Negativas , Mama/patologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Grupos Raciais , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/genética , Neoplasias de Mama Triplo Negativas/etnologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
2.
Cancer Epidemiol Biomarkers Prev ; 31(4): 704-706, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35373264

RESUMO

In the past decades, multigene prognostic testing, such as Oncotype DX (ODX), has been increasingly used to inform treatment decisions for patients with early-stage breast cancer. This advance in precision oncology has increased existing concerns about differential access to genomic testing across racial and ethnic groups. The investigation by Moore and colleagues, analyzing real-world data from the National Cancer Database, shows that patients of color with breast cancer were less likely to receive ODX testing and Black patients were more likely to have a high risk Recurrence Score (RS) compared with White patients. This study emphasizes that the appropriate adoption of ODX testing is critical to promote equitable cancer care for patients with breast cancer. The reported associations on overall survival across specific racial and ethnic groups provided here give additional insight to the known associations between the ODX RS and outcomes of distant recurrence and cancer-specific mortality. Analyses of contemporary, real-world data from diverse populations with long-term follow-up should continue to keep pace with the expansion of precision breast cancer care to better understand and mitigate potentially widening inequities in genomic testing. See related article by Moore et al., p. 821.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/etnologia , Feminino , Perfilação da Expressão Gênica , Humanos , Medicina de Precisão , Prognóstico
3.
Breast Cancer Res Treat ; 193(1): 217-224, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35278150

RESUMO

PURPOSE: BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin. METHODS: We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls. RESULTS: We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C > A, and c.9693delA. Only c.5159C > A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]). CONCLUSION: EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted.


Assuntos
Proteína BRCA2 , Neoplasias da Mama Masculina , Neoplasias da Mama , Judeus , Proteína BRCA2/genética , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Neoplasias da Mama Masculina/etnologia , Neoplasias da Mama Masculina/genética , Etiópia/epidemiologia , Feminino , Efeito Fundador , Predisposição Genética para Doença , Humanos , Judeus/genética , Masculino , Estudos Retrospectivos
4.
Cancer ; 128(11): 2174-2181, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35285940

RESUMO

BACKGROUND: African ancestry (AA) and obesity are associated with worse survival in early-stage breast cancer. Obesity disproportionately affects women of AA; however, the intersection between ancestry and obesity on breast cancer outcomes remains unclear. METHODS: A total of 2854 patients in the adjuvant trial E5103 were analyzed. Genetic ancestry was determined using principal components from a genome-wide array. The impact of continuous or binary body mass index (BMI) on disease-free survival (DFS) and overall survival (OS) was evaluated by multivariable Cox proportional hazards models in AA patients and European ancestry (EA) patients. RESULTS: There were 2471 EA patients and 383 AA patients. Higher BMI was significantly associated with worse DFS and OS only in AA patients (DFS hazard ratio [HR], 1.25; 95% CI, 1.07-1.46; OS HR, 1.38; 95% CI, 1.10-1.73), not in EA patients (DFS HR, 0.97; 95% CI, 0.90-1.05; OS HR, 1.03; 95% CI, 0.93-1.14). Severe obesity (BMI ≥40) was significantly associated with worse survival in AA patients (DFS HR, 2.04; 95% CI, 1.21-3.43; OS HR, 2.21; 95% CI, 1.03-4.75) but had no impact on that of EA patients. In the estrogen receptor-positive (ER+) and triple-negative breast cancer subgroups, BMI was significantly associated with worse outcomes only in those AA patients with ER+ disease. Within the AA group, BMI remained associated with worse survival regardless of the AA proportion. CONCLUSIONS: Higher BMI was statistically significantly associated with worse breast cancer outcomes in AA but not EA patients. This association was most significant for severe obesity and those with ER+ disease. These observations help define optimal populations for weight change interventions designed to affect disparities and survival in early-stage breast cancer. LAY SUMMARY: African ancestry and obesity are both risk factors for worse survival after early-stage breast cancer. Women of African descent are also disproportionately affected by obesity; however, it is unclear what impact body weight has on racial disparities in breast cancer. Data from a large phase 3 clinical trial in high-risk, early-stage breast cancer were used to determine how body weight affects survival outcomes in European versus African Americans. Study results demonstrate that a higher body mass index is associated with increased risk of breast cancer recurrence and worse survival in women of African ancestry but not in women of European ancestry.


