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1.
Trials ; 20(1): 744, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852492

RESUMO

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer mortality among Latinas. As more is learned about the association between mammographic breast density (MBD) and breast cancer risk, a number of U.S. states adopted legislation and now a federal law mandates written notification of MBD along with mammogram results. These notifications vary in content and readability, though, which may limit their effectiveness and create confusion or concern, especially among women with low health literacy or barriers to screening. The purpose of this study is to determine whether educational enhancement of MBD notification results in increased knowledge, decreased anxiety, and adherence to continued mammography screening among Latina women in a limited-resources setting. METHODS: Latinas LEarning About Density (LLEAD) is a randomized clinical trial (RCT) comparing the impact of three notification approaches on behavioral and psychological outcomes in Latina women. Approximately 2000 Latinas undergoing screening mammography in a safety-net community clinic will be randomized 1:1:1 to mailed notification (usual care); mailed notification plus written educational materials (enhanced); or mailed notification, written educational materials, plus verbal explanation by a promotora (interpersonal). The educational materials and verbal explanations are available in Spanish or English. Mechanisms through which written or verbal information influences future screening motivation and behavior will be examined, as well as moderating factors such as depression and worry about breast cancer, which have been linked to diagnostic delays among Latinas. The study includes multiple psychological measures (anxiety, depression, knowledge about MBD, perceived risk of breast cancer, worry, self-efficacy) and behavioral outcomes (continued adherence to mammography). Measurement time points include enrollment, 2-4 weeks post-randomization, and 1 and 2 years post-randomization. Qualitative inquiry related to process and outcomes of the interpersonal arm and cost analysis related to its implementation will be undertaken to understand the intervention's delivery and transferability. DISCUSSION: Legislation mandating written MBD notification may have unintended consequences on behavioral and psychological outcomes, particularly among Latinas with limited health literacy and resources. This study has implications for cancer risk communication and will offer evidence on the potential of generalizable educational strategies for delivering information on breast density to Latinas in limited-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02910986. Registered on 21 September 2016. Items from the WHO Trial Registration Data Set can be found in this protocol.

2.
J Am Coll Radiol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756308

RESUMO

PURPOSE: To assess changes in breast density (BD) awareness, knowledge, and attitudes among US women over a period of 5 years. METHODS: Using a probability-based web panel representative of the US population, we administered an identical BD survey in 2012 and 2017 to women aged 40 to 74 years. RESULTS: In 2017, 65.8% had heard of BD (versus 57.5% in 2012; P = .0002). BD awareness in both 2012 and 2017 was significantly associated with race, income, and education. Among women aware of BD in 2017, 76.5% had knowledge of BD's relationship to masking (versus 71.5% in 2012; P = .04); 65.5% had knowledge of BD's relationship to cancer risk (versus 58.5%; P = .009); and 47.3% had discussed BD with a provider (versus 43.1% in 2012; P = .13). After multivariable adjustment, residence in a state with BD legislation was associated in 2017 with knowledge of BD's relationship to risk but not to masking. Most women wanted to know their BD (62.5% in 2017 versus 59.8% in 2012; P = .46); this information was anticipated to cause anxiety in 44.8% (versus 44.9% in 2012; P = .96); confusion in 35.9% (versus 43.0%; P = .002); and feeling informed in 89.7% (versus 90.4%; P = .64). Over three-quarters supported federal BD legislation in both surveys. Response rate to the 2017 survey was 55% (1,502 of 2,730) versus 65% (1,506 of 2,311) in 2012. CONCLUSION: Although BD awareness has increased, important disparities persist. Knowledge of BD's impact on risk has increased; knowledge about masking and BD discussions with providers have not. Most women want to know their BD, would not feel anxious or confused as a result of knowing, and would feel empowered to make decisions. The federal BD notification legislation presents an opportunity to improve awareness and knowledge and encourage BD conversations with providers.

