Assessment of a fully automated,high-throughput mammographic density measurement tool for use with processed digital mammograms

Purpose

The ImageJ model is a recently developed automated breast density measurement tool based on analysis of Cumulus outcomes. It has been validated on digitized film-screen mammograms. In this study, the ImageJ model was assessed on processed full-field digital mammograms and correlated with the Breast Imaging Reporting and Data System (BI-RADS) density classification. Also, the association with breast cancer risk factors is observed.

Methods

Women with mammographies between 2001 and 2011 at the University Medical Center Utrecht, The Netherlands were included. We composed a training set, read with Cumulus, for building the ImageJ model [n = 100 women, 331 images; craniocaudal (CC) and mediolateral oblique (MLO) views, left and right] and a validation set for model assessment and correlation with the BI-RADS classification [n = 530 women, 1,977 images; average of available CC and MLO views, left and right]. Pearson product-moment correlation coefficient was used to compare Cumulus with ImageJ, Spearman correlation coefficient for ImageJ with BI-RADS density, and generalized linear models for association with breast cancer risk factors.

Results

The correlation between ImageJ and Cumulus in the training set was 0.90 [95 % confidence interval (CI) 0.86–0.93]. After application to the validation set, we observed a high correlation between ImageJ and the BI-RADS readings (Spearman r = 0.86, 95 % CI 0.84–0.88). Women with higher density were significantly younger, more often premenopausal, had lower parity, more often a benign breast lesion or family history of breast cancer.

Conclusions

The ImageJ model can be used on processed digital mammograms. The measurements strongly correlate with Cumulus, the BI-RADS density classification, and breast cancer risk factors.     

Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study

Introduction

Mammographic breast density is one of the strongest known risk factors for breast cancer. We present a novel technique for estimating breast density based on 3D T1-weighted Magnetic Resonance Imaging (MRI) and evaluate its performance, including for breast cancer risk prediction, relative to two standard mammographic density-estimation methods.

Methods

The analyses were based on MRI (n = 655) and mammography (n = 607) images obtained in the course of the UK multicentre magnetic resonance imaging breast screening (MARIBS) study of asymptomatic women aged 31 to 49 years who were at high genetic risk of breast cancer. The MRI percent and absolute dense volumes were estimated using our novel algorithm (MRIBview) while mammographic percent and absolute dense area were estimated using the Cumulus thresholding algorithm and also using a 21-point Visual Assessment scale for one medio-lateral oblique image per woman. We assessed the relationships of the MRI and mammographic measures to one another, to standard anthropometric and hormonal factors, to BRCA1/2 genetic status, and to breast cancer risk (60 cases) using linear and Poisson regression.

Results

MRI percent dense volume is well correlated with mammographic percent dense area (R = 0.76) but overall gives estimates 8.1 percentage points lower (P < 0.0001). Both show strong associations with established anthropometric and hormonal factors. Mammographic percent dense area, and to a lesser extent MRI percent dense volume were lower in BRCA1 carriers (P = 0.001, P = 0.010 respectively) but there was no association with BRCA2 carrier status. The study was underpowered to detect expected associations between percent density and breast cancer, but women with absolute MRI dense volume in the upper half of the distribution had double the risk of those in the lower half (P = 0.009).

Conclusions

The MRIBview estimates of volumetric breast density are highly correlated with mammographic dense area but are not equivalent measures; the MRI absolute dense volume shows potential as a predictor of breast cancer risk that merits further investigation.     

Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk

Purpose

To investigate the association between intake of flaxseed—the richest source of dietary lignans (a class of phytoestrogens)—and breast cancer risk.

Methods

A food frequency questionnaire was used to measure the consumption of flaxseed and flax bread by 2,999 women with breast cancer and 3,370 healthy control women who participated in the Ontario Women’s Diet and Health Study (2002–2003). Logistic regression was used to investigate associations between consumption of flaxseed and flax bread and breast cancer risk. Confounding by established and suspected breast cancer risk factors, as well as dietary factors, was assessed.

Results

Flaxseed or flax bread was consumed at least weekly by 21 % of control women. None of the 19 variables assessed were identified as confounders of the associations between flaxseed or flax bread and breast cancer risk. Consumption of flaxseed was associated with a significant reduction in breast cancer risk (odds ratio (OR) = 0.82, 95 % confidence interval (CI) 0.69–0.97), as was consumption of flax bread (OR = 0.77, 95 % CI 0.67–0.89).