Assuntos
Negros , Neoplasias da Mama , Obesidade , Índice de Massa Corporal , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Feminino , Disparidades nos Níveis de Saúde , Humanos , Estadiamento de Neoplasias , Obesidade/complicações , Obesidade/etnologia , Prognóstico , Análise de Sobrevida , Brancos
5.
PLoS One ; 17(2): e0263374, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35139096

RESUMO

PURPOSE: This study aimed to determine the effect of reproductive, hormonal, lifestyle and nutritional factors on breast cancer development among Tanzanian black women. METHODOLOGY: We undertook a case-control study age-matched to ±5years in 2018 at Muhimbili National Hospital. The study recruited 105 BC patients and 190 controls giving it 80% power to detect an odds ratio of ≥2 at the alpha error of <5% for exposure with a prevalence of 30% in the control group with 95% confidence. Controls were recruited from in patients being treated for non-cancer related conditions. Information regarding hormonal, reproductive, nutritional and lifestyle risk for breast cancer and demography was collected by interviews using a predefined data set. Conditional multinomial logistic regression used to determine the adjusted odds ratio for variables that had significant p-value in the binomial logistic regression model with 5% allowed error at 95% confidence interval. RESULTS: The study recruited 105 cases and 190 controls. Only old age at menopause had a significant risk, a 2.6 fold increase. Adolescent obesity, family history of breast cancer, cigarette smoking and alcohol intake had increased odds for breast cancer but failed to reach significant levels. The rural residency had 61% reduced odds for developing breast cancer though it failed to reach significant levels. CONCLUSION: Older age at menopause is a significant risk factor for the development of breast cancer among Tanzanian women. This study has shed light on the potential role of modifiable risk factors for breast cancer which need to be studied further for appropriate preventive strategies in similar settings.


Assuntos
Neoplasias da Mama/epidemiologia , Hormônios/sangue , Estilo de Vida , Estado Nutricional/fisiologia , Reprodução/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Feminino , Hormônios/fisiologia , Humanos , Estilo de Vida/etnologia , Menopausa/fisiologia , Pessoa de Meia-Idade , Paridade/fisiologia , Obesidade Pediátrica/complicações , Obesidade Pediátrica/epidemiologia , Gravidez , Fatores de Risco , Fatores Socioeconômicos , Tanzânia/epidemiologia , Adulto Jovem
6.
Breast Cancer Res Treat ; 192(2): 447-455, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35034243

RESUMO

PURPOSE: Black women have a 40% increased risk of breast cancer-related mortality. These outcome disparities may reflect differences in tumor pathways and a lack of targetable therapies for specific subtypes that are more common in Black women. Hepatocyte growth factor (HGF) is a targetable pathway that promotes breast cancer tumorigenesis, is associated with basal-like breast cancer, and is differentially expressed by race. This study assessed whether a 38-gene HGF expression signature is associated with recurrence and survival in Black and non-Black women. METHODS: Study participants included 1957 invasive breast cancer cases from the Carolina Breast Cancer Study. The HGF signature was evaluated in association with recurrence (n = 1251, 171 recurrences), overall, and breast cancer-specific mortality (n = 706, 190/328 breast cancer/overall deaths) using Cox proportional hazard models. RESULTS: Women with HGF-positive tumors had higher recurrence rates [HR 1.88, 95% CI (1.19, 2.98)], breast cancer-specific mortality [HR 1.90, 95% CI (1.26, 2.85)], and overall mortality [HR 1.69; 95% CI (1.17, 2.43)]. Among Black women, HGF positivity was significantly associated with higher 5-year rate of recurrence [HR 1.73; 95% CI (1.01, 2.99)], but this association was not significant in non-Black women [HR 1.68; 95% CI (0.72, 3.90)]. Among Black women, HGF-positive tumors had elevated breast cancer-specific mortality [HR 1.80, 95% CI (1.05, 3.09)], which was not significant in non-Black women [HR 1.52; 95% CI (0.78, 2.99)]. CONCLUSION: This multi-gene HGF signature is a poor-prognosis feature for breast cancer and may identify patients who could benefit from HGF-targeted treatments, an unmet need for Black and triple-negative patients.


