Percent Breast Research Articles

Abstract 2779: Relationship of mammographic density with breast cancer subtypes

Abstract Background: Mammographic density (MD), a measure of the amount of radiologically dense breast tissue, is one of the strongest breast cancer risk factors. Studies have found that high MD increases risk for both estrogen receptor (ER)-negative and positive breast cancers, but data relating MD to breast cancer subtypes are limited. Methods: We used data from the population-based Polish Breast Cancer Study to explore relationships between MD and breast cancer characteristics. This analysis includes 227 invasive breast cancers, which were available as frozen samples and used for mRNA and cytogenetic profiling, and fixed tissues, which were prepared as tissue microarrays for immunohistochemical analysis. Pre-treatment mammograms of the unaffected breast were retrieved for 184 (81%) cases ages 28-75 years. Craniocaudal views of digitized films were used to assess percent MD with Cumulus, a computer-assisted thresholding method. Analysis of variance (ANOVA) models were used to test the null hypothesis of no mean difference in MD between the breast cancer subtypes. Results: Tumor subtypes were classified by key immunohistochemical markers as luminal A (ER+ and/or progesterone receptor (PR)+, human epidermal growth factor receptor-2 (HER2)-; n=129), luminal B (ER+ and/or PR+, HER2+; n=6), HER2-expressing (ER-, PR-, HER2+; n=13), basal-like (ER-, PR-, HER2-, cytokeratin 5+, and/or HER1+; n=23), and unclassified (negative for all five markers; n=8). Five cases did not have interpretable staining for all five markers and were excluded. MD values were approximately normally distributed. Preliminary ANOVA models revealed no differences in mean percent MD by tumor subtypes (p=0.29) as follows: luminal A, 27.5% (95% confidence interval (CI): 24.9-30.2); luminal B, 27.0% (95% CI: 14.8-39.2); HER2-expressing, 27.2% (95% CI: 18.9-35.5); basal-like, 24.6% (95% CI: 18.4-30.8); and unclassified, 15.7% (95% CI: 5.2-26.3). In analysis of covariance models adjusted for age there was marginal evidence of elevated MD with the HER2-expressing subtype (p=0.04), but we cannot exclude the possibility that this is a chance finding. Conclusions: Our results do not provide strong support for an association between percent MD and breast cancer subtypes. To identify additional clues as to the biology underlying the MD-breast cancer relationship, ongoing analyses will relate MD to mRNA and cytogenetic profiles and data for protein expression via immunohistochemistry available for additional markers as previously reported. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2779.

Serum vitamin D and breast density in breast cancer survivors.

Vitamin D influences cellular proliferation and proliferation-related breast tissue characteristics, such as mammographic breast density. Little is known about vitamin D status, assessed by serum 25-hydroxyvitamin D [25(OH)D], and its relationship to breast density in breast cancer survivors. Participants were 426 postmenopausal breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Women from New Mexico, Los Angeles, and western Washington were enrolled postdiagnosis. Data for this report are from an examination conducted 24 months postenrollment. Participants completed health-related questionnaires, gave fasting blood samples, and completed height and weight measurements. Serum [25(OH)D] was assayed by radioimmunoabsorbant assay. Breast dense area and percent density were measured from postdiagnosis-digitized mammograms. Multivariate linear regression tested associations of serum [25(OH)D] with mammographic breast density measures. Of the 426 participants, 22.8% were African-American, 11.3% were Hispanic, and 62.8% were non-Hispanic white. We observed no associations of serum [25(OH)D] with either breast density or breast dense area. Among women with vitamin D deficiency (serum [25(OH)D], <16.0 ng/mL; n = 103), mean percent breast density was 8.0%, and among those with sufficient status (n = 99; serum [25(OH)D], > or = 32.0 ng/mL), mean percent density was 8.5%. Breast dense area averaged 27.2 and 26.2 cm2 for women with vitamin D deficiency and sufficiency, respectively. Data from this multiethnic cohort of breast cancer survivors do not support the hypothesis that serum vitamin D, [25(OH)D], is associated with breast density in cancer survivors.

