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Breast (Edinburgh, Scotland) Oct 2021Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this...
PURPOSE
Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients.
METHODS
A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status.
RESULTS
After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect.
CONCLUSIONS
Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.
Topics: Breast Density; Breast Neoplasms; Disease-Free Survival; Female; Humans; Prognosis; Retrospective Studies
PubMed: 34157655
DOI: 10.1016/j.breast.2021.06.004 -
Scientific Reports Oct 2023Mammography shifted to digital breast tomosynthesis (DBT) in the US. An automated percentage of breast density (PD) technique designed for two-dimensional (2D)...
Mammography shifted to digital breast tomosynthesis (DBT) in the US. An automated percentage of breast density (PD) technique designed for two-dimensional (2D) applications was evaluated with DBT using several breast cancer risk prediction measures: normalized-volumetric; dense volume; applied to the volume slices and averaged (slice-mean); and applied to synthetic 2D images. Volumetric measures were derived theoretically. PD was modeled as a function of compressed breast thickness (CBT). The mean and standard deviation of the pixel values were investigated. A matched case-control (CC) study (n = 426 pairs) was evaluated. Odd ratios (ORs) were estimated with 95% confidence intervals. ORs were significant for PD: identical for volumetric and slice-mean measures [OR = 1.43 (1.18, 1.72)] and [OR = 1.44 (1.18, 1.75)] for synthetic images. A 2nd degree polynomial (concave-down) was used to model PD as a function of CBT: location of the maximum PD value was similar across CCs, occurring at 0.41 × CBT, and PD was significant [OR = 1.47 (1.21, 1.78)]. The means from the volume and synthetic images were also significant [ORs ~ 1.31 (1.09, 1.57)]. An alternative standardized 2D synthetic image was constructed, where each pixel value represents the percentage of breast density above its location. Several measures were significant and an alternative method for constructing a standardized 2D synthetic image was produced.
Topics: Humans; Female; Breast Density; Mammography; Breast Neoplasms; Breast; Case-Control Studies; Radiographic Image Enhancement
PubMed: 37907569
DOI: 10.1038/s41598-023-45402-x -
Breast Cancer Research : BCR Dec 2022Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its...
BACKGROUND
Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density.
METHODS
Longitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25-29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation.
RESULTS
Of the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity-%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV.
CONCLUSIONS
Additional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.
Topics: Child; Young Adult; Female; Humans; Adult; Breast Density; Breast Neoplasms; Adiposity; Follow-Up Studies; Mammography; Body Mass Index
PubMed: 36536390
DOI: 10.1186/s13058-022-01588-y -
International Journal of Occupational... Oct 2022Mammographic density (MD) refers to the percentage of dense tissue of an entire breast and was proposed to be used as a surrogate marker for breast cancer. High-dose...
OBJECTIVES
Mammographic density (MD) refers to the percentage of dense tissue of an entire breast and was proposed to be used as a surrogate marker for breast cancer. High-dose ionizing radiation (IR) has been recognized as a breast cancer risk factor. The aim of our study was to investigate association between lifetime low dose ionizing radiation (LDIR) and MD.
MATERIAL AND METHODS
A cross-sectional study included 467 women aged 40-60 years who underwent screening mammography in Łódź, Poland. The digital mammography examination of the breasts included both craniocaudal and mediolateral oblique views. The volumetric breast density (VBD) (%) and fibrograndular tissue volume (FG) (cm) were determined based on the analysis of mammographic image ("for processing") using Volpara Imaging Software. The exposure to IR was estimated for each individual, based on the data from interviews about diagnostic or therapeutic medical procedures performed in the area of the neck, chest, abdomen and spine, which involved X-rays and γ rays and the data about the doses derived from literature. Linear and logistic regression were fitted with VBD and FG as the outcomes and organ breast dose, effective dose and number of mammographies as the determinants, adjusted for major confounders.
RESULTS
The analyses showed no association between VBD or FG and the breast organ dose or the effective dose. The only significant finding observed concerned the association between the number of mammographies and the FG volume with β coefficient: 0.028 (95% CI: 0.012-0.043), and predicted mean FG volume >13.4 cm3 among the women with >3 mammographies when compared to those with none.
CONCLUSIONS
This study does not, in general, provide support for the positive association between LDIR and MD. The weak association of the FG volume with the number of mammographies warrants further verification in larger independent studies. Int J Occup Med Environ Health. 2022;35(5):635-49.