Assuntos
Neoplasias da Mama , Fator de Crescimento de Hepatócito , Negros , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Feminino , Fator de Crescimento de Hepatócito/biossíntese , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Modelos de Riscos Proporcionais , Fatores Raciais , Brancos
7.
Sci Rep ; 12(1): 100, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997107

RESUMO

Breast cancer is the most common malignancy among women globally. Development of a reliable plasma biomarker panel might serve as a non-invasive and cost-effective means for population-based screening of the disease. Transcriptomic profiling of breast tumour, paired normal and apparently normal tissues, followed by validation of the shortlisted genes using TaqMan® Low density arrays and Quantitative real-time PCR was performed in South Asian women. Fifteen candidate protein markers and 3 candidate epigenetic markers were validated first in primary breast tumours and then in plasma samples of cases [N = 202 invasive, 16 DCIS] and controls [N = 203 healthy, 37 benign] using antibody array and methylation specific PCR. Diagnostic efficiency of single and combined markers was assessed. Combination of 6 protein markers (Adipsin, Leptin, Syndecan-1, Basic fibroblast growth factor, Interleukin 17B and Dickopff-3) resulted in 65% sensitivity and 80% specificity in detecting breast cancer. Multivariate diagnostic analysis of methylation status of SOSTDC1, DACT2, WIF1 showed 100% sensitivity and up to 91% specificity in discriminating BC from benign and controls. Hence, combination of SOSTDC1, DACT2 and WIF1 was effective in differentiating breast cancer [non-invasive and invasive] from benign diseases of the breast and healthy individuals and could help as a complementary diagnostic tool for breast cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Perfilação da Expressão Gênica , Proteínas Adaptadoras de Transdução de Sinal/sangue , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Estudos de Casos e Controles , Metilação de DNA , Epigênese Genética , Feminino , Humanos , Índia , Células MCF-7 , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Transcriptoma
8.
JNCI Cancer Spectr ; 6(1)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35047750

RESUMO

Background: As Asian American breast cancer incidence rises, it is necessary to investigate the origins of differential breast cancer outcomes among Asian ethnic subgroups. This study aimed to examine disparities in delays of breast cancer surgery among Asian ethnic subgroups. Methods: We obtained California Cancer Registry data on female breast cancer diagnoses and treatment from 2012 to 2017. Our main independent variable was patient race and ethnicity, including 6 Asian ethnic subgroups. Dependent variables included time to surgical treatment for breast cancer and receipt of surgical treatment within 30 and 90 days of diagnosis. We conducted multivariable logistic regression to determine the odds of receiving surgery within 30 and 90 days of diagnosis and multivariable Cox proportional hazards regression to determine the risk of prolonged time to surgery. Results: In our cohort of 93 168 breast cancer patients, Hispanic (odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.82 to 0.89) and non-Hispanic Black (OR = 0.83, 95% CI = 0.78 to 0.88) patients were statistically significantly less likely than non-Hispanic White patients to receive surgery within 30 days of breast cancer diagnosis, whereas Asian Indian or Pakistani (OR = 1.23, 95% CI = 1.09 to 1.40) and Chinese (OR = 1.30, 95% CI = 1.20 to 1.40) patients were statistically significantly more likely to receive surgery within 30 days of diagnosis. Conclusions: This large, population-based retrospective cohort study of female breast cancer patients is the first, to our knowledge, to demonstrate that time to surgical treatment is not equal for all Asians. Distinct differences among Asian ethnic subgroups suggest the necessity of further investigating breast cancer treatment patterns to fully understand and target disparities in breast cancer treatment.


