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Polygenic risk scores (PRSs) are rapidly emerging as a way to measure disease risk by aggregating multiple genetic variants. Understanding the interplay of the PRS with environmental factors is critical for interpreting and applying PRSs in a wide variety of settings. We develop an efficient method for simultaneously modeling gene-environment correlations and interactions using the PRS in case-control studies. We use a logistic-normal regression modeling framework to specify the disease risk and PRS distribution in the underlying population and propose joint inference across the 2 models using the retrospective likelihood of the case-control data. Extensive simulation studies demonstrate the flexibility of the method in trading-off bias and efficiency for the estimation of various model parameters compared with standard logistic regression or a case-only analysis for gene-environment interactions, or a control-only analysis, for gene-environment correlations. Finally, using simulated case-control data sets within the UK Biobank study, we demonstrate the power of our method for its ability to recover results from the full prospective cohort for the detection of an interaction between long-term oral contraceptive use and the PRS on the risk of breast cancer. This method is computationally efficient and implemented in a user-friendly R package. [ABSTRACT FROM AUTHOR]

Simple Summary: Pathogenic variants in the PALB2 gene significantly increase the risk of developing breast, ovarian, and pancreatic cancers. However, the prevalence of these mutations in East Asian populations, particularly Koreans, has not been well studied. This research aims to estimate the prevalence of PALB2 variants in these populations by analyzing large-scale genomic databases. Understanding the frequency of PALB2 variants can help in identifying individuals at higher risk for these cancers and guide the development of targeted screening and prevention strategies. The findings from this study provide valuable reference data that can enhance genetic counseling and improve cancer risk management in East Asian populations, ultimately contributing to better health outcomes in these communities. PALB2 is a tumor suppressor gene. Heterozygous germline pathogenic variants of PALB2 significantly increase the lifetime risk of breast cancer and moderately increase the risk of ovarian and pancreatic cancers. This study analyzed the estimated prevalence of PALB2 variants globally, focusing on East Asian and Korean populations, where limited data were previously available. We examined 125,748 exomes from the Genome Aggregation Database (gnomAD), including 9197 East Asians, and additional data from 5305 individuals in the Korean Variant Archive and 1722 in the Korean Reference Genome Database. All PALB2 variants were interpreted according to guidelines from the American College of Medical Genetics and Genomics and the Clinical Genome Resource. The global prevalence of PALB2 variants was 0.18%, with the highest prevalence in Finnish populations (0.41%) and the lowest in Ashkenazi Jewish populations (0.04%). East Asians had a prevalence of 0.09%. By combining data from Korean genome databases and gnomAD totaling 8936 individuals, the overall prevalence of PALB2 variants in the Korean population was determined to be 0.13%. This study is the first comprehensive investigation of PALB2 variant prevalence in East Asians and Koreans using gnomAD and Korean genome databases. These findings provide essential reference data for future research and highlight the importance of region-specific genetic studies that will inform genetic counseling and hereditary cancer risk management. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial. Methods: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer. Results: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e., AUC: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive. Conclusion: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis. [ABSTRACT FROM AUTHOR]

Objective: Schizophrenia seems to have a complex association with various types of cancer, exerting a protective effect against some cancers while being a risk factor against some others. Therefore, we intended to conduct an updated systematic review and meta-analysis in order to examine the relationship between schizophrenia and the risk of breast cancer incidence. Method: We did a systematic search of databases, namely Web of Science, Scopus, Embase, PubMed, and PsycINFO up to August 15, 2024. Screening and data extraction were performed independently. Data was analyzed using Stata16 software. We used the random effect model to pool the results, while the heterogeneity between studies was calculated using Cochran's Q test and (I2) index. Results: We found 15 studies, among which 12 were included in this meta-analysis. The results indicated that the risk of breast cancer development is significantly increased in women with schizophrenia (SIR: 1.43, 95% CI: 1.08-1.85, P < 0.01; IRR: 1.19, 95% CI: 1.13-1.26, P < 0.01). Subgroup analysis revealed significant differences in the incidence of breast cancer rates among women with schizophrenia based on geographic location and duration of follow-up. Conclusion: The results indicate that schizophrenia increases the risk of developing breast cancer. Therefore, taking preventive measures concerning breast cancer among women with schizophrenia is crucial. Additionally, regular screening programs should be implemented to ensure early diagnosis and treatment in case breast cancer is detected. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most frequent female malignancy in the UK. Around 20% of cases are linked to weight gain, excess weight and health behaviours. We designed a weight gain prevention, health behaviour intervention for young women at increased risk. Methods: The study comprised a single arm observational study over 2 months testing acceptability and usability of the intervention: online group welcome event, app and private Facebook group. Females aged 18–35 years at moderate or high risk of breast cancer (>17% lifetime risk) were recruited via invite letters and social media posts. The app included behaviour change techniques and education content. Online questionnaires were completed at baseline, as well as at 1 and 2 months. We also assessed feasibility of study procedures. Results: Both recruitment methods were successful. Thirty‐five women were recruited, 26% via social media posts. Median age was 33 (interquartile range = 28.2–34.5) years, the majority (94.1%) were of White ethnicity. Thirty‐four participants were included in the analyses, of which 94% downloaded the app. Median self‐monitoring logs per participant during the study period was 10.0 (interquartile range = 4.8–28.8). App quality mean (SD) score was 3.7 (0.6) at 1 and 2 months (scale: 1–5). Eighty‐nine per cent rated the app at average or above at 1 month and 75.0% at 2 months. Nineteen women (55.9%) joined the Facebook group and there were 61 comments and 83 reactions and votes from participants during the study period. Conclusions: This first iteration of the app and intervention was well received and is suitable to progress to the next stage of refining and further testing. Highlights: The newly developed intervention that focused on weight gain prevention and health behaviour change was tested in young women at increased risk of breast cancer and was well‐received by the target population.Both recruitment methods, by mailshot and social media, were successful.The study was unable to recruit and ethnically diverse population.Future research should retest the intervention in a larger population, after making refinements. [ABSTRACT FROM AUTHOR]

