Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.

Mammographic breast features and risk of cardiovascular diseases in korean women.

BACKGROUND: There is a growing amount of evidence on the association between cardiovascular diseases (CVDs) and breast calcification. Thus, mammographic breast features have recently gained attention as CVD predictors. OBJECTIVE: This study assessed the association of mammographic features, including benign calcification, microcalcification, and breast density, with cardiovascular diseases. METHODS: This study comprised 6,878,686 women aged ≥40 who underwent mammographic screening between 2009 and 2012 with follow-up until 2020. The mammographic features included benign calcification, microcalcification, and breast density. The cardiovascular diseases associated with the mammographic features were assessed using logistic regression. RESULTS: The prevalence of benign calcification, microcalcification, and dense breasts were 9.6 %, 0.9 % and 47.3 % at baseline, respectively. Over a median follow-up of 10 years, benign calcification and microcalcification were positively associated with an increased risk of chronic ischaemic heart disease whereas breast density was inversely associated with it; the corresponding aOR (95 % CI) was 1.14 (1.10-1.17), 1.19 (1.03-1.15), and 0.88 (0.85-0.90), respectively. A significantly increased risk of chronic ischaemic heart disease (IHD) was observed among women with benign calcifications (aHR, 1.14; 95 % CI 1.10-1.17) and microcalcifications (aOR, 1.19; 95 % CI 1.06-1.33). Women with microcalcifications had a 1.16-fold (95 % CI 1.03-1.30) increased risk of heart failure. CONCLUSIONS: Mammographic calcifications were associated with an increased risk of chronic ischaemic heart diseases, whereas dense breast was associated with a decreased risk of cardiovascular disease. Thus, the mammographic features identified on breast cancer screening may provide an opportunity for cardiovascular disease risk identification and prevention.

Comparison of Mammography and Mammography with Supplemental Whole-Breast US Tomography for Cancer Detection in Patients with Dense Breasts.

BACKGROUND: Women with dense breasts benefit from supplemental cancer screening with US, but US has low specificity. PURPOSE: To evaluate the performance of breast US tomography (UST) combined with full-field digital mammography (FFDM) compared with FFDM alone for breast cancer screening in women with dense breasts. MATERIALS AND METHODS: This retrospective multireader multicase study included women with dense breasts who underwent FFDM and UST at 10 centers between August 2017 and October 2019 as part of a prospective case collection registry. All patients in the registry with cancer were included; patients with benign biopsy or negative follow-up imaging findings were randomly selected for inclusion. Thirty-two Mammography Quality Standards Act-qualified radiologists independently evaluated FFDM followed immediately by FFDM plus UST for suspicious findings and assigned a Breast Imaging Reporting and Data System (BI-RADS) category. The superiority of FFDM plus UST versus FFDM alone for cancer detection (assessed with area under the receiver operating characteristic curve [AUC]), BI-RADS 4 sensitivity, and BI-RADS 3 sensitivity and specificity were evaluated using the two-sided significance level of α = .05. Noninferiority of BI-RADS 4 specificity was evaluated at the one-sided significance level of α = .025 with a -10% margin. RESULTS: Among 140 women (mean age, 56 years ±10 [SD]; 36 with cancer, 104 without), FFDM plus UST achieved superior performance compared with FFDM alone (AUC, 0.60 [95% CI: 0.51, 0.69] vs 0.54 [95% CI: 0.45, 0.64]; P = .03). For FFDM plus UST versus FFDM alone, BI-RADS 4 mean sensitivity was superior (37% [428 of 1152] vs 30% [343 of 1152]; P = .03) and BI-RADS 4 mean specificity was noninferior (82% [2741 of 3328] vs 88% [2916 of 3328]; P = .004). For FFDM plus UST versus FFDM, no difference in BI-RADS 3 mean sensitivity was observed (40% [461 of 1152] vs 33% [385 of 1152]; P = .08), but BI-RADS 3 mean specificity was superior (75% [2491 of 3328] vs 69% [2299 of 3328]; P = .04). CONCLUSION: In women with dense breasts, FFDM plus UST improved cancer detection by radiologists versus FFDM alone. Clinical trial registration nos. NCT03257839 and NCT04260620 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Mann in this issue.

Fair evaluation of federated learning algorithms for automated breast density classification: The results of the 2022 ACR-NCI-NVIDIA federated learning challenge.