3.
Breast Cancer Res ; 21(1): 118, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660981

RESUMO

BACKGROUND: Given that breast cancer and normal dense fibroglandular tissue have similar radiographic attenuation, we examine whether automated volumetric density measures identify a differential change between breasts in women with cancer and compare to healthy controls. METHODS: Eligible cases (n = 1160) had unilateral invasive breast cancer and bilateral full-field digital mammograms (FFDMs) at two time points: within 2 months and 1-5 years before diagnosis. Controls (n = 2360) were matched to cases on age and date of FFDMs. Dense volume (DV) and volumetric percent density (VPD) for each breast were assessed using Volpara™. Differences in DV and VPD between mammograms (median 3 years apart) were calculated per breast separately for cases and controls and their difference evaluated by using the Wilcoxon signed-rank test. To simulate clinical practice where cancer laterality is unknown, we examined whether the absolute difference between breasts can discriminate cases from controls using area under the ROC curve (AUC) analysis, adjusting for age, BMI, and time. RESULTS: Among cases, the VPD and DV between mammograms of the cancerous breast decreased to a lesser degree (- 0.26% and - 2.10 cm3) than the normal breast (- 0.39% and - 2.74 cm3) for a difference of 0.13% (p value < 0.001) and 0.63 cm3 (p = 0.002), respectively. Among controls, the differences between breasts were nearly identical for VPD (- 0.02 [p = 0.92]) and DV (0.05 [p = 0.77]). The AUC for discriminating cases from controls using absolute difference between breasts was 0.54 (95% CI 0.52, 0.56) for VPD and 0.56 (95% CI, 0.54, 0.58) for DV. CONCLUSION: There is a small relative increase in volumetric density measures over time in the breast with cancer which is not found in the normal breast. However, the magnitude of this difference is small, and this measure alone does not appear to be a good discriminator between women with and without breast cancer.

4.
Blood Cancer J ; 9(8): 59, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383849

RESUMO

Chronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n = 154), (2) sporadic CLL (n = 302), (3) familial MBL (n = 87), (4) unaffected first-degree relatives from CLL/MBL families (n = 263), and (5) reference population (n = 15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p's < 0.05). However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p's > 0.05). Unaffected relatives and MBL cases from CLL/MBL families, ages >60 years, showed elevated monoclonal sFLC, compared to the reference population (p's < 0.05). This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls. Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.

5.
Cancer Causes Control ; 30(10): 1103-1111, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352658

RESUMO

PURPOSE: High mammographic breast density is a strong, well-established breast cancer risk factor. Whether stem cells may explain high breast cancer risk in dense breasts is unknown. We investigated the association between breast density and breast cancer risk by the status of stem cell markers CD44, CD24, and ALDH1A1 in the tumor. METHODS: We included 223 women with primary invasive or in situ breast cancer and 399 age-matched controls from Mayo Clinic Mammography Study. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were assessed using computer-assisted thresholding technique. Immunohistochemical analysis of the markers was performed on tumor tissue microarrays according to a standard protocol. We used polytomous logistic regression to quantify the associations of breast density measures with breast cancer risk across marker-defined tumor subtypes. RESULTS: Of the 223 cancers in the study, 182 were positive for CD44, 83 for CD24 and 52 for ALDH1A1. Associations of PD were not significantly different across t marker-defined subtypes (51% + vs. 11-25%: OR 2.83, 95% CI 1.49-5.37 for CD44+ vs. OR 1.87, 95% CI 0.47-7.51 for CD44-, p-heterogeneity = 0.66; OR 2.80, 95% CI 1.27-6.18 for CD24+ vs. OR 2.44, 95% CI 1.14-5.22 for CD24-, p-heterogeneity = 0.61; OR 3.04, 95% CI 1.14-8.10 for ALDH1A1+ vs. OR 2.57. 95% CI 1.30-5.08 for ALDH1A1-, p-heterogeneity = 0.94). Positive associations of DA and inverse associations of NDA with breast cancer risk were similar across marker-defined subtypes. CONCLUSIONS: We found no evidence of differential associations of breast density with breast cancer risk by the status of stem cell markers. Further studies in larger study populations are warranted to confirm these associations.