Topics: Breast Density; Breast Neoplasms; Cross-Sectional Studies; Early Detection of Cancer; Female; Humans; Mammography; Radiation, Ionizing
PubMed: 35913368
DOI: 10.13075/ijomeh.1896.01916 -
JNCI Cancer Spectrum Jul 2023Mammographic density is a strong predictor of breast cancer but only slightly increased the discriminatory ability of existing risk prediction models in previous studies...
Mammographic density is a strong predictor of breast cancer but only slightly increased the discriminatory ability of existing risk prediction models in previous studies with limited racial diversity. We assessed discrimination and calibration of models consisting of the Breast Cancer Risk Assessment Tool (BCRAT), Breast Imaging-Reporting and Data System density and quantitative density measures. Patients were followed up from the date of first screening mammogram until invasive breast cancer diagnosis or 5-year follow-up. Areas under the curve for White women stayed consistently around 0.59 for all models, whereas the area under the curve increased slightly from 0.60 to 0.62 when adding dense area and area percent density to the BCRAT model for Black women. All women saw underprediction in all models, with Black women having less underprediction. Adding quantitative density to the BCRAT did not statistically significantly improve prediction for White or Black women. Future studies should evaluate whether volumetric breast density improves risk prediction.
Topics: Female; Humans; Breast Neoplasms; Breast Density; Risk Factors; Risk Assessment; Breast
PubMed: 37289565
DOI: 10.1093/jncics/pkad041 -
Nutrients Dec 2022Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and... (Review)
Review
BACKGROUND
Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and it is of interest, for prevention purposes, to consider lifestyle factors that may modulate both MBD and BC risk. Here, we conducted a systematic review of the most up-to-date evidence on the association between diet as a whole and MBD.
METHODS
We considered as eligible for inclusion in our review (PROSPERO registration code CRD42022335289) the studies published until 31 December 2021, that reported on the association between a priori or a posteriori dietary patterns (in observational studies) or dietary interventions (in randomized controlled trials) and MBD.
RESULTS
In total, twelve studies were included. MBD tended to be inversely associated with adherence to dietary patterns characterized by high consumption of plant-based foods and low in meat, animal fats, and alcohol, defined both a priori (e.g., Mediterranean diet and WCRF/AICR guidelines) or a posteriori (e.g., "fruit-vegetable-cereal" and "salad-sauce-pasta/grains" patterns). Findings from intervention studies were in fair agreement with those from observational studies.
CONCLUSIONS
While further studies are needed, we found suggestive evidence that the adoption of a healthy diet is associated with lower MBD.
Topics: Breast Density; Risk Factors; Diet, Mediterranean; Fruit; Vegetables
PubMed: 36558470
DOI: 10.3390/nu14245312 -
The Cochrane Database of Systematic... Oct 2021Endocrine therapy is effective at preventing or treating breast cancer. Some forms of endocrine therapy have been shown to reduce mammographic density. Reduced... (Review)
Review
BACKGROUND
Endocrine therapy is effective at preventing or treating breast cancer. Some forms of endocrine therapy have been shown to reduce mammographic density. Reduced mammographic density for women receiving endocrine therapy could be used to estimate the chance of breast cancer returning or developing breast cancer in the first instance (a prognostic biomarker). In addition, changes in mammographic density might be able to predict how well a woman responds to endocrine therapy (a predictive biomarker). The role of breast density as a prognostic or predictive biomarker could help improve the management of breast cancer.
OBJECTIVES
To assess the evidence that a reduction in mammographic density following endocrine therapy for breast cancer prevention in women without previous breast cancer, or for treatment in women with early-stage hormone receptor-positive breast cancer, is a prognostic or predictive biomarker.
SEARCH METHODS
We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers on 3 August 2020 along with reference checking, bibliographic searching, and contact with study authors to obtain further data.
SELECTION CRITERIA
We included randomised, cohort and case-control studies of adult women with or without breast cancer receiving endocrine therapy. Endocrine therapy agents included were selective oestrogen receptor modulators and aromatase inhibitors. We required breast density before start of endocrine therapy and at follow-up. We included studies published in English.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently extracted data and assessed risk of bias using adapted Quality in Prognostic Studies (QUIPS) and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools. We used the GRADE approach to evaluate the certainty of the evidence. We did not perform a quantitative meta-analysis due to substantial heterogeneity across studies.
MAIN RESULTS
Eight studies met our inclusion criteria, of which seven provided data on outcomes listed in the protocol (5786 women). There was substantial heterogeneity across studies in design, sample size (349 to 1066 women), participant characteristics, follow-up (5 to 14 years), and endocrine therapy agent. There were five breast density measures and six density change definitions. All studies had at least one domain as at moderate or high risk of bias. Common concerns were whether the study sample reflected the review target population, and likely post hoc definitions of breast density change. Most studies on prognosis for women receiving endocrine therapy reported a reduced risk associated with breast density reduction. Across endpoints, settings, and agents, risk ratio point estimates (most likely value) were between 0.1 and 1.5, but with substantial uncertainty. There was greatest consistency in the direction and magnitude of the effect for tamoxifen (across endpoints and settings, risk ratio point estimates were between 0.3 and 0.7). The findings are summarised as follows. Prognostic biomarker findings: Treatment Breast cancer mortality Two studies of 823 women on tamoxifen (172 breast cancer deaths) reported risk ratio point estimates of ~0.4 and ~0.5 associated with a density reduction. The certainty of the evidence was low. Recurrence Two studies of 1956 women on tamoxifen reported risk ratio point estimates of ~0.4 and ~0.7 associated with a density reduction. There was risk of bias in methodology for design and analysis of the studies and considerable uncertainty over the size of the effect. One study of 175 women receiving an aromatase inhibitor reported a risk ratio point estimate of ~0.1 associated with a density reduction. There was considerable uncertainty about the effect size and a moderate or high risk of bias in all domains. One study of 284 women receiving exemestane or tamoxifen as part of a randomised controlled trial reported risk ratio point estimates of ~1.5 (loco-regional recurrence) and ~1.3 (distance recurrence) associated with a density reduction. There was risk of bias in reporting and study confounding, and uncertainty over the size of the effects. The certainty of the evidence for all recurrence endpoints was very low. Incidence of a secondary primary breast cancer Two studies of 451 women on exemestane, tamoxifen, or unknown endocrine therapy reported risk ratio point estimates of ~0.5 and ~0.6 associated with a density reduction. There was risk of bias in reporting and study confounding, and uncertainty over the effect size. The certainty of the evidence was very low. We were unable to find data regarding the remaining nine outcomes prespecified in the review protocol. Prevention Incidence of invasive breast cancer and ductal carcinoma in situ (DCIS) One study of 507 women without breast cancer who were receiving preventive tamoxifen as part of a randomised controlled trial (51 subsequent breast cancers) reported a risk ratio point estimate of ~0.3 associated with a density reduction. The certainty of the evidence was low. Predictive biomarker findings: One study of a subset of 1065 women from a randomised controlled trial assessed how much the effect of endocrine therapy could be explained by breast density declines in those receiving endocrine therapy. This study evaluated the prevention of invasive breast cancer and DCIS. We found some evidence to support the hypothesis, with a risk ratio interaction point estimate ~0.5. However, the 95% confidence interval included unity, and data were based on 51 women with subsequent breast cancer in the tamoxifen group. The certainty of the evidence was low.
AUTHORS' CONCLUSIONS
There is low-/very low-certainty evidence to support the hypothesis that breast density change following endocrine therapy is a prognostic biomarker for treatment or prevention. Studies suggested a potentially large effect size with tamoxifen, but the evidence was limited. There was less evidence that breast density change following tamoxifen preventive therapy is a predictive biomarker than prognostic biomarker. Evidence for breast density change as a prognostic treatment biomarker was stronger for tamoxifen than aromatase inhibitors. There were no studies reporting mammographic density change following endocrine therapy as a predictive biomarker in the treatment setting, nor aromatase inhibitor therapy as a prognostic or predictive biomarker in the preventive setting. Further research is warranted to assess mammographic density as a biomarker for all classes of endocrine therapy and review endpoints.
Topics: Biomarkers; Breast Density; Breast Neoplasms; Female; Humans; Prognosis; Randomized Controlled Trials as Topic; Tamoxifen
PubMed: 34697802
DOI: 10.1002/14651858.CD013091.pub2 -
International Journal of Occupational... Dec 2021High mammographic breast density (MBD) is one of the strongest breast cancer risk factors. The results of some epidemiological studies suggest that one of the lifestyle...
OBJECTIVES
High mammographic breast density (MBD) is one of the strongest breast cancer risk factors. The results of some epidemiological studies suggest that one of the lifestyle factors likely altering breast density is cigarette smoking. The aim of this study was to assess the association between active smoking, considering in detail the duration and intensity of smoking, and MBD among Polish women.
MATERIAL AND METHODS
A cross-sectional study included 467 women aged 40-60 years who underwent screening mammography in Łódź, Poland. Volumetric mammographic density, fibroglandular tissue volume and non-fibroglandular tissue volume were determined based on the analysis of mammographic image (in the "for processing" format) using Volpara Imaging Software. Current and lifetime intensity of cigarette smoking was assessed based on the data from interviews. Linear and logistic regressions were fitted with estimated MBD parameters as the outcomes, and life-long smoking duration and intensity as the determinants, adjusted for major confounders.
RESULTS
The former smokers had a significantly lower volumetric mammographic density compared to the non-smokers in the crude analysis (p = 0.022). However, the associations became insignificant after adjustments for important confounding factors. The analyses adjusted for important confounders revealed an inverse statistically significant association between the number of pack-years and volumetric mammographic density among the current smokers (p = 0.048).
CONCLUSIONS
The observed result is consistent with the majority of previous studies that analyzed the associations between mammographic density and life-long smoking duration. Int J Occup Med Environ Health. 2021;34(6):805-15.
Topics: Breast Density; Breast Neoplasms; Cigarette Smoking; Cross-Sectional Studies; Early Detection of Cancer; Female; Humans; Mammography; Poland
PubMed: 34524273
DOI: 10.13075/ijomeh.1896.01832 -
Journal of General Internal Medicine Feb 2019
Topics: Breast Density; Breast Neoplasms; Humans; Mammography; Massachusetts; Safety-net Providers
PubMed: 30478631
DOI: 10.1007/s11606-018-4754-6 -
JAMA Network Open Feb 2022Family history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic...
IMPORTANCE
Family history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic breast density in premenopausal women is not well understood.
OBJECTIVES
To investigate the association of FHBC and mammographic breast density in premenopausal women using both quantitative and qualitative measurements.
DESIGN, SETTING, AND PARTICIPANTS
This single-center cohort study examined 2 retrospective cohorts: a discovery set of 375 premenopausal women and a validation set of 14 040 premenopausal women. Data from women in the discovery set was collected between December 2015 and October 2016, whereas data from women in the validation set was collected between June 2010 and December 2015. Data analysis was performed between June 2018 and June 2020.
EXPOSURES
Family history of breast cancer (FHBC).
MAIN OUTCOMES AND MEASURES
The primary outcomes were mammographic breast density measured quantitatively as volumetric percent density using Volpara (discovery set) and qualitatively using BI-RADS (Breast Imaging Reporting and Data System) breast density (validation set). Multivariable regressions were performed using a log-transformed normal distribution for the discovery set and a logistic distribution for the validation set.
RESULTS
Of 14 415 premenopausal women included in the study, the discovery set and validation set had similar characteristics (discovery set with FHBC: mean [SD] age, 47.1 [5.6] years; 15 [17.2%] were Black or African American women and 64 [73.6%] were non-Hispanic White women; discovery set with no FHBC: mean [SD] age, 47.7 [4.5] years; 87 [31.6%] were Black or African American women and 178 [64.7%] were non-Hispanic White women; validation set with FHBC: mean [SD] age, 46.8 [7.3] years; 720 [33.4%] were Black or African American women and 1378 [64.0%] were non-Hispanic White women]; validation set with no FHBC: mean [SD] age, 47.5 [6.1] years; 4572 [38.5%] were Black or African American women and 6632 [55.8%] were non-Hispanic White women]). In the discovery set, participants who had FHBC were more likely to have a higher mean volumetric percent density compared with participants with no FHBC (11.1% vs 9.0%). In the multivariable-adjusted model, volumetric percent density was 25% higher (odds ratio [OR], 1.25 ;95% CI, 1.12-1.41) in women with FHBC compared with women without FHBC; and 24% higher (OR, 1.24; 95% CI, 1.10-1.40) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.40; 95% CI, 0.95-2.07) compared with women with no relatives affected. In the validation set, women with a positive FHBC were more likely to have dense breasts (BI-RADS 3-4) compared with women with no FHBC (BI-RADS 3: 41.1% vs 38.8%; BI-RADS 4: 10.5% vs 7.7%). In the multivariable-adjusted model, the odds of having dense breasts (BI-RADS 3-4) were 30% higher (OR, 1.30; 95% CI, 1.17-1.45) in women with FHBC compared with women without FHBC; and 29% higher (OR, 1.29; 95% CI, 1.14-1.45) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.38; 95% CI, 0.85-2.23) compared with women with no relatives affected.
CONCLUSIONS AND RELEVANCE
In this cohort study, having an FHBC was positively associated with mammographic breast density in premenopausal women. Our findings highlight the heritable component of mammographic breast density and underscore the need to begin annual screening early in premenopausal women with a family history of breast cancer.
Topics: Adult; Female; Humans; Middle Aged; Breast; Breast Density; Breast Neoplasms; Mammography; Medical History Taking; Premenopause; Retrospective Studies; White; Black or African American
PubMed: 35175341
DOI: 10.1001/jamanetworkopen.2021.48983