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Aims: This evaluation combines clinical and non-clinical collaborative breast referral triage to gain an understanding relating to the value of triage, by identifying 'suspected cancer' and 'cancer not suspected' populations, improve the patient pathway, and facilitate optimised resource availability. Method: An iterative service improvement method was used, with distinct phases of the process outlined to facilitate testing of ideas. The evaluation ran for 13 weeks in 2022. Regular team member meetings were arranged to discuss and agree improvement aims and outcomes. Findings: A triage flowchart was developed collaboratively, and subsequently adopted by the non-clinical booking team. Bespoke clinics were established, demonstrating no evidence of increased risk to patients, and meeting 28-day Faster Diagnosis Standard (FDS) requirements. Conclusion: breast referral triage of 'suspected cancer' and 'cancer not suspected' patients, using a clinical and non-clinical collaborative approach facilitates improved service visibility, prioritisation, management, and measurement. This also supports delivery of the 2019 NHS Long Term Plan to enhance earlier and faster cancer diagnosis by optimising access to diagnostic resources where required. [ABSTRACT FROM AUTHOR]

Introduction. Breast cancer is currently the most frequently detected cancer in women and the primary cause of cancer‐related deaths globally. The incidence of breast cancer has significantly increased in countries across sub‐Saharan Africa, counting Ethiopia. There are multiple determinants of breast cancer, a few of these can be changeable whereas others are not. Evidence suggests that breastfeeding, which is a changeable determinant, reduces breast cancer risk. However, there is a lack of evidence specifically linking the duration of breastfeeding to breast cancer risk. To date, no study has been conducted on the association between the duration of breastfeeding and the likelihood of breast cancer among Ethiopian women. Objective. The aim of this study was to evaluate the relationship between breastfeeding duration and breast cancer risk in Ethiopian mothers who had breastfed, taking into account other significant determinants. Methods. A hospital‐based case‐control study was carried out in Bahir Dar, Ethiopia, involving 203 women (70 cases and 133 controls). Face‐to‐face interviews were performed using a standardized, validated questionnaire that assessed various sociodemographic, reproductive, lifestyle, and dietary characteristics. Differences between cases and controls were evaluated using the chi‐square test. The associations among factors were examined through bivariate and multivariable binary logistic regression, with results presented as odds ratios and 95% confidence intervals. Results. The multivariable investigation revealed that an inverse relationship between breastfeeding duration and breast cancer risk. Mothers who breastfed for a longer period had a 93% lower risk of breast cancer (AOR = 0.07; 95% CI: 0.021–0.21) compared to those who breastfed for a shorter duration. Younger mothers had a 95% lower likelihood of developing breast cancer (AOR = 0.05; 95% CI: 0.003–0.91) than older mothers. Additionally, mothers with sedentary behaviour were 10.53 times more likely to develop breast cancer (AOR = 10.53; 95% CI: 5.21–21.36) than those who were moderately or highly active. Mothers who experienced chest therapy were 6.43 times more likely to develop breast cancer (AOR = 6.43; 95% CI: 3.20–13.90) compared to those who had not. Conclusions. Interventions such as breastfeeding counselling and promoting the recommended duration of breastfeeding are crucial in minimizing the risk of breast cancer. Enhancing physical activity should also be viewed as a vital approach for lowering breast cancer risk. Additionally, healthcare professionals need to limit exposure to chest radiation therapy to reduce the likelihood of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Mammographic density has been associated with breast cancer risk, and is modulated by established breast cancer risk factors, such as reproductive and hormonal history, as well as lifestyle. Recent epidemiological and biological findings underscore the recognized benefits of breastfeeding in reducing breast cancer risk, especially for aggressive subtypes. Current research exploring the association among mammographic density, breastfeeding, and breast cancer is sparse. Main findings: Changes occur in the breasts during pregnancy in preparation for lactation, characterized by the proliferation of mammary gland tissues and the development of mammary alveoli. During lactation, the alveoli fill with milk, and subsequent weaning triggers the involution and remodeling of these tissues. Breastfeeding influences the breast microenvironment, potentially altering mammographic density. When breastfeeding is not initiated after birth, or is abruptly discontinued shortly after, the breast tissue undergoes forced and abrupt involution. Conversely, when breastfeeding is sustained over an extended period and concludes gradually, the breast tissue undergoes slow remodeling process known as gradual involution. Breast tissue undergoing abrupt involution displays denser stroma, altered collagen composition, heightened inflammation and proliferation, along with increased expression of estrogen receptor α (ERα) and progesterone receptor. Furthermore, elevated levels of pregnancy-associated plasma protein-A (PAPP-A) surpass those of its inhibitors during abrupt involution, enhancing insulin-like growth factor (IGF) signaling and collagen deposition. Prolactin and small molecules in breast milk may also modulate DNA methylation levels. Drawing insights from contemporary epidemiological and molecular biology studies, our review sheds light on how breastfeeding impacts mammographic density and explores its role in influencing breast cancer. Conclusion: This review highlights a clear protective link between breastfeeding and reduced breast cancer risk via changes in mammographic density. Future research should investigate the effects of breastfeeding on mammographic density and breast cancer risk among various ethnic groups and elucidate the molecular mechanisms underlying these associations. Such comprehensive research will enhance our understanding and facilitate the development of targeted breast cancer prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mammographic breast density (MBD) is a strong risk factor and an intermediate phenotype for breast cancer, yet there are limited studies on how environmental pollutants are associated with MBD. OBJECTIVE: We investigated associations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) levels with measures of MBD and evaluated if early life factors modified any associations. METHODS: Metabolon performed metabolomics analysis using ultrahigh-performance liquid chromatography/tandem accurate mass spectrometry in fasting blood from 705 premenopausal women completing their annual screening mammogram in St. Louis, Missouri. We calculated least square means (LSM) of mammographic volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV) by quartiles (Q) of PFOS, PFOA, and PFHxS from multivariable linear regression modeling overall and stratified by recruitment period, race, age at menarche, and body shape at age 10. Models were adjusted for age, age at menarche, body fat percentage, race, family history of breast cancer, oral contraceptive use, alcohol consumption, parity/age at first birth, and body shape at age 10. RESULTS: PFOS, PFOA, and PFHxS were not significantly associated with VPD or NDV. PFHxS was significantly positively associated with DV (Q1=67.64 cm³, Q2=69.91 cm³, Q3=69.06 cm³, Q4=75.79 cm³; 푝-trend=0.03). PFOS was positively associated with DV (Q1=65.45 cm³, Q2=70.74 cm³, Q3=73.31 cm³, Q4=73.52 cm³; 푝-trend=0.06) with DV being 8.1%, 12%, and 12.3% higher in Q2, Q3, and Q4 compared to Q1. Among women who were underweight/normal weight at age 10, PFOS was positively associated with VPD (Q1=9.02%, Q2=9.11%, Q3=9.48%, Q4=9.92%; 푝-trend=0.04) while there was an inverse association among women who were overweight/obese at age 10 (Q1=7.46%, Q2=6.94%, Q3=6.78%, Q4=5.47%; 푝-trend=0.005) (푝-interaction=0.04). DISCUSSION: We report novel associations of PFHxS and PFOS with DV in premenopausal women. PFOS, PFOA, and PFHxS were not associated with VPD and NDV. In addition, body shape at age 10 may modify the associations of PFOS with MBD. Further studies are needed to validate our findings and to evaluate the associations of other per- and polyfluoroalkyl substances (PFAS), as well as mixtures of PFAS, with MBD. [ABSTRACT FROM AUTHOR]

