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Tumors resembling tenosynovial giant cell tumor (TGCT) but additionally forming chondroid matrix (C-TGCT) are rare and most often involve the temporomandibular joint (TMJ). We studied 21 tumors consisting of synoviocytes (large, eosinophilic mononuclear cells containing hemosiderin) and chondroid matrix to better understand these unusual neoplasms. The tumors occurred in 10 males and 11 females, ranging from 31-80 years (median, 50 years) and involved the temporomandibular joint region (16), extremities (4), and spine (1). As in conventional TGCT, all were composed of synoviocytes, small histiocytes, foamy macrophages, siderophages and osteoclast-like giant cells in variably hyalinized background. Expansile nodules of large, moderately atypical synoviocytes were present, in addition to "chondroblastoma-like", "chondroma-like", or "phosphaturic mesenchymal tumor-like" calcified matrix. The synoviocytes expressed clusterin (17/19) and less often desmin (3/15). The tumors were frequently CSF1-positive by CISH (8/13) but at best weakly positive for CSF1 by IHC (0/3). Background small histiocytes were CD163-positive (12/12). All were FGF23-negative (0/10). Cells within lacunae showed a synoviocytic phenotype (clusterin-positive; S100 protein and ERG-negative). RNA-seq was successful in 13 cases; fusions were present in 7 tumors, including FN1::TEK (5 cases), FN1::PRG4 (2 cases), MALAT1::FN1, PDGFRA::USP35 and TIMP3::ZCCHC7 (1 case each). Three tumors contained more than one fusion (FN1::PRG4 with TIMP3::ZCCHC7, FN1::TEK with FN1::PRG4, and FN1::TEK with MALAT1::FN1). Clinical follow up (17 patients; median follow up duration 38 months; range 4-173 months) showed 13 (76%) to be alive without evidence of disease and 4 (24%) to be alive with persistent/recurrent local disease. No metastases or deaths from disease were observed. We conclude that these unusual tumors represent a distinct category of synoviocytic neoplasia, which we term "chondroid synoviocytic neoplasm", rather than simply ordinary TGCT with cartilage. Despite potentially worrisome morphologic features, they appear to behave in at most a locally aggressive fashion.
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BACKGROUND: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. METHODS: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. RESULTS: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. CONCLUSIONS: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.
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Neoplasias da Mama , Menopausa , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/etiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/etnologia , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Pessoa de Meia-Idade , Adulto , Idoso , Estudos de Casos e Controles , Fatores de Risco , California/epidemiologia , História Reprodutiva , Gravidez , Paridade , Etnicidade/estatística & dados numéricos , Minorias Étnicas e Raciais , Hispânico ou Latino/estatística & dados numéricosRESUMO
BACKGROUND: Breast cancer incidence rates in women of Asian descent have been increasing in the United States and Asia. METHODS: In a case-control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort. RESULTS: Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951-1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women [OR = 1.40; 95% confidence interval (CI), 0.97-2.03] and two-fold among foreign-born Chinese women (OR = 2.16; 95% CI, 1.21-3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics. CONCLUSIONS: In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women. IMPACT: It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs.
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Neoplasias da Mama , Emigrantes e Imigrantes , Estados Unidos/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Adulto , Asiático , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , São Francisco/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Women diagnosed with breast cancer prior to age 45 years (<45y) and within the first 5 years postpartum (postpartum breast cancer, PPBC) have the greatest risk for distal metastatic recurrence. METHODS: Pooling data from the Colorado Young Women Breast Cancer cohort and the Breast Cancer Health Disparities Study (N = 2519 cases), we examined the association of parity, age, and clinical factors with overall survival (OS) of breast cancer over 15 years of follow-up. RESULTS: Women with PPBC diagnosed at <45y had the lowest OS (p < 0.0001), while OS of nulliparous cases diagnosed at <45y did not differ from OS of cases diagnosed at 45-65y regardless of parity status. After adjustment for study site, race/ethnicity, clinical stage, year of diagnosis and stratification for oestrogen receptor status, PPBC remained an independent factor associated with poor OS. Among cases diagnosed at <45y, nulliparous cases had 1.6 times better OS (hazard ratio (HR) = 0.61, 95%CI 0.42-0.87) compared to those with PPBC, with a more pronounced survival difference among stage I breast cancers (HR = 0.30, 95%CI 0.11-0.79). Among very young women diagnosed at age ≤35y, nulliparous cases had 2.3 times better OS (HR = 0.44, 95%CI 0.23-0.84) compared to PPBC. CONCLUSION: Our results suggest that postpartum status is the main driver of poor prognosis in young women with breast cancer, with the strongest association in patients diagnosed at age ≤35y and in those with stage I disease.