The correct interpretation of breast density is important in the assessment of breast cancer risk. AI has been shown capable of accurately predicting breast density, however, due to the differences in imaging characteristics across mammography systems, models built using data from one system do not generalize well to other systems. Though federated learning (FL) has emerged as a way to improve the generalizability of AI without the need to share data, the best way to preserve features from all training data during FL is an active area of research. To explore FL methodology, the breast density classification FL challenge was hosted in partnership with the American College of Radiology, Harvard Medical Schools' Mass General Brigham, University of Colorado, NVIDIA, and the National Institutes of Health National Cancer Institute. Challenge participants were able to submit docker containers capable of implementing FL on three simulated medical facilities, each containing a unique large mammography dataset. The breast density FL challenge ran from June 15 to September 5, 2022, attracting seven finalists from around the world. The winning FL submission reached a linear kappa score of 0.653 on the challenge test data and 0.413 on an external testing dataset, scoring comparably to a model trained on the same data in a central location.

[Development of Auto Dense-breast Classification on Mammography Images Using Image Similarity].

PURPOSE: In Japan, radiologists perform qualitative visual classification to define four categories of mammary gland density. However, an objective estimation of mammary gland density is necessary. To address this, we developed an automatic classification software using image similarity. METHODS: We prepared 741 cases of mediolateral oblique images (MLO) for evaluation, and they were diagnosed as normal among the mammography images taken at our hospital. Image matching was performed using the evaluation images and an image database for breast density determination. In this study, the image similarity used zero normalized cross-correlation (ZNCC) as an index. In addition, if the breast thickness is less than 30 mm and each breast density category ZNNC has the same value, the category is evaluated on the fat side. We compared the results of qualitative visual classification and automatic classification methods to assess consistency. RESULTS: The agreement with the subjective breast composition classification was 78.5%, and the weighted kappa coefficient was 0.98. One mismatched case was evaluated on the higher density side with the same ZNCC value between categories and a breast thickness greater than 30 mm. CONCLUSION: Image similarity provides an excellent estimation of quantification of breast density. This system could contribute to improving the efficiency of the mammography screening system.

Cancer detection rate of breast-MR in supplemental screening after negative mammography in women with dense breasts. Preliminary results of the MA-DETECT-Study after 200 participants.

BACKGROUND: Due to increased cancer detection rates (CDR), breast MR (breast MRI) can reduce underdiagnosis of breast cancer compared to conventional imaging techniques, particularly in women with dense breasts. The purpose of this study is to report the additional breast cancer yield by breast MRI in women with dense breasts after receiving a negative screening mammogram. METHODS: For this study we invited consecutive participants of the national German breast cancer Screening program with breast density categories ACR C & D and a negative mammogram to undergo additional screening by breast MRI. Endpoints were CDR and recall rates. This study reports interim results in the first 200 patients. At a power of 80% and considering an alpha error of 5%, this preliminary population size is sufficient to demonstrate a 4/1000 improvement in CDR. RESULTS: In 200 screening participants, 8 women (40/1000, 17.4-77.3/1000) were recalled due to positive breast MRI findings. Image-guided biopsy revealed 5 cancers in 4 patients (one bilateral), comprising four invasive cancers and one case of DCIS. 3 patients revealed 4 invasive cancers presenting with ACR C breast density and one patient non-calcifying DCIS in a woman with ACR D breast density, resulting in a CDR of 20/1000 (95%-CI 5.5-50.4/1000) and a PPV of 50% (95%-CI 15.7-84.3%). CONCLUSION: Our initial results demonstrate that supplemental screening using breast MRI in women with heterogeneously dense and very dense breasts yields an additional cancer detection rate in line with a prior randomized trial on breast MRI screening of women with extremely dense breasts. These findings are highly important as the population investigated constitutes a much higher proportion of women and yielded cancers particularly in women with heterogeneously dense breasts.

Association of area- and volumetric-mammographic density and breast cancer risk in women of Asian descent: a case control study.