• Higher intake of green and white vegetables/fruits is linked to reduced breast cancer (BrCa) risk. • The role of diet in reducing BrCa is emphasized, highlighting the importance of the color of vegetables/fruits. • Our study provides information supporting dietary guidelines to lower BrCa risk. Breast cancer (BrCa) remains a significant health concern globally, influenced by both nonmodifiable and modifiable risk factors. Limited studies have explored the role of color-specific vegetables and fruits, which are rich in specific phytonutrients, on BrCa risk. We hypothesized that consuming color-specific vegetables and fruits may decrease BrCa risk in Korean women. This case-control study examined the relationship between the intake of different-colored vegetables and fruits and the risk of BrCa, considering menopausal, hormone receptor status, tumor subtypes. We matched 395 patients and 395 controls by age and recruited from the National Cancer Center in Korea. Dietary data was collected via food frequency questionnaire, categorizing by colors: green, orange/yellow, red/purple, and white. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression models, with subgroup analyses for menopausal, hormone receptor status, and tumor subtypes. Results shown BrCa patients consumed less vegetables and fruits than control group. Higher consumption of green, other orange/yellow, and white vegetables and fruits was negatively associated with BrCa risk [OR (95% CIs) of Q4 vs Q1 = 0.59 (0.36-0.94); 0.55 (0.33-0.89); and 0.60 (0.37-0.96), respectively]. Particularly, a greater intake of dark green leafy vegetables was significantly associated with reduced BrCa risk (OR of Q4 vs Q1 = 0.55, 95% CI = 0.34-0.89). Subgroup analysis consistently demonstrated inverse associations between higher intake of green-color vegetables and fruits and BrCa risk. Our findings suggest that a diet rich in green and white-color vegetables and fruits may lower BrCa risk among Korean women. [Display omitted] This case-control study examined the link between color-type vegetables and fruits and BrCa risk among Korean women, categorizing by colors: green, orange/yellow, red/purple, and white. Subgroup analyses considered menopausal status, hormone receptor status, tumor subtypes, and cancer stages. Findings indicate higher intake of green-, orange/yellow-, and white vegetables and fruits is linked to lower BrCa risk, especially in postmenopausal women with triple-negative BrCa and stage III. These data may support nutritional guidelines based on BrCa types. Abbreviations: BrCa, breast cancer [ABSTRACT FROM AUTHOR]

