JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Comparison of sound speed measurements on two different ultrasound tomography devices.
Proc Soc Photo Opt Instrum Eng
PUBLISHED: 10-14-2014
Show Abstract
Hide Abstract
Ultrasound tomography (UST) employs sound waves to produce three-dimensional images of breast tissue and precisely measures the sound speed of breast tissue composition. High breast density is a strong breast cancer risk factor and sound speed is directly proportional to breast density. UST provides a quantitative measure of breast density based on three-dimensional imaging without compression, thereby overcoming the shortcomings of many other imaging modalities. The quantitative nature of the UST breast density measures are tied to an external standard, so sound speed measurement in breast tissue should be independent of specific hardware. The work presented here compares breast sound speed measurement obtained with two different UST devices. The Computerized Ultrasound Risk Evaluation (CURE) system located at the Karmanos Cancer Institute in Detroit, Michigan was recently replaced with the SoftVue ultrasound tomographic device. Ongoing clinical trials have used images generated from both sets of hardware, so maintaining consistency in sound speed measurements is important. During an overlap period when both systems were in the same exam room, a total of 12 patients had one or both of their breasts imaged on both systems on the same day. There were 22 sound speed scans analyzed from each system and the average breast sound speeds were compared. Images were either reconstructed using saved raw data (for both CURE and SoftVue) or were created during the image acquisition (saved in DICOM format for SoftVue scans only). The sound speed measurements from each system were strongly and positively correlated with each other. The average difference in sound speed between the two sets of data was on the order of 1-2 m/s and this result was not statistically significant. The only sets of images that showed a statistical difference were the DICOM images created during the SoftVue scan compared to the SoftVue images reconstructed from the raw data. However, the discrepancy between the sound speed values could be easily handled by uniformly increasing the DICOM sound speed by approximately 0.5 m/s. These results suggest that there is no fundamental difference in sound speed measurement for the two systems and support combining data generated with these instruments in future studies.
Related JoVE Video
Terminal duct lobular unit involution of the normal breast: implications for breast cancer etiology.
J. Natl. Cancer Inst.
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
Greater degrees of terminal duct lobular unit (TDLU) involution have been linked to lower breast cancer risk; however, factors that influence this process are poorly characterized.
Related JoVE Video
Benign Breast Tissue Composition in Breast Cancer Patients: Association with Risk Factors, Clinical Variables, and Gene Expression.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 09-23-2014
Show Abstract
Hide Abstract
Breast tissue composition (epithelium, non-fatty stroma, and adipose) changes qualitatively and quantitatively throughout the lifespan, and may mediate relationships between risk factors and breast cancer initiation. We sought to identify relationships between tissue composition, risk factors, tumor characteristics, and gene expression.
Related JoVE Video
Relationships between computer-extracted mammographic texture pattern features and BRCA1/2 mutation status: a cross-sectional study.
Breast Cancer Res.
PUBLISHED: 08-23-2014
Show Abstract
Hide Abstract
Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers.
Related JoVE Video
Comparison of Mammographic Density Assessed as Volumes and Areas among Women Undergoing Diagnostic Image-Guided Breast Biopsy.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
Mammographic density (MD), the area of non-fatty-appearing tissue divided by total breast area, is a strong breast cancer risk factor. Most MD analyses have used visual categorizations or computer-assisted quantification, which ignore breast thickness. We explored MD volume and area, using a volumetric approach previously validated as predictive of breast cancer risk, in relation to risk factors among women undergoing breast biopsy.
Related JoVE Video
Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk.
Nat Commun
PUBLISHED: 03-14-2014
Show Abstract
Hide Abstract
Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5 × 10(-8)) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B and SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23 and TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease-susceptibility loci.
Related JoVE Video
Breast cancer risk in older women: results from the NIH-AARP Diet and Health Study.
Cancer Causes Control
PUBLISHED: 02-27-2014
Show Abstract
Hide Abstract
Divergent risk factors exist for premenopausal and postmenopausal breast cancers, but it is unclear whether differences by age exist among postmenopausal women.
Related JoVE Video
Cigarette smoking and endometrial carcinoma risk: the role of effect modification and tumor heterogeneity.
Cancer Causes Control
PUBLISHED: 01-18-2014
Show Abstract
Hide Abstract
The inverse relationship between cigarette smoking and endometrial carcinoma risk is well established. We examined effect modification of this relationship and associations with tumor characteristics in the National Institutes of Health-AARP Diet and Health Study.
Related JoVE Video
Circulating estrogens and estrogens within the breast among postmenopausal BRCA1/2 mutation carriers.
Breast Cancer Res. Treat.