Associations between Polymorphisms in Glucuronidation and Sulfation Enzymes and Mammographic Breast Density in Premenopausal Women in the United States

Sex hormones are metabolized to less active compounds via (a) glucuronidation catalyzed by UDP-glucuronosyltransferases (UGT) and (b) sulfation catalyzed by sulfotransferases (SULT). Functional UGT and SULT polymorphisms can affect clearance of sex hormones, thereby influencing exposure in hormone-sensitive tissues, such as the breast. We assessed relationships between functional polymorphisms in the UGT and SULT genes and breast density in premenopausal women. One hundred seventy-five women ages 40 to 45 years, who had a screening mammogram taken within the previous year, provided a genomic DNA sample. Mammograms were digitized to obtain breast density measures. Using generalized linear regression, we assessed associations between percent breast density and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the SULT1A1(H213/H213) genotype had 16% lower percent breast density compared with women with the SULT1A1(R213/R213) genotype after controlling for ethnicity (P = 0.001). Breast density was 5% lower among women carrying at least one copy of the UGT1A1(TA7)-UGT1A3(R11)-UGT1A3(A47) haplotype compared with the UGT1A1(TA6)-UGT1A3(W11R)-UGT1A3(V47A) haplotype (P = 0.07). No associations were observed between polymorphisms in the UGT2B family or SULT1E1 and breast density. Polymorphisms in SULT1A1 and the UGT1A locus may influence percent breast density in premenopausal women.

Abstract A2: Genetic variation in estrogen receptor genes and mammographic breast density

Abstract Mammographic density is one of the strongest, independent risk factors in the development of breast cancer. Women with mammographically dense breasts, those with greater than or equal to 75% dense tissue, are at a four to six-fold greater risk of developing breast cancer when compared to those with “no measurable dense tissue,” in which the breasts are composed entirely of fat. Many of the established risk factors for breast cancer have been shown to be associated with variations in breast density (i.e., age, menopausal status, parity, BMI, and postmenopausal hormone use). Additionally, twin studies have also shown that heritability accounts for approximately 60% of the variance in mammographic density. Given the established role of estrogens in the development and progression of breast cancer, we have evaluated the role of 17 single-nucleotide polymorphisms (SNPs) in the estrogen receptor 1 and 2 genes (ESR1 and ESR2), and the recently identified G-Protein Coupled Estrogen Receptor 1 (GPER) gene, which has been demonstrated to regulate physiologic responses to estrogens independent of the traditional estrogen receptors. This study population consisted of 370 cancer-free (excluding cancers of the skin) Caucasian, postmenopausal women enrolled in the Mammograms and Masses Study (MAMS). Three different measures of mammographic density were computed: dense breast area, total breast area, and percent breast density, using the classification system developed by Wolfe in 1976, and a compensating polar planimeter, wax pencil, and transparent overlay. Breast density was calculated as the proportion of visibly dense breast to total breast area, expressed as a percentage. DNA was extracted from buffy coat samples, and genotyping was done using the Sequenom iPLEX Gold Assay. Heterozygote and homozygous variant genotypes were collapsed and compared to the common allele genotype for all statistical analyses. General linear models and χ2 analyses were conducted. We arranged our percent density variable into tertiles for further analysis. We observed that three SNPs in ESR2 (rs12435857, rs1256044, and rs1256031) were significantly associated with percent mammographic density. For ESR2 rs1256044 and rs1256031, mean percent mammographic density was significantly higher among women with at least one rare allele compared to women homozygous for the common allele (respectively, P=0.02 and P=0.03). Conversely, mean percent mammographic density was significantly higher among women with ESR2 rs12435857 GG genotype compared to those with GA/AA genotypes, 29.0 and 23.7, respectively (P=0.03). Our results suggest that common genetic variation in ESR2 is associated with percent mammographic density. Since estrogen receptor genes are highly expressed in breast tissue, functional SNPs in these genes may alter breast cancer risk, by altering mammographic density. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A2.