Assuntos
Neoplasias da Mama/cirurgia , Tempo para o Tratamento , Adulto , Afro-Americanos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Americanos Asiáticos/estatística & dados numéricos , /etnologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etnologia , California , Intervalos de Confiança , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Tempo , /estatística & dados numéricos
9.
Cancer ; 128(4): 727-736, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34873682

RESUMO

BACKGROUND: Although racial disparities in breast cancer (BC) mortality have been well documented in the United States, little is known about the impact of coexisting cardiovascular disease (CVD) and other clinical factors on Black-White survival disparities after the diagnosis of BC. This study examined the associations of race, CVD, and clinical factors at diagnosis with the hazard of BC and CVD-related mortality among patients with BC identified from the Maryland Cancer Registry. METHODS: A total of 36,088 women (25,181 Whites and 10,907 Blacks) diagnosed with incident invasive BC between 2007 and 2017 were included. Subdistribution hazard ratios (sdHRs) for CVD-related and BC mortality were estimated with Fine and Gray regression models, which accounted for the influence of competing events. RESULTS: After a median follow-up of 5.8 years, 8019 deaths occurred; 3896 were BC deaths, and 1167 deaths were CVD-related. Black women had a higher hazard of BC mortality (sdHR, 1.66; 95% confidence interval [CI], 1.55-1.77) and CVD mortality (sdHR, 1.33; 95% CI, 1.17-1.51) in comparison with White women. Associations with CVD mortality were significantly stronger among Black women aged 50 to 59 years (sdHR, 2.86; 95% CI, 1.84-4.44; P for interaction < .001). Among Black women with CVD, the hazard of BC death was 41% higher in comparison with White women. By treatment, a significant association with CVD mortality was observed only among Black women undergoing surgery and radiation (sdHR, 1.61; 95% CI, 1.22-2.13). CONCLUSIONS: Clinicians should consider the impact of younger age, preexisting CVD, and BC treatments among Black patients. Early identification of those at risk for worse survival may improve surveillance and outcomes.


Assuntos
Neoplasias da Mama , Doenças Cardiovasculares , Disparidades em Assistência à Saúde/etnologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , Feminino , Humanos , Maryland/epidemiologia , Pessoa de Meia-Idade
10.
Br J Cancer ; 126(5): 797-803, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34949788

RESUMO

BACKGROUND AND AIMS: CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities. METHODS: We evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3). RESULTS: CDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3. CONCLUSION: We report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings.


Assuntos
Antígenos CD/genética , Neoplasias da Mama/genética , Caderinas/genética , Carcinoma Lobular/genética , Carcinoma de Células em Anel de Sinete/genética , Neoplasias Colorretais/genética , Mutação em Linhagem Germinativa , Neoplasias Gástricas/genética , Adulto , Idoso , Neoplasias da Mama/etnologia , Carcinoma Lobular/etnologia , Carcinoma de Células em Anel de Sinete/etnologia , Neoplasias Colorretais/etnologia , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Prevalência , Análise de Sequência de DNA , Neoplasias Gástricas/etnologia , Adulto Jovem
11.
Genome Med ; 13(1): 186, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861889

RESUMO

BACKGROUND: Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function in homologous recombination (HR) of DNA, could involve pathogenic variants in other DNA repair pathway genes. METHODS: Whole exome sequencing was used to identify rare variants in HR genes in a BRCA1 and BRCA2 pathogenic variant negative OC family of French Canadian (FC) ancestry, a population exhibiting genetic drift. OC cases and cancer-free individuals from FC and non-FC populations were investigated for carrier frequency of FANCI c.1813C>T; p.L605F, the top-ranking candidate. Gene and protein expression were investigated in cancer cell lines and tissue microarrays, respectively. RESULTS: In FC subjects, c.1813C>T was more common in familial (7.1%, 3/42) than sporadic (1.6%, 7/439) OC cases (P = 0.048). Carriers were detected in 2.5% (74/2950) of cancer-free females though female/male carriers were more likely to have a first-degree relative with OC (121/5249, 2.3%; Spearman correlation = 0.037; P = 0.011), suggesting a role in risk. Many of the cancer-free females had host factors known to reduce risk to OC which could influence cancer risk in this population. There was an increased carrier frequency of FANCI c.1813C>T in BRCA1 and BRCA2 pathogenic variant negative OC families, when including the discovery family, compared to cancer-free females (3/23, 13%; OR = 5.8; 95%CI = 1.7-19; P = 0.005). In non-FC subjects, 10 candidate FANCI variants were identified in 4.1% (21/516) of Australian OC cases negative for pathogenic variants in BRCA1 and BRCA2, including 10 carriers of FANCI c.1813C>T. Candidate variants were significantly more common in familial OC than in sporadic OC (P = 0.04). Localization of FANCD2, part of the FANCI-FANCD2 (ID2) binding complex in the Fanconi anaemia (FA) pathway, to sites of induced DNA damage was severely impeded in cells expressing the p.L605F isoform. This isoform was expressed at a reduced level, destabilized by DNA damaging agent treatment in both HeLa and OC cell lines, and exhibited sensitivity to cisplatin but not to a poly (ADP-ribose) polymerase inhibitor. By tissue microarray analyses, FANCI protein was consistently expressed in fallopian tube epithelial cells and only expressed at low-to-moderate levels in 88% (83/94) of OC samples. CONCLUSIONS: This is the first study to describe candidate OC variants in FANCI, a member of the ID2 complex of the FA DNA repair pathway. Our data suggest that pathogenic FANCI variants may modify OC risk in cancer families.