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Neoplasias da Mama , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Paridade , Período Pós-Parto , Gravidez , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner's Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Metabolismo Energético/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Polimorfismo de Nucleotídeo Único , Adulto , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pré-Menopausa , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
Reproductive and hormonal factors may influence breast cancer risk via endogenous estrogen exposure. Cumulative menstrual months (CMM) can be used as a surrogate measure of this exposure. Using harmonized data from four population-based breast cancer studies (7284 cases and 7242 controls), we examined ethnicity-specific associations between CMM and breast cancer risk using logistic regression, adjusting for menopausal status and other risk factors. Higher CMM was associated with increased breast cancer risk in non-Hispanic Whites, Hispanics and Asian Americans regardless of menopausal status (all FDR adjusted P trends = .0004), but not in African Americans. In premenopausal African Americans, there was a suggestive trend of lower risk with higher CMM. Stratification by body mass index (BMI) among premenopausal African American women showed a nonsignificant positive association with CMM in nonobese (BMI <30 kg/m2 ) women and a significant inverse association in obese women (OR per 50 CMM = 0.56, 95% CI 0.37-0.87, Ptrend = .03). Risk patterns were similar for hormone receptor positive (HR+; ER+ or PR+) breast cancer; a positive association was found in all premenopausal and postmenopausal ethnic groups except in African Americans. HR- (ER- and PR-) breast cancer was not associated with CMM in all groups combined, except for a suggestive positive association among premenopausal Asian Americans (OR per 50 CMM = 1.33, P = .07). In summary, these results add to the accumulating evidence that established reproductive and hormonal factors impact breast cancer risk differently in African American women compared to other ethnic groups, and also differently for HR- breast cancer than HR+ breast cancer.
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Neoplasias da Mama/etiologia , Etnicidade/estatística & dados numéricos , Menstruação , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adolescente , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Prognóstico , Adulto JovemRESUMO
We pooled multiethnic data from four population-based studies and examined associations of menstrual and reproductive characteristics with breast cancer (BC) risk by tumor hormone receptor (HR) status [defined by estrogen receptor (ER) and progesterone receptor (PR)]. We estimated odds ratios and 95% confidence intervals using multivariable logistic regression, stratified by age (<50, ≥50 years) and ethnicity, for 5,186 HR+ (ER+ or PR+) cases, 1,365 HR- (ER- and PR-) cases and 7,480 controls. For HR+ BC, later menarche and earlier menopause were associated with lower risk in non-Hispanic whites (NHWs) and Hispanics, and higher parity and longer breast-feeding were associated with lower risk in Hispanics and Asian Americans, and suggestively in NHWs. Positive associations with later first full-term pregnancy (FTP), longer interval between menarche and first FTP and shorter time since last FTP were limited to younger Hispanics and Asian Americans. Except for nulliparity, reproductive characteristics were not associated with risk in African Americans. For HR- BC, lower risk was associated with later menarche, except in African Americans and older Asian Americans and with longer breast-feeding in Hispanics and Asian Americans only. In younger African Americans, HR- BC risk associated with higher parity (≥3 vs. 1 FTP) was increased fourfold in women who never breast-fed, but not in those with a breast-feeding history, suggesting that breast-feeding may mitigate the adverse effect of higher parity in younger African American women. Further work needs to evaluate why menstrual and reproductive risk factors vary in importance according to age and ethnicity.
