Percent Mammographic Density Research Articles

Ethnic Variations in Mammographic Density: A British Multiethnic Longitudinal Study

It is not known whether the 20-30% lower breast cancer incidence rates in first-generation South Asian and Afro-Caribbean women relative to Caucasian women in the United Kingdom are reflected in mammographic density. The authors conducted a United Kingdom population-based multiethnic study of mammographic density at ages 50-64 years in 645 women. Data on breast cancer risk factors were obtained using a questionnaire/telephone interview. Threshold percent density was assessed on 5,277 digitized mammograms taken in 1995-2004 and was analyzed using multilevel models. Both ethnic minorities were characterized by more protective breast cancer risk factor distributions than Caucasians, such as later menarche, shorter stature, higher parity, earlier age at first birth, and less use of hormone therapy, but they had a higher mean body mass index; the last four factors were associated with lower mammographic density. Age-adjusted percent mammographic densities in Afro-Caribbeans and South Asians were 5.6% (95% confidence interval (CI): 3.5, 7.5) and 5.9% (95% CI: 3.6, 8.0) lower, respectively, than in Caucasians. Lower densities were partly attributed to higher body mass index, less use of hormone therapy, and a protective reproductive history, but these factors did not account entirely for ethnic differences, since fully adjusted mean densities were 1.3% (95% CI: -1.3, 3.7) and 3.8% (95% CI: 1.1, 6.3) lower, respectively. Ethnic differences in mammographic density are consistent with those for breast cancer risk.

Dietary patterns across the life course, mammographic density and implications for breast cancer: results from a British prospective cohort

Background : Previous epidemiological studies have investigated the relationship between individual nutrients such as vitamin D and vitamin B12 and mammographic density, a strong marker of breast cancer risk [1], with varied results. There has been limited research on overall dietary patterns and most studies have focused on adult dietary patterns [2]. We examine prospective data to determine whether dietary patterns from childhood to adult life affect mammographic density. Methods : The Medical Research Council National Survey of Health and Development is a national representative sample of 2,815 men and 2,547 women followed since their birth in March 1946 [3]. A wealth of medical and social data has been collected in over 25 follow-ups by home visits, medical examinations and postal questionnaires. Dietary intakes at age 4 years were determined by 24-hour recalls and in adulthood (ages 36, 43 years) by 5-day food records. Copies of the mammograms (two views for each breast) taken when the women were closest to age 50 years were obtained from the relevant NHS centres. A total of 1,319 women were followed up since birth in 1946 for whom a mammogram at age 50 years was retrieved, and the percentage mammographic density was measured using the computer-assisted threshold method for all 1,161 women. Breast cancer incidence for the whole cohort is being ascertained through the National Health Service Central Register. Statistical analysis : Reduced rank regression analysis, a relatively new approach to dietary pattern analysis, is being used to identify dietary patterns associated with mammographic density [4]. This approach identifies patterns in food intake that are predictive of an intermediate outcome of the disease process, such as mammographic density, and subsequently examines the relationship between the identified dietary patterns and breast cancer risk. Results : Preliminary analyses so far suggest that variations in dietary patterns in adulthood might explain more than 10% of the variation in percentage mammographic density at age 50 years (age 36 years: 13%; age 43 years: 14%), with variations in patterns in childhood explaining slightly less. Further work is being carried out on the characteristics of these dietary patterns and their effects on percentage mammographic density and its two components (that is, absolute areas of dense and nondense tissues) and on breast cancer risk, after adjusting for socioeconomic status, anthropometric variables and reproductive factors. Conclusion : The present study will provide for the first time information on the relationship between dietary patterns across the life course and mammographic density, and will help to clarify the pathways through which diet may affect breast cancer risk.