BACKGROUND: Mammographic density (MD) has been shown to be a strong and independent risk factor for breast cancer in women of European and Asian descent. However, the majority of Asian studies to date have used BI-RADS as the scoring method and none have evaluated area and volumetric densities in the same cohort of women. This study aims to compare the association of MD measured by two automated methods with the risk of breast cancer in Asian women, and to investigate if the association is different for premenopausal and postmenopausal women. METHODS: In this case-control study of 531 cases and 2297 controls, we evaluated the association of area-based MD measures and volumetric-based MD measures with breast cancer risk in Asian women using conditional logistic regression analysis, adjusting for relevant confounders. The corresponding association by menopausal status were assessed using unconditional logistic regression. RESULTS: We found that both area and volume-based MD measures were associated with breast cancer risk. Strongest associations were observed for percent densities (OR (95% CI) was 2.06 (1.42-2.99) for percent dense area and 2.21 (1.44-3.39) for percent dense volume, comparing women in highest density quartile with those in the lowest quartile). The corresponding associations were significant in postmenopausal but not premenopausal women (premenopausal versus postmenopausal were 1.59 (0.95-2.67) and 1.89 (1.22-2.96) for percent dense area and 1.24 (0.70-2.22) and 1.96 (1.19-3.27) for percent dense volume). However, the odds ratios were not statistically different by menopausal status [p difference = 0.782 for percent dense area and 0.486 for percent dense volume]. CONCLUSIONS: This study confirms the associations of mammographic density measured by both area and volumetric methods and breast cancer risk in Asian women. Stronger associations were observed for percent dense area and percent dense volume, and strongest effects were seen in postmenopausal individuals.

Breast density prediction from low and standard dose mammograms using deep learning: effect of image resolution and model training approach on prediction quality.

Purpose. To improve breast cancer risk prediction for young women, we have developed deep learning methods to estimate mammographic density from low dose mammograms taken at approximately 1/10th of the usual dose. We investigate the quality and reliability of the density scores produced on low dose mammograms focussing on how image resolution and levels of training affect the low dose predictions.Methods. Deep learning models are developed and tested, with two feature extraction methods and an end-to-end trained method, on five different resolutions of 15,290 standard dose and simulated low dose mammograms with known labels. The models are further tested on a dataset with 296 matching standard and real low dose images allowing performance on the low dose images to be ascertained.Results. Prediction quality on standard and simulated low dose images compared to labels is similar for all equivalent model training and image resolution versions. Increasing resolution results in improved performance of both feature extraction methods for standard and simulated low dose images, while the trained models show high performance across the resolutions. For the trained models the Spearman rank correlation coefficient between predictions of standard and low dose images at low resolution is 0.951 (0.937 to 0.960) and at the highest resolution 0.956 (0.942 to 0.965). If pairs of model predictions are averaged, similarity increases.Conclusions. Deep learning mammographic density predictions on low dose mammograms are highly correlated with standard dose equivalents for feature extraction and end-to-end approaches across multiple image resolutions. Deep learning models can reliably make high quality mammographic density predictions on low dose mammograms.

Breast Density: Where Are We Now?

Breast density refers to the amount of fibroglandular tissue relative to fat on mammography and is determined either qualitatively through visual assessment or quantitatively. It is a heritable and dynamic trait associated with age, race/ethnicity, body mass index, and hormonal factors. Increased breast density has important clinical implications including the potential to mask malignancy and as an independent risk factor for the development of breast cancer. Breast density has been incorporated into breast cancer risk models. Given the impact of dense breasts on the interpretation of mammography, supplemental screening may be indicated.

Sonographic Evaluation of Nigerian Women with Mammographic Focal Asymmetric Density.

BACKGROUND AND OBJECTIVE: Focal asymmetric breast densities (FABD) present a diagnostic challenge concerning the need for a further histologic workup to rule out malignancy. We therefore aim to correlate ultrasonography and mammographic findings in women with FABD and evaluate the use of ultrasonography as a workup tool. METHODOLOGY: This is a retrospective study of women who underwent targeted breast sonography due to FABD with a mammogram in a private diagnostic centre in Abuja over three years (2016-2018). Demographic details, clinical indication, mammographic and ultrasonography features were documented and statistical analysis was done using SAS software version 9.3 with the statistical level of significance set at 0.05. RESULT: The age range of 44 patients was 32-69 years with a majority (79.5%) presenting for screening mammography. The predominant breast density pattern in those <60 years was heterogeneous (ACR C). FABD in mammography was noted mostly in the upper outer quadrant and retro-areolar regions (34.1 and 38.6%). Ultrasonography findings were normal breast tissue (56.8%), 4 simple cysts, 1 abscess, 4 solid masses, 2 focal fibrocystic changes, and 4 cases of duct ectasia. Twenty-nine (65.9%) of the abnormal cases were on the same side as the mammogram, while all the incongruent cases were recorded in heterogeneously dense breasts (ACR C). Final BIRADS Scores on USS showed that 41(93.2%) of mammographic FABD had normal and benign findings while only 2(4.6%) had sonographic features of malignancy. CONCLUSION: Breast ultrasonography allows for optimal lesion characterization and is a veritable tool in the workup of patients with focal asymmetric breast densities with the majority presenting as normal breast tissue and benign pathologies.

CONTEXTE ET OBJECTIF: Les densités asymétriques mammographiques focales mammographiques, FABD présentent un défi diagnostique en ce qui concerne la nécessité d'un examen histologique supplémentaire pour exclure une tumeur maligne. Nous visons donc à corréler les résultats échographiques et mammographiques chez les femmes ayant une densité mammaire focale asymétrique et à établir la nécessité d'un bilan plus approfondi. METHODOLOGIE: Une étude rétrospective de 44 femmes ayant subi une échographie ciblée du sein en raison de FABD à la mammographie dans un centre de diagnostic privé à Abuja sur trois ans (2016-2018) Les détails démographiques, les présentations cliniques, les caractéristiques mammographiques et échographiques ont été documentés et analysés statistiquement fait à l'aide du logiciel SAS version 9.3 avec un niveau de signification statistique fixé à 0,05. RESULTAT: La tranche d'âge des patients était de 32 à 69 ans (SD 1), la majorité (79,5%) se présentant pour une mammographie de dépistage. Le schéma de densité mammaire prédominant chez les moins de 60 ans était hétérogène (ACR C). FABD en mammographie a presque la même distribution dans le quadrant externe supérieur et les régions rétroaréolaires (38,4 vs 36,8%). Les résultats échographiques étaient: tissu mammaire normal (65,9%), 4 kystes simples, 1 kyste complexe, 4 masses solides, 2 fibrokystiques focales et 4 cas d'ectasie canalaire.29 (65,9%) des cas anormaux étaient du même côté que la mammographie, alors que tous les cas incongruents ont été enregistrés dans des seins denses de manière hétérogène (ACR C). Les scores finaux BIRADS sur USS ont montré que 41 (93,2%) des FABD mammographiques avaient des résultats normaux et bénins, tandis que seulement 2 (4,6%) avaient des caractéristiques échographiques de malignité. CONCLUSION: L'échographie mammaire permet une caractérisation optimale des lésions et constitue un véritable outil dans le bilan des patientes présentant des densités mammaires asymétriques focales dont la majorité se présente comme un tissu mammaire normal et des pathologies bénignes. MOTS CLES: Sein, Asymétrie focale, Échographie, Mammographie.

Patient Characteristics Impact Performance of AI Algorithm in Interpreting Negative Screening Digital Breast Tomosynthesis Studies.

Background Artificial intelligence (AI) is increasingly used to manage radiologists' workloads. The impact of patient characteristics on AI performance has not been well studied. Purpose To understand the impact of patient characteristics (race and ethnicity, age, and breast density) on the performance of an AI algorithm interpreting negative screening digital breast tomosynthesis (DBT) examinations. Materials and Methods This retrospective cohort study identified negative screening DBT examinations from an academic institution from January 1, 2016, to December 31, 2019. All examinations had 2 years of follow-up without a diagnosis of atypia or breast malignancy and were therefore considered true negatives. A subset of unique patients was randomly selected to provide a broad distribution of race and ethnicity. DBT studies in this final cohort were interpreted by a U.S. Food and Drug Administration-approved AI algorithm, which generated case scores (malignancy certainty) and risk scores (1-year subsequent malignancy risk) for each mammogram. Positive examinations were classified based on vendor-provided thresholds for both scores. Multivariable logistic regression was used to understand relationships between the scores and patient characteristics. Results A total of 4855 patients (median age, 54 years [IQR, 46-63 years]) were included: 27% (1316 of 4855) White, 26% (1261 of 4855) Black, 28% (1351 of 4855) Asian, and 19% (927 of 4855) Hispanic patients. False-positive case scores were significantly more likely in Black patients (odds ratio [OR] = 1.5 [95% CI: 1.2, 1.8]) and less likely in Asian patients (OR = 0.7 [95% CI: 0.5, 0.9]) compared with White patients, and more likely in older patients (71-80 years; OR = 1.9 [95% CI: 1.5, 2.5]) and less likely in younger patients (41-50 years; OR = 0.6 [95% CI: 0.5, 0.7]) compared with patients aged 51-60 years. False-positive risk scores were more likely in Black patients (OR = 1.5 [95% CI: 1.0, 2.0]), patients aged 61-70 years (OR = 3.5 [95% CI: 2.4, 5.1]), and patients with extremely dense breasts (OR = 2.8 [95% CI: 1.3, 5.8]) compared with White patients, patients aged 51-60 years, and patients with fatty density breasts, respectively. Conclusion Patient characteristics influenced the case and risk scores of a Food and Drug Administration-approved AI algorithm analyzing negative screening DBT examinations. © RSNA, 2024.

Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

The incidence of breast cancer in Egyptian females in correlation to different mammographic ACR densities.

INTRODUCTION: The density of breast tissue, radiologically referred to as fibroglandular mammary tissue, was found to be a predisposing factor for breast cancer (BC). However, the stated degree of elevated BC risk varies widely in the literature.

Mammographic density mediates the protective effect of early-life body size on breast cancer risk.

The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)), and their effects on breast cancer. We use Mendelian randomization (MR) and multivariable MR to estimate the total and direct effects of adiposity and age at menarche on MD phenotypes. Childhood adiposity has a decreasing effect on DA, while adulthood adiposity increases NDA. Later menarche increases DA/PD, but when accounting for childhood adiposity, this effect is attenuated. Next, we examine the effect of MD on breast cancer risk. DA/PD have a risk-increasing effect on breast cancer across all subtypes. The MD SNPs estimates are heterogeneous, and additional analyses suggest that different mechanisms may be linking MD and breast cancer. Finally, we evaluate the role of MD in the protective effect of childhood adiposity on breast cancer. Mediation MR analysis shows that 56% (95% CIs [32%-79%]) of this effect is mediated via DA. Our finding suggests that higher childhood adiposity decreases mammographic DA, subsequently reducing breast cancer risk. Understanding this mechanism is important for identifying potential intervention targets.

Screening for Breast Cancer.

In this JAMA Patient Page, the US Preventive Services Task Force provides a guide to screening for breast cancer.

Inter- and intra-observer variability of qualitative visual breast-composition assessment in mammography among Japanese physicians: a first multi-institutional observer performance study in Japan.

BACKGROUND: Visual assessment of mammographic breast composition remains the most common worldwide, although subjective variability limits its reproducibility. This study aimed to investigate the inter- and intra-observer variability in qualitative visual assessment of mammographic breast composition through a multi-institutional observer performance study for the first time in Japan. METHODS: This study enrolled 10 Japanese physicians from five different institutions. They used the new Japanese breast-composition classification system 4th edition to subjectively evaluate the breast composition in 200 pairs of right and left normal mediolateral oblique mammograms (number determined using precise sample size calculations) twice, with a 1-month interval (median patient age: 59 years [range 40-69 years]). The primary endpoint of this study was the inter-observer variability using kappa (κ) value. RESULTS: Inter-observer variability for the four and two classes of breast-composition assessment revealed moderate agreement (Fleiss' κ: first and second reading = 0.553 and 0.587, respectively) and substantial agreement (Fleiss' κ: first and second reading = 0.689 and 0.70, respectively). Intra-observer variability for the four and two classes of breast-composition assessment demonstrated substantial agreement (Cohen's κ, median = 0.758) and almost perfect agreement (Cohen's κ, median = 0.813). Assessments of consensus between the 10 physicians and the automated software Volpara® revealed slight agreement (Cohen's κ; first and second reading: 0.104 and 0.075, respectively). CONCLUSIONS: Qualitative visual assessment of mammographic breast composition using the new Japanese classification revealed excellent intra-observer reproducibility. However, persistent inter-observer variability, presenting a challenge in establishing it as the gold standard in Japan.

Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.

PURPOSE: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR). METHODS: We applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European ancestry. We performed analyses overall and by menopausal status. RESULTS: Genetically predicted BMI was positively associated with non-dense area (IVW: ß = 1.79; 95% CI = 1.58, 2.00; p = 9.57 × 10-63) and inversely associated with dense area (IVW: ß = - 0.37; 95% CI = - 0.51,- 0.23; p = 4.7 × 10-7). We observed weak evidence for an association of circulating sex hormone concentrations with mammographic density phenotypes, specifically inverse associations between genetically predicted testosterone concentration and dense area (ß = - 0.22; 95% CI = - 0.38, - 0.053; p = 0.009) and between genetically predicted estradiol concentration and non-dense area (ß = - 3.32; 95% CI = - 5.83, - 0.82; p = 0.009), although results were not consistent across a range of MR approaches. CONCLUSION: Our findings support a positive causal association between BMI and mammographic non-dense area and an inverse association between BMI and dense area. Evidence was weaker and inconsistent for a causal effect of circulating sex hormone concentrations on mammographic density phenotypes. Based on our findings, associations between circulating sex hormone concentrations and mammographic density phenotypes are weak at best.

Mammographic features at primary breast cancer diagnosis in relation to recurrence-free survival.

PURPOSE: The number of women living with breast cancer (BC) is increasing, and the efficacy of surveillance programs after BC treatment is essential. Identification of links between mammographic features and recurrence could help design follow up strategies, which may lead to earlier detection of recurrence. The aim of this study was to analyze associations between mammographic features at diagnosis and their potential association with recurrence-free survival (RFS). METHODS: Women with invasive BC in the prospective Malmö Diet and Cancer Study (n = 1116, 1991-2014) were assessed for locoregional and distant recurrences, with a median follow-up of 10.15 years. Of these, 34 women were excluded due to metastatic disease at diagnosis or missing recurrence data. Mammographic features (breast density [BI-RADS and clinical routine], tumor appearance, mode of detection) and tumor characteristics (tumor size, axillary lymph node involvement, histological grade) at diagnosis were registered. Associations were analyzed using Cox regression, yielding hazard ratios (HR) with 95 % confidence intervals (CI). RESULTS: Of the 1082 women, 265 (24.4 %) had recurrent disease. There was an association between high mammographic breast density at diagnosis and impaired RFS (adjusted HR 1.32 (0.98-1.79). In analyses limited to screen-detected BC, this association was stronger (adjusted HR 2.12 (1.35-3.32). There was no association between mammographic tumor appearance and recurrence. CONCLUSION: RFS was impaired in women with high breast density compared to those with low density, especially among women with screen-detected BC. This study may lead to insights on mammographic features preceding BC recurrence, which could be used to tailor follow up strategies.

Implementing supplementary breast cancer screening in women with dense breasts: Insights from European radiographers and radiologists.

INTRODUCTION: In response to the critical need for enhancing breast cancer screening for women with dense breasts, this study explored the understanding of challenges and requirements for implementing supplementary breast cancer screening for such women among clinical radiographers and radiologists in Europe. METHOD: Fourteen (14) semi-structured online interviews were conducted with European clinical radiologists (n = 5) and radiographers (n = 9) specializing in breast cancer screening from 8 different countries: Denmark, Finland, Greece, Italy, Malta, the Netherlands, Switzerland, United Kingdom. The interview schedule comprised questions regarding professional background and demographics and 13 key questions divided into six subgroups, namely Supplementary Imaging, Training, Resources and Guidelines, Challenges, Implementing supplementary screening and Women's Perspective. Data analysis followed the six phases of reflexive thematic analysis. RESULTS: Six significant themes emerged from the data analysis: Understanding and experiences of supplementary imaging for women with dense breasts; Challenges and requirements related to training among clinical radiographers and radiologists; Awareness among radiographers and radiologists of guidelines on imaging women with dense breasts; Challenges to implement supplementary screening; Predictors of Implementing Supplementary screening; Views of radiologists and radiographers on women's perception towards supplementary screening. CONCLUSION: The interviews with radiographers and radiologists provided valuable insights into the challenges and potential strategies for implementing supplementary breast cancer screening. These challenges included patient and staff related challenges. Implementing multifaceted solutions such as Artificial Intelligence integration, specialized training and resource investment can address these challenges and promote the successful implementation of supplementary screening. Further research and collaboration are needed to refine and implement these strategies effectively. IMPLICATIONS FOR PRACTICE: This study highlights the urgent need for specialized training programs and dedicated resources to enhance supplementary breast cancer screening for women with dense breasts in Europe. These resources include advanced imaging technologies, such as MRI or ultrasound, and specialized software for image analysis. Moreover, further research is imperative to refine screening protocols and evaluate their efficacy and cost-effectiveness, based on the findings of this study.