Simple Summary: Hundreds of common genetic variants have been linked to breast cancer, but their exact mechanisms of action remain unclear. Understanding these mechanisms could lead to better prevention strategies and improved survival rates. Our study focused on how these variants influence splicing—a process by which a gene's coding elements are rearranged to produce different proteins. By analysing data from healthy breast tissue, we identified 43 variants within twelve genes associated with both alternative splicing and breast cancer risk. We then used advanced computational tools and existing experimental data to explore the biological significance of these findings. Genome-wide association studies (GWASs) have revealed numerous loci associated with breast cancer risk, yet the precise causal variants, their impact on molecular mechanisms, and the affected genes often remain elusive. We hypothesised that specific variants exert their influence by affecting cis-regulatory alternative splice elements. An analysis of splicing quantitative trait loci (sQTL) in healthy breast tissue from female individuals identified multiple variants linked to alterations in splicing ratios. Through colocalisation analysis, we pinpointed 43 variants within twelve genes that serve as candidate causal links between sQTL and GWAS findings. In silico splice analysis highlighted a potential mechanism for three genes—FDPS, SGCE, and MRPL11—where variants in proximity to or on the splice site modulate usage, resulting in alternative splice transcripts. Further in vitro/vivo studies are imperative to fully understand how these identified changes contribute to breast oncogenesis. Moreover, investigating their potential as biomarkers for breast cancer risk could enhance screening strategies and early detection methods for breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Germline mutation rates and spectra across three cohorts of Chinese patients: a high-risk breast cancer cohort, an unselected breast cancer cohort, and a benign breast lesion cohort were compared. The high-risk cohort had the highest mutation rate at 11.9%, while the unselected cancer and benign lesion cohorts had rates of 6.5% and 8.1%, respectively. Notably, 29.3% of the unselected breast cancer patients met genetic testing criteria, and this subgroup had a mutation rate similar to the high-risk cohort. High-penetrance gene mutations were only found in the high-risk and unselected cancer cohorts. Unexpectedly, a 2% mutation rate was observed in the benign lesion cohort. These findings highlight the need for broader genetic testing of all breast cancer patients, not just those deemed high-risk, to identify more individuals harboring clinically relevant germline mutations. Mutation study for high-risk breast and ovarian cancer (HBOC) has been extensively studied in patients of different ethnicities. Here we compared the germline mutation rate and mutation spectrum of patients (n = 4341) with benign breast diseases or breast cancers, with and without other risk factors. Three cohorts of Chinese patients were recruited. The first cohort, high-risk cohort (HR, n = 3935) included high-risk breast cancer patients fulfilling high-risk HBOC criteria and who are recruited at our genetics clinic. The second cohort, unselected cancer cohort (CC, n = 307) was from general recruitment of patients with breast cancer at breast surgery clinics. The third cohort, benign breast lesion cohort (NC, n = 99) comprised 99 patients with benign breast diseases such as fibroadenoma, fibroadenomatoid hyperplasia, and intraductal papilloma. Thirty HBOC related genes were sequenced on the above-mentioned patient cohorts. The germline mutation rates of HR, CC, and NC cohort were 11.9%, 6.5%, and 8.1%, respectively. In the CC cohort, 29.3% (90/307) of patients fulfilled the National Comprehensive Cancer Network (NCCN) high-risk genetic test criteria 2022 v.2. The mutation rate for this group of patients was 11.1%, similar to that of the HR cohort, while the mutation rate for those not fulfilling testing criteria was 4.6%, like that of the NC cohort. High penetrance genes (BRCA1/2, CDH1, PALB2, PTEN, and TP53) mutations were only found in the HR (10.6%) and CC (3.3%) cohorts but were not found in the NC cohort. ATM, BRIP1, RAD51C, and RAD51D mutations were identified in all cohorts. RAD51C and RAD51D mutations showed conflicting penetrance. An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Allostatic load (AL) is the accumulation of physiological dysregulation attributed to repeated activation of the stress response over a lifetime. We assessed the utility of AL as a prognostic measure for high-risk benign breast biopsy pathology results. Method: Eligible patients were women 18 years or older, with a false-positive outpatient breast biopsy between January and December 2022 at a tertiary academic health center. AL was calculated using 12 variables representing four physiological systems: cardiovascular (pulse rate, systolic and diastolic blood pressures, total cholesterol, high-density lipoprotein, and low-density lipoprotein); metabolic (body mass index, albumin, and hemoglobin A1C); renal (creatinine and estimated glomerular filtration rate); and immune (white blood cell count). Multivariable logistic regression was used to assess the association between AL before biopsy and breast biopsy outcomes controlling for patients' sociodemographics. Results: In total, 170 women were included (mean age, 54.1 ± 12.9 years): 89.4% had benign and 10.6% had high-risk pathologies (radial scar/complex sclerosing lesion, atypical ductal or lobular hyperplasia, flat epithelial atypia, intraductal papilloma, or lobular carcinoma in-situ). A total of 56.5% were White, 24.7% Asian, and 17.1% other races. A total of 32.5% identified as Hispanic. The mean breast cancer risk score using the Tyrer–Cuzick model was 11.9 ± 7.0. In multivariable analysis, with every one unit increase in AL, the probability of high-risk pathology increased by 37% (odds ratio, 1.37; 95% confidence interval, 1.03, 1.81; p = 0.03). No significant association was seen between high-risk pathology and age, ethnicity, breast cancer risk, or area deprivation index. Conclusion: Our findings support that increased AL, a biological marker of stress, is associated with high-risk pathology among patients with false-positive breast biopsy results. [ABSTRACT FROM AUTHOR]

