Differences In Mammographic Density Research Articles

Abstract B065: Percent mammographic density and breast cancer risk among U.S. Black women

Abstract Background: High mammographic density is a well-established risk factor for breast cancer. A few studies have suggested a difference in mammographic density by race wherein Black women – who have a high risk of aggressive breast cancer subtypes – are more likely to have dense breasts compared to women of other racial/ethnic groups. It is unknown whether mammographic density may contribute to differences in breast cancer risk by tumor hormone subtype across race and ethnicity. Methods: We used a case-cohort study design to examine the association between percent mammographic density (PMD) and breast cancer risk among Black women in the United States using data from the Black Women’s Health Study (BWHS). Our study consisted of 5,904 women with digital screening (i.e., pre-diagnostic) mammograms of which 363 (6.15%) were women with breast cancer (cases) and 5,541 (93.85%) were women without breast cancer (non-cases). We used Cumulus to assess PMD. Quartiles for PMD were determined based on the distribution in the non-cases. We used logistic regression, adjusted for age and body mass index (BMI) at mammography, to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association of PMD with breast cancer overall and by estrogen receptor (ER) status. Fully adjusted models additionally included other established breast cancer risk factors. We also stratified analyses by age at mammography (<55 vs. ≥ 55 years). Results: The mean age at mammography was 56 years for both cases and non-cases and approximately 70% of participants were postmenopausal. Cases had a lower mean BMI at age 18 years (20.9 kg/m2) compared to non-cases (21.4 kg/m2), while there was no difference in mean BMI at mammography between cases and non-cases. As expected, cases were more likely than non-cases to have a family history of breast cancer (25% vs. 19%). Additionally, cases had a higher mean PMD than did non-cases (26.3% vs. 24.5%). Overall, women in the highest quartile of PMD had a 58% higher risk of breast cancer compared to those in the lowest quartile (RRQ4vsQ1 1.58; 95% CI: 1.14, 2.18). Corresponding RRs were 1.46 (95% CI: 0.99, 2.14) for ER+ cancer and 1.57 (95% CI: 0.79, 3.14) for ER– cancer. Among women under 55 years of age, the RR for the highest quartile of PMD relative to the lowest quartile was 1.35, 95% CI: 0.83, 2.19). Among the older women, the comparable RR was 1.75, 95% CI: 1.13, 2.69). Associations were largely unchanged in multivariable models. Conclusion: In the largest study of mammographic density in U.S. Black women to date, we confirmed that higher PMD is associated with both ER+ and ER– breast cancer risk in this population. Associations were statistically significant among women ≥55 years of age. Findings from this study reinforce the importance of breast density as a risk factor for breast cancer across racial/ethnic groups. Citation Format: Etienne X. Holder, Zahna Bigham, Kerrie P. Nelson, Julie R. Palmer, Kimberly A. Bertrand. Percent mammographic density and breast cancer risk among U.S. Black women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B065.

Risk Analysis of Breast Cancer by Using Bilateral Mammographic Density Differences: A Case-Control Study.

The identification of risk factors helps radiologists assess the risk of breast cancer. Quantitative factors such as age and mammographic density are established risk factors for breast cancer. Asymmetric breast findings are frequently encountered during diagnostic mammography. The asymmetric area may indicate a developing mass in the early stage, causing a difference in mammographic density between the left and right sides. Therefore, this paper aims to propose a quantitative parameter named bilateral mammographic density difference (BMDD) for the quantification of breast asymmetry and to verify BMDD as a risk factor for breast cancer. To quantitatively evaluate breast asymmetry, we developed a semi-automatic method to estimate mammographic densities and calculate BMDD as the absolute difference between the left and right mammographic densities. And then, a retrospective case-control study, covering the period from July 2006 to October 2014, was conducted to analyse breast cancer risk in association with BMDD. The study included 364 women diagnosed with breast cancer and 364 matched control patients. As a result, a significant difference in BMDD was found between cases and controls (P < 0.001) and the case-control study demonstrated that women with BMDD > 10% had a 2.4-fold higher risk of breast cancer (odds ratio, 2.4; 95% confidence interval, 1.3-4.5) than women with BMDD ≤ 10%. In addition, we also demonstrated the positive association between BMDD and breast cancer risk among the subgroups with different ages and the Breast Imaging Reporting and Data System (BI-RADS) mammographic density categories. This study demonstrated that BMDD could be a potential risk factor for breast cancer.

True and Missed Interval Cancer in Organized Mammographic Screening: A Retrospective Review Study of Diagnostic and Prior Screening Mammograms

To explore radiological aspects of interval breast cancer in a population-based screening program. We performed a consensus-based informed review of mammograms from diagnosis and prior screening from women diagnosed with interval cancer 2004-2016 in BreastScreen Norway. Cases were classified as true (no findings on prior screening mammograms), occult (no findings at screening or diagnosis), minimal signs (minor/non-specific findings) and missed (obvious findings). We analyzed mammographic findings, density, time since prior screening, and histopathological characteristics between the classification groups. The study included 1010 interval cancer cases. Mean age at diagnosis was 61 years (SD = 6), mean time between screening and diagnosis 14 months (SD = 7). A total of 48% (479/1010) were classified as true or occult, 28% (285/1010) as minimal signs and 24% (246/1010) as missed. We observed no differences in mammographic density between the groups, except from a higher percentage of dense breasts in women with occult cancer. Among cancers classified as missed, about 1/3 were masses and 1/3 asymmetries at prior screening. True interval cancers were diagnosed later in the screening interval than the other classification categories. No differences in histopathological characteristics were observed between true, minimal signs and missed cases. In an informed review, 24% of the interval cancers were classified as missed based on visibility and mammographic findings on prior screening mammograms. Three out of four true interval cancers were diagnosed in the second year of the screening interval. We observed no statistical differences in histopathological characteristics between true and missed interval cancers.

Radiological review of prior screening mammograms of screen-detected breast cancer

ObjectiveTo perform a radiological review of mammograms from prior screening and diagnosis of screen-detected breast cancer in BreastScreen Norway, a population-based screening program.MethodsWe performed a consensus-based informed review of mammograms from prior screening and diagnosis for screen-detected breast cancers. Mammographic density and findings on screening and diagnostic mammograms were classified according to the Breast Imaging-Reporting and Data System®. Cases were classified based on visible findings on prior screening mammograms as true (no findings), missed (obvious findings), minimal signs (minor/non-specific findings), or occult (no findings at diagnosis). Histopathologic tumor characteristics were extracted from the Cancer Registry of Norway. The Bonferroni correction was used to adjust for multiple testing; p < 0.001 was considered statistically significant.ResultsThe study included mammograms for 1225 women with screen-detected breast cancer. Mean age was 62 years ± 5 (SD); 46% (567/1225) were classified as true, 22% (266/1225) as missed, and 32% (392/1225) as minimal signs. No difference in mammographic density was observed between the classification categories. At diagnosis, 59% (336/567) of true and 70% (185/266) of missed cancers were classified as masses (p = 0.004). The percentage of histological grade 3 cancers was higher for true (30% (138/469)) than for missed (14% (33/234)) cancers (p < 0.001). Estrogen receptor positivity was observed in 86% (387/469) of true and 95% (215/234) of missed (p < 0.001) cancers.ConclusionsWe classified 22% of the screen-detected cancers as missed based on a review of prior screening mammograms with diagnostic images available. One main goal of the study was quality improvement of radiologists’ performance and the program. Visible findings on prior screening mammograms were not necessarily indicative of screening failure.Key Points• After a consensus-based informed review, 46% of screen-detected breast cancers were classified as true, 22% as missed, and 32% as minimal signs.• Less favorable prognostic and predictive tumor characteristics were observed in true screen-detected breast cancer compared with missed.• The most frequent mammographic finding for all classification categories at the time of diagnosis was mass, while the most frequent mammographic finding on prior screening mammograms was a mass for missed cancers and asymmetry for minimal signs.

Racial differences in mammographic density in Brazil: implications for mammographic screening

Abstract Background Mammographic density (MD)-the amount of radio-dense fibroglandular tissue seen on a mammogram - is a stronger biomarker of susceptibility to breast cancer and a major determinant of the sensitivity of mammographic screening. This study examined for the first time racial differences in MD in Brazil. Methods 555 women (215 from the Longitudinal Study of Adult Health - ELSA-Brasil and 340 users of the Unified Health System - SUS) in Bahia were enrolled into the study. Participants completed an interview, had their heights and weights measured, and underwent a 2-view (cranio-caudal (CC) and medio-lateral-oblique (MLO)) digital mammography of each breast. MD was measured on the left MLO image using the semi-automated Cumulus software, and expressed as the percentage (PMD) of the breast area occupied by fibroglandular tissue. Linear regression models were fitted to assess ethnicity-PMD associations adjusting for age at mammography, body mass index (BMI) and reading batch (minimally-adjusted) and further for socio-economic and reproductive variables. Results The study population comprised 95 White (W), 270 Brown-mixed (Bm) and 169 Black (B) women, with a mean age at mammography of 58 (SD = 5.4) years. 63% W, 69% Bm and 49% B women had low educational level; 24% W, 47% Bm and 31% B women had ≥4 children. Minimally-adjusted analysis showed that relative to W women, PMD was 23% (1.23; 95% CI 1.04-1.45) higher in Bm and 4% (1.04; 0.89-1.21) higher in B; however, further adjustment for socio-economic and reproductive variables attenuated the racial differences (fully-adjusted model: 16% (1.16; 0.96-1.40) and 9% (1.09; 0.92-1.29) for Bm and B, respectively. Conclusions The racial differences in PMD were mainly accounted by ethnic differences in socio-economic and reproductive-related factors. Implications Further studies should examine whether racial differences in PMD in Brazil lead to racial differences in false negative and interval cancer rates of mammographic screening. Key messages In Brazil, ethnic differences in socio-economic and reproductive-related factors are responsible for racial differences in mammographic density. More research is needed to address racial differences in breast cancer risk in Brazil.

Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy

Current evidences state clear that both normal development of breast tissue as well as its malignant progression need many-sided local and systemic communications between epithelial cells and stromal components. During development, the stroma, through remarkably regulated contextual signals, affects the fate of the different mammary cells regarding their specification and differentiation. Likewise, the stroma can generate tumour environments that facilitate the neoplastic growth of the breast carcinoma. Mammographic density has been described as a risk factor in the development of breast cancer and is ascribed to modifications in the composition of breast tissue, including both stromal and glandular compartments. Thus, stroma composition can dramatically affect the progression of breast cancer but also its early detection since it is mainly responsible for the differences in mammographic density among individuals. This review highlights both the pathological and biological evidences for a pivotal role of the breast stroma in mammographic density, with particular emphasis on dense and malignant stromas, their clinical meaning and potential therapeutic implications for breast cancer patients.

Differences in mammographic density between Asian and Caucasian populations: a comparative analysis.

Mammographic density is a measurable and modifiable biomarker that is strongly and independently associated with breast cancer risk. Paradoxically, although Asian women have lower risk of breast cancer, studies of minority Asian women in predominantly Caucasian populations have found that Asian women have higher percent density. In this cross-sectional study, we compared the distribution of mammographic density for a matched cohort of Asian women from Malaysia and Caucasian women from Sweden, and determined if variations in mammographic density could be attributed to population differences in breast cancer risk factors. Volumetric mammographic density was compared for 1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass index. We used multivariable log-linear regression to determine the risk factors associated with mammographic density and mediation analysis to identify factors that account for differences in mammographic density between the two cohorts. Compared to Caucasian women, percent density was 2.0% higher among Asian women (p<0.001), and dense volume was 5.7cm3 higher among pre-menopausal Asian women (p<0.001). Dense volume was 3.0cm3 lower among post-menopausal Asian women (p=0.009) compared to post-menopausal Caucasian women, and this difference was attributed to population differences in height, weight, and parity (p<0.001). Our analysis suggests that among post-menopausal women, population differences in mammographic density and risk to breast cancer may be accounted for by height, weight, and parity. Given that pre-menopausal Asian and Caucasian women have similar population risk to breast cancer but different dense volume, development of more appropriate biomarkers of risk in pre-menopausal women is required.

Abstract P6-02-04: Screen detected and interval cancers; genomic analysis points to different molecular etiology?

Abstract Breast cancers diagnosed after a negative mammogram but prior to the next screening episode are termed "interval cancers" and comprise as many as 25% of all cancers detected in women attending population-based screening programs. The high interval cancer rate is a major problem affecting the effectiveness of mammographic screening. It is unclear whether interval cancers represent a distinct biological entity compared to screen-detected cancers or whether their designation is simply an arbitrary outcome of screening timing. Using an Australian prospective population-based cohort of over 53,000 women (lifepool), 537 cases of breast carcinoma (in situ and invasive breast cancer) were identified, of which 293 had known screening status at time of diagnosis. Pathology reports, mammographic density data, germline DNA and tumor tissue were available for analysis. Screen and interval cases showed no significant differences in mammographic density or PR status but there were trends towards higher proportions of ER negative and HER2 positive cases in interval cancers (p&amp;lt;0.1). Interval cancers also had a younger age at diagnosis (p&amp;lt;0.01), increased tumor size (p&amp;lt;0.01) and higher grade (p&amp;lt;0.01). Copy number analysis was performed on a subset of invasive breast cancer cases using OncoScan MIP arrays. No difference in the overall number of copy number aberrations or fraction of the genome altered were observed, however specific differences were noted between interval and screen detected cases. These included copy number changes on chromosomes 8 and 11. Analysis of germline DNA was performed using a panel sequencing approach of known breast cancer genes as well as lower-penetrance SNPs. Pathogenic mutations in BRCA1, BRCA2, TP53 and PALB2 were identified in 1/13 interval cases (in BRCA2), 1/66 screen-detected cases and 8/74 cases with currently unknown screen/interval status. Screen detected cancers may thus have a reduced contribution from high-penetrance predisposing variants. Citation Format: Gorringe KL, Hunter SM, Byrne D, Devereux L, Rowley SM, Elder K, Huynh R, Pridmore V, Hopper J, Kavanagh A, Mitchell G, Mann BG, Fox SB, Campbell IG. Screen detected and interval cancers; genomic analysis points to different molecular etiology?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-02-04.

The association of alcohol consumption with mammographic density in a multiethnic urban population.

BackgroundAlcohol consumption is associated with higher breast cancer risk. While studies suggest a modest association between alcohol intake and mammographic density, few studies have examined the association in racial/ethnic minority populations.MethodsWe assessed dense breast area and total breast area from digitized film mammograms in an urban cohort of African American (42%), African Caribbean (22%), white (22%), and Hispanic Caribbean (9%) women (n = 189, ages 40-61). We examined the association between alcohol intake and mammographic density (percent density and dense area). We used linear regression to examine mean differences in mammographic density across alcohol intake categories. We considered confounding by age, body mass index (BMI), hormone contraceptive use, family history of breast cancer, menopausal status, smoking status, nativity, race/ethnicity, age at first birth, and parity.ResultsFifty percent currently consumed alcohol. Women who consumed >7 servings/week of alcohol, but not those consuming ≤7 servings/week, had higher percent density compared to nondrinkers after full adjustments (servings/week >7 β = 8.2, 95% Confidence Interval (CI) 1.8, 14.6; ≤7 β = -0.5, 95% CI -3.7, 2.8). There was a positive association between high alcohol intake and dense area after full adjustments (servings/week >7 β = 5.8, 95% CI -2.7, 14.2; ≤7 β = -0.1, 95% CI -4.4, 4.2). We did not observe race/ethnicity modification of the association between alcohol intake and percent density. In women with a BMI of <25 kg/m2, drinkers consuming >7 servings/week of alcohol had a 17% increase in percent density compared to nondrinkers (95% CI 5.4, 29.0) and there was no association in women with a BMI ≥ 25 kg/m2 (BMI ≥ 25-30 kg/m2 > 7 β = 5.1, 95% CI -8.5, 18.7 and BMI > 30 kg/m2 > 7 β = 0.5, 95% CI -6.5, 7.5) after adjusting for age and BMI (continuous).ConclusionIn a racially/ethnically diverse cohort, women who consumed >7 servings/week of alcohol, especially those with a BMI < 25 kg/m2, had higher percent density.

Abstract OT3-3-02: Phase IIB randomized double-blind placebo-controlled biomarker modulation study of high dose vitamin D in premenopausal women at high-risk for breast cancer: SWOG S0812

Abstract Background: Priorities in breast cancer chemoprevention include developing agents effective against estrogen receptor (ER)-negative breast cancer and validating intermediate biomarkers which correlate with breast cancer risk. Vitamin D is a fat-soluble vitamin which regulates calcium and bone homeostasis, but also has diverse biological effects relevant to breast carcinogenesis. The biologically active form of vitamin D [1,25(OH)D] interacts with the vitamin D receptor (VDR) to modulate cell proliferation, differentiation, apoptosis, and angiogenesis. Epidemiologic data suggests that serum 25(OH)D levels &amp;gt;40-50 ng/ml are associated with a 40-50% reduction in breast cancer risk compared to women with vitamin D deficiency (&amp;lt;20 ng/ml). Given the high prevalence of vitamin D deficiency in the general population, vitamin D3 3000-4000 IU daily would be required to raise 25(OH)D to this putative target level. The central hypothesis of this proposal is that high-dose vitamin D will modulate biomarkers of breast cancer risk. Trial Design: This trial is a phase IIB, randomized, double-blind, placebo-controlled study of oral vitamin D3 (cholecalciferol) 20,000 IU (2 capsules) weekly for one year in 200 premenopausal women at high-risk for breast cancer. Both groups will be supplemented with a standard dose of vitamin D3 600 IU daily. Participants will undergo a mammogram and optional random core breast biopsy timed within 10 days after the start of their menstrual cycle at baseline and 1 year and blood collections at baseline, 6, and 12 months. Participants will be monitored for toxicity, particularly hypercalcemia and hypercalciuria, every 3 months during the 1-year intervention. Main Eligibility Criteria: High-risk is defined as a 5-year Gail risk score ≥1.67% or lifetime risk ≥20%, history of atypical hyperplasia, lobular or ductal carcinoma in situ, germline mutations in BRCA1, BRCA2, p53, or PTEN, history of stage I-II breast cancer in remission for &amp;gt;5 years, or baseline mammographic density &amp;gt;50%. Other eligibility criteria include baseline serum 25(OH)D ≤32 ng/ml, normal serum calcium and urine calcium/creatinine ratio, and no history of kidney stones. Specific Aims: The primary endpoint is change in mammographic density at 12 months compared to baseline between the vitamin D and placebo groups. Secondary exploratory endpoints include breast tissue-based biomarkers (Ki-67, cleaved caspase-3, ER, VDR, and 1α-hydroxylase) and blood-based biomarkers (25(OH)D, 1,25(OH)D, PTH, IGF-1, IGFBP-3, VDR polymorphisms). Statistical Methods: Power calculations are based on a two-sample comparison of normal deviates, using a 2-sided, 0.05-level test. To be conservative, we assume that 15% will have missing breast density data at 12 months and a 2% difference in mammographic density between intervention and control at 12 months with a the standard deviation for each arm of 4%. With 200 women randomized, the study will have 90% power to detect this difference. Target Accrual: 200. Sixty-seven patients accrued as of June 2013. Accrual completion expected December 2014. Contact: Katherine Crew, Columbia University Medical Center, kd59@columbia.edu. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-3-02.

Influence of Lifestyle Factors on Mammographic Density in Postmenopausal Women

BackgroundMammographic density is a strong risk factor for breast cancer. Apart from hormone replacement therapy (HRT), little is known about lifestyle factors that influence breast density.MethodsWe examined the effect of smoking, alcohol and physical activity on mammographic density in a population-based sample of postmenopausal women without breast cancer. Lifestyle factors were assessed by a questionnaire and percentage and area measures of mammographic density were measured using computer-assisted software. General linear models were used to assess the association between lifestyle factors and mammographic density and effect modification by body mass index (BMI) and HRT was studied.ResultsOverall, alcohol intake was positively associated with percent mammographic density (P trend = 0.07). This association was modified by HRT use (P interaction = 0.06): increasing alcohol intake was associated with increasing percent density in current HRT users (P trend = 0.01) but not in non-current users (P trend = 0.82). A similar interaction between alcohol and HRT was found for the absolute dense area, with a positive association being present in current HRT users only (P interaction = 0.04). No differences in mammographic density were observed across categories of smoking and physical activity, neither overall nor in stratified analyses by BMI and HRT use.ConclusionsIncreasing alcohol intake is associated with an increase in mammography density, whereas smoking and physical activity do not seem to influence density. The observed interaction between alcohol and HRT may pose an opportunity for HRT users to lower their mammographic density and breast cancer risk.