Assuntos
Neoplasias da Mama , Proteínas de Grupos de Complementação da Anemia de Fanconi , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Canadá , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/genética
12.
Ann Clin Lab Sci ; 51(6): 861-867, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34921040

RESUMO

OBJECTIVE: Multiple studies indicate that interleukin-18 (IL-18) promoter-607C>A polymorphism has been associated with an increased risk of breast cancer (BC); however, conflicting results were yielded. Therefore, the present meta-analysis was conducted to provide a comprehensive assessment of the association of IL-18 gene polymorphisms with the risk of BC. MATERIALS: Following electronic databases searches and study screening, six eligible studies including 1,952 subjects were selected for the meta-analysis. RESULTS: The results suggested a significant association of IL-18 promoter-607C>A polymorphism with risk of BC. They also demonstrated that IL-18 gene promoter-607C>A polymorphism may confer increased risk to BC under the allelic model (OR, 1.167; 95% CI, 1.028-1.326; p=0.017), homozygote model (OR, 1.371; 95% CI, 1.062-1.770; p=0.015), and recessive model (OR, 1.348; 95% CI, 1.081-1.683; p=0.008). Furthermore, the sub-group analysis revealed no significant association of the -607C>A gene polymorphism with BC risk in Asian. CONCLUSION: The present meta-analysis provided evidence for the association of IL-18-607C>A polymorphism with increased risk of developing BC, particularly, women exhibiting AA genotype at IL-18 promoter-607 C>A polymorphism showed a significantly higher risk for BC.


Assuntos
Neoplasias da Mama , Interleucina-18/genética , Polimorfismo Genético , /genética , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Humanos , Regiões Promotoras Genéticas/genética , Medição de Risco , Fatores de Risco
13.
BMC Cancer ; 21(1): 1330, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906122

RESUMO

BACKGROUND: We investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population. METHODS: We attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses. RESULTS: Patients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients. CONCLUSIONS: Our study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias Pulmonares/mortalidade , Neoplasias Primárias Múltiplas/mortalidade , /etnologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , China/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/etnologia , Neoplasias Primárias Múltiplas/patologia , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida
14.
Asian Pac J Cancer Prev ; 22(12): 3985-3991, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34967580