Conclusions

This Canadian study is, to our knowledge, the first to report on the association between flaxseed alone and breast cancer risk and has found that flaxseed intake is associated with a reduction in breast cancer risk. As dietary intake of flaxseed is modifiable, this finding may be of public health importance with respect to breast cancer prevention.     

Urinary bisphenol A-glucuronide and postmenopausal breast cancer in Poland

Purpose

Concerns regarding a possible link between bisphenol A (BPA) and breast cancer have been mounting, but studies in human populations are lacking. We evaluated the association between the major urinary BPA metabolite [BPA-glucuronide (BPA-G)] and postmenopausal breast cancer risk in a large population-based case–control study conducted in two cities in Poland (2000–2003); we further explored the association of BPA-G levels with known postmenopausal breast cancer risk factors in our control population.

Methods

We analyzed creatinine-adjusted urinary BPA-G levels among 575 postmenopausal cases matched on age and study site to 575 controls without breast cancer using a recently developed assay. Odds ratios and 95 % confidence intervals were used to estimate the association between urinary BPA-G level and breast cancer using conditional logistic regression. Among controls, geometric mean BPA-G levels were compared across categories of breast cancer risk factors using linear regression models.

Results

There was no indication that increased BPA-G was associated with postmenopausal breast cancer (p-trend = 0.59). Among controls, mean BPA-G was higher among women reporting extended use of menopausal hormones, a prior screening mammogram, and residence in Warsaw. Other comparisons across strata of postmenopausal breast cancer risk factors were not related to differences in BPA-G.

Conclusions

Urinary BPA-G, measured at the time of diagnosis, is not linked to postmenopausal breast cancer.     

Dietary intake and breast density in high-risk women: a cross-sectional study

Background

Women with a family history of breast cancer may be at higher risk for breast cancer, but few previous studies evaluating diet and breast cancer have focused on such women. The objective of the present study was to determine whether diet, a modifiable risk factor, is related to breast density among women at high genetic risk for breast cancer.

Methods

Women with at least one first-degree or second-degree relative with breast cancer or ovarian cancer participating in the Fox Chase Cancer Center Family Risk Assessment Program completed health history and food frequency questionnaires and received standard screening mammograms. Cranial–caudal mammographic images were classified into the four Breast Imaging Reporting and Data System categories ranging from 'entirely fatty' to 'extremely dense'. Logistic regression analysis using proportional odds models for polychotomous outcomes provided estimates of odds ratios for having a higher category versus a lower category of breast density.

Results

Among 157 high-risk women, breast density was inversely associated with vitamin D intake (odds ratio for third tertile versus first tertile, 0.5; 95% confidence interval, 0.2–1.0). In contrast, intakes above the median level for protein (odds ratio, 3.0; 95% confidence interval, 1.3–6.9) and above the median level for animal protein (odds ratio, 4.3; 95% confidence interval, 1.8–10.3) were associated with higher breast density, but only among women whose family history did not reflect a known familial cancer syndrome or a breast cancer predisposition gene.

Conclusion

For women with a strong family history that was not associated with known cancer syndromes, dietary factors may be associated with breast density, a strong predictor of breast cancer risk. Since women with strong family history are often very motivated to change their lifestyle habits, further studies are needed to confirm whether changes in diet will change the breast density and the subsequent onset of breast cancer in these women.     

A prospective study of smoking and breast cancer risk among African-American women

Purpose

Active smoking and passive smoking have been associated with increased risk of breast cancer. The purpose of the present study was to prospectively assess associations of smoking with breast cancer and identify subgroups at higher risk among African-American women.

Methods

Based on 1,377 incident cases identified during 14 years of follow-up in the Black Women’s Health Study, we assessed active and passive smoking in relation to breast cancer incidence by menopausal status, estrogen receptor status, and other factors. Incidence rate ratios (IRR) and 95 % confidence intervals (CI) for categories of smoking relative to no active or passive smoking were calculated from Cox proportional hazards models, controlling for breast cancer risk factors.

Results

Active smoking was associated with increased risk of premenopausal breast cancer. The IRR was 1.21 (95 % CI 0.90–1.62) for premenopausal breast cancer overall and 1.70 (95 % CI 1.05–2.75) for premenopausal breast cancer associated with beginning smoking before age 18 together with accumulation of ≥20 pack years. The positive association with premenopausal breast cancer was most apparent for estrogen-receptor-positive cancer. Passive smoking was also associated with increased risk of premenopausal breast cancer (IRR = 1.42, 95 % CI 1.09–1.85), based on information on passive smoking at home and work. Neither active nor passive smoking was associated with increased risk of postmenopausal breast cancer.