Assuntos
Biomarcadores Tumorais/metabolismo , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Mamografia , Idoso , Mama/diagnóstico por imagem , Mama/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Células-Tronco/metabolismo
6.
Cancer Epidemiol Biomarkers Prev ; 28(8): 1324-1330, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31186265

RESUMO

BACKGROUND: Mammographic breast density declines during menopause. We assessed changes in volumetric breast density across the menopausal transition and factors that influence these changes. METHODS: Women without a history of breast cancer, who had full field digital mammograms during both pre- and postmenopausal periods, at least 2 years apart, were sampled from four facilities within the San Francisco Mammography Registry from 2007 to 2013. Dense breast volume (DV) was assessed using Volpara on mammograms across the time period. Annualized change in DV from pre- to postmenopause was estimated using linear mixed models adjusted for covariates and per-woman random effects. Multiplicative interactions were evaluated between premenopausal risk factors and time to determine whether these covariates modified the annualized changes. RESULTS: Among the 2,586 eligible women, 1,802 had one premenopausal and one postmenopausal mammogram, 628 had an additional perimenopausal mammogram, and 156 had two perimenopausal mammograms. Women experienced an annualized decrease in DV [-2.2 cm3 (95% confidence interval, -2.7 to -1.7)] over the menopausal transition. Declines were greater among women with a premenopausal DV above the median (54 cm3) versus below (DV, -3.5 cm3 vs. -1.0 cm3; P < 0.0001). Other breast cancer risk factors, including race, body mass index, family history, alcohol, and postmenopausal hormone therapy, had no effect on change in DV over the menopausal transition. CONCLUSIONS: High premenopausal DV was a strong predictor of greater reductions in DV across the menopausal transition. IMPACT: We found that few factors other than premenopausal density influence changes in DV across the menopausal transition, limiting targeted prevention efforts.

8.
Obstet Gynecol ; 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31083119

RESUMO

OBJECTIVE: To determine the effect of tubal ligation on age at natural menopause, as a marker of long-term ovarian function. METHODS: Three preexisting population-based cohorts were included in this cross-sectional study. Data from each cohort was analyzed separately. The cohorts were restricted to women who never smoked and had reached natural menopause, without prior hysterectomy or oophorectomy. The following variables were collected: race, age at menarche, age at menopause, history of hysterectomy or oophorectomy, gravidity and parity, tobacco use, and ever use of hormonal contraception. The type of tubal ligation and age at tubal ligation were manually abstracted in cohort 1. For cohorts 2 and 3, history of tubal ligation was obtained from an institutional form, completed by patient report. The primary outcome, age at natural menopause, was compared between the two groups (those with and without a history of tubal ligation). RESULTS: Inclusion criteria was met by 555 women from cohort 1, 1,816 women from cohort 2, and 1,534 women from cohort 3. Baseline characteristics did not differ between cohorts. The percentage with tubal ligation was the same in all cohorts: 26.0%, 25.5%, and 25.0%, respectively. Women with a tubal ligation were more likely to have had at least one pregnancy and to have used hormonal contraception compared with women without a tubal ligation. There was no significant difference in age at natural menopause in women who underwent tubal ligation (50.1, 49.9, 50.0 years, respectively) compared with those who did not (50.7, 49.6, 50.0 years, respectively). The type of tubal ligation (cohort 1 only) had no effect on age at menopause. CONCLUSIONS: Tubal ligation did not affect age at natural menopause in the three large cohorts included in this study.

9.
Breast Cancer Res Treat ; 177(1): 165-173, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31129803

RESUMO

BACKGROUND: Breast density and body mass index (BMI) are used for breast cancer risk stratification. We evaluate whether the positive association between volumetric breast density and breast cancer risk is strengthened with increasing BMI. METHODS: The San Francisco Mammography Registry and Mayo Clinic Rochester identified 781 premenopausal and 1850 postmenopausal women with breast cancer diagnosed between 2007 and 2015 that had a screening digital mammogram at least 6 months prior to diagnosis. Up to three controls (N = 3535) were matched per case on age, race, date, mammography machine, and state. Volumetric percent density (VPD) and dense volume (DV) were measured with Volpara™. Breast cancer risk was assessed with logistic regression stratified by menopause status. Multiplicative interaction tests assessed whether the association of density measures was differential by BMI categories. RESULTS: The increased risk of breast cancer associated with VPD was strengthened with higher BMI for both premenopausal (pinteraction = 0.01) and postmenopausal (pinteraction = 0.0003) women. For BMI < 25, 25-30, and ≥ 30 kg/m2, ORs for breast cancer for a 1 SD increase in VPD were 1.24, 1.65, and 1.97 for premenopausal, and 1.20, 1.55, and 2.25 for postmenopausal women, respectively. ORs for breast cancer for a 1 SD increase in DV were 1.39, 1.33, and 1.51 for premenopausal (pinteraction = 0.58), and 1.31, 1.34, and 1.65 (pinteraction = 0.03) for postmenopausal women for BMI < 25, 25-30 and ≥ 30 kg/m2, respectively. CONCLUSIONS: The effect of volumetric percent density on breast cancer risk is strongest in overweight and obese women. These associations have clinical relevance for informing prevention strategies.

10.
Obstet Gynecol ; 133(6): 1247-1254, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31135741

RESUMO

OBJECTIVE: To determine the effect of tubal ligation on age at natural menopause, as a marker of long-term ovarian function. METHODS: Three preexisting population-based cohorts were included in this cross-sectional study. Data from each cohort was analyzed separately. The cohorts were restricted to women who never smoked and had reached natural menopause, without prior hysterectomy or oophorectomy. The following variables were collected: race, age at menarche, age at menopause, history of hysterectomy or oophorectomy, gravidity and parity, tobacco use, and ever use of hormonal contraception. The type of tubal ligation and age at tubal ligation were manually abstracted in cohort 1. For cohorts 2 and 3, history of tubal ligation was obtained from an institutional form, completed by patient report. The primary outcome, age at natural menopause, was compared between the two groups (those with and without a history of tubal ligation). RESULTS: Inclusion criteria was met by 555 women from cohort 1, 1,816 women from cohort 2, and 1,534 women from cohort 3. Baseline characteristics did not differ between cohorts. The percentage with tubal ligation was the same in all cohorts: 26.0%, 25.5%, and 25.0%, respectively. Women with a tubal ligation were more likely to have had at least one pregnancy and to have used hormonal contraception compared with women without a tubal ligation. There was no significant difference in age at natural menopause in women who underwent tubal ligation (50.1, 49.9, 50.0 years, respectively) compared with those who did not (50.7, 49.6, 50.0 years, respectively). The type of tubal ligation (cohort 1 only) had no effect on age at menopause. CONCLUSIONS: Tubal ligation did not affect age at natural menopause in the three large cohorts included in this study.

11.
Breast Cancer Res ; 21(1): 68, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118087

RESUMO

BACKGROUND: Mammographic breast density, adjusted for age and body mass index, and a polygenic risk score (PRS), comprised of common genetic variation, are both strong risk factors for breast cancer and increase discrimination of risk models. Understanding their joint contribution will be important to more accurately predict risk. METHODS: Using 3628 breast cancer cases and 5126 controls of European ancestry from eight case-control studies, we evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS and quantitative mammographic density measures with breast cancer. Mammographic percent density and absolute dense area were evaluated using thresholding software and examined as residuals after adjusting for age, 1/BMI, and study. PRS and adjusted density phenotypes were modeled both continuously (per 1 standard deviation, SD) and categorically. We fit logistic regression models and tested the null hypothesis of multiplicative joint associations for PRS and adjusted density measures using likelihood ratio and global and tail-based goodness of fit tests within the subset of six cohort or population-based studies. RESULTS: Adjusted percent density (odds ratio (OR) = 1.45 per SD, 95% CI 1.38-1.52), adjusted absolute dense area (OR = 1.34 per SD, 95% CI 1.28-1.41), and the 77-SNP PRS (OR = 1.52 per SD, 95% CI 1.45-1.59) were associated with breast cancer risk. There was no evidence of interaction of the PRS with adjusted percent density or dense area on risk of breast cancer by either the likelihood ratio (P > 0.21) or goodness of fit tests (P > 0.09), whether assessed continuously or categorically. The joint association (OR) was 2.60 in the highest categories of adjusted PD and PRS and 0.34 in the lowest categories, relative to women in the second density quartile and middle PRS quintile. CONCLUSIONS: The combined associations of the 77-SNP PRS and adjusted density measures are generally well described by multiplicative models, and both risk factors provide independent information on breast cancer risk.