Associations between mammographic density and body composition in Hispanic and non-Hispanic white women by menopause status

To evaluate the associations of body composition, including percentage of lean and fat mass, with the percentage of mammographic density and mammographic dense area among pre- and postmenopausal Hispanic and non-Hispanic white women. In this cross-sectional study, a total of 238 women aged 41 to 50 or 56 to 70 years were recruited from local mammography clinics and community health centers. Postmenopausal status was defined as an absence of any menstrual cycle within the past 12 calendar months or having a follicle-stimulating hormone level between 22 and 138 mIU/mL. The participants' most recent mammograms were used for the mammographic density analysis. Body composition was measured by dual-energy x-ray absorptiometry. The associations between the percentage of mammographic density or mammographic dense area and body composition components were analyzed using logistic regression. Mammographic dense areas were similar in Hispanic and non-Hispanic white women. The percentage of mammographic density varied by ethnicity in premenopausal (P = 0.023), but not in postmenopausal women. Body composition, both higher lean mass and lower fat mass, was associated with a higher percentage of mammographic density (P < 0.05). Interestingly, a higher percentage of total body fat mass and a lower percentage of total body lean mass were correlated with larger breast dense areas in premenopausal women but with lower breast dense areas in postmenopausal women. These relationships between body composition and mammographic density measurements were not significantly affected by factors such as age, ethnicity, and body weight. Body composition is highly correlated with mammographic density and should be examined as a possible confounding factor in studies involving mammographic density measurements and breast cancer risk.

Physical Activity and Mammographic Density in a Cohort of Midlife Women

Physical activity (PA) is one of few modifiable breast cancer risk factors. There have been few studies of the relation between PA and mammographic density, especially in multiethnic populations. In a cohort of pre- and early perimenopausal women of non-Hispanic white (N = 373), African American (N = 55), Chinese (N = 178), and Japanese (N = 166) ethnicity, we used multivariable linear regression to examine the association between two measures of mammographic density (percent density and area of density) and mutually exclusive components of recent physical activity (sports, household/caregiving and work activity, active living). After adjusting for race/ethnicity, menopausal status, parity, past use of hormones, body mass index, waist circumference and education, we observed nonsignificant inverse associations for percent mammographic density and the highest versus the lowest category of each of our PA domains. For example, the adjusted beta for active living = -2.62, 95% confidence interval (CI) (-5.84, 0.60). Nonsignificant inverse associations also were observed for area of density and each PA domain except work activity. However, most associations were nonlinear. Our results are consistent with a modest inverse association between multiple domains of PA and mammographic density, although findings may have been attributable to chance alone.

Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN)

Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of radiographic density and total breast area on mammograms from 801 participants in the Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of pre- and early perimenopausal women. From multivariable linear regression, the following menstrual or reproductive factors were independently associated with percent mammographic density (area of dense breast/breast area): older age at menarche (beta=10.3, P<0.01, for >13 vs. <12 years), premenstrual cravings and bloating (beta=-3.36, P=0.02), younger age at first full-term birth (beta=-8.12, P<0.01 for <or=23 years versus no births), greater number of births (beta=-6.80, P<0.01 for >or=3 births versus no births), and premenopausal status (beta=3.78, P<0.01 versus early perimenopausal). Only number of births remained associated with percent density after adjustment for age, race/ethnicity, study site, body mass index (BMI), and smoking. In addition, stratified analyses revealed that the association with number of births was confined to women within the lowest BMI tertile (beta=-12.2, P<0.01 for >or=3 births versus no births). Our data support a mechanism for parity and breast cancer that involves mammographic density among pre- and early perimenopausal women that may be modified by body size.