RESUMO

OBJECTIVE: Several studies have recently indicated a huge shifting pattern toward early age onset cases in breast cancer (BC) patients. However, the studies exerted relatively limited to the Caucasian population. This preliminary study is aimed to investigate the genetic risk factors for young BC patients specifically in Indonesia population. METHODS: DNA samples were extracted from 79 BC patients aged younger than 40 years old and 90 healthy samples. These DNA samples were sequenced using Illumina NextSeq 500 platform and preprocessed to extract the single-nucleotide polymorphisms (SNPs) data. Firstly, multiple univariate logistic regressions were performed to test the association between each SNP and BC incidence in young patients. Furthermore, to analyze the polygenic effects derived from multiple SNPs, we employed a multivariate logistics regression. RESULTS: There were only 15 SNPs passed our 95% call rate threshold thus subsequently were used in the association test. One of these variants, rs3219493, emerged to be significantly associated with early-onset BC (p-value = 0.025, OR = 3.750, 95% CI = 1.178-11.938). This result is consistent with the multivariate logistic regression model, where the pertinent variant was found statistically significant (p-value = 0.008, OR = 8.398, 95% CI = 1.720-40.920). This variant was identified as an intronic variant within MUTYH gene which has been reported in several published studies to exhibit an association with the incidence of breast cancer in China, Italy and Sephardi Jews population. However, there is no evident this gene impacting the risk of developing early onset of BC in Indonesia population. CONCLUSION: Despite our limitation in terms of sample size analyzed in this preliminary study, our finding on significant association of intronic MUTHY with the early onset of BC in Indonesia led to a broadened insight of population-based unique aspect to being taken into an in-depth account for and advancement of chemotherapy.


Assuntos
Asiáticos/genética , Neoplasias da Mama/genética , DNA Glicosilases/genética , Predisposição Genética para Doença/genética , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/etnologia , Humanos , Incidência , Indonésia/epidemiologia , Modelos Logísticos , Polimorfismo de Nucleotídeo Único
15.
Breast Cancer Res ; 23(1): 108, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809694

RESUMO

BACKGROUND: Research on psychosocial stress and risk of breast cancer has produced conflicting results. Few studies have assessed this relation by breast cancer subtype or specifically among Black women, who experience unique chronic stressors. METHODS: We used prospective data from the Black Women's Health Study, an ongoing cohort study of 59,000 US Black women, to assess neighborhood- and individual-level psychosocial factors in relation to risk of breast cancer. We used factor analysis to derive two neighborhood score variables after linking participant addresses to US Census data (2000 and 2010) on education, employment, income and poverty, female-headed households, and Black race for all households in each residential block group. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for established breast cancer risk factors. RESULTS: During follow-up from 1995 to 2017, there were 2167 incident invasive breast cancer cases (1259 estrogen receptor positive (ER +); 687 ER negative (ER-)). For ER- breast cancer, HRs were 1.26 (95% CI 1.00-1.58) for women living in the highest quartile of neighborhood disadvantage relative to women in the lowest quartile, and 1.24 (95% CI 0.98-1.57) for lowest versus highest quartile of neighborhood socioeconomic status (SES). For ER+ breast cancer, living in the lowest quartile of neighborhood SES was associated with a reduced risk of ER+ breast cancer (HR = 0.83, 95% CI 0.70-0.98). With respect to individual-level factors, childhood sexual abuse (sexual assault ≥ 4 times vs. no abuse: HR = 1.35, 95% CI 1.01-1.79) and marital status (married/living together vs. single: HR = 1.29, 95% CI 1.08-1.53) were associated with higher risk of ER+, but not ER- breast cancer. CONCLUSION: Neighborhood disadvantage and lower neighborhood SES were associated with an approximately 25% increased risk of ER- breast cancer in this large cohort of Black women, even after control for multiple behaviors and lifestyle factors. Further research is need to understand the underlying reasons for these associations. Possible contributing factors are biologic responses to the chronic stress/distress experienced by individuals who reside in neighborhoods characterized by high levels of noise, crime and unemployment or the direct effects of environmental toxins.


Assuntos
Afro-Americanos/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Características de Residência/estatística & dados numéricos , Saúde da Mulher/estatística & dados numéricos , Adulto , Afro-Americanos/psicologia , Idoso , Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/psicologia , Feminino , Disparidades nos Níveis de Saúde , Humanos , Incidência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Adulto Jovem
16.
Nat Commun ; 12(1): 6946, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836952

RESUMO

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Evolução Clonal , Disparidades nos Níveis de Saúde , Adulto , Idoso , Biópsia , /genética , Mama/patologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Análise Mutacional de DNA , Feminino , Fator de Transcrição GATA3/genética , Heterogeneidade Genética , Instabilidade Genômica , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Nigéria/epidemiologia , Nigéria/etnologia , RNA-Seq , Medição de Risco , Sinaptofisina/genética , Transativadores/genética , Microambiente Tumoral/genética , /genética , Sequenciamento Completo do Genoma
18.
Ann Intern Med ; 174(12): 1637-1646, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34662151