12.
Breast Cancer Res ; 21(1): 48, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944014

RESUMO

BACKGROUND: Obesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. However, their joint effects on ER subtype-specific risk are unknown. Understanding this relationship could enhance risk stratification for screening and prevention. Thus, we assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status. METHODS: We conducted a case-control study nested within two mammography screening cohorts, the Mayo Mammography Health Study and the San Francisco Bay Area Breast Cancer SPORE/San Francisco Mammography Registry. Our pooled analysis contained 1538 ER-positive and 285 ER-negative invasive breast cancer cases and 4720 controls matched on age, menopausal status at time of mammogram, and year of mammogram. Percent density was measured on digitized film mammograms using computer-assisted techniques. We used polytomous logistic regression to evaluate the association between percent density and ER subtype by BMI subgroup (normal/underweight, < 25 kg/m2 versus overweight/obese, ≥ 25 kg/m2). We used Wald chi-squared tests to assess for interactions between percent density and BMI. Our analysis was stratified by menopausal status and hormone therapy usage at the time of index mammogram. RESULTS: Percent density was associated with increased risk of overall breast cancer regardless of menopausal status or BMI. However, when analyzing breast cancer across ER subtype, we found a statistically significant (p = 0.008) interaction between percent density and BMI in premenopausal women only. Specifically, elevated percent density was associated with a higher risk of ER-negative than ER-positive cancer in overweight/obese premenopausal women [OR per standard deviation increment 2.17 (95% CI 1.50-3.16) vs 1.33 (95% CI 1.11-1.61) respectively, Pheterogeneity = 0.01]. In postmenopausal women, elevated percent density was associated with similar risk of ER-positive and ER-negative cancers, and no substantive differences were seen after accounting for BMI or hormone therapy usage. CONCLUSIONS: The combination of overweight/obesity and elevated breast density in premenopausal women is associated with a higher risk of ER-negative compared with ER-positive cancer. Eighteen percent of premenopausal women in the USA have elevated BMI and breast density and may benefit from lifestyle modifications involving weight loss and exercise.

13.
Breast Cancer Res ; 21(1): 38, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30850011

RESUMO

BACKGROUND: High background parenchymal uptake (BPU) on molecular breast imaging (MBI) has been identified as a breast cancer risk factor. We explored the feasibility of offering a short-term intervention of low-dose oral tamoxifen to women with high BPU and examined whether this intervention would reduce BPU. METHODS: Women with a history of high BPU and no breast cancer history were invited to the study. Participants had an MBI exam, followed by 30 days of low-dose oral tamoxifen at either 5 mg or 10 mg/day, and a post-tamoxifen MBI exam. BPU on pre- and post-tamoxifen MBI exams was quantitatively assessed as the ratio of average counts in breast fibroglandular tissue vs. average counts in subcutaneous fat. Pre-tamoxifen and post-tamoxifen BPU were compared with paired t tests. RESULTS: Of 47 women invited, 22 enrolled and 21 completed the study (10 taking 5 mg tamoxifen, 11 taking 10 mg tamoxifen). Mean age was 47.7 years (range 41-56 years). After 30 days low-dose tamoxifen, 8 of 21 women (38%) showed a decline in BPU, defined as a decrease from the pre-tamoxifen MBI of at least 15%; 11 of 21 (52%) had no change in BPU (within ± 15%); 2 of 21 (10%) had an increase in BPU of greater than 15%. Overall, the average post-tamoxifen BPU was not significantly different from pre-tamoxifen BPU (1.34 post vs. 1.43 pre, p = 0.11). However, among women taking 10 mg tamoxifen, 5 of 11 (45%) showed a decline in BPU; average BPU was 1.19 post-tamoxifen vs. 1.34 pre-tamoxifen (p = 0.005). In women taking 5 mg tamoxifen, 2 of 10 (20%) showed a decline in BPU; average BPU was 1.51 post-tamoxifen vs.1.53 pre-tamoxifen (p = 0.99). CONCLUSIONS: Short-term intervention with low-dose tamoxifen may reduce high BPU on MBI for some patients. Our preliminary findings suggest that 10 mg tamoxifen per day may be more effective than 5 mg for inducing declines in BPU within 30 days. Given the variability in BPU response to tamoxifen observed among study participants, future study is warranted to determine if BPU response could predict the effectiveness of tamoxifen for breast cancer risk reduction within an individual. TRIAL REGISTRATION: ClinicalTrials.gov NCT02979301 . Registered 01 December 2016.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Mamografia/métodos , Imagem Molecular/métodos , Tamoxifeno/administração & dosagem , Administração Oral , Adulto , Mama/patologia , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/patologia , Estudos de Viabilidade , Feminino , Câmaras gama , Humanos , Mamografia/instrumentação , Pessoa de Meia-Idade , Imagem Molecular/instrumentação , Projetos Piloto , Estudos Prospectivos , Cintilografia/instrumentação , Cintilografia/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Tecnécio Tc 99m Sestamibi/administração & dosagem , Fatores de Tempo
14.
Mayo Clin Proc ; 94(3): 465-471, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30713046