Considering the significant involvement of insulin resistance in various forms of cancer, it is postulated that the implementation of a diabetic diet, which effectively mitigates insulin resistance, may potentially decrease the susceptibility to breast cancer among female individuals. In this literature review, a comprehensive electronic search of different databases was done using the keywords "Breast cancer" OR "breast tumor" OR "Breast Neoplasms" AND "diet" OR "diabetic diet" OR "Low Carbohydrate Diet" OR "Carbohydrate restricted diet" OR "High-Protein Low-Carbohydrate Diet" OR "diabetes risk reduction diet" OR "DRRD" as the main keywords. Research has shown that the DRRD score is inversely correlated with breast cancer risk. In fact, for every three-point increase in the DRRD score, the risk of breast cancer decreases by 7%. Studies have shown that higher DRRD scores in breast cancer patients are associated with a reduced risk of cancer and a higher chance of survival. The results of this study indicate a positive correlation between a higher level of adherence to the diabetes risk reduction diet (DRRD) and improved survival rates. This suggests that breast cancer survivors may benefit from making dietary modifications in line with a diabetic diet following their diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: According to the conducted studies, breast cancer is one of the most common malignant tumors, and its incidence rate is increasing yearly. One of the measures to reduce the mentalities from breast cancer is early diagnosis of biomarkers, such as Leptin polymorphisms (rs7799039 and rs2167270), and timely treatment. Leptin is an adipocytokine made by fat cells, playing a crucial role in cell proliferation, survival, migration, and immune response. The present study aimed to assess the association between polymorphisms in the Leptin gene and breast cancer risk in Arak, Iran. Materials & Methods: Two SNPs of the Leptin gene (rs7799039 and rs2167270) were genotyped by PCR-RFLP method (polymerase chain reaction-restriction fragment length polymorphism) in a case-control study, including 80 breast cancer patients and 80 healthy controls. In this study, all statistical analyses were performed in SPSS software (version 26) using the Chi-Squared test at P˂ 0.05 significant level. Results: Based on the results, rs7799039 and rs2167270 showed no significant association with breast cancer risk (P=0.183 and P=0.86, respectively). In this study, the mean age in the patient group was 47 ( an age range of 28-79 years). Conclusion: As evidenced by the obtained results, Leptin gene polymorphisms (rs7799039 and rs2167270) did not increase the risk of breast cancer in the Arak population in Iran. Although based on the present study results, there was no significant association between Leptin gene polymorphisms and breast cancer risk, according to the prominent role of the Leptin gene, the polymorphisms of this gene could be used as biomarkers to predict breast cancer in other populations. [ABSTRACT FROM AUTHOR]

Objective This study aims to determine which qualitative and quantitative US features are independently associated with malignancy, including those derived from grayscale imaging morphology, shear wave elastography (SWE), and texture analysis. Methods This single-center retrospective study was approved by the institutional research ethics board. Consecutive breast US studies performed between January and December 2020 were included. Images were acquired using a Canon Aplio i800 US unit (Canon Medical Systems, Inc. CA) and i18LX5 wideband linear matrix transducer. Grayscale US features, SWE mean, and median elasticity were obtained. Single representative grayscale images were analyzed using dedicated software (LIFEx, version 6.30). First-order and gray-level co-occurrence matrix second-order texture features were extracted. Multivariate logistic regression was performed to assess for predictors of malignancy (STATA v16.1). Results One hundred forty-seven cases with complete SWE data were selected for analysis (mean age 54.3, range 21-92). The following variables were found to be independently associated with malignancy: age (P  <.001), family history (P  = .013), irregular mass shape (P  = .024), and stiffness on SWE (mean SWE ≥40 kPa; P  <.001). Remaining variables (including texture features) were not found to be independently associated with malignancy (P  >.05). Conclusion US texture analysis features were not associated with malignancy independent of other qualitative and quantitative US characteristics currently utilized in clinical practice. This suggests texture analysis may not be warranted when differentiating benign and malignant breast masses on US. In contrast, irregular mass shape on grayscale imaging and increased stiffness on SWE were found to be independent predictors of malignancy. [ABSTRACT FROM AUTHOR]

Background Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2−) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. Patients and Methods The study cohort comprised HR+/HER2−, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. Results The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). Conclusion In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the leading cause of cancer-related death among women worldwide. Mortality from breast cancer can be reduced through early detection and prevention. Despite the availability of breast cancer screening methods, the uptake of screening services remains very low, especially in low-resource countries like Tanzania. This low uptake of screening services may be attributed to a lack of awareness regarding the importance of early detection of the disease. Objectives: This study was set to determine breast cancer awareness and the uptake of breast cancer screening services among undergraduate female students in Dar es Salaam, Tanzania. Design: The study was a descriptive cross-sectional study using the quantitative approach. Methods: The sample size calculated for this study was 434 undergraduate female students. The tool used for data collection was self-administered questionnaires, with data collection taking place in July 2022. Data were analyzed using Stata Version 15 and presented using descriptive and inferential statistics. Results: We found that most of the participants (92.38%) had heard about breast cancer, and only 39% of the participants were able to correctly identify the risk factors for breast cancer. Participants who had ever used breast cancer screening services by at least 1 method were 37 (9.23%), and the most common screening method practiced by the study participants was breast self-examination (48.65%). Conclusions: Most of the participants were not aware of the screening methods for early detection of breast cancer. In addition, they lacked knowledge of some of the risk factors as evidenced by the low uptake of breast cancer screening services among the study participants. This calls for an awareness-raising campaign on the importance of breast cancer screening. [ABSTRACT FROM AUTHOR]