Serum 25-hydroxyvitamin D levels and mammographic density among premenopausal women in a multiethnic population

Although some evidence suggests a protective role of vitamin D against breast cancer, epidemiological findings are inconsistent. The current study investigated the relation of serum 25-hydroxyvitamin D (25(OH)D) levels with mammographic density. Baseline serum samples from 182 premenopausal women including 67 Caucasians and 74 Asians from a nutritional trial were analyzed for 25(OH)D. Mammographic density was assessed using a computer-assisted method. Serum 25(OH)D was not associated with mammographic density after adjustment for confounders (body mass index (BMI), age at mammogram, Asian ethnicity, age at first birth, parity and age at menarche). 25(OH)D levels were significantly lower in Asians than in Caucasians, but no significant ethnic differences in mammographic density were observed after adjusting for BMI. Although the current results indicate that serum 25(OH)D levels were not associated with mammographic density among premenopausal women, a possible protective effect of vitamin D against breast cancer may be mediated through other pathways.

Differences in Measured Mammographic Density in the Menstrual Cycle

In premenopausal women, the sensitivity of screening mammography for detecting breast cancer has been reported to be greater in the follicular phase than in the luteal phase of the menstrual cycle, which may be due to differences in mammographic density. To examine this possible effect, we compared mammographic density in premenopausal women who had mammograms at different phases of the menstrual cycle. We recruited premenopausal women ages 40 to 49 years from two mammography units in Toronto, recorded the first day of the last menstrual period (LMP) and measured mammographic density using Cumulus software. We classified the time of the mammography examination as having occurred in one of four intervals, 1 (first week after LMP), 2 (second week after LMP), 3 (third week after LMP) and 4 (>3 weeks after LMP), and compared mammographic density across intervals. Of the 936 women included in the analysis, 620 were examined by film and 316 by digital mammography. There were small and statistically nonsignificant variations in breast dense, nondense area, and percent density over the menstrual cycle in women examined by film mammography. Marginally significant variation in percent density was observed in the digital subset due to significant differences in the amount of nondense tissue over the menstrual cycle. Variations in mammographic density over the menstrual cycle were small and nonsignificant for women examined by either film or digital mammography. Thus, timing of mammography in menstrual cycle is unlikely to have a significant influence in breast cancer detection by screening mammography.

The Relative Importance of Genetics and Environment on Mammographic Density

Although several environmental factors predict mammographic density, estimates of its heritability have been quite high. We investigated whether part of the presumed heritability might be attributed to differential sharing of modifiable risk factors in monozygotic (MZ) and dizygotic (DZ) twins. We measured percent and absolute mammographic density using mammograms from 257 MZ and 296 DZ twin pairs. The correlation of intrapair mammographic density was compared according to zygosity across strata of modifiable risk factors. Portions of variance attributable to additive genetic factors, shared environment, and individual environment were calculated using a variance component methodology in the entire set, and within twin pairs stratified by environmental trait similarity. Both percent density and absolute mammographic density were more highly correlated between MZ twins than DZ twins, but the correlations varied across strata. Body mass index (BMI) and parity strongly predicted differences in mammographic density within MZ twin pairs. After adjusting for covariates, 53% of the total variance in percent density and 59% of that in absolute density seemed attributable to genetic effects, but these estimates varied greatly by stratum. For twins dissimilar on BMI (difference >2.5 kg/m(2)), the additive genetic component of absolute density was estimated at only 20% (+/-19%), and the common and individual environment at 21% (+/-14%) and 49%, respectively (P value for heterogeneity across BMI = 0.0001). Our results confirm that the genome is an important determinant of mammographic density but suggest that an unknown portion of the mammographic density effect attributed to the genome may be due to shared modifiable environmental factors.

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.