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Neoplasias da Mama , Menarca , Menopausa , Receptores de Estrogênio , Receptores de Progesterona , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Asiático/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Hispânico ou Latino/estatística & dados numéricos , Modelos Logísticos , Menarca/etnologia , Menopausa/etnologia , Menstruação , Paridade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estados Unidos/etnologia , BrancosRESUMO
Universities have been called upon to integrate research experiences into early, introductory courses to better prepare our STEM workforce. This call is primarily based on short-term studies that link research experiences with knowledge and perception gains. However, the influence of pre-existing student characteristics has not been fully disentangled from the research experience, and the long-term stability of these gains is uncertain. To address these issues, we integrated a course-based undergraduate research experience (CURE) into randomly assigned sections of a required freshman-level biology laboratory course. We previously reported that this CURE resulted in immediate targeted knowledge and perception gains. Here, we evaluate the stability of these gains as students progressed through a biology degree program. At sophomore year, the impact of the CURE on student perception was still apparent. When compared to controls, students who participated in the CURE perceived a greater understanding of what researchers do and an increased interest in pursuing a research career. However, by senior year, these positive perceptions had fallen to levels shared by control groups. Targeted knowledge gains persisted throughout this study. Our results support CURE logic models predicting that multiple CUREs will be required to sustain perception gains.
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BACKGROUND: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women. METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth. CONCLUSIONS: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.
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Aleitamento Materno/etnologia , Neoplasias da Mama/etnologia , Hispânico ou Latino/estatística & dados numéricos , Paridade , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Idoso , Aleitamento Materno/estatística & dados numéricos , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two-fold for parous women who never breast-fed compared to nulliparous women (OR = 2.02, 95% CI = 1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR = 0.52, 95% CI = 0.26-1.04, Ptrend = 0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ≥3 full-term pregnancies (FTPs) and no or short-term (<12 months) breast-feeding compared to women with 1-2 FTPs and breast-feeding ≥12 months (OR = 2.56, 95% CI = 1.22-5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short-term breast-feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%) and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of FTPs in women under age 50 years.
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Aleitamento Materno/efeitos adversos , História Reprodutiva , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/etiologia , Adulto , Fatores Etários , Idoso , California/epidemiologia , California/etnologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Sistema de Registros , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study. METHODS: Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native American (NA) ancestry and alcohol consumption. RESULTS: A total of 443 deaths occurred over a median follow-up time of 11 years. After adjusting all results for multiple comparisons, rs7027604 was significantly associated with all-cause mortality (HRAA = 1.40; 95% CI 1.13-1.73, P adj = 0.018). The rs1424482 CC genotype (HRCC = 1.69; 95% CI 1.20-2.37, P adj = 0.027) and the rs7027604 AA genotype (HRAA = 1.65; 95% CI 1.21-2.26, P adj = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HRCG/GG = 0.36; 95% CI 0.20-0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P interation = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HRAA = 1.53; 95% CI 1.19-1.97). CONCLUSIONS: Multiple SNPs in ALDH1A1 were associated with increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should consider the modifying effects of alcohol consumption and NA ancestry.
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Consumo de Bebidas Alcoólicas/etnologia , Aldeído Desidrogenase/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Disparidades nos Níveis de Saúde , Adulto , Fatores Etários , Idoso , Família Aldeído Desidrogenase 1 , Neoplasias da Mama/mortalidade , Estudos de Casos e Controles , Feminino , Seguimentos , Hispânico ou Latino/genética , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Retinal Desidrogenase , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , População Branca/genéticaAssuntos
Fumar Cigarros , Hispânico ou Latino , Mama , Neoplasias da Mama , Feminino , Humanos , Fatores de Risco , População BrancaRESUMO
Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown.Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study.Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00-1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29-2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI <25 versus >30: OR = 0.65 (95% CI, 0.44-0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29-0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry.Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry.Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692-701. ©2016 AACR.