PUBLISHED: 01-18-2014
Show Abstract
Hide Abstract
Accurately quantifying parent estrogens (PE) estrone (E1) and estradiol (E2) and their metabolites (EM) within breast tissue and serum may permit detailed investigations of their contributions to breast carcinogenesis among BRCA1/2 mutation carriers. We conducted a study of PE/EM in serum, nipple aspirate fluid (NAF), and ductal lavage supernatant (DLS) among postmenopausal BRCA1/2 mutation carriers. PE/EM (conjugated and unconjugated) were measured in paired serum/NAF (n = 22 women) and paired serum/DLS samples (n = 24 women) using quantitative liquid chromatography-tandem mass spectrometry (LC/MS/MS). The relationships between serum and tissue-specific PE/EM were measured using Pearson's correlation coefficients. Conjugated forms of PE/EM constituted the majority of estrogen in serum (88 %), NAF (59 %) and DLS (69 %). PE/EM in NAF and serum were highly correlated [E1 (r = 0.97, p < 0.0001), E2 (r = 0.90, p < 0.0001) and estriol (E3) (r = 0.74, p < 0.0001)] as they were in DLS and serum [E1 (r = 0.92, p < 0.0001; E2 (r = 0.70, p = 0.0001; E3 (r = 0.67, p = 0.0004)]. Analyses of paired total estrogen values for NAF and serum, and DLS and serum yielded ratios of 0.22 (95 % CI 0.19-0.25) and 0.28 (95 % CI 0.24-0.32), respectively. This report is the first to employ LC/MS/MS to quantify PE/EM in novel breast tissue-derived biospecimens (i.e., NAF and DLS). We demonstrate that circulating PE and EM are strongly and positively correlated with tissue-specific PE and EM measured in NAF and DLS among postmenopausal BRCA1/2 mutation carriers. If confirmed, future etiologic studies could utilize the more readily obtainable serum hormone levels as a reliable surrogate measure of exposure at the tissue level.
Related JoVE Video
Relationship of mammographic density and gene expression: analysis of normal breast tissue surrounding breast cancer.
Clin. Cancer Res.
PUBLISHED: 08-05-2013
Show Abstract
Hide Abstract
Previous studies of breast tissue gene expression have shown that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 patients with breast cancer from the population-based Polish Womens Breast Cancer Study.
Related JoVE Video
Large-scale genotyping identifies a new locus at 22q13.2 associated with female breast size.
J. Med. Genet.
PUBLISHED: 07-03-2013
Show Abstract
Hide Abstract
Individual differences in breast size are a conspicuous feature of variation in human females and have been associated with fecundity and advantage in selection of mates. To identify common variants that are associated with breast size, we conducted a large-scale genotyping association meta-analysis in 7169 women of European descent across three independent sample collections with digital or screen film mammograms.
Related JoVE Video
Risk factors for specific histopathological types of postmenopausal breast cancer in the NIH-AARP Diet and Health Study.
Am. J. Epidemiol.
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
Risk factor associations for rare breast cancer variants are often imprecise, obscuring differences between tumor types. To clarify differences, we examined risk factors for 5 histological types of breast cancer in the National Institutes of Health-AARP Diet and Health Study. Risk factor information was self-reported. We followed 192,076 postmenopausal women aged 50-71 years from 1995-1996 through 2006. During that time period, 5,334 ductal, 836 lobular, 639 mixed ductal-lobular, 216 mucinous, and 132 tubular breast cancers were diagnosed. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Heterogeneity was evaluated using case-only logistic regression. The strongest differences were for menopausal hormone therapy (Pheterogeneity < 0.01) and age at first birth (Pheterogeneity < 0.01). Risk of tubular cancer in relation to current menopausal hormone therapy (for current use vs. never use, hazard ratio (HR) = 4.39, 95% confidence interval (CI): 2.77, 6.96) was several times stronger than risk of other histological types (range of HRs, 1.39-1.75). Older age at first birth was unassociated with risk of mucinous (for ?30 years vs. 20-24 years, HR = 0.62, 95% CI: 0.27, 1.42) or tubular (HR = 1.08, 95% CI: 0.51, 2.29) tumors, in contrast to clear positive associations with lobular (HR = 1.82, 95% CI: 1.39, 2.37) and mixed ductal-lobular (HR = 1.87, 95% CI: 1.39, 2.51) tumors. Differing associations for hormonal factors and mucinous and tubular cancers suggest etiologies distinct from those of common breast cancers.
Related JoVE Video
Ovarian cancer incidence trends in relation to changing patterns of menopausal hormone therapy use in the United States.
J. Clin. Oncol.
PUBLISHED: 05-06-2013
Show Abstract
Hide Abstract
After a report from the Womens Health Initiative (WHI) in 2002, a precipitous decline in menopausal hormonal therapy (MHT) use in the United States was linked to a decline in breast cancer incidence rates. Given that MHT use is also associated with increased ovarian cancer risk, we tested whether ovarian cancer incidence rates changed after 2002.