Mammographic density: a hormonally responsive risk factor for breast cancer

Mammographic density refers to radiologically dense breast tissue, and reflects variations in the tissue composition of the breast. It is positively associated with collagen and epithelial and non-epithelial cells, and negatively associated with fat. There is extensive evidence that mammographic density is a risk factor for breast cancer, independent of other risk factors, and is associated with large relative and attributable risks for the disease. The epidemiology of mammographic density, notably the inverse association with age, is consistent with it being a marker of susceptibility to breast cancer. Cumulative exposure to mammographic density may be an important determinant of the age-specific incidence of breast cancer in the population. All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for at least some risk factors, this influence includes an effect on the number of cells and the quantity of collagen in the breast, which is reflected in differences in mammographic density. Many of the genetic and environmental factors that influence the risk of breast cancer affect the proliferative activity and quantity of stromal and epithelial tissue in the breast, and these effects are reflected in differences in mammographic density among women of the same age. Some of these influences include endogenous and exogenous hormones, and the menopause. A better understanding of the factors that influence the response of breast tissue to these hormonal exposures may lead to an improved understanding of the aetiology of mammographic density and of breast cancer.

Associations Between Soy, Diet, Reproductive Factors, and Mammographic Density in Singapore Chinese Women

: Although the evidence is not completely consistent, soy intake has been inversely associated with breast cancer risk, and the strongest results have been observed in certain Asian populations. To address this issue and to examine the association between mammographic density and reproductive factors in this population, we conducted a crosssectional analysis of mammograms and validated food-frequency questionnaires from 380 Chinese women living in Singapore. Percent mammographic density, a biomarker for breast cancer risk, was assessed using a validated computer-assisted method. We used generalized linear models to estimate mean mammographic density by quartiles of soy intake and intake of other dietary factors while adjusting for potential confounders. Percent mammographic density was inversely associated with age, body mass index, parity, breastfeeding, and soy intake. The difference in mammographic density between the highest and lowest quartiles of soy intake was 4–5%; this difference was statistically significant for soy protein and soy isoflavone intake and is similar in magnitude to what has been reported in Western populations when women undergo menopause or commence hormone therapy. We found no evidence that high fiber, fruit, or vegetable intake has protective effects on mammographic density. Our results suggest that the effect of soy intake on percent mammographic density is moderate but possibly of clinical relevance.

Ethnic and geographic differences in mammographic density and their association with breast cancer incidence

The objective of this pooled analysis was to compare differences in dense areas and percent mammographic densities to breast cancer incidence in populations at different breast cancer risk. The data set included 1,327 women aged 40-80: Caucasians from Norway, Arizona, and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. One reader performed computer-assisted quantitative density assessment for all mammographic films. Multiple linear regression models evaluated the influence of the covariates on breast density. Spearman correlation coefficients (r (s)) estimated the association between breast density and breast cancer incidence for the seven populations. After adjustment for covariates, ethnicity, but not location, was significantly associated with breast density. In the full model, 19% of the variation in the dense areas and 46% in the variation of percent densities were explained by measured risk factors. Native Hawaiians had the largest dense areas and women in Japan the smallest, whereas percent densities were highest among Native Hawaiians and Japanese in Hawaii and lowest among Norwegian women. The mean age-adjusted dense area had the strongest association with breast cancer incidence (r (s) = 0.93, P = 0.003); the relation with percent density was considerably weaker (r (s) = 0.32, P = 0.48). The correlation between age-adjusted dense area and breast cancer incidence remained strong after selectively removing individual data points. This comparison of mammographic densities suggests that, on a group level, age-adjusted dense areas may reflect breast cancer incidence better than percent densities.

Long-term effects of tibolone on mammographic density

To investigate the long-term effect of tibolone on mammographic density. Open-label, nonrandomized study. Academic research environment. Postmenopausal women. Tibolone was administered orally, mammograms were performed annually. Mammographic density according to the Wolfe classification, performed by two independent radiologists, both of whom were blinded to treatment group. No statistically significant differences were found between the two groups in baseline demographic data. There were no statistically significant differences in mammographic density between the control and active groups at baseline or at 10 years. This pilot study shows that tibolone does not adversely alter the mammographic density of the breasts over 10 years of treatment.