Reduction of Breast Density Following Tamoxifen Treatment Evaluated by 3-D MRI.

Abstract Background: It has been reported that MRI-based density measurement is more sensitive than mammographic density to evaluate the small changes of breast density. This study analyzed the change of breast density in women receiving tamoxifen treatment using 3-D MRI.Material and Methods: Twenty-two breasts in 20 women were studied. Two MRI studies were performed at 1.5T, the baseline scan acquired after surgery and prior to receiving tamoxifen, and the follow-up scan at 10 months to 30 months after tamoxifen treatment. Non-fat-suppression T1-weighted images were used for the density measurement. The breast and the fibroglandular tissue were segmented using a computer-assisted algorithm recently published by our group. For each breast, the total fibroglandular tissue volume and the total breast volume were calculated, and then the ratio was calculated as the percent breast density (%BD). The changes in breast volume, fibroglandular tissue volume, and the percent density in the F/U scan compared to the B/L scan were evaluated. The reduction in the fibroglandular volume (ΔFV=FV2-FV1, ml), and in the percent breast density (Δ%BD= %BD2-%BD1) were analyzed.Results: The total breast volume did not show significant changes between F/U and B/L. For analysis of fibroglandular volume, 20 breasts showed volume reduction and 2 showed slight increase of volume. Overall, the mean ΔFV was 20.7ml, with 33% reduction. The ΔFV was correlated with the baseline FV (r=0.82) (Figure 1), indicating that when the fibroglandular tissue volume was higher, more reduction was found.For analysis of %BD, 19 breasts showed reduction, and 3 showed increased density, with a mean Δ%BD of 4.7%. The 22 breasts were further divided into three categories based on their B/L density as: fatty breast (%BD&amp;lt; 8%, N=4), moderately dense breast (%BD 8-20%, N=9), and dense breast (%BD &amp;gt;20%, N=9). The amount of density reduction was associated with the B/L density, showing 10.9, 17.2, and 28.6 ml for ΔFV; and 1.2%, 3.9%, and 7.2% for Δ%BD respectively in these 3 groups. Statistically, only Δ%BD between the fatty and the dense groups showed a significant difference (P=0.02).Discussion: MRI provides strong soft tissue contrast, thus it may have advantages for revealing detailed density distribution compared to mammography. The %BD can be measured by normalizing the FV to the total breast volume, analogous to the mammographic density. However, this will be subjective to the variations in the measurement of breast volume. The FV within the breast was a more robust parameter, which showed reduction in 20 of 22 breasts with a mean reduction of 33%, also a significant correlation with B/L FV. The reduction of density is expected to be through decreased hormonal level in the breast, and the reduction of fibroglandular tissue density should be correlated with the baseline density. Our results are consistent with this expectation, and demonstrate that MRI can be used to evaluate the density change induced by tamoxifen. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4021.

Quantitative analysis of breast parenchymal patterns using 3D fibroglandular tissues segmented based on MRI

Mammographic density and breast parenchymal patterns (the relative distribution of fatty and fibroglandular tissue) have been shown to be associated with the risk of developing breast cancer. Percent breast density as determined by mammography is a well-established risk factor, but on the other hand, studies on parenchymal pattern have been scarce, possibly due to the lack of reliable quantitative parameters that can be used to analyze parenchymal tissue distribution. In this study the morphology of fibroglandular tissue distribution was analyzed using three-dimensional breast MRI, which is not subject to the tissue overlapping problem. Four parameters, circularity, convexity, irregularity, and compactness, which are sensitive to the shape and margin of segmented fibroglandular tissue, were analyzed for 230 patients. Cases were assigned to one of two distinct parenchymal breast patterns: Intermingled pattern with intermixed fatty and fibroglandular tissue (Type I, N = 141), and central pattern with confined fibroglandular tissue inside surrounded by fatty tissue outside (Type C, N = 89). For each analyzed parameter, the differentiation between these two patterns was analyzed using a two-tailed t-test based on transformed parameters to normal distribution, as well as distribution histograms and ROC analysis. These two groups of patients were well matched both in age (50 +/- 11 vs 50 +/- 11) and in fibroglandular tissue volume (Type I: 104 +/- 62 cm3 vs Type C: 112 +/- 73 cm3). Between Type I and Type C breasts, all four morphological parameters showed significant differences that could be used to differentiate between the two breast types. In the ROC analysis, among all four parameters, the "compactness" could achieve the highest area under the curve of 0.84, and when all four parameters were combined, the AUC could be further increased to 0.94. The results suggest that these morphological parameters analyzed from 3D MRI can be used to distinguish between intermingled and central dense tissue distribution patterns, and hence may be used to characterize breast parenchymal pattern quantitatively. The availability of these quantitative morphological parameters may facilitate the investigation of the relationship between parenchymal pattern and breast cancer risk.