Related JoVE Video
Erythrocyte omega-6 and omega-3 fatty acids and mammographic breast density.
Nutr Cancer
PUBLISHED: 03-28-2013
Show Abstract
Hide Abstract
Diets low in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high in omega-3 (n-3) PUFAs may protect against breast cancer development. Associations of PUFA intake with mammographic density, an intermediate marker of breast cancer risk, have been inconsistent; however, prior studies have relied on self-reported dietary PUFA intake. We examined the association between circulating erythrocyte n-6 and n-3 PUFAs with mammographic density in 248 postmenopausal women who were not taking exogenous hormones. PUFAs in erythrocytes were measured by gas-liquid chromatography, and mammographic density was assessed quantitatively by planimetry. Spearmans correlation coefficients and generalized linear models were used to evaluate the relationships between PUFA measures and mammographic density. None of the erythrocyte n-6 or n-3 PUFA measures were associated with percent density or dense breast area.
Related JoVE Video
Association between mammographic density and basal-like and luminal A breast cancer subtypes.
Breast Cancer Res.
PUBLISHED: 02-15-2013
Show Abstract
Hide Abstract
Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer.
Related JoVE Video
Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study.
Breast Cancer Res.
PUBLISHED: 01-17-2013
Show Abstract
Hide Abstract
INTRODUCTION: Elevated levels of circulating estrogens are linked to breast cancer risk among postmenopausal women but little is known about the importance of estrogen metabolism. A recently developed liquid chromatography tandem mass spectrometry-based method (LC-MS/MS) measuring a panel of 15 estrogen metabolites (EM) has been evaluated in one study, linking high levels of 2-pathway metabolites relative to the parent estrogens to reduced breast cancer risk. We analyzed this panel of EM in a nested case-control study of postmenopausal breast cancer. METHODS: Between 1977 and 1987, 6915 women provided blood samples to the Columbia Missouri Serum Bank and were followed for incident breast cancer through December 2002. We studied 215 postmenopausal breast cancer cases and 215 matched controls that were postmenopausal and not using exogenous hormones at the time of blood draw. EM were examined individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring), and by ratios of the groupings. Logistic regression models controlling for matching and breast cancer risk factors were used to calculate quartile-specific odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Significant elevated risks were not observed for individual EM, except for quartiles of 16-epiestriol (p trend =0.07). OR for total EM, the parent estrogens estrone and estradiol, and 2-pathway catechol EM (2-hydroxyestrone and 2-hydroxyestradiol) were elevated but trends were not statistically significant. Among 2-pathway metabolites, risks for the highest levels of 2-hydroxyestrone-3-methyl ether, and 2-methoxyestradiol were reduced; ORs for women in the highest vs. lowest quartiles were 0.57 (95% CI=0.33-0.99) and 0.53 (95% CI=0.30-0.96), respectively. Overall, women with higher levels of 2-pathway EM had a reduced risk of breast cancer, which remained after accounting for levels of parent EM, 4-pathway EM, and 16-pathway EM (all trends, p<0.11). CONCLUSIONS: Women with more extensive hydroxylation along the 2-pathway may have a reduced risk of postmenopausal breast cancer. Further studies are needed to clarify the risks for specific EM and complex patterns of estrogen metabolism. This will require aggregation of EM results from several studies.
Related JoVE Video
Prediagnosis body mass index, physical activity, and mortality in endometrial cancer patients.
J. Natl. Cancer Inst.
PUBLISHED: 01-07-2013
Show Abstract
Hide Abstract
Background Higher body mass index (BMI) and inactivity have been associated with a higher risk of developing endometrial cancer, but the impact on endometrial cancer survival is unclear. Methods Among incident endometrial cancer case subjects in the National Institutes of Health-AARP Diet and Health Study, we examined associations of prediagnosis BMI (n = 1400) and physical activity (n = 875) with overall and disease-specific 5- and 10-year mortality. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for tumor characteristics, treatment, and other risk factors. All statistical tests were two-sided. Results Compared with women with a BMI in the range of 18.5 to less than 25kg/m(2), the hazard ratios for 5-year all-cause mortality were 1.74 (95% CI = 1.13 to 2.66) for BMI in the range of 25 to less than 30kg/m(2), 1.84 (95% CI = 1.17 to 2.88) for BMI in the range of 30 to less than 35kg/m(2), and 2.35 (95% CI = 1.48 to 3.73) for BMI greater than or equal to 35kg/m(2) (P trend < .001). Higher BMI was also statistically significantly associated with poorer endometrial cancer-specific but not cardiovascular disease 5-year mortality. Hazard ratio estimates for 10-year all-cause and endometrial cancer-specific mortality as related to BMI were similar to 5-year hazard ratio estimates, whereas 10-year cardiovascular disease mortality became statistically significant (HR = 4.08; 95% CI = 1.56 to 10.71 comparing extreme BMI groups). More physical activity was related to lower all-cause 5-year mortality (HR = 0.57, 95% CI = 0.33 to 0.98 for >7 hours/week vs never/rarely), but the association was attenuated after adjustment for BMI (HR = 0.64, 95% CI = 0.37 to 1.12). No association was observed between physical activity and disease-specific mortality. Conclusions Our findings suggest that higher prediagnosis BMI increases risk of overall and disease-specific mortality among women diagnosed with endometrial cancer, whereas physical activity lowers risk. Intervention studies of the effect of these modifiable lifestyle factors on mortality are needed.
Related JoVE Video
Beyond breast cancer: mammographic features and mortality risk in a population of healthy women.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Breast fibroglandular (dense) tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features.
Related JoVE Video
Anthropometric measures and physical activity and the risk of lung cancer in never-smokers: a prospective cohort study.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Worldwide, lung cancer in never-smokers is ranked the seventh most common cause of cancer death; however, the etiology of lung cancer in never-smokers is unclear. We investigated associations for body mass index (BMI) at various ages, waist circumference, hip circumference, and physical activity with lung cancer in 158,415 never-smokers of the NIH-AARP Diet and Health Study. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated from Cox proportional hazards models. Over 11 years of follow-up, 532 lung cancer cases occurred. The risk estimate for obese (BMI ? 30 kg/m(2)) participants at baseline was 1.21 (95%CI = 0.95-1.53) relative to those with a normal BMI between 18.5 ? BMI<25.0. Overweight (25.0 ? BMI<30.0) at age 18 (HR(overweight-vs-normal) = 1.51;95%CI = 1.01-2.26) and time spent sitting (HR(? 3 hrs-vs-<3 hrs) = 1.32;95%CI = 1.00-1.73) was each associated with lung cancer after adjustment for baseline BMI, as was waist (HR(Q4-vs-Q1) = 1.75;95%CI = 1.09-2.79) and hip circumference (HRQ4-vs-Q1 = 0.62;95%CI = 0.39-0.99), after mutual adjustment for each other and baseline BMI. No associations were observed for vigorous activity or television watching. In summary, using a large prospective cohort study, we found no evidence that BMI at baseline or middle age was associated with decreased lung cancer risk in never smokers. If anything, we observed some evidence for positive associations with a larger BMI or waist circumference.
Related JoVE Video
Reproductive and hormonal factors and lung cancer risk in the NIH-AARP Diet and Health Study cohort.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 04-05-2011
Show Abstract
Hide Abstract
Lung cancer exhibits unique patterns among women including high adenocarcinoma rates among nonsmokers. Inconsistent findings about hormonal factors on risk may reflect incomplete control for confounding, misclassification of exposures, or insufficient attention to variation by histology.
Related JoVE Video
Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort.
Int. J. Cancer
PUBLISHED: 03-05-2011
Show Abstract
Hide Abstract
There are several biologic mechanisms whereby coffee might reduce breast cancer risk. Caffeine and caffeic acid, major coffee constituents, have been shown to suppress mammary tumor formation in animal models and to inhibit DNA methylation in human breast cancer cells, respectively. Coffee may also reduce risk through decreasing inflammation and influencing estrogen metabolism. However, epidemiologic studies have been inconsistent and few studies have examined the association by estrogen and progesterone receptor (ER/PR) status. We evaluated coffee intake for its effect on incident breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort, which included 198,404 women aged 50-71 with no history of cancer, who in 1995-1996 completed a questionnaire capturing usual coffee intake over the past year. State cancer registry and mortality index linkage identified 9,915 primary incident breast carcinomas through December 2006; available information on hormone receptor (HR) status identified 2,051 ER+/PR+ and 453 ER-/PR- cancers. In multivariable proportional hazards models, coffee intake was not associated with breast cancer risk (p-value for trend = 0.38; relative risk = 0.98, 95% confidence interval: 0.91-1.07, for four or more cups per day as compared to women who never drank coffee), and results did not vary by body mass index or history of benign breast biopsy (p-value for interaction > 0.10). We found no evidence of a relationship with either caffeinated or decaffeinated coffee. Null findings persisted for risk of both HR-positive and -negative breast cancers. These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis.
Related JoVE Video
Alcohol and endometrial cancer risk in the NIH-AARP diet and health study.
Int. J. Cancer
PUBLISHED: 06-22-2010
Show Abstract
Hide Abstract
Previous investigations have provided conflicting results regarding whether alcohol consumption affects endometrial cancer risk, although in many of these studies the highest category of alcohol intake examined was limited. Further, most were unable to resolve how alcohol associations are affected by beverage type, the presence of other endometrial cancer risk factors, or tumor characteristics. To address these issues, we prospectively evaluated the association between alcohol intake and incident endometrial cancer (n = 1,491) in a cohort of 114,414 US women enrolled in the NIH-AARP Diet and Health Study. We calculated relative risks (RR) and 95% confidence intervals (CI) using Cox proportional hazards regression. After adjustment for age, body mass index (BMI), smoking and other potential confounders, the multivariable RRs (and 95% CIs) compared with nondrinkers were 0.97 (0.87-1.09) for >0-<12 g of alcohol/day, 1.06 (0.87-1.31) for 12-<24 g/day and 0.93 (0.71-1.20) for ? 24 g/day (p trend = 0.90). There was, however, some suggestion of higher risks associated with alcohol consumption among lean women (BMI, <25) and users of menopausal hormone therapy, with significant interactions with both parameters (respective interaction p-values of 0.002 and 0.005). The relationship was also enhanced, albeit nonsignificantly so, for low grade cancers. Our results do not support that alcohol is a strong contributor to endometrial cancer risk, but slight risk increases may prevail among some users or for selected tumor characteristics.
Related JoVE Video
Epidemiology of triple negative breast cancers.
Breast Dis
PUBLISHED: 03-18-2010
Show Abstract
Hide Abstract
Triple negative (TN) breast cancers fail to express the three most common breast cancer receptors; i.e., estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Accumulating data demonstrate that epidemiological risk factor profiles also vary between TN (ER-PR-HER2-) and other breast cancers, especially the so-called Luminal A breast cancers (ER+PR ± HER2-) [1]. A more comprehensive understanding of the epidemiology of TN breast cancers has important public health implications for risk assessment [2], prevention and treatment. The epidemiology of TN breast cancers can be first understood in the age-related reproductive risk factor patterns for ER, PR, and HER2. For example, there is a clear and strong association between older age at diagnosis (and therefore postmenopausal status) and the development of ER positive, PR positive, and HER2 negative breast cancers. On the other hand, younger age at diagnosis (and premenopausal status) is related to the development of ER negative, PR negative, and HER2 positive breast cancers. This gives rise to the somewhat counterintuitive suggestion that menopause has a greater relative impact upon hormone receptor negative than positive breast cancers [3,4]. Throughout this review, we will primarily contrast ER-PR-HER2- (TN) with ER+PR ± HER2- (Luminal A) breast cancers. We will first summarize the population-based age-specific incidence rate patterns and clinical outcomes, and then will review the available analytical studies. Information sources for this review included the National Cancer Institutes Surveillance, Epidemiology, and End Results 13 Registries Public-Use Database [5], CANCERLIT, Index Medicus, and PubMed.
Related JoVE Video
Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?
Cancer Epidemiol
PUBLISHED: 02-22-2010
Show Abstract
Hide Abstract
Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years.
Related JoVE Video
Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 01-11-2010
Show Abstract
Hide Abstract
Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institutes Clinical Genetics Branchs Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Centers Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density.
Related JoVE Video
Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics.
Breast Cancer Res. Treat.
PUBLISHED: 10-06-2009
Show Abstract
Hide Abstract
The transforming growth factor beta (TGF-beta) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-beta signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case-control study conducted in Poland from 2000 to 2003. TGF-beta signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-beta1 (78%), TGF-beta2 (91%), TGF-beta3 (93%), TGF-betaR2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-beta1 was expressed in 32% of tumors. Expression of TGF-beta ligands (beta1, beta2, and beta3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-betaR2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-beta. In addition, expression of extracellular-TGF-beta1 (P = 0.005), TGF-betaR2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment.
Related JoVE Video
Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: the prospective NIH-AARP diet and health study.
BMC Cancer
PUBLISHED: 06-19-2009
Show Abstract
Hide Abstract
Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known.
Related JoVE Video
Nonsteroidal anti-inflammatory drug use and endometrial cancer risk in the NIH-AARP Diet and Health Study.
