Mammographic Density In Women Research Articles

Evaluation of SNPs associated with mammographic density in European women with mammographic density in Asian women from South-East Asia.

Mammographic density (MD), after accounting for age and body mass index (BMI), is a strong heritable risk factor for breast cancer. Genome-wide association studies (GWAS) have identified 64 SNPs in 55 independent loci associated with MD in women of European ancestry. Their associations with MD in Asian women, however, are largely unknown. Using linear regression adjusting for age, BMI, and ancestry-informative principal components, we evaluated the associations of previously reported MD-associated SNPs with MD in a multi-ethnic cohort of Asian ancestry. Area and volumetric mammographic densities were determined using STRATUS (N = 2450) and Volpara™ (N = 2257). We also assessed the associations of these SNPs with breast cancer risk in an Asian population of 14,570 cases and 80,870 controls. Of the 61 SNPs available in our data, 21 were associated with MD at a nominal threshold of P value < 0.05, all in consistent directions with those reported in European ancestry populations. Of the remaining 40 variants with a P-value of association > 0.05, 29 variants showed consistent directions of association as those previously reported. We found that nine of the 21 MD-associated SNPs in this study were also associated with breast cancer risk in Asian women (P < 0.05), seven of which showed a direction of associations that was consistent with that reported for MD. Our study confirms the associations of 21 SNPs (19/55 or 34.5% out of all known MD loci identified in women of European ancestry) with area and/or volumetric densities in Asian women, and further supports the evidence of a shared genetic basis through common genetic variants for MD and breast cancer risk.

Mammographic density: intersection of advocacy, science, and clinical practice.

Here we aim to review the association between mammographic density, collagen structure and breast cancer risk. While mammographic density is a strong predictor of breast cancer risk in populations, studies by Boyd show that mammographic density does not predict breast cancer risk in individuals. Mammographic density is affected by age, parity, menopausal status, race/ethnicity, and body mass index (BMI).New studies normalize mammographic density to BMI may provide a more accurate way to compare mammographic density in women of diverse race and ethnicity. Preclinical and tissue-based studies have investigated the role collagen composition and structure in predicting breast cancer risk. There is emerging evidence that collagen structure may activate signaling pathways associated with aggressive breast cancer biology. Measurement of film mammographic density does not adequately capture the complex signaling that occurs in women with at-risk collagen. New ways to measure at-risk collagen potentially can provide a more accurate view of risk.

Do Birth Weight and Weight Gain During Infancy and Early Childhood Explain Variation in Mammographic Density in Women in Midlife? Results From Cohort and Sibling Analyses.

High birth weight is associated with increased breast cancer risk and, less consistently, with higher mammographic density. In contrast, adolescent body size has been consistently, negatively associated with both MD and breast cancer risk. It is unclear when the direction of these associations changes and whether weight gain in infancy is associated with MD. We evaluated the associations of birth weight and postnatal weight (measured at 4 months, 1 year, and 4 years) by absolute and velocity measures (relative within-cohort percentile changes) with adult mammographic density, assessed using a computer-assisted thresholding program (Cumulus), using linear regression models with generalized estimating equations to account for correlation between siblings in the Early Determinants of Mammographic Density study (1959-2008; n = 700 women with 116 sibling sets; mean age = 44.1 years). Birth weight was positively associated with dense area (per 1-kg increase, β = 3.36, 95% confidence interval (CI): 0.06, 6.66). Weight gains from 0 months to 4 months and 1 year to 4 years were negatively associated with dense area (for 10-unit increase in weight percentile, β = -0.65, 95% CI: -1.23, -0.07, and β = -1.07, 95% CI: -1.98, -0.16, respectively). Findings were similar in the sibling subset. These results support the hypothesis that high birth weight is positively associated with increased breast density and suggest that growth spurts starting in early infancy reduce mammographic dense area in adulthood.