Impact of skin removal on quantitative measurement of breast density using MRI

In breast MRI, skin and fibroglandular tissue commonly possess similar signal intensities, and as such, the inclusion of skin as dense tissue leads to an overestimation in the measured density. This study investigated the impact of skin to the quantitative measurement of breast density using MRI. The analysis was performed on the normal breasts of 50 women using nonfat-saturated (nonfat-sat) T1 weighted MR images. The skin was segmented by using a dynamic searching algorithm, which was based on the change in signal intensities from the background air (dark), to the skin (moderate), and then to the fatty tissue (bright). Tissue with moderate intensities that fell between the two boundaries determined based on the intensity gradients (from air to skin, and from skin to fat) was categorized as skin. The percent breast density measured with and without skin exclusion was compared. Also the relationship between the skin volume and the breast volume was investigated. Then, this relationship was used to estimate the skin volume from the breast volume for skin correction. The percentage of the skin volume normalized to the breast volume ranged from 5.0% to 15.2% (median 8.6%, mean +/- STD 8.8 +/- 2.6%) among 50 women. The percent breast densities measured with skin (y) and without skin (x) were highly correlated, y = 1.23x+7% (r = 0.94, p < 0.001). The relationship between the skin volume and the breast volume was analyzed based on transformed data (the square root of the skin volume vs the cube root of breast volume) using the linear regression, and yielded r = 0.87, p < 0.001. When this model was used to estimate the skin volume for correction in the density analysis, it provided a better fit to the measured density with skin exclusion (with adjusted R2 = 0.98, and root mean square error = 1.6) compared to the correction done by using a fixed cutoff value of 8% (adjusted R2 = 0.83, root mean square error = 4.7). The authors have shown that the skin volume is related to the breast volume, and this relationship may be used to correct for the skin effect in the MRI-based density measurement. A reliable quantitative density analysis method will aid in clinical investigation to evaluate the role of breast density for cancer risk assessment or for prediction of the efficacy of risk-modifying drugs using hormonal therapy.

A randomized, placebo-controlled trial (NCIC CTG MAP1) examining the effects of letrozole on mammographic breast density and other end organs in postmenopausal women

Mammographically detected breast density has been correlated with breast cancer risk. Breast density appears to be influenced by hormonal factors including increasing age, postmenopausal status, number of pregnancies, lower body weight, hormone replacement therapy, and tamoxifen therapy. The aromatase inhibitor letrozole profoundly reduces breast and circulating estrogen levels in postmenopausal women. We hypothesize that letrozole may reduce breast density and report here on its effects on mammographic breast density, bone mineral density (BMD), bone biomarkers, plasma hormone, and serum lipid levels. MAP1 was a multicenter, randomized, double-blind, placebo-controlled, feasibility trial in which postmenopausal women with or without prior invasive breast cancer were randomized in a 2:1 ratio of letrozole (2.5 mg daily) or placebo for 12 months and followed for a total of 24 months. Eligible women had an estimated >25% breast density on baseline mammogram. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms as estimated by a computer-assisted thresholding program. Baseline and 12-month mammographic density was also assessed in a blinded manner by visual inspection. Secondary endpoints included changes in serum hormones, plasma lipid levels, bone biomarkers, and BMD. Data are available for 67 women (44 on letrozole and 23 on placebo). No significant changes in PD were noted between the treatment arms at either 12 or 24 months. No distinguishable difference in density measurements by visual inspection were noted between baseline and 12-month mammograms. A significant decrease in percentage change in T-score of the femoral neck at 12 months was noted in the letrozole arm without other significant changes in BMD parameters. Lipid values did not differ between treatment groups except for a borderline significant decrease in total cholesterol at 3 months among women treated with letrozole. Letrozole therapy was associated with a significant reduction in mean serum estradiol, estrone, and estrone sulfate levels at 12 months, but not at 24 months. A significant increase in serum IGF-1 levels was also noted in the letrozole group compared to the placebo group at both 12 and 24 months. To conclude, compared with placebo, 12 months of letrozole therapy does not appear to have a significant effect on mammographic PD. Twelve months of letrozole was associated with a decrease of uncertain clinical significance in the T-score of the femoral neck at 12 months which was reversible at 24 months with recovery of estrogen levels. Letrozole therapy was found to increase IGF-1 levels at 12 and 24 months.