RESUMO

OBJECTIVE: To determine the incidence of immunoglobulin light chain amyloidosis (AL amyloidosis) in a strictly defined geographic area from 1990 through 2015. PATIENTS AND METHODS: We searched a computerized database for the records of all Olmsted County, Minnesota, residents with a diagnosis of AL amyloidosis from January 1, 1990, through December 31, 2015. In addition, records of all residents with a mention of amyloidosis were obtained from the Rochester Epidemiology Project, which contains the medical records of Mayo Clinic and Olmsted Medical Group. The diagnosis of AL amyloidosis was determined by mass spectrometry, immunohistochemical analysis, or positive Congo red staining. RESULTS: Thirty-five patients were identified as having AL amyloidosis. The median age at diagnosis was 76 years (range, 38-90 years), with men accounting for 54%. The incidence rate of AL amyloidosis from 1990 through 2015 adjusted for age and sex was 1.2 per 100,000 person-years (95% CI, 0.8-1.6 per 100,000 person-years). Rates were similar across the decades 1990-1999, 2000-2009, and 2010-2015 at 1.1, 0.9, and 1.6 per 100,000 person-years, respectively, with no suggestion of an increasing rate during the 26 years. There was a trend toward an increasing incidence over time from 1950 through 2015 in Olmsted County, but it was not significant (P=.15). Applying the rate of 1.2 per 100,000 person-years to the US population of 321 million in 2015, one would expect 3852 new cases of AL amyloidosis in the United States each year. CONCLUSION: The incidence of AL amyloidosis in Olmsted County has not changed significantly in the past 66 years.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/epidemiologia , Registros Médicos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloide/análise , Anticorpos Monoclonais/análise , Feminino , Humanos , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Distribuição por Sexo
15.
Leukemia ; 33(2): 499-507, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30201985

RESUMO

We and others have shown increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first-degree relatives of patients with multiple myeloma (MM). Whether familial risk of MGUS differs by the MM proband's age at onset, tumor or clinical characteristics is unknown. MM and smoldering MM (SMM) cases (N = 430) were recruited from the Mayo Clinic in Rochester, Minnesota between 2005-2015. First-degree relatives over age 40 provided serum samples for evaluation of MGUS (N = 1179). Age and sex specific rates of MGUS among first-degree relatives were compared to a population-based sample. Cytogenetic subtypes were classified by Fluorescence in situ hybridization. MGUS was detected in 75 first-degree relatives for an age- and sex- adjusted prevalence of 5.8% (95% CI: 4.5-7.2). Prevalence of MGUS in first-degree relatives was 2.4 fold (95% CI: 1.9-2.9) greater than expected rates. Familial risk did not differ by proband's age at diagnosis, gender, isotype, IgH translocation, or trisomy. This study confirms first-degree relatives of MM cases have a significantly higher risk of MGUS compared to the general population, regardless of age, gender, or tumor characteristics. In selected situations, such as multiple affected first-degree relatives, screening of first-degree relatives of MM cases could be considered for follow-up and prevention strategies.