Conclusion

These results strengthen the evidence that both active and passive smoking increase the incidence of premenopausal breast cancer.     

A case–control study of lifetime occupational sitting and likelihood of breast cancer

Purpose

Sedentary behavior may be a unique risk factor for some cancers, including breast cancer. The objective of this study was to determine the association between lifetime occupational sitting and likelihood of breast cancer.

Methods

A case–control study of 2,452 women was conducted in Alberta, Canada, between 1995 and 1997. A comprehensive measure of lifetime physical activity assessed frequency and duration of sedentary jobs. Logistic regression estimated the odds of being diagnosed with breast cancer across quartiles of lifetime occupational sitting, by menopausal status and family history of breast cancer, and within body mass index categories and physical activity quartiles.

Results

There was no association between occupational sitting and breast cancer among pre-menopausal women and women with a family history of breast cancer. Unexpectedly, higher amounts of occupational sitting were associated with lower odds of breast cancer in post-menopausal women (top versus bottom categories of occupational sitting OR = 0.71, 95 % CI 0.52, 0.97), women without a family history of breast cancer (OR = 0.77, 95 % CI 0.60, 1.00), and women in the third highest quartile of total lifetime physical activity (OR = 0.57, 95 % CI 0.33, 0.97).

Conclusion

Occupational sitting levels were lower than would be expected in a contemporary study. Exposures may have been insufficient to make a determinable contribution to breast cancer risk.     

Breast cancer risk prediction and individualised screening based on common genetic variation and breast density measurement

Introduction

Over the last decade several breast cancer risk alleles have been identified which has led to an increased interest in individualised risk prediction for clinical purposes.

Methods

We investigate the performance of an up-to-date 18 breast cancer risk single-nucleotide polymorphisms (SNPs), together with mammographic percentage density (PD), body mass index (BMI) and clinical risk factors in predicting absolute risk of breast cancer, empirically, in a well characterised Swedish case-control study of postmenopausal women. We examined the efficiency of various prediction models at a population level for individualised screening by extending a recently proposed analytical approach for estimating number of cases captured.

Results

The performance of a risk prediction model based on an initial set of seven breast cancer risk SNPs is improved by additionally including eleven more recently established breast cancer risk SNPs (P = 4.69 × 10^-4). Adding mammographic PD, BMI and all 18 SNPs to a Swedish Gail model improved the discriminatory accuracy (the AUC statistic) from 55% to 62%. The net reclassification improvement was used to assess improvement in classification of women into low, intermediate, and high categories of 5-year risk (P = 8.93 × 10^-9). For scenarios we considered, we estimated that an individualised screening strategy based on risk models incorporating clinical risk factors, mammographic density and SNPs, captures 10% more cases than a screening strategy using the same resources, based on age alone. Estimates of numbers of cases captured by screening stratified by age provide insight into how individualised screening programs might appear in practice.

Conclusions

Taken together, genetic risk factors and mammographic density offer moderate improvements to clinical risk factor models for predicting breast cancer.     

Cost-effectiveness of monitoring endoxifen levels in breast cancer patients adjuvantly treated with tamoxifen

Purpose

Increased mammographic breast density is a significant risk factor for breast cancer. It is not clear if it is also a risk factor for the development of contralateral breast cancer.

Methods

The data were obtained from Breast Cancer Surveillance Consortium and included women diagnosed with invasive breast cancer or ductal carcinoma in situ between ages 18 and 88 and years 1995 and 2009. Each case of contralateral breast cancer was matched with three controls based on year of first breast cancer diagnosis, race, and length of follow-up. A total of 847 cases and 2541 controls were included. The risk factors included in the study were mammographic breast density, age of first breast cancer diagnosis, family history of breast cancer, anti-estrogen treatment, hormone replacement therapy, menopausal status, and estrogen receptor status, all from the time of first breast cancer diagnosis. Both univariate analysis and multivariate conditional logistic regression analysis were performed.

Results

In the final multivariate model, breast density, family history of breast cancer, and anti-estrogen treatment remained significant with p values less than 0.01. Increasing breast density had a dose-dependent effect on the risk of contralateral breast cancer. Relative to ‘almost entirely fat’ category of breast density, the adjusted odds ratios (and p values) in the multivariate analysis for ‘scattered density,’ ‘heterogeneously dense,’ and ‘extremely dense’ categories were 1.65 (0.036), 2.10 (0.002), and 2.32 (0.001), respectively.