Poster — Wed Eve—10: An X‐Ray Attenuation Approach to Breast Density for Full Field Digital Mammography

Mammography, in principal, is x‐ray imaging with high resolution and contrast and based on the fact that the intensity of the x‐ray radiation reduced different amount as it traverses different matter. Starting from this basic definition we have explored the possibility of using x‐ray attenuation for quantitative determination of the density of the sample along the path of the x‐ray beam, which in our case corresponds to the product of the breast thickness and actual density of the breast. We have observed that x‐ray attenuation is strongly correlated with the percent breast density and developed a simple method based on this simple physical principle in order to estimate the percent breast density from digital mammography images. Comparison of the results with the radiologist evaluation for breast density demonstrates the applicability of the x‐ray attenuation measurements to determine breast density using a physical model without any assumptions.

Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women

Mammographic breast and bone mineral densities (BMD) have been associated with luteal phase hormone concentrations in premenopausal women. We assessed the associations of breast and bone densities with follicular phase hormones and sex hormone binding globulin (SHBG) in premenopausal women, given that follicular phase hormones have been shown to be positively associated with premenopausal breast cancer risk. One hundred and ninety-two 40-45-year-old women provided a spot urine and/or blood sample during the follicular phase. Hormone and SHBG concentrations, and bone density were measured and routine mammograms were accessed and digitized to obtain breast density measures. Regression models were fit to assess the associations between hormones and SHBG, and breast and bone densities. Positive associations were observed between percent breast density and SHBG (p trend = 0.02), as well as estradiol (p trend = 0.08), after controlling for body mass index (BMI), number of pregnancies, and breast feeding history. In addition, a statistically significant inverse association was observed between total testosterone and head BMD (p trend = 0.01), after controlling for BMI. Associations were observed between breast and bone densities, and serum hormone concentrations during the follicular phase of the menstrual cycle.

Longitudinal association of anthropometry with mammographic breast density in the Study of Women's Health Across the Nation

High percent mammographic breast density is strongly associated with increased breast cancer risk. Though body mass index (BMI) is positively associated with risk of postmenopausal breast cancer, BMI is negatively associated with percent breast density in cross-sectional studies. Few longitudinal studies have evaluated associations between BMI and weight and mammographic breast density. We studied the longitudinal relationships between anthropometry and breast density in a prospective cohort of 834 pre- and perimenopausal women enrolled in an ancillary study to the Study of Women's Health Across the Nation (SWAN). Routine screening mammograms were collected and read for breast density. Random intercept regression models were used to evaluate whether annual BMI change was associated with changes over time in dense breast area and percent density. The study population was 7.4% African-American, 48.8% Caucasian, 21.8% Chinese, and 21.9% Japanese. Mean follow-up was 4.8 years. Mean annual weight change was +0.32 kg/year, mean change in dense area was -0.77 cm(2)/year, and mean change in percent density was -1.14%/year. In fully adjusted models, annual change in BMI was not significantly associated with changes in dense breast area (-0.17 cm(2), 95% CI -0.64, 0.29). Borderline significant negative associations were observed between annual BMI change and annual percent density change, with percent density decreasing 0.36% (95% CI -0.74, 0.02) for a one unit increase in BMI over a year. This longitudinal study provides modest evidence that changes in BMI are not associated with changes in dense area, yet may be negatively associated with percent density.

An Automated Approach for Estimation of Breast Density

Breast density is a strong risk factor for breast cancer; however, no standard assessment method exists. An automated breast density method was modified and compared with a semi-automated, user-assisted thresholding method (Cumulus method) and the Breast Imaging Reporting and Data System four-category tissue composition measure for their ability to predict future breast cancer risk. The three estimation methods were evaluated in a matched breast cancer case-control (n = 372 and n = 713, respectively) study at the Mayo Clinic using digitized film mammograms. Mammograms from the craniocaudal view of the noncancerous breast were acquired on average 7 years before diagnosis. Two controls with no previous history of breast cancer from the screening practice were matched to each case on age, number of previous screening mammograms, final screening exam date, menopausal status at this date, interval between earliest and latest available mammograms, and residence. Both Pearson linear correlation (R) and Spearman rank correlation (r) coefficients were used for comparing the three methods as appropriate. Conditional logistic regression was used to estimate the risk for breast cancer (odds ratios and 95% confidence intervals) associated with the quartiles of percent breast density (automated breast density method, Cumulus method) or Breast Imaging Reporting and Data System categories. The area under the receiver operator characteristic curve was estimated and used to compare the discriminatory capabilities of each approach. The continuous measures (automated breast density method and Cumulus method) were highly correlated with each other (R = 0.70) but less with Breast Imaging Reporting and Data System (r = 0.49 for automated breast density method and r = 0.57 for Cumulus method). Risk estimates associated with the lowest to highest quartiles of automated breast density method were greater in magnitude [odds ratios: 1.0 (reference), 2.3, 3.0, 5.2; P trend < 0.001] than the corresponding quartiles for the Cumulus method [odds ratios: 1.0 (reference), 1.7, 2.1, and 3.8; P trend < 0.001] and Breast Imaging Reporting and Data System [odds ratios: 1.0 (reference), 1.6, 1.5, 2.6; P trend < 0.001] method. However, all methods similarly discriminated between case and control status; areas under the receiver operator characteristic curve were 0.64, 0.63, and 0.61 for automated breast density method, Cumulus method, and Breast Imaging Reporting and Data System, respectively. The automated breast density method is a viable option for quantitatively assessing breast density from digitized film mammograms.

Abstract A123: Serum levels of hormones and breast tissue composition in young women

Abstract A123 Background Percent mammographic density (PMD) is a strong and heritable risk factor for breast cancer with characteristics that suggest it may be a marker of susceptibility to the disease. We have examined serum hormone levels and other factors associated with breast tissue composition in young women, when susceptibility to breast carcinogens is greatest. Methods In 400 young women aged 15-30 years we obtained quantitative measures of breast water, which reflects fibro-glandular tissue, and breast fat using magnetic resonance (MR), and collected anthropometric and other data. All examinations were performed in the follicular phase of the menstrual cycle and fasting blood samples for hormone assays were obtained on the morning of the MR examination. Results Serum levels of growth hormone (GH) and sex hormone binding globulin (SHBG) were positively associated with percent breast water content in all young women aged 15-30, and the associations remained statistically significant after adjustment for height, weight and other covariates. IGF-I was not associated with any MR breast measures. Serum levels of estradiol, progesterone, and testosterone, were not associated with MR breast measures in all young women, or in those aged 20-30, but did show evidence of positive associations with percent water in those aged 15-19 years. After adjustment for other covariates, interactions of age and serum levels of testosterone (p=0.02) and progesterone (p=0.03) were associated with percent water, and estradiol with total water (p=0.07). Conclusions Serum levels of sex hormones were associated with breast tissue composition in young women aged less than 20, while GH and SHBG were associated with breast tissue composition in all young women. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A123.

Dietary calcium and vitamin D intakes in childhood and throughout adulthood and mammographic density in a British birth cohort

We examined the role of dietary calcium and vitamin D intakes in childhood and throughout adulthood in relation to mammographic density using data from a nationally representative cohort of 1161 women followed up since their birth in 1946. Dietary intakes at the age of 4 years were determined by 24-h recalls and at the ages of 36, 43 and 53 years by 5-day food records. After adjusting for known risk factors and confounders, no evidence of a relationship between dietary calcium or vitamin D intakes and mammographic density approximately at the age of 50 years was found, except for a cross-sectional relationship between dietary calcium intake at the age of 53 years and breast density in women who were post-menopausal at the time of mammography, with those in the top fifth of the distribution of calcium intake having a 0.53 s.d. lower percent breast density than those in the lowest fifth (P-value <0.01 for linear trend).

Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view

IntroductionMammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies.MethodsOur aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years.ResultsWhere only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67).ConclusionThis indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals.

Kangaroo Care and Breastfeeding of Mother–Preterm Infant Dyads 0–18 Months: A Randomized, Controlled Trial

To determine the effects of kangaroo care (KC) (skin-to-skin contact) on breastfeeding status in mother-preterm infant dyads from postpartum through 18 months. Randomized, controlled trial. The control group received standard nursery care; in the intervention group, unlimited KC was encouraged. A subsample of 66 mothers and their preterm infants (32-36 completed weeks gestation, 1,300-3,000 g, 5 minute Apgar > or = 6) who intended to breastfeed. Breastfeeding status at hospital discharge and at 1.5, 3, 6, 12, and 18 months as measured by the Index of Breastfeeding Status. KC dyads, compared to control dyads, breastfed significantly longer (5.08 months vs 2.05 months), p = .003. KC dyads also breastfed more exclusively at each measurement, p = .047. More KC dyads than control dyads breastfed at full exclusivity (100 percent breast milk, index of breastfeeding status levels 1 or 2) at discharge and at 1.5, 3, and 6 months. Mean KC contact per day was 4.47 hours.

Genetic Polymorphisms Involved in Insulin-like Growth Factor (IGF) Pathway in Relation to Mammographic Breast Density and IGF Levels

The insulin-like growth factor (IGF) pathway is believed to play a role in carcinogenesis of the mammary gland. Single nucleotide polymorphisms (SNPs) of IGF-I, IGF-binding protein-3 (IGFBP-3), IGF receptor 1, insulin receptor substrate 1, and phosphoinositide-3-kinase, catalytic, beta polypeptide genes, which are members of the IGF pathway, have been associated with risk of common cancers, breast density, and/or IGF levels but results remain inconclusive. Thus, we evaluated the association of 11 targeted IGF pathway SNPs with circulating IGF levels and mammographic breast density. Among 741 white premenopausal women, blood samples were collected at time of screening mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Percent and absolute breast density were estimated using a computer-assisted method. Multivariate linear models were used to examine the associations. Women carrying increasing number of copies of the rare allele of IGF-I rs1520220 and rs6220 SNPs had increased percent breast density (P(trend) = 0.04 and 0.06, respectively). Carriers of increasing number of copies of the rare allele of phosphoinositide-3-kinase, catalytic, beta polypeptide rs361072 SNP had decreased percent (P(trend) = 0.04) and absolute (P(trend) = 0.02) breast density. An association of insulin receptor substrate 1 rs1801278 SNP with absolute density (P(trend) = 0.03) was also observed. All four IGFBP-3 SNPs (including rs2854744) were associated with IGF-I and IGFBP-3 levels. This study shows that several components of the IGF pathway are associated with breast density or IGF levels. Our findings provide additional support for the idea that several components of the IGF pathway may affect breast cancer risk and that this effect on breast cancer development may be mediated, at least in part, through its influence on the morphogenesis of breast tissue.