A new method for quantitative analysis of mammographic density

Women with mammographic percent density >50% have a approximately three-fold increased risk of developing breast cancer, potentially making them screening candidates for breast MRI scanning. The purpose of this work is to introduce a new method to quantify mammographic percent density (MPD), and to compare the results with the current standard of care for breast density assessment. Craniocaudal (CC) and mediolateral oblique (MLO) mammograms for 104 patients were digitized and analyzed using an interactive computer-assisted segmentation routine implemented for two purposes: (1) to segment the breast area from background and radiographic markers, and (2) to segment dense from fatty portions of the breast. Our technique was evaluated by comparing the results to qualitative estimates determined by a certified breast radiologist using the BI-RADS Categorical Assessment (1 (fatty) to 4 (dense) scale). Statistically significant correlations (two-tailed, p < 0.01) were observed between calculated MPD and BI-RADS for both CC (Spearman rho = 0.67) and MLO views (Spearman rho = 0.71). For the CC view, statistically significant differences were revealed between the mean MPD for each BI-RADS category except between fatty (BI-RADS 1) and scattered (BI-RADS 2). Finally, for the MLO views, statistically significant differences in the mean MPD between all BI-RADS categories were observed. Comparing the CC and MLO views revealed a strong positive correlation (Pearson r = 0.8) in calculated MPD. In addition, an evaluation of the reproducibility of our segmentation demonstrated the average standard deviation of MPD for a subsample of eight patients, measured five times, was 1.9% (range: 0.03%-9.9%). Eliminating one misassignment reduced the average standard deviation to 0.75% (range: 0.03%-3.16%). Further analysis of approximately 10% of the patient sample revealed strong agreement (ICC = 0.80-0.85) in the reliability of MPD estimates for both mammographic views. Overall, these results demonstrate the feasibility of utilizing our approach for quantitative breast density segmentation, which may be useful for detecting small changes in MPD introduced through chemoprevention, diet, or other interventions.

Different measures of smoking exposure and mammographic density in postmenopausal Norwegian women: a cross-sectional study

BackgroundRecent cohort studies have suggested an increased risk of breast cancer with long duration of smoking, and with smoking initiation before first birth. Cigarette smoking may have both carcinogenic effects and antiestrogenic effects on the breast tissue. We decided to examine the relationship between different measures of smoking exposure and mammographic density.MethodsLifetime smoking history was collected through interview and questionnaires among 907 postmenopausal participants in the Tromsø Mammography and Breast Cancer study. The mammograms were obtained from the governmental Norwegian Breast Cancer Screening Program. Mammograms were classified according to the percentage and absolute mammographic densities using a previously validated computer-assisted method.ResultsSixty-five percent of the women reported having ever smoked cigarettes, while 34% were current smokers. After adjustment for age, age at first birth, parity, age at menopause, postmenopausal hormone therapy use, and body mass index, smoking was inversely associated with both measures of mammographic density (both trends P < 0.01). Both current smokers and former smokers had significantly lower adjusted mean percentage mammographic density compared with never smokers (P = 0.003 and P = 0.006, respectively). An inverse dose–response relationship with mammographic density was found between both the number of cigarettes and the number of pack-years smoked among current smokers. Current smokers who smoked 11 cigarettes or more daily had a 3.7% absolute (36% relative difference) lower percentage mammographic density compared with current smokers who smoked seven cigarettes or less daily (P = 0.008). When former smokers were stratified according to time since smoking cessation, we found that women who had stopped smoking less than 24 years ago had a significantly lower mean percentage mammographic density compared with never smokers (P < 0.001).ConclusionWe found modest inverse dose–response associations between numbers of cigarettes and of pack-years smoked and both measures of mammographic density among current smokers. Former smokers who had stopped smoking less than 24 years ago also had a statistically significantly lower mean percentage mammographic density when compared with never smokers. These findings are consistent with an antiestrogenic effect of cigarette smoking on the breast tissue.