Conclusion

Breast density is an independent and significant risk factor for development of contralateral breast cancer. This risk factor should contribute to clinical decision making.

     

Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression

Objective

To comprehensively summarize the associations between retinol, vitamins A, C, and E and breast cancer, and quantitatively estimate their dose?Cresponse relationships.

Methods

We searched PubMed, Embase, and Cochrane databases (from January 1982 to 15 March 2011) and the references of the relevant articles in English with sufficient information to estimate relative risk or odds ratio and the 95% confidence intervals, and comparable categories of vitamins. Two reviewers independently extracted data using a standardized form, with any discrepancy adjudicated by the third reviewer.

Results

Overall, 51 studies met the inclusion criteria. Comparing the highest with the lowest intake, total vitamin A intake reduced the breast cancer risk by 17% (pooled OR = 0.83, 95% CI: 0.78?C0.88). Further subgroup analysis based on study design did not change the significant reduction. Although the dietary vitamin A, dietary vitamin E, and total vitamin E intake all reduced breast cancer risk significantly when data from all studies were pooled, the results became nonsignificant when data from cohort studies were pooled. The significant association between total retinol intake and breast cancer in all studies became nonsignificant in case?Ccontrol studies but remain significant in cohort studies. No significant dose?Cresponse relationship was observed in the higher intake of these vitamins with reduced breast cancer risk.

Conclusions

Our results indicate that both the total intake of vitamin A and retinol could reduce breast cancer risk. However, associations between other vitamins and breast cancer seem to be limited.     

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis

Background:

Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause.

Methods:

We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies.

Results:

Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27).

Conclusion:

Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk.     

First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants

Purpose

Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype.

Methods

The Marin Women’s Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry.

Results

A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = ?0.31, 95 % CI ?0.52, ?0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95 % CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants.

Conclusion

These findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes.     

Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study

Purpose

This study aimed to determine the prevalence of sarcopenia and examine whether sarcopenia was associated with overall and breast-cancer-specific mortality in a cohort of women diagnosed with breast cancer (stages I?CIIIA).

Methods

A total of 471 breast cancer patients from western Washington State and New Mexico who participated in the prospective Health, Eating, Activity, and Lifestyle Study were included in this study. Appendicular lean mass was measured using dual X-ray absorptiometry scans at study inception, on average, 12?months after diagnosis. Sarcopenia was defined as two standard deviations below the young healthy adult female mean of appendicular lean mass divided by height squared (<5.45?kg/m²). Total and breast-cancer-specific mortality data were obtained from Surveillance Epidemiology and End Results registries. Multivariable Cox proportional hazard models assessed the associations between sarcopenia and mortality.

Results

Median follow-up was 9.2?years; 75 women were classified as sarcopenic, and among 92 deaths, 46 were attributed to breast cancer. In multivariable models that included age, race-ethnicity/study site, treatment type, comorbidities, waist circumference, and total body fat percentage, sarcopenia was independently associated with overall mortality (hazard ratio (HR)?=?2.86; 95?% CI, 1.67?C4.89). Sarcopenic women had increased risk of breast-cancer-specific mortality, although the association was not statistically significant (HR?=?1.95, 95?% CI, 0.87?C4.35).

Conclusion

Sarcopenia is associated with an increased risk of overall mortality in breast cancer survivors and may be associated with breast-cancer-specific mortality. The development of effective interventions to maintain and/or increase skeletal muscle mass to improve prognosis in breast cancer survivors warrants further study.

Implications for Cancer Survivors

Such interventions may help breast cancer patients live longer.     

Risk factors associated with breast cancer-related lymphedema in the WHEL Study

Introduction

Lymphedema is a significant health problem faced by a large percentage of breast cancer survivors. The Women’s Healthy Eating and Living (WHEL) Study has a unique dataset collected after the completion of breast cancer treatment, which allowed a focused analysis of risk factors for breast cancer-related lymphedema.

Methods

Participant characteristics, treatment modalities, and health behaviors were examined as potential predictors of lymphedema among breast cancer survivors with univariate analyses and multivariate logistic regression.