RESUMO

BACKGROUND: Screening mammography guidelines do not explicitly consider racial differences in breast cancer epidemiology, treatment, and survival. OBJECTIVE: To compare tradeoffs of screening strategies in Black women versus White women under current guidelines. DESIGN: An established model from the Cancer Intervention and Surveillance Modeling Network simulated screening outcomes using race-specific inputs for subtype distribution; breast density; mammography performance; age-, stage-, and subtype-specific treatment effects; and non-breast cancer mortality. SETTING: United States. PARTICIPANTS: A 1980 U.S. birth cohort of Black and White women. INTERVENTION: Screening strategies until age 74 years with varying initiation ages and intervals. MEASUREMENTS: Outcomes included benefits (life-years gained [LYG], breast cancer deaths averted, and mortality reduction), harms (mammographies, false positives, and overdiagnoses), and benefit-harm ratios (tradeoffs) by race. Efficiency (benefits per unit resource), mortality disparity reduction, and equity in tradeoffs were evaluated. Equitable strategies for Black women were defined as those with tradeoffs closest to benchmark values for screening White women biennially from ages 50 to 74 years. RESULTS: Biennial screening from ages 45 to 74 years was most efficient for Black women, whereas biennial screening from ages 40 to 74 years was most equitable. Initiating screening 10 years earlier in Black versus White women reduced Black-White mortality disparities by 57% with similar LYG per mammogram for both populations. Selection of the most equitable strategy was sensitive to assumptions about disparities in real-world treatment effectiveness: The less effective treatment was for Black women, the more intensively Black women could be screened before tradeoffs fell short of those experienced by White women. LIMITATION: Single model. CONCLUSION: Initiating biennial screening in Black women at age 40 years reduces breast cancer mortality disparities and yields benefit-harm ratios that are similar to tradeoffs of White women screened biennially from ages 50 to 74 years. PRIMARY FUNDING SOURCE: National Cancer Institute at the National Institutes of Health.


Assuntos
Afro-Americanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/etnologia , Mamografia , Programas de Rastreamento/métodos , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Simulação por Computador , Feminino , Acesso aos Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
19.
BMC Cancer ; 21(1): 1131, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34670536

RESUMO

BACKGROUND: The V-Akt murine thymoma viral oncogene (AKT) 1 (E17K) is a subfamily of serine/threonine protein kinases that affects the survival, proliferation, and invasion of cancer cells. The clinicopathological features and frequencies in Asian populations with AKT1 mutations in breast and endometrial cancers are unclear. Hence, we aimed to determine the frequencies and relationships between clinicopathological features and AKT1 mutations in Asian women with cancer. METHODS: We extracted DNA from 311 and 143 samples derived from patients with breast and endometrial cancers to detect the AKT1 point mutation (hotspot), E17K. We examined correlations between clinicopathological features and AKT1 mutation status. RESULTS: The frequency of AKT1 mutations in breast cancer was 7.4%, and they were found more frequently in human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtypes, although this was not statistically significant (P = 0.08). The frequency of AKT1 mutations in endometrial cancer was 4.1%, and the mutations were histologically detected only in endometrioid types. However, AKT1 mutations did not correlate with relapse-free or overall survival of patients with breast or endometrial cancer. CONCLUSIONS: AKT1 mutations are associated with HER2-negative subtype in breast cancer and in endometrial cancer with endometrioid histology. The frequencies of AKT1 mutations in breast and endometrial cancers were similar between Asian and other regional women. The frequency of mutations is too low in both tumor types to talk about predictive significance.