Strong Evidence of a Genetic Determinant for Mammographic Density, a Major Risk Factor for Breast Cancer

Increased mammographic density (MD), the proportion of dense tissue visible on a mammogram, is a strong risk factor for breast cancer, common in the population and clusters in families. We conducted the first genome-wide linkage scan to identify genes influencing MD. DNA was obtained from 889 relatives (756 women, 133 men) from 89 families. Percent MD was estimated on 618 (82%) female family members using a validated computer-assisted thresholding method. The genome-wide scan included 403 microsatellite DNA markers with an average spacing of 9 cM. Fine mapping of a region of chromosome 5p (5p13.1-5p15.1) was done using 21 additional closely spaced DNA markers. Linkage analyses were conducted to quantify the evidence for a gene responsible for MD across the genome. The maximum log odds for linkage (LOD) score from the genome-wide scan was on chromosome 5p (LOD = 2.9, supporting linkage by a factor of 10(2.9) or 794 to 1) with a 1-LOD interval spanning 28.6 cM. Two suggestive regions for linkage were also identified on chromosome 12 (LOD = 2.6, 1-LOD interval of 14.8 cM; and LOD = 2.5, 1-LOD interval of 17.2 cM). Finer mapping of the region surrounding the maximum LOD on chromosome 5p resulted in stronger and statistically significant evidence for linkage (LOD = 4.2) and a narrowed 1-LOD interval (13.4 cM). The putative locus on chromosome 5p is likely to account for up to 22% of variation in MD. Hence, 1 or more of the 45 candidate genes in this region could explain a large proportion of MD and, potentially, breast cancer.

Randomized Dose-Ranging Trial of Tamoxifen at Low Doses in Hormone Replacement Therapy Users

The combination of hormone replacement therapy (HRT) and low-dose tamoxifen may retain the benefits while reducing the risks of either agent. We assessed the optimal biologic dose and schedule of tamoxifen in HRT users using surrogate end point biomarkers and menopausal symptoms. Two hundred ten current or de novo HRT users were randomly assigned to one of the following four arms: tamoxifen 1 mg/day and placebo/week, placebo/day and tamoxifen 10 mg/week, tamoxifen 5 mg/day and placebo/week, or both placebos for 12 months. The primary end point was the change of plasma insulinlike growth factor 1 (IGF-I) through 12 months, and secondary end points were IGF-I/IGF binding protein-3 (IGFBP-3) ratio, fibrinogen, antithrombin III, C reactive protein, C-telopeptide, mammographic percent density, and endometrial thickness. Endometrial proliferation was assessed by Pipelle biopsy in superficial, deep glandular, and stromal compartments after 12 months. Compared with placebo, IGF-I declined in all tamoxifen arms (P = .005), with a greater change on 5 mg/day (P = .019 v 10 mg/week or 1 mg/day). Tamoxifen increased IGFBP-3 and lowered antithrombin-III, C reactive protein, and mammographic density, with greater effects of 5 mg/day. Tamoxifen increased endometrial thickness but not Ki-67 expression, which was lower on 5 mg/day among the three doses. Menopausal symptoms were not significantly worsened by tamoxifen. Doses of tamoxifen < or = 5 mg/day modulate favorably biomarkers of breast carcinogenesis and cardiovascular risk in HRT users with no increase of endometrial proliferation and menopausal symptoms. A dose of 5 mg/day was the most effective and has been selected for a phase III trial in HRT users.

IGF‐I and mammographic density in four geographic locations: A pooled analysis

Insulin-like growth factor (IGF-I) and prolactin have been found to be associated with breast cancer risk and with mammographic density. In a pooled analysis from 4 geographic locations, we investigated the association of percent mammographic density with serum levels of IGF-I, IGFBP-3 and prolactin. The pooled data set included 1,327 pre- and postmenopausal women: Caucasians from Norway, Arizona and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. Serum samples were assayed for IGF-I, IGFBP-3 and prolactin levels using ELISA assays. Mammographic density was quantified using a computer-assisted density method. After stratification by menopausal status, multiple regression models estimated the relation between serum analytes and breast density. All serum analytes except prolactin among postmenopausal women differed significantly by location/ethnicity group. Among premenopausal subjects, IGF-I levels and the molar ratio were highest in Hawaii, intermediate in Japan and lowest in Arizona. For IGFBP-3, the order was reversed. Among postmenopausal subjects, Norwegian women had the highest IGF-I levels and women in Arizona had the lowest while women in Japan and Hawaii had intermediate levels. We observed no significant relation between percent density and IGF-I or prolactin levels among pre-and postmenopausal women. The significant differences in IGF-I levels by location but not ethnicity suggest that environmental factors influence IGF-I levels, whereas percent breast density varies more according to ethnic background than by location. Based on this analysis, the influence of circulating levels of IGF-I, IGFBP-3, and prolactin on percent density appears to be very small.

Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women

The associations between endogenous sex hormone levels and breast cancer risk in postmenopausal women are well established. Mammographic density is a strong risk factor for breast cancer, and possibly an intermediate marker. However, the results from studies on the associations between endogenous sex hormones and mammographic density are conflicting. The authors examined the associations between circulating levels of sex hormones, sex hormone binding globulin (SHBG) and prolactin and mammographic densities among postmenopausal women not currently using postmenopausal hormone therapy (HT). The authors also examined if insulin-like growth factor-I (IGF-I) levels influenced the association between estrogen and mammographic density. Altogether, 722 postmenopausal participants in the Norwegian governmental mammographic screening program had endogenous hormone concentrations measured. Mammograms were classified according to percent and absolute mammographic density using a previously validated computer-assisted method. After adjustment for age, number of children, age at menopause, body mass index and HT use, both plasma concentrations of SHBG (p-trend = 0.003) and estrone (p-trend = 0.07) were positively associated with percent mammographic density. When the analyses were stratified according to median IGF-I concentration, the weak association between estrone and mammographic density was strengthened among women with IGF-I levels below median, while the association disappeared among women with over median IGF-I levels (p for interaction = 0.02). In summary, the authors found a positive association between plasma SHBG levels and mammographic densities among 722 postmenopausal Norwegian women not currently using HT. Further, the authors found a positive but weak association between plasma estrone concentration and mammographic density, which appeared to be modified by IGF-I levels.

Mammographic Density and Candidate Gene Variants: A Twins and Sisters Study

Mammographic density, the light/white radiographic appearance on a mammogram that represents connective and epithelial tissue, is a strong risk factor for breast cancer which seems to be highly heritable. Little is known about its genetic determinants. We studied 457 women from 207 sisterhoods (104 monozygotic twins, 182 dizygotic twins, and 171 singletons). Percentage mammographic density (PMD) as well as dense area and nondense area were calculated using a computer-assisted method. We measured six single nucleotide polymorphisms from six candidate genes (COMT, HSD3B1, IGFBP3, HER2, XPD, and XRCC3). Associations between genotypes and mammographic measures were tested (a) cross-sectionally using a multivariate normal model fitted using FISHER that allowed separate correlations for monozygotic, dizygotic, and nontwin pairs and (b) within sister pairs using paired t tests. Cross-sectionally, each additional copy of the HSD3B1 Asn(367)Thr variant allele was associated with lower PMD (-3.47% per allele; SE = 1.65; P = 0.035). Within-pair regression estimates confirmed this association. There was no evidence for an association between the mammographic density measures and any of the other variants studied. We have replicated an association between a variant in the HSD3B1 gene and PMD, which suggests that HSD3B1 may be genetic determinant of mammographic density.

Measures of energy balance and mammographic density in the Nurses’ Health Study

Mammographic density is a strong risk factor for breast cancer; however the mechanism that underlies this association is unclear. We hypothesized that measures of energy balance early in life and in adulthood may be associated with mammographic density. We conducted a cross-sectional analysis of 1,398 women in the Nurses' Health Study to examine associations between physical activity, childhood and current body fatness, weight gain from age 18 years to present and mammographic density. Percent mammographic density was measured from digitized mammograms by a computer-assisted method. Demographic and lifestyle data were obtained from prospectively collected questionnaires. For all analyses, subjects were stratified into three groups: premenopausal women, postmenopausal women not currently taking hormones, and postmenopausal women currently taking hormones. Childhood body fatness was inversely associated with mammographic density. The correlations ranged from -0.15 to -0.19 in the three strata of women (P<or=0.001). The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 6.2 to 9.9%. Similarly, adult body fatness was inversely associated with percent mammographic density. The correlations ranged from -0.41 to -0.48 in the three strata of women (P<0.0001). The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 22.3 to 35.1%. Weight gain from age 18 was also inversely associated with mammographic density. There was no association between recent physical activity and mammographic density. These findings indicate that childhood and adult body fatness and weight change from age 18 are inversely associated with mammographic density.

The effect of raloxifene on breast MRI volume in premenopausal women at increased risk for invasive breast cancer

1518 Background: Breast MRI volume (MRIV) and mammographic density (MD) assess the amount of fibroglandular tissue in the breast. While increased MD is associated with a 4 to 6 fold increase in breast cancer risk, the association between MRIV and breast cancer is unknown. Previous studies have shown that MRIV and MD can be modulated with hormonal interventions. We evaluated the effect of raloxifene on MRIV in premenopausal women at increased risk for breast cancer. We have previously reported that raloxifene did not change MD in this cohort. Raloxifene is indicated for the prevention and treatment of osteoporosis but not for prevention of breast cancer or for use in premenopausal women. Methods: Premenopausal women at increased risk by virtue of: Gail model risk &gt; 1.7% over 5 years; lobular neoplasia, ductal carcinoma in situ, BRCA1/2 mutation positive, or a very strong family history were eligible for this phase II chemoprevention study. MRIs obtained at baseline and after two years on raloxifene 60 mg daily, and one year after discontinuing the drug were evaluated.T1 weighted spoiled gradient-echo MRI with fat suppression was used to determine volume using a semiautomatic method, after visual verification. Median relative change in MRIV was assessed by the Wilcoxon signed rank test. Results: 19 of 30 subjects who started study drug had breast MRI at baseline and after 2 years on raloxifene; median relative change was -16% (range -57 to +25%) (p=0.0004). 17 subjects had MRI at year 2 and one year after stopping drug. No significant change in MRIV was observed after stopping raloxifene, median relative change -9% (p=0.64). Conclusions: MRIV significantly declined while on raloxifene. In contrast no significant change in percent mammographic density in this same cohort was seen. Our findings suggest that MRIV may be a better surrogate biomarker than MD in premenopausal women at risk for breast cancer because of less variation in its measurement. MRIV should be further evaluated as a potential surrogate biomarker in prevention studies. No significant financial relationships to disclose.

Association of Childhood and Adolescent Anthropometric Factors, Physical Activity, and Diet with Adult Mammographic Breast Density

Early-life exposures may influence the development of breast cancer. The authors examined the association of childhood and adolescent anthropometric factors, physical activity levels, and diet with adult mammographic breast density, a strong risk factor for breast cancer. Women in the Minnesota Breast Cancer Family Study cohort who had undergone mammograms but had not had breast cancer (n=1,893) formed the sample. Information on adolescent exposures, including relative height, weight, and physical activity at ages 7, 12, and 18 years and diet at age 12-13 years, was self-reported during two follow-up studies (1990-2003). Mammographic percent density was estimated using a computer-assisted thresholding program. Statistical analyses were performed using linear mixed-effects models with two-sided tests. Positive associations with height at ages 7 (p<0.001), 12 (p<0.001), and 18 (p<0.001) years and percent density were evident overall and within menopausal status categories. The minimum difference in percent density between the tallest and shortest girls was 3 percent, with a maximum of 7 percent. Weight at age 12 years (p=0.005) and adiposity at age 12 years (p=0.005) were both inversely associated with adult percent density. Adolescent physical activity and diet were unrelated to percent density. These results suggest that adolescent height, a known risk factor for breast cancer, is also associated with mammographic percent density.

TH-E-L100J-07: Comparison of Mammographic Percent Density and Volumetric Percent Density Determined From Ultrasound Tomography Images

Purpose: Previous ultrasound tomography work conducted by our group showed a direct correlation between measured sound speed and physical density in vitro, and increased in vivo sound speed with increasing mammographic density, a known risk factor for breast cancer. Building on these empirical results, we investigated the use of volumetric ultrasound percent density (USPD) for breast density estimation. Method and Materials: A breast phantom comprised of fat inclusions embedded in fibroglandular tissue was scanned four times with both ultrasound tomography and CT. The coronal transmission tomograms and corresponding CT images were analyzed using a semi-automatic segmentation routine. Next, a cohort of ∼100 patients was imaged encompassing the entire breast volume (50–75 tomograms/patient). USPD was determined by segmenting high sound speed areas from each slice using a k-means clustering routine, integrating these results over the entire breast, and dividing by total breast area. USPD was evaluated using two mammographic density measures: (1) qualitative, as determined by a radiologist's visual assessment using BI-RADS Criteria and (2) quantitative, via digitization and semi-automatic segmentation of craniocaudal and medio-lateral oblique mammograms. Results: The integrated areas of the phantom's fat inclusions were compared using both transmission ultrasound and CT for four repeated scans. The average variability for inclusion segmentation was ∼2% and ∼10%, respectively, and a close correlation was observed in the integrated areas between the two modalities. A strong positive association between BI-RADS category and USPD was demonstrated. Furthermore, comparing USPD to calculated mammographic density yielded moderate to strong positive associations (Pearson r = 0.76–0.84) for MLO and CC views, respectively. Conclusion: These results support the hypothesis that utilizing USPD as an analogue to mammographic breast density is feasible. USPD has the potential to provide a non-ionizing, whole-breast analysis of breast density, which may better elucidate the relationship between breast density and breast cancer risk.

The Association Between Mammographic Breast Density and Bone Mineral Density in the Study of Women's Health Across the Nation

Bone mineral density and mammographic breast density are each associated with markers of lifetime estrogen exposure. The association between mammographic breast density and bone mineral density in early perimenopausal women is unknown. We analyzed data from a cohort (n = 501) of premenopausal (no change in menstrual regularity) and early perimenopausal (decreased menstrual regularity in past 3 months) participants of African-American, Caucasian, Chinese, and Japanese ethnicity in the Study of Women's Health Across the Nation. Using multivariable linear regression, we examined the cross-sectional association between percent mammographic density and bone mineral density (BMD). Percent mammographic density was statistically significantly inversely associated with hip BMD and lumbar spine BMD after adjustment (body mass index, ethnicity, age, study site, parity, alcohol intake, cigarette smoking, physical activity, age at first childbirth) in early perimenopausal, but not premenopausal, women. In early perimenopausal women, every 0.1g/cm(2) greater hip BMD predicted a 2% lower percent mammographic density (95% confidence interval -37.0 to -0.6%, p = 0.04). Mammographic breast density is inversely associated with BMD in the perimenopausal participants of this community-based cohort. The biological underpinnings of these findings may reflect differential responsiveness of breast and bone mineral density to the steroid milieu.