High mammographic density in women is associated with protumor inflammation

BackgroundEpidemiological studies have consistently shown that increased mammographic density (MD) is a strong risk factor for breast cancer. We previously observed an elevated number of vimentin+/CD45+ leukocytes in high MD (HMD) epithelium. In the present study, we aimed to investigate the subtypes of immune cell infiltrates in HMD and low MD (LMD) breast tissue.MethodsFifty-four women undergoing prophylactic mastectomy at Peter MacCallum Cancer Centre or St. Vincent’s Hospital were enrolled. Upon completion of mastectomy, HMD and LMD areas were resected under radiological guidance in collaboration with BreastScreen Victoria and were subsequently fixed, processed, and sectioned. Fifteen paired HMD and LMD specimens were further selected according to their fibroglandular characteristics (reasonable amount [> 20%] of tissue per block on H&E stains) for subsequent IHC analysis of immune cell infiltration.ResultsOverall, immune cell infiltrates were predominantly present in breast ducts and lobules rather than in the stroma, with CD68+ macrophages and CD20+ B lymphocytes also surrounding the vasculature. Macrophages, dendritic cells (DCs), B lymphocytes, and programmed cell death protein 1 (PD-1) expression were significantly increased in HMD epithelium compared with LMD. Moreover, significantly higher levels of DCs, CD4+ T cells, and PD-1 were also observed in HMD stroma than in LMD stroma. The increased expression of interleukin (IL)-6 and IL-4, with unaltered interferon-γ, indicate a proinflammatory microenvironment.ConclusionsOur work indicates that the immune system may be activated very early in breast cancer development and may in part underpin the breast cancer risk associated with HMD.

Vaginal estrogen and mammogram results: case series and review of literature on treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors.

To examine mammographic density before and after at least 1 year of vaginal estrogen use in a small cohort of healthy postmenopausal women and women with a personal history of breast cancer. We extracted data via chart review of patients from a single practitioner's menopause specialty clinic in Baltimore, MD. Mammographic change was primarily determined via the Bi-RADS scoring system, including the Bi-RADS density score. In addition, we conduct a narrative review of the current literature on the usage of local estrogen therapy, and systemic and local alternatives in the treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors. Twenty healthy postmenopausal women and three breast cancer survivors fit our inclusion criteria. Amongst these two groups, we did not find an increase in mammographic density after at least 1 year and up to 18 years of local vaginal estrogen. Ospemifene use in one patient did not appear to be associated with any change in Bi-RADS score. Our narrative review found little data on the effects of vaginal estrogen therapy or newer alternative systemic therapies such as ospemifene on mammographic density. Low-dose vaginal estrogen use for 1 or more years in a small cohort of women with GSM did not appear to be associated with any changes in breast density or Bi-RADS breast cancer risk scores in the majority of study participants, including three breast cancer survivors. Larger long-term controlled clinical trials should be conducted to examine the effects of low-dose vaginal estrogen on mammographic density in women with and without a personal history of breast cancer. Furthermore, relative efficacy and risk of vaginal estrogen compared with other forms of treatment for GSM should also be studied in long-term trials.

Does mammographic density in women with previous breast cancer predict further breast cancer?

Does mammographic density in women with previous breast cancer predict further breast cancer?

Alcohol consumption and mammographic density in the Danish Diet, Cancer and Health cohort.

We examined the association between alcohol consumption and mammographic density (MD) considering in detail the time of exposure and the type of alcohol. Of 5,356 women (4,489 post-menopausal) from the Danish Diet, Cancer and Health cohort (1993-1997) who attended mammographic screening in Copenhagen (1993-2001), we used MD (mixed/dense or fatty) assessed at the first screening after cohort entry. Alcohol consumption was assessed at the time of recruitment. Logistic regression was used to estimate associations [odds ratios (OR), 95% confidence intervals (CI)] between alcohol consumption and MD. The mean age was 56.2 years, 56.5% of women had mixed/dense MD, and 91.8% were alcohol consumers. There was no association between current alcohol consumption and MD at baseline (age 50-65, on average 1year before MD assessment) neither between age at drinking initiation and MD, in the fully adjusted model. There was a borderline statistically significantly increased OR of having mixed/dense MD in women who consumed > 7 drinks/week at age 20-29 (1.31, 95% CI 1.00-1.72) compared to non-drinkers in this age group, and no effect of drinking at age 30-39, 40-49 or after > 50 years, when adjusting for current drinking. However, when considering different types of alcohol, drinking spirits at age 20-29 was positively associated with mixed/dense breast (3-7 drinks/week: OR 1.74, 95% CI 1.12-2.72); >7 drinks/week: (OR 1.76, 95% CI 0.73-4.23). No consistent pattern was found with beer, wine, or fortified wine. We found higher MD among women with high alcohol consumption in early adulthood (ages 20-29), in those drinking spirits.