Purpose: Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach. Design: This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high). Results: A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk. Conclusion: These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations. Registry: The protocol is registered at clinicaltrials.gov as NCT03285230. [ABSTRACT FROM AUTHOR]

Purpose: It has been proposed that a higher habitual protein intake may increase cancer risk, possibly via upregulated insulin-like growth factor signalling. Since a systematic evaluation of human studies on protein intake and cancer risk based on a standardised assessment of systematic reviews (SRs) is lacking, we carried out an umbrella review of SRs on protein intake in relation to risks of different types of cancer. Methods: Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and cancer risk published before January 22th 2024, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria. Results: Ten SRs were identified, of which eight included meta-analyses. Higher total protein intake was not associated with risks of breast, prostate, colorectal, ovarian, or pancreatic cancer incidence. The methodological quality of the included SRs ranged from critically low (kidney cancer), low (pancreatic, ovarian and prostate cancer) and moderate (breast and prostate cancer) to high (colorectal cancer). The outcome-specific certainty of the evidence underlying the reported findings on protein intake and cancer risk ranged from very low (pancreatic, ovarian and prostate cancer) to low (colorectal, ovarian, prostate, and breast cancer). Animal and plant protein intakes were not associated with cancer risks either at a low (breast and prostate cancer) or very low (pancreatic and prostate cancer) outcome-specific certainty of the evidence. Overall, the evidence for the lack of an association between protein intake and (i) colorectal cancer risk and (ii) breast cancer risk was rated as possible. By contrast, the evidence underlying the other reported results was rated as insufficient. Conclusion: The present findings suggest that higher total protein intake may not be associated with the risk of colorectal and breast cancer, while conclusions on protein intake in relation to risks of other types of cancer are restricted due to insufficient evidence. [ABSTRACT FROM AUTHOR]

This review and meta-analysis assessed the relationship between vitamin D levels and the risk of breast and endometrial cancers, and the efficacy of vitamin D supplementation as a preventive strategy. We searched PubMed and the Cochrane Library using "vitamin D" and "breast and endometrial cancer," focusing on human studies in English. Ten high-quality studies were selected based on robust design and data integrity. We analyzed effect sizes--odds ratios, risk ratios, and hazard ratios with 95% confidence intervals--using a random-effects model. Our findings suggest that higher vitamin D levels are linked to a lower risk of these cancers, especially in premenopausal women and those with greater sun exposure. Although some studies found no significant links, the overall evidence supports vitamin D's protective potential. Further randomized trials are necessary to confirm these results and define vitamin D deficiency standards in cancer risk assessment. [ABSTRACT FROM AUTHOR]

Alcohol is a causal factor in about 10% of breast cancer (BCa) cases, but awareness of this link is low. This study explored how to raise awareness and inform the development of an intervention using the COM-B model (capability, opportunity, motivation, behavior) framework. Eight online focus groups were conducted with 36 participants (6 expert stakeholders,and 30 women aged 40–65). Participants reflected on a package of information about alcohol and BCa and discussed how to impart this information and encourage women to reduce drinking. Thematic analysis of focus group transcripts was undertaken. Three themes were identified: understanding ineffective messaging; transitions and challenges; and message acceptability. Current health information about alcohol was perceived as judgmental and BCa was put down to chance. Mid-life consisted of many challenges that could lead to increased consumption, but menopause transition may be a key moment for alcohol reduction. Barriers and enablers to communicating risk information and encouraging alcohol reduction were mapped onto the COM-B model. Psychological capability (relating to knowledge), social opportunity (in the form of social pressure) and automatic motivation (relating to drinking to cope) were barriers to behavior change. These will be targeted in an alcohol reduction intervention. It is important to tailor information to women's experiences, taking into account the social benefits of drinking, and encourage the development of healthy coping strategies. Acceptable intervention messages may include personal stories, clear statistics, and suggest healthy alternatives to drinking. It is vital that messaging does not appear judgmental or patronizing. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is the second leading cause of death globally, and the causes of cancer are numerous and multifactorial, including genetic and environmental factors. There is a developing interest in the role of sleep and light at night (LAN) exposure in cancer development. The aim of our study is to further understand the relationship between LAN exposure and the risk of cancer by systematically reviewing existing literature assessing LAN exposure and the risk of various cancer types. We found a positive association between LAN exposure and breast cancer risk, but there was insufficient data to convincingly draw a conclusion for other cancer types. This emphasizes the need for further research not only assessing LAN exposure and the incidence of other cancers but also the pathophysiology of sleep interruption on the formation of cancer. Background: Emerging interest surrounds the role of environmental factors, notably exposure to light at night (LAN), as a potential cause of cancer. The aim of this study was to conduct a systematic review and, if possible, meta-analysis of observational studies on LAN and cancer risk of multiple types. Methods: A systematic literature search in PubMed, Web of Science, and Embase, spanning from inception to May 2023, was conducted. Studies focusing on the association between LAN exposure and cancer risk in adult populations were included. We used random effects models to calculate pooled risk estimates (RR) and 95% confidence intervals (CI). We assessed study quality using the Risk of Bias in Non-randomized Studies of Interventions. Results: Among 8492 initially identified studies, 26 met the inclusion criteria (13 were case–control and 13 were cohort studies). These studies were published from 2001 to 2023 and assessed diverse cancer types in North America, Asia, Europe, and Australia. Except for breast cancer, there was a paucity of site-specific cancer studies. In the meta-analysis of 19 breast cancer studies, higher exposure to indoor (summary RR, 1.08; 95% CI 1.01–1.15) and outdoor (summary RR, 1.10; 95% CI, 1.04–1.15) LAN were associated with increased risk. After excluding one low-quality study, the results were unchanged. Conclusions: We found a positive association between LAN exposure and breast cancer risk in women. However, data are lacking for other cancer types, and further studies are required to better understand the role of LAN on cancer. [ABSTRACT FROM AUTHOR]

This quality improvement project implemented a nurse-led high-risk screening referral protocol for earlier identification of women at increased risk for breast cancer. The Breast Cancer Risk Assessment Tool was used at the mammography appointment, which led to improved electronic communication and significant increases in high-risk clinic consultations, breast magnetic resonance imaging, genetic counseling, and additional testing. Patients reported high satisfaction with advanced practice providers, which indicates increased comfort levels. [ABSTRACT FROM AUTHOR]

Breast cancer screening guidelines vary for women at intermediate risk (15%-20% lifetime risk) for developing breast cancer across jurisdictions. Currently available risk assessment models have differing strengths and weaknesses, creating difficulty and ambiguity in selecting the most appropriate model to utilize. Clarifying which model to utilize in individual circumstances may help determine the best screening guidelines to use for each individual. [ABSTRACT FROM AUTHOR]

We synthesized the epidemiologic evidence on the associations between per- and polyfluoroalkyl substances (PFAS) exposure and breast cancer risk. Our systematic review and meta-analysis included 18 and 11 articles, respectively, covering studies up to February 2023. The summary relative risks (RRs) estimated by random-effects meta-analyses did not support an association between PFAS and overall breast cancer risk (eg, a natural log (ln)-unit increase in serum/plasma concentrations [ng/mL] for perfluorooctanoate [PFOA] RR = 0.95; 95% CI, 0.77-1.18; perfluorooctane sulfonate [PFOS] RR = 0.98; 95% CI, 0.87-1.11). However, when limiting to studies that assessed exposures prior to a breast cancer diagnosis, we observed a positive association with PFOA (a ln-unit increase, RR = 1.16; 95% CI, 0.96-1.40). We also observed some possible heterogeneous associations by tumor estrogen and progesterone receptor status among postmenopausal breast cancer cases. No meaningful changes were observed after excluding the studies with high risk of bias (Tier 3). Based on the evaluation tool developed by the National Toxicology Program, given the heterogeneity across studies and the variability in timing of exposure measurements, the epidemiologic evidence needed to determine the association between PFAS exposure and breast cancer remains inadequate. Our findings support the need for future studies with improved study designs to determine this association. [ABSTRACT FROM AUTHOR]

Aim: Reduction mammoplasty (RM) operations are frequently performed for breast reduction and asymmetry correction. Evaluation of these materials is important in patients at high risk of developing invasive breast carcinoma (IBC) to detect precancerous lesions or lesions that may accompany cancer. This study aimed to evaluate the histopathologic and clinical features of proliferative and non-proliferative lesions in RM materials. Material and Methods: In this study, 214 cases (402 specimens) of RM operated for aesthetic purposes (except gynecomastia) at Eskişehir Osmangazi University Hospital between the years 2020 and 2023 were included. The age of cases, location and bilaterality of the lesions, and proliferative and non-proliferative lesions were evaluated. Results: The mean age of RM cases was 38.5±10.9 years. The most common lesion was apocrine metaplasia in RM materials. Proliferative and non-proliferative lesions were found bilaterally in 24.8% (n=53) of all RM cases. The most common bilaterality was intraductal papilloma and the most common unilateral lesion was ductal ectasia. 0.2% (n=1) case of ductal carcinoma in situ and 0.9% (n=4) cases of lobular carcinoma in situ was found. Conclusion: Detection of high-risk lesions is important for appropriate clinical follow-up. In this study, high-risk proliferative lesions were found considerably in RM cases. Patients with high-risk proliferative lesions should be followed up more closely in terms of cancer risk in the future. In addition, it is crucial to perform a careful macroscopic examination in mammoplasty operations performed for aesthetic purposes to avoid missing these lesions. [ABSTRACT FROM AUTHOR]