Assuntos
Proteínas Sanguíneas/análise , Isotipos de Imunoglobulinas/genética , Gamopatia Monoclonal de Significância Indeterminada/patologia , Mieloma Múltiplo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Família , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/etiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Prevalência , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologia
16.
Breast Cancer Res Treat ; 173(3): 667-677, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30387004

RESUMO

PURPOSE: In post-menopausal women, high body mass index (BMI) is an established breast cancer risk factor and is associated with worse breast cancer prognosis. We assessed the associations between BMI and gene expression of both breast tumor and adjacent tissue in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) diseases to help elucidate the mechanisms linking obesity with breast cancer biology in 519 post-menopausal women from the Nurses' Health Study (NHS) and NHSII. METHODS: Differential gene expression was analyzed separately in ER+ and ER- disease both comparing overweight (BMI ≥ 25 to < 30) or obese (BMI ≥ 30) women to women with normal BMI (BMI < 25), and per 5 kg/m2 increase in BMI. Analyses controlled for age and year of diagnosis, physical activity, alcohol consumption, and hormone therapy use. Gene set enrichment analyses were performed and validated among a subset of post-menopausal cases in The Cancer Genome Atlas (for tumor) and Polish Breast Cancer Study (for tumor-adjacent). RESULTS: No gene was differentially expressed by BMI (FDR < 0.05). BMI was significantly associated with increased cellular proliferation pathways, particularly in ER+ tumors, and increased inflammation pathways in ER- tumor and ER- tumor-adjacent tissues (FDR < 0.05). High BMI was associated with upregulation of genes involved in epithelial-mesenchymal transition in ER+ tumor-adjacent tissues. CONCLUSIONS: This study provides insights into molecular mechanisms of BMI influencing post-menopausal breast cancer biology. Tumor and tumor-adjacent tissues provide independent information about potential mechanisms.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Pós-Menopausa , Adulto , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Biologia Computacional/métodos , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Vigilância em Saúde Pública , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Transcriptoma
17.
Radiology ; 290(1): 41-49, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30375931

RESUMO

Purpose To identify phenotypes of mammographic parenchymal complexity by using radiomic features and to evaluate their associations with breast density and other breast cancer risk factors. Materials and Methods Computerized image analysis was used to quantify breast density and extract parenchymal texture features in a cross-sectional sample of women screened with digital mammography from September 1, 2012, to February 28, 2013 (n = 2029; age range, 35-75 years; mean age, 55.9 years). Unsupervised clustering was applied to identify and reproduce phenotypes of parenchymal complexity in separate training (n = 1339) and test sets (n = 690). Differences across phenotypes by age, body mass index, breast density, and estimated breast cancer risk were assessed by using Fisher exact, χ2, and Kruskal-Wallis tests. Conditional logistic regression was used to evaluate preliminary associations between the detected phenotypes and breast cancer in an independent case-control sample (76 women diagnosed with breast cancer and 158 control participants) matched on age. Results Unsupervised clustering in the screening sample identified four phenotypes with increasing parenchymal complexity that were reproducible between training and test sets (P = .001). Breast density was not strongly correlated with phenotype category (R2 = 0.24 for linear trend). The low- to intermediate-complexity phenotype (prevalence, 390 of 2029 [19%]) had the lowest proportion of dense breasts (eight of 390 [2.1%]), whereas similar proportions were observed across other phenotypes (from 140 of 291 [48.1%] in the high-complexity phenotype to 275 of 511 [53.8%] in the low-complexity phenotype). In the independent case-control sample, phenotypes showed a significant association with breast cancer (P = .001), resulting in higher discriminatory capacity when added to a model with breast density and body mass index (area under the curve, 0.84 vs 0.80; P = .03 for comparison). Conclusion Radiomic phenotypes capture mammographic parenchymal complexity beyond conventional breast density measures and established breast cancer risk factors. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Pinker in this issue.