Assuntos
Neoplasias da Mama/genética , Neoplasias do Endométrio/genética , Mutação Puntual , Proteínas Proto-Oncogênicas c-akt/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias do Endométrio/etnologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2 , Adulto Jovem
20.
JAMA Netw Open ; 4(10): e2128977, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34668945

RESUMO

Importance: Women with ductal carcinoma in situ (DCIS) may develop a subsequent invasive second breast cancer (SBC). Understanding the association of racial and ethnic factors with the development of invasive SBC may help reduce overtreatment and undertreatment of women from minority groups. Objective: To evaluate risk factors associated with developing invasive ipsilateral SBC (iiSBC) and invasive contralateral SBC (icSBC) among women with an initial diagnosis of DCIS who are from racial and ethnic minority populations. Design, Setting, and Participants: This retrospective cohort study used deidentified data from the Hawai'i Tumor Registry of 6221 female Hawai'i residents aged 20 years or older who received a diagnosis of DCIS between January 1, 1973, and December 31, 2017. The 5 most populous ethnic groups were compared (Chinese, Filipino, Japanese, Native Hawaiian, and White). Data analysis was performed from 2020 to 2021. Exposures: Patient demographic and clinical characteristics and the first course of treatment. Main Outcome and Measures: The a priori study outcome was the development of invasive SBC. Logistic regression was used to identify factors associated with invasive SBC. Factors that were significant on unadjusted analyses were included in the adjusted models (ie, age, race and ethnicity, diagnosis year, DCIS histologic characteristics, laterality, hormone status, and treatment). Results: The racial and ethnic distribution of patients with DCIS across the state's most populous groups were 2270 Japanese women (37%), 1411 White women (23%), 840 Filipino women (14%), 821 Native Hawaiian women (13%), and 491 Chinese women (8%). Women of other minority race and ethnicity collectively comprised 6% of cases (n = 388). A total of 6221 women (age range, 20 to ≥80 years) were included in the study; 4817 (77%) were 50 years of age or older, 4452 (72%) received a diagnosis between 2000 and 2017, 2581 (42%) had well or moderately differentiated histologic characteristics, 2383 (38%) had noninfiltrating intraductal DCIS, and 2011 (32%) were treated with mastectomy only. Of these 6221 women, 444 (7%) developed invasive SBC; 190 developed iiSBC (median time to SBC diagnosis, 7.8 years [range, 0.5-30 years]) and 254 developed icSBC (median time to SBC diagnosis, 5.9 years [range, 0.5-28.8 years]). On adjusted analysis, women who developed iiSBC were more likely to be younger than 50 years (adjusted odds ratio [aOR], 1.49; 95% CI, 1.08-2.06), Native Hawaiian (aOR, 3.28; 95% CI, 2.01-5.35), Filipino (aOR, 1.94; 95% CI, 1.11-3.42), Japanese (aOR, 1.58; 95% CI, 1.01-2.48), and untreated (aOR, 2.29; 95% CI, 1.09-4.80). Compared with breast-conserving surgery (BCS) alone, there was a decreased likelihood of iiSBC among women receiving BCS and radiotherapy (aOR, 0.45; 95% CI, 0.27-0.75), BCS and systemic treatment with or without radiotherapy (aOR, 0.40; 95% CI, 0.23-0.69), mastectomy only (aOR, 0.23; 95% CI, 0.13-0.39), and mastectomy and systemic treatment (aOR, 0.57; 95% CI, 0.33-0.96). Women who developed an icSBC were more likely to be Native Hawaiian (aOR, 1.69; 95% CI, 1.10-2.61) or Filipino (aOR, 1.70; 95% CI, 1.10-2.63). Risk of both iiSBC and icSBC decreased in the later years of diagnosis (2000-2017) compared with the earlier years (1973-1999). Conclusions and Relevance: This study suggests that Native Hawaiian and Filipino women who initially received a diagnosis of DCIS were more likely to subsequently develop both iiSBC and icSBC. Japanese women and younger women were more likely to develop iiSBC. Subpopulation disaggregation may help guide clinical treatment and screening decisions for at-risk subpopulations.


Assuntos
Neoplasias da Mama/complicações , Carcinoma Ductal/etiologia , Fatores Raciais/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Carcinoma Ductal/epidemiologia , Feminino , Hawaii/epidemiologia , Hawaii/etnologia , Humanos , Pessoa de Meia-Idade , /estatística & dados numéricos , Razão de Chances , Recidiva
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