Cancer Prev Res (Phila)
PUBLISHED: 04-28-2009
Show Abstract
Hide Abstract
Chronic inflammation may play an etiologic role in endometrial cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammatory activity by inhibiting the proinflammatory cyclooxygenase enzymes and, therefore, may decrease cancer risk. However, few studies have examined the association between NSAID use and endometrial cancer. We conducted a prospective study among 72,524 women in the NIH-AARP Diet and Health Study. Women completed a questionnaire in 1996-1997 on lifestyle and health-related factors, including type and frequency of NSAID use within the past year, and were followed through 2003 by linkages to cancer registries and vital status databases. During 488,261 person-years of follow-up, there were 732 incident endometrial cancers. NSAID use, compared with nonuse of NSAIDs, was not significantly associated with endometrial cancer risk [relative risk (RR), 0.90; 95% confidence interval (95% CI), 0.74-1.09]. Null associations were also observed by type of NSAID use [aspirin only: RR, 0.88; 95% CI, 0.70-1.11; nonaspirin NSAID (NA-NSAID) only: RR, 1.01; 95% CI, 0.79-1.29; both aspirin and NA-NSAIDs: RR, 0.85; 95% CI, 0.68-1.06]. Generally, results were not statistically significant by frequency of use for aspirin or NA-NSAIDs. Results did not change when women with a history of heart disease, hypertension, or diabetes were excluded to minimize the potential for confounding by indication. Overall, our data do not support an association between aspirin or NA-NSAID use and endometrial cancer risk.
Related JoVE Video
Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical care system database.
Breast Cancer Res. Treat.
PUBLISHED: 03-12-2009
Show Abstract
Hide Abstract
The etiology of male breast cancer is largely unknown, reflecting its relative rarity. Although a number of previous studies have suggested relationships with a variety of medical conditions, the results have largely derived from case-control studies and may reflect recall biases. Within the large U.S. Veterans Affairs computerized medical care system database, we had the opportunity to access 26 million hospital discharge records over the period 1969-1996 and to relate various documented medical conditions to the risk of subsequent male breast cancer. This allowed us to calculate relative risks (RR) and 95% confidence intervals (CI) for male breast cancer associated with conditions occurring one or more years after initial hospitalization, adjusted for age, race, calendar year, duration of follow-up, and number of hospital visits. Among 4,501,578 men aged 18-100 years, a total of 642 cases of primary male breast cancer were identified (523 among whites, 119 among blacks). Medical conditions that were significantly related to risk were diabetes (RR 1.30, 95% CI 1.05-1.60), obesity (1.98, 1.55-2.54), orchitis/epididymitis (1.84, 1.10-3.08), Klinefelter syndrome (29.64, 12.26-71.68), and gynecomastia (5.86, 3.74-9.17). Additionally, among black patients, cholelithiasis emerged as a significant risk predictor (3.45, 1.59-7.47). Diseases that have previously been related to male breast cancer risk that were not supported by our study results included thyroid diseases, smoking-related conditions, liver cirrhosis, prostatic hyperplasia, and fractures. After adjustment for obesity, the association with diabetes disappeared, but that with gynecomastia persisted. In multivariate models that simultaneously considered all important medical predictors of risk, significant risks were seen for Klinefelter syndrome (16.83, 6.81-41.62), gynecomastia (5.08, 3.21-8.03), obesity (1.91, 1.50-2.44), and orchitis/epididymitis (1.80, 1.08-3.01). These results support previous speculations that male breast cancer is influenced not only by tissue at risk, but also by hormonal and inflammatory factors.
Related JoVE Video
Physical activity and postmenopausal breast cancer risk in the NIH-AARP diet and health study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-07-2009
Show Abstract
Hide Abstract
Although physical activity has been associated with reduced breast cancer risk, whether this association varies across breast cancer subtypes or is modified by reproductive and lifestyle factors is unclear.
Related JoVE Video
Physical activity, sedentary behavior, and endometrial cancer risk in the NIH-AARP Diet and Health Study.
Int. J. Cancer
PUBLISHED: 01-07-2009
Show Abstract
Hide Abstract
Consistent with a strong hormonal etiology, endometrial cancer is thought to be influenced by both obesity and physical activity. Although obesity has been consistently related to risk, associations with physical activity have been inconclusive. We examined relationships of activity patterns with endometrial cancer incidence in the NIH-AARP Diet and Health Study cohort, which included 109,621 women, ages 50-71, without cancer history, who in 1995-1996 completed a mailed baseline questionnaire capturing daily routine and vigorous (defined as any period of >or=20 min of activity at work or home causing increases in breathing, heart rate, or sweating) physical activity. A second questionnaire, completed by 70,351 women, in 1996-1997 collected additional physical activity information. State cancer registry linkage identified 1,052 primary incident endometrial cancers from baseline through December 31, 2003. In multivariate proportional hazards models, vigorous activity was inversely associated with endometrial cancer in a dose-response manner (p for trend = 0.02) (relative risk (RR) for >or=5 times/week vs. never/rarely = 0.77, 95% confidence interval (CI): 0.63-0.95); this association was more pronounced among overweight and obese women (body mass index >or=25; RR = 0.61, 95% CI: 0.47-0.79) than among lean women (body mass index <25; RR = 0.76, 95% CI: 0.52-1.10; p for interaction = 0.12). Although we observed no associations with light/moderate, daily routine or occupational physical activities, risk did increase with number of hours of daily sitting (p for trend = 0.02). Associations with vigorous activities, which may interact with body mass index, suggest directions for future research to clarify underlying biologic mechanisms, including those relating to hormonal alterations.