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Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Predisposição Genética para Doença/etnologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Hispânico ou Latino , Humanos , México , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Estados UnidosRESUMO
BACKGROUND: U.S. Hispanic women have high rates of parity, breastfeeding, and obesity. It is unclear whether these reproductive factors are associated with breast cancer (BC) mortality. We examined the associations between breastfeeding, parity, adiposity and BC-specific and overall mortality in Hispanic and non-Hispanic white (NHW) BC cases. METHODS: The study population included 2921 parous women (1477 Hispanics, 1444 NHWs) from the Breast Cancer Health Disparities Study with invasive BC diagnosed between 1995 and 2004. Information on reproductive history and lifestyle factors was collected by in-person interview. Overall and stratified Cox proportional hazard regression models by ethnicity, parity, and body mass index (BMI) at age 30 years were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: After a median follow-up time of 11.2 years, a total of 679 deaths occurred. Pre-diagnostic breastfeeding was associated with a 16% reduction in mortality (HR 0.84; 95% 0.72-0.99) irrespective of ethnicity. Parity significantly modified the association between breastfeeding duration and mortality (p interaction = 0.05), with longer breastfeeding duration associated with lower risk among women who had ≤2 births (p trend = 0.02). Breastfeeding duration was associated with reduced risk of both BC-specific and overall mortality among women with BMI <25 kg/m2, while positive associations were observed among women with BMI ≥25 kg/m2 (p interactions <0.01). CONCLUSION: Pre-diagnostic breastfeeding was inversely associated with risk of mortality after BC, particularly in women of low parity or normal BMI. These results provide another reason to encourage breastfeeding and weight management among young women.
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Adiposidade , Aleitamento Materno , Neoplasias da Mama/epidemiologia , Hispânico ou Latino , População Branca , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Causas de Morte , Feminino , Disparidades em Assistência à Saúde , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Paridade , Vigilância da População , Fatores de Risco , Programa de SEER , Adulto JovemRESUMO
Background: There is no model to estimate absolute invasive breast cancer risk for Hispanic women. Methods: The San Francisco Bay Area Breast Cancer Study (SFBCS) provided data on Hispanic breast cancer case patients (533 US-born, 553 foreign-born) and control participants (464 US-born, 947 foreign-born). These data yielded estimates of relative risk (RR) and attributable risk (AR) separately for US-born and foreign-born women. Nativity-specific absolute risks were estimated by combining RR and AR information with nativity-specific invasive breast cancer incidence and competing mortality rates from the California Cancer Registry and Surveillance, Epidemiology, and End Results program to develop the Hispanic risk model (HRM). In independent data, we assessed model calibration through observed/expected (O/E) ratios, and we estimated discriminatory accuracy with the area under the receiver operating characteristic curve (AUC) statistic. Results: The US-born HRM included age at first full-term pregnancy, biopsy for benign breast disease, and family history of breast cancer; the foreign-born HRM also included age at menarche. The HRM estimated lower risks than the National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT) for US-born Hispanic women, but higher risks in foreign-born women. In independent data from the Women's Health Initiative, the HRM was well calibrated for US-born women (observed/expected [O/E] ratio = 1.07, 95% confidence interval [CI] = 0.81 to 1.40), but seemed to overestimate risk in foreign-born women (O/E ratio = 0.66, 95% CI = 0.41 to 1.07). The AUC was 0.564 (95% CI = 0.485 to 0.644) for US-born and 0.625 (95% CI = 0.487 to 0.764) for foreign-born women. Conclusions: The HRM is the first absolute risk model that is based entirely on data specific to Hispanic women by nativity. Further studies in Hispanic women are warranted to evaluate its validity.
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Neoplasias da Mama/etnologia , Carcinoma Ductal de Mama/etnologia , Hispânico ou Latino/estatística & dados numéricos , Adulto , Idoso , Área Sob a Curva , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Modelos Logísticos , Estudos Longitudinais , Pessoa de Meia-Idade , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/etnologia , Saúde da MulherRESUMO
Gene co-expression analysis has proven to be a powerful tool for ascertaining the organization of gene products into networks that are important for organ function. An organ, such as the liver, engages in a multitude of functions important for the survival of humans, rats, and other animals; these liver functions include energy metabolism, metabolism of xenobiotics, immune system function, and hormonal homeostasis. With the availability of organ-specific transcriptomes, we can now examine the role of RNA transcripts (both protein-coding and non-coding) in these functions. A systems genetic approach for identifying and characterizing liver gene networks within a recombinant inbred panel of rats was used to identify genetically regulated transcriptional networks (modules). For these modules, biological consensus was found between functional enrichment analysis and publicly available phenotypic quantitative trait loci (QTL). In particular, the biological function of two liver modules could be linked to immune response. The eigengene QTLs for these co-expression modules were located at genomic regions coincident with highly significant phenotypic QTLs; these phenotypes were related to rheumatoid arthritis, food preference, and basal corticosterone levels in rats. Our analysis illustrates that genetically and biologically driven RNA-based networks, such as the ones identified as part of this research, provide insight into the genetic influences on organ functions. These networks can pinpoint phenotypes that manifest through the interaction of many organs/tissues and can identify unannotated or under-annotated RNA transcripts that play a role in these phenotypes.