Dietary patterns and breast density in the Minnesota Breast Cancer Family Study

Whether dietary patterns, rather than single foods or nutrients, are associated with breast density is not known. We investigated this in the Minnesota Breast Cancer Family Study. Participants completed a 153-item food frequency questionnaire and provided screening mammograms for breast density assessment using a computer-assisted method. We used multivariate linear regression to quantify dietary pattern-breast density associations. Among 3,147 women with dietary information, three dietary patterns emerged from principal components analysis: a fruit-vegetable-cereal pattern, a salad-sauce-pasta/grain pattern, and a meat-starch pattern. Among 1,286 women with breast density estimates, the fruit-vegetable-cereal and salad-sauce-pasta/grain patterns were inversely associated with percent breast density only in stratified analyses. The fruit-vegetable-cereal pattern was inversely associated with breast density among premenopausal women (beta = -0.13, p = 0.09; interaction p = 0.009) and current smokers, (beta = -0.30, p = 0.02; interaction p = 0.05), while the salad-sauce-pasta/grain was inversely associated with breast density among current smokers (beta = -0.27, p = 0.06; interaction p = 0.006). Overall our results do not provide strong evidence for associations of dietary patterns with breast density. Suggestive inverse associations for the fruit-vegetable-cereal and salad-sauce-pasta/grain dietary patterns among smokers are consistent with previous reports and leave open the possibility that some dietary patterns influence breast density in population subsets. Nevertheless, these findings require confirmation, and their underlying reasons have yet to be clarified.

Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density

High breast density is one of the strongest known risk factors for developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong mitogen and has been suggested to increase breast cancer risk by increasing the amount of dense tissue in the female breast. We wanted to investigate the effect of common variation in the IGF-1 gene on serum IGF-I levels and on breast density. Mammograms and blood samples of 1,928 premenopausal participants of the Dutch Prospect-EPIC cohort were collected at baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms (SNP) from three blocks covering the IGF-1 gene were genotyped in all study participants. Breast density was assessed using a quantitative computer-assisted method. For a subgroup of women, who went through menopause within 5 years after recruitment (n=656), premenopausal IGF-I levels and additionally postmenopausal breast density were determined. False positive report probabilities (FPRP) for statistically significant relations were calculated using the Wacholder method. The minor alleles of five SNPs in block 3 were significantly associated with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220; P-values: 0.01-0.04). The same SNPs were related with modestly higher percent breast density before menopause and-in the subgroup of women that became postmenopausal during follow-up-with a modestly higher percent breast density after menopause. The most significant result, i.e. the relation between rs6220 and IGF-I levels, had an FPRP<0.5 assuming prior probabilities of 0.01 and higher. Common genetic variation in the IGF-1 gene is related to circulating levels of IGF-I, but the relationship with breast density is indecisive.

Associations of Physical Activity, Sedentary Time, and Insulin with Percent Breast Density in Hispanic Women

In a previous study of Hispanic women, we reported a positive association between sedentary time and percent breast density, a marker of breast cancer risk. It is unclear whether associations between sedentary time or physical activity and percent breast density are mediated through serum insulin levels or insulin resistance, factors also associated with physical activity and breast cancer risk. In the Chicago Breast Health Project phase II pilot study, detailed information on health and lifestyle factors, including sitting time and total physical activity over the previous 7 days, was collected from 95 Hispanic women aged 40-77 years. We also assessed percent breast density and measured fasting serum insulin and glucose to calculate the Homeostasis Model Assessment (HOMA) index, a measure of insulin resistance. Multivariable linear regression was used to assess associations of total physical activity, time spent sitting, serum insulin, and HOMA index with percent breast density. There was no association between total physical activity and percent breast density (p = 0.98), whereas there was a positive association between sedentary time and percent density (beta = 0.25% per 100 metabolic equivalent (MET)-minutes/week, p = 0.06). Percent breast density was not associated with insulin or with HOMA index. The strength of the association between time spent sitting and percent density was unchanged after inclusion of insulin or the HOMA index in the model. These results are consistent with our previous finding of an association between sedentary time and percent breast density and suggest that insulin or insulin resistance is unlikely to mediate this relation.