Longitudinal Trends in Mammographic Percent Density and Breast Cancer Risk

Mammographic density is a strong risk factor for breast cancer. However, whether changes in mammographic density are associated with risk remains unclear. A study of 372 incident breast cancer cases and 713 matched controls was conducted within the Mayo Clinic mammography screening practice. Controls were matched on age, exam date, residence, menopause, interval between, and number of mammograms. All serial craniocaudal mammograms 10 years before ascertainment were digitized, and quantitative measures of percent density (PD) were estimated using a thresholding method. Data on potential confounders were abstracted from medical records. Logistic regression models with generalized estimating equations were used to evaluate the interactions among PD at earliest mammogram, time from earliest to each serial mammogram, and absolute change in PD between the earliest and subsequent mammograms. Analyses were done separately for PD measures from the ipsilateral and contralateral breast and also by use of hormone therapy (HT). Subjects had an average of five mammograms available, were primarily postmenopausal (83%), and averaged 61 years at the earliest mammogram. Mean PD at earliest mammogram was higher for cases (31%) than controls (27%; ipsilateral side). There was no evidence of an association between change in PD and breast cancer risk by time. Compared with no change, an overall reduction of 10% PD (lowest quartile of change) was associated with an odds ratio of 0.9997 and an increase of 6.5% PD (highest quartile of change) with an odds ratio of 1.002. The same results held within the group of 220 cases and 340 controls never using HT. Among the 124 cases and 337 controls known to use HT during the interval, there was a statistically significant interaction between change in PD and time since the earliest mammogram (P = 0.01). However, in all groups, the risk associated with the earliest PD remained a stronger predictor of risk than change in PD. We observed no association between change in PD with breast cancer risk among all women and those never using HT. However, the interaction between change in PD and time should be evaluated in other populations.

Relationships between circulating hormone levels, mammographic percent density and breast cancer risk factors in postmenopausal women

Endogenous hormones and insulin-like growth factors (IGF) play a central role in breast cancer development. Mammographic density, an important breast cancer risk factor, has been associated with these biomarkers in premenopausal women. The aim of this study was to assess the relationships between circulating hormones, clinical features related to breast cancer risk and mammographic density in postmenopausal women. The study included 226 postmenopausal women participating in a clinical prevention trial. We performed baseline measurements of mammographic percent density and circulating levels of estradiol, sex-hormone binding globulin (SHBG), follicle stimulating hormone (FSH), prolactin, C-terminal cross-link telopeptide, IGF-I, and IGF binding protein-3. Median age and time since last menses were 52 years and 15 months, respectively. Median body mass index was 24.1 kg/m(2). After adjusting for age and body mass index, estradiol was the only biomarker significantly correlated with mammographic density (r = 0.17; P = 0.04). Women with normal body mass index had higher mammographic density (P < 0.001), higher SHBG (P < 0.0001), higher FSH (P = 0.002) and lower estradiol levels (P = 0.01) than those who were overweight. Women who had previous biopsies for benign breast disease had a higher mammographic density (P = 0.006). In these recently postmenopausal women, mammographic percent density is directly associated with circulating estradiol levels. Our results provide further support to the role of circulating hormones in breast cancer risk.

Association of diabetes with mammographic breast density and breast cancer in the Minnesota breast cancer family study

Data from the Minnesota Breast Cancer Family Study cohort (n=6,130 women) were used to examine the association of type II diabetes with mammographic percent density and incident breast cancer (BC). Exposures and outcomes were self-reported. The first set of analyses evaluated diabetes (DM) as a risk factor for breast cancer. A total of 403 women (6.6%) reported a diagnosis of type II diabetes and 333 women reported an incident breast cancer. Women who reported type II diabetes had an age-adjusted relative risk (RR) for breast cancer of 1.44 (95% CI 0.89-2.32) compared to those who did not. Adjustment for covariates strengthened the association (RR 1.61, 95% CI 0.98-2.62). Mammograms were retrieved on women over the age of 40 and percent density was estimated with a user-assisted thresholding program. Cross-sectional analyses revealed that mean levels of mammographic density were not statistically significantly different between diabetic and non-diabetic women. Results were similar within strata of menopausal status. Breast cancer cases with diabetes did not have a significantly higher percent density than cases without diabetes. Our findings suggest that breast cancer risk may be increased among women with type II diabetes, but that type II diabetes does not significantly influence mammographic breast density.