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Fígado/metabolismo , RNA/metabolismo , Animais , Feminino , Ontologia Genética , Sistema Imunitário/metabolismo , Desequilíbrio de Ligação , Fígado/imunologia , Escore Lod , Masculino , Locos de Características Quantitativas , RNA/genética , Ratos Endogâmicos SHR , Análise de Sequência de RNA , TranscriptomaRESUMO
The contribution of type 2 diabetes and obesity on mortality in breast cancer (BC) patients has not been well studied among Hispanic women, in whom these exposures are highly prevalent. In a multi-center population-based study, we examined the associations between diabetes, multiple obesity measures, and mortality in 1180 Hispanic and 1298 non-Hispanic white (NHW) women who were diagnosed with incident invasive BC from the San Francisco Bay Area, New Mexico, Utah, Colorado, and Arizona. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards regression models. The median follow-up time from BC diagnosis to death was 10.8 years. In ethnic-stratified results, the association for BC-specific mortality among Hispanics was significantly increased (HR 1.85 95 % CI 1.11, 3.09), but the ethnic interaction was not statistically significant. In contrast, obesity at age 30 increased BC-specific mortality risk in NHW women (HR 2.33 95 % CI 1.36, 3.97) but not Hispanics (p-interaction = 0.045). Although there were no ethnic differences for all-cause mortality, diabetes, obesity at age 30, and post-diagnostic waist-hip ratio were significantly associated with all-cause mortality in all women. This study provides evidence that diabetes and adiposity, both modifiable, are prognostic factors among Hispanic and NHW BC patients.
Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Adulto , Idade de Início , Idoso , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , SobreviventesRESUMO
PURPOSE: There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women. METHODS: The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels. RESULTS: When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups. CONCLUSIONS: Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.
Assuntos
Neoplasias da Mama/epidemiologia , Hispânico ou Latino/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adulto , Idoso , Animais , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Feminino , Peixes , Humanos , Carne , Pessoa de Meia-Idade , Aves Domésticas , Carne Vermelha , Fatores de RiscoRESUMO
OBJECTIVE: Few epidemiological studies have included Hispanics with the evaluation of the effects of cigarette smoking and breast cancer. We examined the relationship between cigarette smoking, ethnicity, and breast cancer risk using data from the Breast Cancer Health Disparities Study (BCHDS). MATERIALS AND METHODS: The BCHDS is a consortium of three population-based case-control studies, including U.S. non-Hispanic whites (NHWs) (1,525 cases; 1,593 controls), U.S. Hispanics/Native Americans (1,265 cases; 1,495 controls), and Mexican women (990 cases; 1,049 controls). Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Breast cancer risk was elevated among Mexican former smokers (OR 1.43, 95% CI 1.04-1.96) and among those who smoked ≥ 31 years (OR 1.95, 95% CI 1.13-3.35), compared to never smokers. In addition, Mexican former smokers with a history of alcohol consumption had increased breast cancer risk (OR 2.30, 95% CI 1.01-5.21). Among NHW premenopausal women, breast cancer risk was increased for smoking ≥ 20 cigarettes per day (OR 1.61, 95% CI 1.07-2.41). CONCLUSION: Our findings suggest the possibility of ethnic differences with the associations between cigarette smoking and breast cancer risk.
Assuntos
Neoplasias da Mama/etnologia , Disparidades em Assistência à Saúde/etnologia , Hispânico ou Latino/estatística & dados numéricos , Fumar/efeitos adversos , População Branca/estatística & dados numéricos , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/etnologia , Índice de Massa Corporal , Neoplasias da Mama/complicações , Estudos de Casos e Controles , Etnicidade/estatística & dados numéricos , Feminino , Disparidades nos Níveis de Saúde , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Pré-Menopausa , Fatores de Risco , Fumar/etnologia , Estados UnidosRESUMO
BACKGROUND: Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. METHODS: We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. RESULTS: We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, <12 months, and >12 months breastfeeding, respectively, Pinteraction 0.014]. CONCLUSIONS: The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. IMPACT: These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk.