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Background Mammographic density (MD) is an established biomarker of breast cancer (BC) risk. However, its relationship to BC pathological subtypes remains unclear. This study aimed to investigate this association and assess whether it differs by body mass index (BMI) and menopausal status. Methods MD percentage was assessed in the diagnostic mammograms of the contralateral breast of 714 BC patients recruited from eight Spanish hospitals. Participants completed an epidemiological questionnaire, and hospital researchers collected clinical and pathological data. Standardized prevalences (SPs) and standardized prevalence ratios (SPRs) for each BC pathological subtype across MD categories were estimated based on multinomial logistic regression models, both overall and stratified by BMI and menopausal status. Results Mean MD was 26.1% (SD = 17.3). Although no statistically significant differences were detected, women with MD ≥ 50% had a 13% lower SP of hormone receptor positive tumors (SPR = 0.87; 95% CI 0.67–1.13), a 36% higher SP of human epidermal growth factor receptor 2 positive (HER2+) tumors (SPR = 1.36; 95% CI 0.72–2.58), and a 23% higher SP of triple negative (TN) tumors (SPR = 1.23; 95% CI 0.47–3.22), compared to those with MD < 10%. These patterns were mainly observed in pre/perimenopausal women and in those with BMI ≥ 25 kg/m 2 . Conclusions High MD might be mainly associated with the development of more aggressive and non-hormone-dependent cancers, such as HER2+ and TN BC, especially among pre/perimenopausal an overweight women.

Background and objective This study has two main objectives. First, to evaluate a feature selection methodology based on SEQENS, an algorithm for identifying relevant variables. Second, to validate machine learning models that predict the risk of complications in patients with acute myeloid leukemia (AML) using data available at diagnosis. Predictions are made at three time points: 90 days, six months, and one year post-diagnosis. These objectives represent fundamental steps toward the development of a tool to assist clinicians in therapeutic decision-making and provide insights into the risk factors associated with AML complications. Methods A dataset of 568 patients, including demographic, clinical, genetic (VAF), and cytogenetic information, was created by combining data from Hospital 12 de Octubre (Madrid, Spain) and Instituto de Investigación Sanitaria La Fe (Valencia, Spain). Feature selection based on an enhanced version of SEQENS was conducted for each time point, followed by the comparison of four classifiers (XGBoost, Multi-Layer Perceptron, Logistic Regression and Decision Tree) to assess the impact of feature selection on model performance. Results SEQENS identified different relevant features for each prediction horizon, with Age, TP53, − 7/7Q, and EZH2 consistently relevant across all time points. The models were evaluated using 5-fold cross-validation, XGBoost achieve the highest average ROC-AUC scores of 0.81, 0.84, and 0.82 for 90-day, 6-month, and 1-year predictions, respectively. Generally, performance remained stable or improved after applying SEQENS-based feature selection. Evaluation on an external test set of 54 patients yielded ROC-AUC scores of 0.72 (90-day), 0.75 (6-month), and 0.68 (1-year). Conclusions The models achieved performance levels that suggest they could serve as therapeutic decision support tools at different times after diagnosis. The selected variables align with the European LeukemiaNet (ELN) 2022 risk classification, and the SEQENS-based feature selection effectively reduced the feature set while maintaining prediction accuracy.

Breast cancer is a major health concern worldwide. Mammography, a cost-effective and accurate tool, is crucial in combating this issue. However, low contrast, noise, and artifacts can limit the diagnostic capabilities of radiologists. Computer-Aided Diagnosis (CAD) systems have been developed to overcome these challenges, with the accurate outlining of the breast being a critical step for further analysis. This study introduces the SAM-breast model, an adaptation of the Segment Anything Model (SAM) for segmenting the breast region in mammograms. This method enhances the delineation of the breast and the exclusion of the pectoral muscle in both medio lateral-oblique (MLO) and cranio-caudal (CC) views. We trained the models using a large, multi-center proprietary dataset of 2492 mammograms. The proposed SAM-breast model achieved the highest overall Dice Similarity Coefficient (DSC) of 99.22% ± 1.13 and Intersection over Union (IoU) 98.48% ± 2.10 over independent test images from five different datasets (two proprietary and three publicly available). The results are consistent across the different datasets, regardless of the vendor or image resolution. Compared with other baseline and deep learning-based methods, the proposed method exhibits enhanced performance. The SAM-breast model demonstrates the power of the SAM to adapt when it is tailored to specific tasks, in this case, the delineation of the breast in mammograms. Comprehensive evaluations across diverse datasets—both private and public—attest to the method’s robustness, flexibility, and generalization capabilities.

Image segmentation plays a central role in computer vision applications such as medical imaging, industrial inspection, and environmental monitoring. However, evaluating segmentation performance can be particularly challenging when ground truth is not clearly defined, as is often the case in tasks involving subjective interpretation. These challenges are amplified by inter- and intra-observer variability, which complicates the use of human annotations as a reliable reference. To address this, we propose a novel validation framework—referred to as the three-blind validation strategy—that enables rigorous assessment of segmentation models in contexts where subjectivity and label variability are significant. The core idea is to have a third independent expert, blind to the labeler identities, assess a shuffled set of segmentations produced by multiple human annotators and/or automated models. This allows for the unbiased evaluation of model performance and helps uncover patterns of disagreement that may indicate systematic issues with either human or machine annotations. The primary objective of this study is to introduce and demonstrate this validation strategy as a generalizable framework for robust model evaluation in subjective segmentation tasks. We illustrate its practical implementation in a mammography use case involving dense tissue segmentation while emphasizing its potential applicability to a broad range of segmentation scenarios.

Breast density assessed from digital mammograms is a known biomarker related to a higher risk of developing breast cancer. Supervised learning algorithms have been implemented to determine this. However, the performance of these algorithms depends on the quality of the ground-truth information, which expert readers usually provide. These expert labels are noisy approximations to the ground truth, as there is both intra- and inter-observer variability among them. Thus, it is crucial to provide a reliable method to measure breast density from mammograms. This paper presents a fully automated method based on deep learning to estimate breast density, including breast detection, pectoral muscle exclusion, and dense tissue segmentation. We propose a novel confusion matrix (CM)—YNet model for the segmentation step. This architecture includes networks to model each radiologist’s noisy label and gives the estimated ground-truth segmentation as well as two parameters that allow interaction with a threshold-based labeling tool. A multi-center study involving 1785 women whose “for presentation” mammograms were obtained from 11 different medical facilities was performed. A total of 2496 mammograms were used as the training corpus, and 844 formed the testing corpus. Additionally, we included a totally independent dataset from a different center, composed of 381 women with one image per patient. Each mammogram was labeled independently by two expert radiologists using a threshold-based tool. The implemented CM-Ynet model achieved the highest DICE score averaged over both test datasets (0.82±0.14) when compared to the closest dense-tissue segmentation assessment from both radiologists. The level of concordance between the two radiologists showed a DICE score of 0.76±0.17. An automatic breast density estimator based on deep learning exhibited higher performance when compared with two experienced radiologists. This suggests that modeling each radiologist’s label allows for better estimation of the unknown ground-truth segmentation. The advantage of the proposed model is that it also provides the threshold parameters that enable user interaction with a threshold-based tool.

We developed a semi-automated tool to assess mammographic density (MD), a phenotype risk marker for breast cancer (BC), in full-field digital images and evaluated its performance testing its reproducibility, comparing our MD estimates with those obtained by visual inspection and using Cumulus, verifying their association with factors that influence MD, and studying the association between MD measures and subsequent BC risk. Three radiologists assessed MD using DM-Scan, the new tool, on 655 processed images (craniocaudal view) obtained in two screening centers. Reproducibility was explored computing pair-wise concordance correlation coefficients (CCC). The agreement between DM-Scan estimates and visual assessment (semi-quantitative scale, 6 categories) was quantified computing weighted kappa statistics (quadratic weights). DM-Scan and Cumulus readings were compared using CCC. Variation of DM-Scan measures by age, body mass index (BMI) and other MD modifiers was tested in regression mixed models with mammographic device as a random-effect term. The association between DM-Scan measures and subsequent BC was estimated in a case–control study. All BC cases in screening attendants (2007–2010) at a center with full-field digital mammography were matched by age and screening year with healthy controls (127 pairs). DM-Scan was used to blindly assess MD in available mammograms (112 cases/119 controls). Unconditional logistic models were fitted, including age, menopausal status and BMI as confounders. DM-Scan estimates were very reliable (pairwise CCC: 0.921, 0.928 and 0.916). They showed a reasonable agreement with visual MD assessment (weighted kappa ranging 0.79-0.81). DM-Scan and Cumulus measures were highly concordant (CCC ranging 0.80-0.84), but ours tended to be higher (4%-5% on average). As expected, DM-Scan estimates varied with age, BMI, parity and family history of BC. Finally, DM-Scan measures were significantly associated with BC (p-trend=0.005). Taking MD<7% as reference, OR per categories of MD were: OR 7%-17% =1.32 (95% CI=0.59-2.99), OR 17%-28% =2.28 (95% CI=1.03-5.04) and OR >=29% =3.10 (95% CI=1.35-7.14). Our results confirm that DM-Scan is a reliable tool to assess MD in full-field digital mammograms.

ObjectivesThe association between occupational exposures and mammographic density (MD), a marker of breast cancer risk, has not been previously explored. Our objective was to investigate the influence of occupational exposure to chemical, physical and microbiological agents on MD in adult women.MethodsThis is a population-based cross-sectional study based on 1476 female workers aged 45–65 years from seven Spanish breast cancer screening programmes. Occupational history was surveyed by trained staff. Exposure to occupational agents was assessed using the Spanish job-exposure matrix MatEmESp. Percentage of MD was measured by two radiologists using a semiautomatic computer tool. The association was estimated using mixed log-linear regression models adjusting for age, education, body mass index, menopausal status, parity, smoking, alcohol intake, type of mammography, family history of breast cancer and hormonal therapy use, and including screening centre and professional reader as random effects terms.ResultsAlthough no association was found with most of the agents, women occupationally exposed to perchloroethylene (eβ=1.51; 95% CI 1.04 to 2.19), ionising radiation (eβ=1.23; 95% CI 0.99 to 1.52) and mould spores (eβ=1.44; 95% CI 1.01 to 2.04) tended to have higher MD. The percentage of density increased 12% for every 5 years exposure to perchloroethylene or mould spores, 11% for every 5 years exposure to aliphatic/alicyclic hydrocarbon solvents and 3% for each 5 years exposure to ionising radiation.ConclusionsExposure to perchloroethylene, ionising radiation, mould spores or aliphatic/alicyclic hydrocarbon solvents in occupational settings could be associated with higher MD. Further studies are needed to clarify the accuracy and the reasons for these findings.

Measurement of mammographic density (MD), one of the leading risk factors for breast cancer, still relies on subjective assessment. However, the consistency of MD measurement in full-digital mammograms has yet to be evaluated. We studied inter- and intra-rater agreement with respect to estimation of breast density in full-digital mammograms, and tested whether any of the women’s characteristics might have some influence on them. After an initial training period, three experienced radiologists estimated MD using Boyd scale in a left breast cranio-caudal mammogram of 1,431 women, recruited at three Spanish screening centres. A subgroup of 50 randomly selected images was read twice to estimate short-term intra-rater agreement. In addition, a reading of 1,428 of the images, performed 2 years before by one rater, was used to estimate long-term intra-rater agreement. Pair-wise weighted kappas with 95% bootstrap confidence intervals were calculated. Dichotomous variables were defined to identify mammograms in which any rater disagreed with other raters or with his/her own assessment, respectively. The association between disagreement and women’s characteristics was tested using multivariate mixed logistic models, including centre as a random-effects term, and taking into account repeated measures when required. All quadratic-weighted kappa values for inter- and intra-rater agreement were excellent (higher than 0.80). None of the studied women’s features, i.e. body mass index, brassiere size, menopause, nulliparity, lactation or current hormonal therapy, was associated with higher risk of inter- or intra-rater disagreement. However, raters differed significantly more in images that were classified in the higher-density MD categories, and disagreement in intra-rater assessment was also lower in low-density mammograms. The reliability of MD assessment in full-field digital mammograms is comparable to that for original or digitised images. The reassuring lack of association between subjects’ MD-related characteristics and agreement suggests that bias from this source is unlikely.