Results

Lymphedema status was assessed for 83 % of the study cohort (2,431 of the 2,917 WHEL participants). Among these respondents, 692 (28.5 %) women reported yes to either a physician’s diagnosis of lymphedema or a question on arm/hand swelling. When compared to other participants, women with lymphedema were diagnosed at a younger age, more likely to have a higher body mass index, had a larger tumor size, had more lymph nodes removed, more likely to have a mastectomy with radiation therapy, and more likely to have chemotherapy. In the final multivariate-adjusted model, body mass index greater than 25 kg/m² (p?<?0.01), the removal of 11 or more lymph nodes (p?<?0.01), and breast cancer surgery plus radiation therapy (p?<?0.01) showed a strong independent association with developing breast cancer-related lymphedema.

Conclusions

The results of this study highlight the importance of educating breast cancer survivors about the modifiable risk factors (e.g., body mass index) associated with the development of lymphedema.

Implications for Cancer Survivors

Breast cancer survivors at risk for lymphedema may benefit from interventions aimed at achieving or maintaining a healthy body weight.     

Reproductive aging-associated common genetic variants and the risk of breast cancer

Introduction

A younger age at menarche and an older age at menopause are well established risk factors for breast cancer. Recent genome-wide association studies have identified several novel genetic loci associated with these two traits. However, the association between these loci and breast cancer risk is unknown.

Methods

In this study, we investigated 19 and 17 newly identified single nucleotide polymorphisms (SNPs) from the ReproGen Consortium that have been associated with age at menarche and age at natural menopause, respectively, and assessed their associations with breast cancer risk in 6 population-based studies among up to 3,683 breast cancer cases and 34,174 controls in white women of European ancestry. In addition, we used these SNPs to calculate genetic risk scores (GRSs) based on their associations with each trait.

Results

After adjusting for age and potential population stratification, two age at menarche associated SNPs (rs1079866 and rs7821178) and one age at natural menopause associated SNP (rs2517388) were associated with breast cancer risk (p values, 0.003, 0.009 and 0.023, respectively). The odds ratios for breast cancer corresponding to per-risk-allele were 1.14 (95% CI, 1.05 to 1.24), 1.08 (95% CI, 1.02 to 1.15) and 1.10 (95% CI, 1.01 to 1.20), respectively, and were in the direction predicted by their associations with age at menarche or age at natural menopause. These associations did not appear to be attenuated by further controlling for self-reported age at menarche, age at natural menopause, or known breast cancer susceptibility loci. Although we did not observe a statistically significant association between any GRS for reproductive aging and breast cancer risk, the 4^th and 5^th highest quintiles of the younger age at menarche GRS had odds ratios of 1.14 (95% CI, 1.01 to 1.28) and 1.13 (95% CI, 1.00 to 1.27), respectively, compared to the lowest quintile.

Conclusions

Our study suggests that three genetic variants, independent of their associations with age at menarche or age at natural menopause, were associated with breast cancer risk and may contribute modestly to breast cancer risk prediction; however, the combination of the 19 age at menarche or the 17 age at natural menopause associated SNPs did not appear to be useful for identifying a high risk subgroup for breast cancer.     

Non-steroidal anti-inflammatory drug (NSAID) use and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study

Objective

Chronic inflammation is suspected to have a role in breast carcinogenesis. Results of studies of non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer have been inconsistent. Timing of exposure and analysis of individual NSAIDs should be considered.

Methods

We conducted a population-based case–control study in western New York State between 1996 and 2001. Cases, 35–79 years, had incident, primary, histologically confirmed breast cancer (n = 1,170). Controls (n = 2,115) were randomly selected from NY Department of Motor Vehicles records (<65 years) or Medicare rolls (≥65 years). Participants were queried on use of aspirin, ibuprofen, and acetaminophen in the year prior and on aspirin during adulthood. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).

Results

Recent aspirin use was inversely associated with breast cancer risk (adjusted OR 0.80, 95% CI: 0.68–0.94); the strongest reduction in risk was observed among those who took ≥2 pills/day on days that aspirin was taken (OR 0.74, 95% CI: 0.61–0. 90). Adult lifetime use was also associated with breast cancer risk (>10 days/month, adjusted OR 0.68, 95% CI: 0.46–1.00). Use of ibuprofen or acetaminophen was not associated with breast cancer.

Conclusions

This is the first study to investigate the association of adult lifetime aspirin intake with breast cancer risk. Our findings provide evidence that aspirin use throughout a woman’s life may confer some benefit.     

Hormone replacement therapy,mammographic density,and breast cancer risk: a cohort study

Purpose

Hormone replacement therapy (HRT) use increases breast cancer risk and mammographic density (MD). We examine whether MD mediates or modifies the association of HRT with the breast cancer.