High Mammographic Density in Long-Term Night-Shift Workers: DDM-Spain/Var-DDM.

Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women.Methods: The study covered 2,752 women aged 45-68 years recruited in 2007-2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center-specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables.Results: Having ever worked in NSW was not associated with MD [Formula: see text]:0.96; 95% confidence interval (CI), 0.86-1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD>15 years:20.7% vs. MDnever:16.5%;[Formula: see text]:1.25; 95% CI,1.01-1.54). This association was mainly observed in postmenopausal participants ([Formula: see text]:1.28; 95% CI, 1.00-1.64). Among NSW-exposed women, those with ≤2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week ([Formula: see text]:1.42; 95% CI, 1.10-1.84).Conclusions: Performing NSW was associated with higher MD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies.Impact: Our findings suggest that MD could play a role in the pathway between long-term NSW and breast cancer. Cancer Epidemiol Biomarkers Prev; 26(6); 905-13. ©2017 AACR.

Sample size and power determination when limited preliminary information is available

BackgroundWe describe a novel strategy for power and sample size determination developed for studies utilizing investigational technologies with limited available preliminary data, specifically of imaging biomarkers. We evaluated diffuse optical spectroscopic imaging (DOSI), an experimental noninvasive imaging technique that may be capable of assessing changes in mammographic density. Because there is significant evidence that tamoxifen treatment is more effective at reducing breast cancer risk when accompanied by a reduction of breast density, we designed a study to assess the changes from baseline in DOSI imaging biomarkers that may reflect fluctuations in breast density in premenopausal women receiving tamoxifen.MethodWhile preliminary data demonstrate that DOSI is sensitive to mammographic density in women about to receive neoadjuvant chemotherapy for breast cancer, there is no information on DOSI in tamoxifen treatment. Since the relationship between magnetic resonance imaging (MRI) and DOSI has been established in previous studies, we developed a statistical simulation approach utilizing information from an investigation of MRI assessment of breast density in 16 women before and after treatment with tamoxifen to estimate the changes in DOSI biomarkers due to tamoxifen.ResultsThree sets of 10,000 pairs of MRI breast density data with correlation coefficients of 0.5, 0.8 and 0.9 were simulated and generated and were used to simulate and generate a corresponding 5,000,000 pairs of DOSI values representing water, ctHHB, and lipid. Minimum sample sizes needed per group for specified clinically-relevant effect sizes were obtained.ConclusionThe simulation techniques we describe can be applied in studies of other experimental technologies to obtain the important preliminary data to inform the power and sample size calculations.

Determinants of percent mammographic density in women with premature ovarian insufficiency

Objective: To evaluate the determinants of breast density in women with premature ovarian insufficiency (POI).Methods: In a cross-sectional study of 163 women with POI undergoing mammography, percent mammographic density (PMD) was evaluated by digitizing the image. PMD was correlated with age, age at menarche, age at POI, time since POI, body mass index (BMI), gestational history and hormone therapy (HT) use (duration, dose, regimen).Results: POI was diagnosed at a mean age of 32.3 ± 5.9 years. The mean age of the women at mammography was 41.3 ± 5.4 years; mean BMI was 27.4 ± 5.4 kg/m2 and mean PMD was 24.3 ± 18.5. Mean PMD did not differ between the different age groups evaluated (29–39, 40–49 and 50–55 years) or between users and non-users of HT. Mean duration of HT use was 5.6 ± 4.7 years. PMD was higher in nulligravidas compared to women who had been pregnant (p = 0.0016); however, POI occurred earlier in nulligravidas (p < 0.0001). PMD correlated negatively with BMI (r = −0.27; p = 0.0005). Conclusion: In women with POI, HT use had no effect on PMD, irrespective of the duration of use, dose or regimen. Pregnancy and BMI were consistently associated with PMD, with density being greater in nulligravidas and in women with lower BMI.

Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy.

BackgroundElevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis.MethodsOne hundred and ninety-five women, ages 40–65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses).ResultsMean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42).ConclusionsOur analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.

Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

AimTo investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.MethodsMammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31) slides and correlated to mammographic density.ResultsIncreasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22) = 0.5226, p = 0.0088) and significantly inversely associated with adipose tissue proportion (rs (22) = -0.5409, p = 0.0064). Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%). There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026).ConclusionsThe proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.

Abstract P3-07-03: Insulin-like growth factor-1 receptor variant associated with decreased breast cancer risk in women with pregnancy-induced hypertension

Abstract Introduction: Studies have reported a lower breast cancer risk in women who have experienced pregnancy induced hypertension (PIH). Current hypotheses for these observations center on placental dysfunction and a subsequent alteration of levels of circulating hormones, growth factors, and angiogenic and immune modulators. The Marin Women's Study (MWS) was initiated in 2006 to examine breast cancer in Marin County, an area with historically high breast cancer rates. Enrollment of 13,365 women occurred at mammography sites that participate in the San Francisco Mammography Registry (SFMR), one of seven registries included in the NCI Breast Cancer Consortium. In a prior analysis of MWS data, we demonstrated that PIH is associated with reduced breast density later in life, and the current two-phased study was designed to assess whether this apparent protective effect is modified by individual genetic differences. Methods: Participants self-reported reproductive history and risk factors on the MWS questionnaire at the time of enrollment. Compositional breast density using single X-ray absorptiometry (SXA) was measured on digital mammography. These readings and breast cancer case status data obtained from the California Cancer Registry was acquired by cooperative agreements with the SFMR. DNA for SNP analyses was extracted from donated saliva specimens. The first phase analysis focused on breast density and assessed the interaction of 7 SNPs of specific selected genes with a history of PIH. A second phase analysis focused on breast cancer case status for any SNP which appeared to demonstrate interaction in the initial analysis. Results: After adjusting for potential confounders, only the IGF1R SNP (rs2016347) demonstrated a statistically significant interaction with PIH on mammographic density (GT, p = 0.01, and TT, p = 0.07 compared to baseline GG), although the VEGF SNP (rs3025039) approached statistical significance (CT, p = 0.06 compared to baseline CC) in our sample size of 1240 women. The second phase of the analysis examined the association of the VEGF and IGF1R SNPs with breast cancer case status in all women in the MWS with a history of PIH, saliva specimen, and case status data (n = 374). There was a statistically significant decrease in breast cancer risk in women with PIH and the IGF1R SNP as shown below: Breast cancer cases in women with PIH by IGF1R genotypeIGF1R GenotypeNumber with genotypeNumber breast cancer cases% breast cancer casesGG9188.79%GT195147.18%TT8800.00%Fisher's exact = 0.008 There was no statistical association between this SNP and PIH incidence or case status in women without PIH, where 27.1% of breast cancer cases had the IGF1R TT genotype (108/398). Conclusions: Women with a history of PIH had a lower risk of breast cancer if they had the TT genotype of the IGF1R SNP (rs2016347), and this genotype was also associated with lower breast density. Since this IGF1R variant has previously been associated with mammographic density and found to be an independent prognostic marker for breast cancer recurrence, its expression may play a breast cancer protective role by reducing mammographic density in women with PIH. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-03.

Mammographic density in birth cohorts of Danish women: a longitudinal study

BackgroundBreast cancer is the leading malignant disease among western women with incidence increasing over time. High mammographic density is a well-established risk factor for breast cancer. We explored trends in mammographic density across birth cohorts to gain further insight into possible time trends in women’s mammographic density that might explain the historical increase in breast cancer incidence.MethodsData derived from two mammography screening programs in Denmark from 1991 to 2001, including on average 41,091 women from Copenhagen and 52,938 women from Funen aged 50–69. Mammographic density was assessed qualitatively (fatty or mixed/dense) by senior screening radiologists. The proportion of women with mixed/dense mammographic density was calculated by age at screening, screening period, and birth cohort. The Generalized Estimating Equations were used to calculate odds ratios and 95% confidence intervals. All statistical tests were two-sided.ResultsThe proportion of women with mixed/dense mammographic density increased from 45% among women born in the 1920s to 75-80% among women born in the 1940s. In Copenhagen, the age-adjusted odds ratio (95% CI) of mixed/dense mammographic density in women born in 1941–42 was 2.48 (2.22-2.76) compared with women born in 1921–22. In Funen, the age-adjusted odds ratio of mixed/dense mammographic density in women born in 1946–47 was 5.89 (5.32-6.51) compared with women born in 1924–25. Hormone use had a greater impact on mammographic density in birth cohorts of the 1920s compared with those of the 1940s.ConclusionsWe found suggestive evidence of a birth cohort pattern in mammographic density and an attenuated impact of hormone use in younger compared with older birth cohorts suggesting that postmenopausal mammographic density could be linked to changing exposures accumulated over time in women’s lives.

High mammographic density in women of Ashkenazi Jewish descent

IntroductionPercent mammographic density (PMD) adjusted for age and body mass index is one of the strongest risk factors for breast cancer and is known to be approximately 60% heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD.MethodsWe selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age-adjusted and body mass index-adjusted PMD. Our final dataset included 474 women with the highest adjusted PMD and 469 with the lowest genotyped on the Illumina 1 M platform. Principal component analysis (PCA) and identity-by-descent analyses allowed us to infer the women's genetic ancestry and correlate it with adjusted PMD.ResultsWomen of Ashkenazi Jewish ancestry, as defined by the first principal component of PCA and identity-by-descent analyses, represented approximately 15% of the sample. Ashkenazi Jewish ancestry, defined by the first principal component of PCA, was associated with higher adjusted PMD (P = 0.004). Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association.ConclusionsWomen of Ashkenazi Jewish ancestry, based on genetic analysis, are more likely to have high age-adjusted and body mass index-adjusted PMD. Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density.

Mammographic density as a predictor of breast cancer survival: the Multiethnic Cohort

IntroductionMammographic density, a strong predictor for breast cancer incidence, may also worsen prognosis in women with breast cancer. This prospective analysis explored the effect of prediagnostic mammographic density among 607 breast cancer cases diagnosed within the Hawaii component of the Multiethnic Cohort (MEC).MethodsFemale MEC participants, aged ≥ 50 years at cohort entry, diagnosed with primary invasive breast cancer, and enrolled in a mammographic density case-control study were part of this analysis. At cohort entry, anthropometric and demographic information was collected by questionnaire. Tumor characteristics and vital status were available through linkage with the Hawaii Tumor Registry. Multiple digitized prediagnostic mammograms were assessed for mammographic density using a computer-assisted method. Cox proportional hazards regression was applied to examine the effect of mammographic density on breast cancer survival while adjusting for relevant covariates.ResultsOf the 607 cases, 125 were diagnosed as in situ, 380 as localized, and 100 as regional/distant stage. After a mean follow-up time of 12.9 years, 27 deaths from breast cancer and 100 deaths from other causes had occurred; 71 second breast cancer primaries were diagnosed. In an overall model, mammographic density was not associated with breast cancer-specific survival (HR = 0.95 per 10%; 95%CI: 0.79-1.15), but the interaction with radiotherapy was highly significant (p = 0.006). In stratified models, percent density was associated with a reduced risk of dying from breast cancer (HR = 0.77; 95%CI: 0.60-0.99; p = 0.04) in women who had received radiation, but with an elevated risk (HR = 1.46; 95% CI: 1.00-2.14; p = 0.05) in patients who had not received radiation. High breast density predicted a borderline increase in risk for a second primary (HR = 1.72; 95% CI: 0.88-2.55; p = 0.15).ConclusionsAssessing mammographic density in women with breast cancer may identify women with a poorer prognosis and provide them with radiotherapy to improve outcomes.

Correlation Between Mammographic Breast Density and Expression of 17ß Hydroxysteroid Desydrogenase Type 1

INTRODUCTION: High Mammographic density is a breast cancer risk factor and it is present over one third of cases of breast cancer. The 17s-hydroxysteroid dehydrogenase (17s-HSD) enzyme has possible local effects on breast tissue by stimulating growth of breast epithelial cells and is associated with mammographic density in women in pre and perimenopause. After a review in the literature, we see the importance of the enzyme 17sHSD1 in the etiology of breast cancer by both local and peripheral steroidogenesis, which may increase breast density. OBJECTIVE: For this reason we studied the correlation between mammographic breast density and immunohistochemical expression of 17s hydroxysteroid desydrogenase type 1 (17sHSD1). Casuistic and METHODS: 48 cases were evaluated with mammographic image classified by BI-RADS® system in four categories. The pattern of density 1 and 2 (measure breast tissue until 50%) was classified like low density and the pattern 3 and 4 (measure breast tissue upper 50%) like high density. Expression of the enzymes were evaluated by tissue microarray (TMA) screened with anti-17sHSD1 monoclonal rabbit antibodies (LS-C49955, Lifespan) diluted 1/200. Specimens were assigned scores on a scale from zero to three according to intensity of staining and number of stained cells. Scores zero and one were considered negative results and scores two and three indicated positive enzyme expression. RESULTS: In relation to breast density, in absolute numbers and percentages, we found the following results in category 1, 17 patients (35.42%), category 2, 17 patients (35.42%), category 3, 6 patients (12 50%) and category 4, 8 patients (16.67%). The 17sHSD1 expression was positive in 18 (37.5%). Statistical analysis showed no significant correlation between the expression of 17sHSD1 (p = 0.00048) with breast density (p = 0.666). No significant correlation between the expression of 17sHSD1 with breast density was found to be unchanged even when the analysis of the proposed subgroups (BMI greater than or less than 25, aged 50 years or less and high and low mammographic density). CONCLUSION: The results of our studies showed that there was no positive association between mammographic breast density and the expression of the enzyme 17sHSD1.

GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening

Genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione S-transferases (GSTM1, GSTT1, and GSTP1) superfamily have been associated with an increased risk for breast cancer (BC). Considering the high incidence of BC in the city of Porto Alegre in southern Brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in GSTM1, GSTT1, and GSTP1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. Molecular tests were performed using the multiplex polymerase chain reaction (PCR) for GSTM1 and GSTT1, and quantitative PCR for GSTP1 polymorphisms. Overall, the frequencies of GSTM1 and GSTT1 null genotypes were 45% and 21%, respectively. For GSTP1 polymorphism, genotypic frequencies were 44% for the Ile/Ile genotype, 44% for the Ile/Val genotype, and 12% for Val/Val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. There was a statistically significant association between the combined GSTM1 and GSTT1 null genotypes (M-/T-) and mammographic density in post menopausal women (p = 0.031). When the GSTT1 null (T-) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). These findings suggest an association of GSTM1 and GSTT1 null genotypes with mammographic density.

Correlations between shear wave elastography and mammographic findings in invasive breast cancer

Shear wave elastography is a new ultrasound technique which shows promise in the differential diagnosis of solid breast masses. This study compares the mean tumour stiffness with mammographic findings and mammographic density in women with invasive breast cancer.

Childhood factors associated with mammographic density in adult women

Growth and development factors could contribute to the development of breast cancer associated with an increase in mammographic density. This study examines the influence of certain childhood-related, socio-demographic and anthropometric variables on mammographic density in adult woman. The study covered 3574 women aged 45-68 years, participating in breast cancer-screening programmes in seven Spanish cities. Based on a craniocaudal mammogram, blind, anonymous measurement of mammographic density was made by a single radiologist, using Boyd's semiquantitative scale. Data associated with the early stages of life were obtained from a direct survey. Ordinal logistic regression and generalised linear models were employed to estimate the association between mammographic density and the variables covered by the questionnaire. Screening programme was introduced as a random effects term. Age, number of children, body mass index (BMI) and other childhood-related variables were used as adjustment variables, and stratified by menopausal status. A total of 811 women (23%) presented mammographic density of over 50%, and 5% of densities exceeded 75%. Our results show a greater prevalence of high mammographic density in women with low prepubertal weight (OR: 1.18; 95% CI: 1.02-1.36); marked prepubertal height (OR: 1.25; 95% CI: 0.97-1.60) and advanced age of their mothers at their birth (>39 years: OR: 1.28; 95% CI: 1.03-1.60); and a lower prevalence of high mammographic density in women with higher prepubertal weight, low birth weight and earlier menarche. The influence of these early-life factors may be explained by greater exposure to hormones and growth factors during the development of the breast gland, when breast tissue would be particularly susceptible to proliferative and carcinogenic stimulus.