Related JoVE Video
Endometrial cancer risk factors by 2 main histologic subtypes: the NIH-AARP Diet and Health Study.
Am. J. Epidemiol.
Show Abstract
Hide Abstract
On the basis of clinical and pathologic criteria, endometrial carcinoma has been distinguished as types I (mainly endometrioid) and II (nonendometrioid). Limited data suggest that these subtypes have different risk factor profiles. The authors prospectively evaluated risk factors for types I (n = 1,312) and II (n = 138) incident endometrial carcinoma among 114,409 women in the National Institutes of Health (NIH)-AARP Diet and Health Study (1995-2006). For individual risk factors, relative risks were estimated with Cox regression by subtype, and P(heterogeneity) was assessed in case-case comparisons with type I as the referent. Stronger relations for type I versus Type II tumors were seen for menopausal hormone therapy use (relative risk (RR) of 1.18 vs. 0.84; P(heterogeneity) = 0.01) and body mass index of ?30 vs. <30 kg/m2 (RR of 2.93 vs. 1.83; P(heterogeneity) = 0.001). Stronger relations for type II versus type I tumors were observed for being black versus white (RR of 2.18 vs. 0.66; P(heterogeneity) = 0.0004) and having a family history of breast cancer (RR of 1.93 vs. 0.80; P(heterogeneity) = 0.002). Other risk factor associations were similar by subtype. In conclusion, the authors noted different risk factor associations for Types I and II endometrial carcinomas, supporting the etiologic heterogeneity of these tumors. Because of the limited number of Type II cancers, additional evaluation of risk factors will benefit from consortial efforts.
Related JoVE Video
Urinary estrogens and estrogen metabolites and mammographic density in premenopausal women.
Breast Cancer Res. Treat.
Show Abstract
Hide Abstract
Mammographic density is a strong and independent risk factor for breast cancer and is considered an intermediate marker of risk. The major predictors of premenopausal mammographic density, however, have yet to be fully elucidated. To test the hypothesis that urinary estrogen metabolism profiles are associated with mammographic density, we conducted a cross-sectional study among 352 premenopausal women in the Nurses Health Study II (NHSII). We measured average percent mammographic density using a computer-assisted method. In addition, we assayed 15 estrogens and estrogen metabolites (jointly termed EM) in luteal-phase urine samples. We used multivariable linear regression to quantify the association of average percent density with quartiles of each individual EM as well as the sum of all EM (total EM), EM groups defined by metabolic pathway, and pathway ratios. In multivariable models controlling for body mass index and other predictors of breast density, women in the top quartile of total EM had an average percent density 3.4 percentage points higher than women in the bottom quartile (95 % confidence interval: -1.1, 8.0; p trend = 0.08). A non-significant positive association was noted for the 2-hydroxylation pathway catechols (breast density was 4.0 percentage points higher in top vs. bottom quartile; p trend = 0.06). In general, we observed no associations with parent estrogens or the 4- or 16-hydroxylation pathways or pathway ratios. These results suggest that urinary luteal estrogen profiles are not strongly associated with premenopausal mammographic density. If these profiles are associated with breast cancer risk, they may not act through influences on breast density.
Related JoVE Video
Relationship between mammographic density and breast cancer death in the Breast Cancer Surveillance Consortium.
J. Natl. Cancer Inst.
Show Abstract
Hide Abstract
Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors.
Related JoVE Video
Mammographic density and breast cancer risk in White and African American Women.
Breast Cancer Res. Treat.
Show Abstract
Hide Abstract
Mammographic density is a strong risk factor for breast cancer, but limited data are available in African American (AA) women. We examined the association between mammographic density and breast cancer risk in AA and white women. Cases (n = 491) and controls (n = 528) were from the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). Mammographic density was reported to CMR using Breast Imaging Reporting and Data System (BI-RADS) categories. Increasing mammographic density was associated with increased breast cancer risk among all women. After adjusting for potential confounders, a monotonically increasing risk of breast cancer was observed between the highest versus the lowest BI-RADS density categories [OR = 2.45, (95 % confidence interval: 0.99, 6.09)]. The association was stronger in whites, with ~40 % higher risk among those with extremely dense breasts compared to those with scattered fibroglandular densities [1.39, (0.75, 2.55)]. In AA women, the same comparison suggested lower risk [0.75, (0.30, 1.91)]. Because age, obesity, and exogenous hormones have strong associations with breast cancer risk, mammographic density, and race in the CBCS, effect measure modification by these factors was considered. Consistent with previous literature, density-associated risk was greatest among those with BMI > 30 and current hormone users (P value = 0.02 and 0.01, respectively). In the CBCS, mammographic density is associated with increased breast cancer risk, with some suggestion of effect measure modification by race, although results were not statistically significant. However, exposures such as BMI and hormone therapy may be important modifiers of this association and merit further investigation.
Related JoVE Video
Accelerometer-based measures of active and sedentary behavior in relation to breast cancer risk.
Breast Cancer Res. Treat.
Show Abstract
Hide Abstract
Epidemiologic studies suggest that physical activity reduces breast cancer risk by 20-40 %. However, prior studies have relied on measures of self-report. In a population-based case-control study, we evaluated accelerometer measures of active and sedentary behavior in relation to breast cancer among 996 incident cases and 1,164 controls, residents of Warsaw, Poland (2000-2003), who were asked to wear an accelerometer for 7 days. Accelerometer values were averaged across valid wear days and summarized as overall activity (counts [ct]/min/day); in minutes spent in sedentary behavior (0-99 ct/min); and light (100-759 ct/min) and moderate-to-vigorous (760+ ct/min) activity. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression. Comparing women in the highest quartile (Q4) of activity to those in the lowest (Q1), time spent in moderate-to-vigorous activity was inversely associated with breast cancer odds after adjustment for known risk factors, sedentary behavior and wear time (OR(Q4vsQ1) 0.39, 95 % CI 0.27-0.56; P-trend < .0001). Sedentary time was positively associated with breast cancer, independent of moderate-to-vigorous activity (OR(Q4vsQ1) 1.81, 95 % CI 1.26-2.60; P-trend = 0.001). Light activity was not associated with breast cancer in multivariable models including both moderate-to-vigorous activity and sedentary behavior. Our findings support an inverse association between accelerometer-based measures of moderate-to-vigorous physical activity and breast cancer while also suggesting potential increases in risk with sedentary time.
Related JoVE Video
Estrogen metabolism and mammographic density in postmenopausal women: a cross-sectional study.
Cancer Epidemiol. Biomarkers Prev.
Show Abstract
Hide Abstract
Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD.
Related JoVE Video
Body mass index and risk of lung cancer among never, former, and current smokers.
J. Natl. Cancer Inst.
Show Abstract
Hide Abstract
Although obesity has been directly linked to the development of many cancers, many epidemiological studies have found that body mass index (BMI)--a surrogate marker of obesity--is inversely associated with the risk of lung cancer. These studies are difficult to interpret because of potential confounding by cigarette smoking, a major risk factor for lung cancer that is associated with lower BMI.
Related JoVE Video
Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk.
Cancer Epidemiol. Biomarkers Prev.
Show Abstract
Hide Abstract
Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures.
Related JoVE Video
Unopposed estrogen and estrogen plus progestin menopausal hormone therapy and lung cancer risk in the NIH-AARP Diet and Health Study Cohort.
Cancer Causes Control
Show Abstract
Hide Abstract
Previous studies have reported that lung cancer risk may be decreased, increased, or unaffected by prior use of menopausal hormone therapy (MHT).
Related JoVE Video
Long-term overall and disease-specific mortality associated with benign gynecologic surgery performed at different ages.
Menopause
Show Abstract
Hide Abstract
As bilateral salpingo-oophorectomy is frequently performed with hysterectomy for nonmalignant conditions, defining health outcomes associated with benign bilateral salpingo-oophorectomy performed at different ages is critical.
Related JoVE Video
Opportunities for molecular epidemiological research on ductal carcinoma in-situ and breast carcinogenesis: Interdisciplinary approaches.
Breast Dis
Show Abstract
Hide Abstract
Most invasive breast cancers arise from ductal carcinoma in-situ (DCIS), a non-obligate precursor of invasive breast cancer. Given that the natural history of individual DCIS lesions is unpredictable, many women with DCIS receive extensive treatments, which may include surgery, radiation and endocrine therapy, even though many of these lesions may have limited potential to progress to invasion and metastasize. In contrast to valid concerns about over-treatment, the fact that invasive breast cancers outnumber DCIS lesions by more than three-to-one, suggests that many cancer precursors (particularly DCIS, but LCIS also) progress to invasion prior to detection. Thus, DCIS poses a dual problem of over diagnosis among some woman and failure of early detection among others. These concerns are heightened by the multi-fold increase in rates of DCIS in conjunction with widespread use of mammographic screening and access to outpatient radiologically-guided biopsies. Accordingly, methods are needed to both specifically detect and identify DCIS lesions with potential to progress to invasive cancer and to discover techniques to triage and conservatively manage indolent cases of DCIS.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.