Methods

For the 4,501 participants in the Danish diet, cancer and health cohort (1993–1997) who attended mammographic screening in Copenhagen (1993–2001), MD (mixed/dense or fatty) was assessed at the first screening after cohort entry. HRT use was assessed by questionnaire and breast cancer diagnoses until 2012 obtained from the Danish cancer registry. The associations of HRT with MD and with breast cancer were analyzed separately using Cox’s regression. Mediation analyses were used to estimate proportion [with 95% confidence intervals (CI)] of an association between HRT and breast cancer mediated by MD.

Results

2,444 (54.3%) women had mixed/dense breasts, 229 (5.4%) developed breast cancer, and 35.9% were current HRT users at enrollment. Compared to never users, current HRT use was statistically significantly associated with having mixed/dense breasts (relative risk and 95% CI 1.24; 1.14–1.35), and higher risk of breast cancer (hazard ratio 1.87; 1.40–2.48). Association between current HRT use and breast cancer risk was partially mediated by MD (percent mediated?=?10%; 95% CI 4–22%). The current HRT use-related breast cancer risk was higher in women with mixed/dense (1.94; 1.37–3.87) than fatty (1.37; 0.80–2.35) breasts (p value for interaction?=?0.15).

Conclusions

MD partially mediates some of the association between HRT and breast cancer risk. The association between HRT and breast cancer seems to be stronger in women with dense breasts.

     

Prevalence of breast arterial calcification by mammography contributes to breast cancer

Background

Mammographic breast arterial calcifications (BACs) are regarded as aging-related benign changes in breast cancer screening practices. BACs have recently attracted attention, because several researchers proposed using them as a surrogate marker of arteriosclerosis or osteoporosis. No studies have thus far evaluated an association between BACs and breast cancer, however.

Method

The percentage of BAC positivity was compared between a group of women aged 40?years or older with breast cancer detected in 2004 through 2009, and a group of women of the same age range in whom breast cancer was not detected by screening mammography in 2009.

Results

The BAC-positive rate in the group of 243 breast cancer patients was 9.88% (24 of the 243) and was lower than that in the group of women without breast cancer, 14.34% (506 of 3528 women). The analysis by age revealed that the differences in this parameter between the two groups were significant in women aged 60?years or older. Multivariate analysis including demographic characteristics revealed that when adjusted for age and body weight, BAC positivity was a significant risk factor for breast cancer.

Conclusion

The study results suggest that BAC positivity and, in turn, arteriosclerosis may have an antinomic relationship with breast cancer.     

Characterizing mammographic images by using generic texture features

Introduction

Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design.

Methods

A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model.

Results

Of the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model.

Conclusions

Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy.     

Determinants of newly diagnosed comorbidities among breast cancer survivors

Purpose

Comorbid conditions have become increasingly relevant for breast cancer care given the large numbers of long-term survivors. Our aim was to identify potential determinants associated with the development of comorbidities after breast cancer.

Methods

Self-reported comorbidities and lifestyle were assessed at recruitment and after a median follow up of 69.4 months from diagnosis in a population-based cohort of breast cancer cases aged 50 to 74 years at diagnosis (MARIEplus study). Tumor and therapy data were extracted from medical records. Determinants potentially associated with incident diagnoses of hypertension, cardiovascular diseases (CVD), and osteoporosis were assessed using multivariable Cox proportional hazard regression models.

Results

Follow-up interview was completed by 2,542 women (76.4 % of eligible patients). A diagnosis of hypertension was significantly associated with age, higher education (hazard ratio (HR) 0.54, CI 0.37–0.79), baseline body mass index (BMI; ≥30 kg/m²; HR, 1.90; CI, 1.24–2.90), and trastuzumab medication (HR, 2.16; CI, 1.09–4.33). An increased risk for CVD was associated with age, BMI, and intake of aromatase inhibitors (AI; HR, 1.42; CI, 1.09–1.84). Risk of osteoporosis was also positively associated with AI treatment (HR, 2.15; CI, 1.64–2.82) but inversely associated with a higher BMI (≥30 kg/m²; HR, 0.50; CI, 0.31–0.79).

Conclusion

In breast cancer survivors, treatment with AI constituted a risk factor for incident CVD and osteoporosis. Besides known risk factors, patients who were treated with trastuzumab may have an increased risk for hypertension.

Implications for cancer survivors

Reducing overweight and regular sport/cycling activities may help to prevent CVD after breast cancer. Patients should be monitored for risk factors and advised on possible cardiac side effects of AI and trastuzumab.