Assuntos
Densidade da Mama/fisiologia , Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Mamografia/métodos , Adulto , Idoso , Estudos de Casos e Controles , Análise por Conglomerados , Detecção Precoce de Câncer , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco
18.
Blood Cancer J ; 8(10): 96, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305608

RESUMO

Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Variação Genética , Paraproteinemias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Bandeamento Cromossômico , Progressão da Doença , Feminino , Rearranjo Gênico , Genes myc , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Razão de Chances , Paraproteinemias/diagnóstico
19.
Cancer Epidemiol Biomarkers Prev ; 27(11): 1307-1319, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30018149

RESUMO

Cohort studies have been central to the establishment of the known causes of cancer. To dissect cancer etiology in more detail-for instance, for personalized risk prediction and prevention, assessment of risks of subtypes of cancer, and assessment of small elevations in risk-there is a need for analyses of far larger cohort datasets than available in individual existing studies. To address these challenges, the NCI Cohort Consortium was founded in 2001. It brings together 58 cancer epidemiology cohorts from 20 countries to undertake large-scale pooling research. The cohorts in aggregate include over nine million study participants, with biospecimens available for about two million of these. Research in the Consortium is undertaken by >40 working groups focused on specific cancer sites, exposures, or other research areas. More than 180 publications have resulted from the Consortium, mainly on genetic and other cancer epidemiology, with high citation rates. This article describes the foundation of the Consortium; its structure, governance, and methods of working; the participating cohorts; publications; and opportunities. The Consortium welcomes new members with cancer-oriented cohorts of 10,000 or more participants and an interest in collaborative research. Cancer Epidemiol Biomarkers Prev; 27(11); 1307-19. ©2018 AACR.


Assuntos
Estudos de Coortes , Humanos , National Cancer Institute (U.S.) , Estados Unidos
20.
Cancer ; 124(16): 3319-3328, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29932456

RESUMO

BACKGROUND: More than 1.5 million women per year have a benign breast biopsy resulting in concern about their future breast cancer (BC) risk. This study examined the performance of 2 BC risk models that integrate clinical and histologic findings in this population. METHODS: The BC risk at 5 and 10 years was estimated with the Breast Cancer Surveillance Consortium (BCSC) and Benign Breast Disease to Breast Cancer (BBD-BC) models for women diagnosed with benign breast disease (BBD) at the Mayo Clinic from 1997 to 2001. Women with BBD were eligible for the BBD-BC model, but the BCSC model also required a screening mammogram. Calibration and discrimination were assessed. RESULTS: Fifty-six cases of BC were diagnosed among the 2142 women with BBD (median age, 50 years) within 5 years (118 were diagnosed within 10 years). The BBD-BC model had slightly better calibration at 5 years (0.89; 95% confidence interval [CI], 0.71-1.21) versus 10 years (0.81; 95% CI, 0.70-1.00) but similar discrimination in the 2 time periods: 0.68 (95% CI, 0.60-0.75) and 0.66 (95% CI, 0.60-0.71), respectively. In contrast, among the 1089 women with screening mammograms (98 cases of BC within 10 years), the BCSC model had better calibration (0.94; 95% CI, 0.85-1.43) and discrimination (0.63; 95% CI, 0.56-0.71) at 10 years versus 5 years (calibration, 1.31; 95% CI, 0.94-2.25; discrimination, 0.59; 95% CI, 0.46-0.71) where discrimination was not different from chance. CONCLUSIONS: The BCSC and BBD-BC models were validated in the Mayo BBD cohort, although their performance differed by 5-year risk versus 10-year risk. Further enhancement of these models is needed to provide accurate BC risk estimates for women with BBD.


Assuntos
Doenças Mamárias/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias/epidemiologia , Medição de Risco , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Mama/patologia , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias/patologia , Fatores de Risco , Adulto Jovem
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