Background PREDICT is a web-based tool for forecasting breast cancer outcomes. PREDICT version 3.0 was recently released. This study aimed to validate this tool for a large population in mainland China and compare v3.0 with v2.2. Methods Women who underwent surgery for nonmetastatic primary invasive breast cancer between 2010 and 2020 from the First Affiliated Hospital of Wenzhou Medical University were selected. Predicted and observed 5-year overall survival (OS) for both v3.0 and v2.2 were compared. Discrimination was compared using receiver-operator curves and DeLong test. Calibration was evaluated using calibration plots and chi-squared test. A difference greater than 5% was deemed clinically relevant. Results A total of 5424 patients were included, with median follow-up time of 58 months (IQR 38-89 months). Compared to v2.2, v3.0 did not show improved discriminatory accuracy for 5-year OS (AUC: 0.756 vs 0.771), same as ER-positive and ER-negative patients. However, calibration was significantly improved in v3.0, with predicted 5-year OS deviated from observed by −2.0% for the entire cohort, −2.9% for ER-positive and −0.0% for ER-negative patients, compared to −7.3%, −4.7% and −13.7% in v2.2. In v3.0, 5-year OS was underestimated by 9.0% for patients older than 75 years, and 5.8% for patients with micrometastases. Patients with distant metastases postdiagnosis was overestimated by 10.6%. Conclusions PREDICT v3.0 reliably predicts 5-year OS for the majority of Chinese patients with breast cancer. PREDICT v3.0 significantly improved the predictive accuracy for ER-negative groups. Furthermore, caution is advised when interpreting 5-year OS for patients aged over 70, those with micrometastases or metastases postdiagnosis. [ABSTRACT FROM AUTHOR]

Background Risk management programs targeting women with genetic predispositions to breast cancer (BC), eg, BRCA1 and BRCA2 , are effective assuming full adherence with the program protocol. However, high risk to BC in women and equal access to care may not result in high and uniform adherence with the program. Objective To elucidate factors influencing adherence with screening program in women with genetic predispositions to BC. Material and Methods We retrieved data from a multicenter pathogenic-related BC surveillance program across 4 French regions. We used multilevel logistic modeling to analyze factors of adherence with the program, with "on-time" or postponed screening as the dependent variable. Results Seven hundred and seventy-eight participants were followed for a 4.7-year median. We observed 2796 annual screening rounds and 5.4% postponed rounds with a 6-month margin. Women with prevalent BC and carriers of BRCA1 and BRCA2 mutations did not have on-time annual screenings any more than women low cancer risk. Better adherence was observed with screenings after the 2nd round, with higher total number of rounds. Having one or more recalls was significantly associated with worse adherence. No contextual factors affected adherence. Furthermore, postponed rounds increased between 2018 and 2020 compared to 2015 and 2017. Conclusion Having a higher BC risk status does not result in better adherence to the risk management program. However, factors directly related to screening rounds reduced postponements. Future research should address the benefits of screening-related organizational factors that contribute to adherence improvement. [ABSTRACT FROM AUTHOR]

Objective: To investigate the features and outcomes of breast cancer in high-risk subgroups. Materials and Methods: REB approved an observational study of women diagnosed with breast cancer from 2010 to 2019. Three radiologists, using the BI-RADS lexicon, blindly reviewed mammogram and MRI screenings without a washout period. Consensus was reached with 2 additional reviewers. Inter-rater agreement was measured by Fleiss Kappa. Statistical analysis included Mann-Whitney U, Chi-square tests for cohort analysis, and Kaplan-Meier for survival rates, with a Cox model for comparative analysis using gene mutation as a reference. Results: The study included 140 high-risk women, finding 155 malignant lesions. Significant age differences noted: chest radiation therapy (median age 44, IQR: 37.0-46.2), gene mutation (median age 49, IQR: 39.8-58.0), and familial risk (median age 51, IQR: 44.5-56.0) (P =.007). Gene mutation carriers had smaller (P =.01), higher-grade tumours (P =.002), and more triple-negative ER- (P =.02), PR- (P =.002), and HER2- (P =.02) cases. MRI outperformed mammography in all subgroups. Substantial to near-perfect inter-rater agreement observed. Over 10 years, no deaths occurred in chest radiation group, with no significant survival difference between gene mutation and familial risk groups, HR = 0.93 (95% CI: 0.27, 3.26), P =.92. Conclusion: The study highlights the importance of age and specific tumour characteristics in identifying high-risk breast cancer subgroups. MRI is confirmed as an effective screening tool. Despite the aggressive nature of cancers in gene mutation carriers, early detection is crucial for survival outcomes. These insights, while necessitating further validation with larger studies, advocate for a move toward personalized medical care, strengthening the existing healthcare guidelines. [ABSTRACT FROM AUTHOR]

Simple Summary: Females prenatally exposed to diethylstilbestrol have an elevated risk of severe cervical dysplasia and some cancers, while testicular cancer is increased in males. We assessed these associations in the prenatally exposed female's offspring (third generation). Based on third-generation females' self-reports, diethylstilbestrol exposure was not associated with risks of overall cancer, breast cancer, or severe cervical dysplasia. Borderline ovarian cancer risk in exposed vs. unexposed was elevated but compatible with chance. Based on mothers' reports, diethylstilbestrol exposure did not increase the risk of overall or other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated but compatible with chance. Testicular cancer risk was not elevated in exposed males, and there were no prostate cancers reported. These data do not provide evidence that diethylstilbestrol is associated with cancer risk in third-generation females or males. The third generation is relatively young and requires follow-up to assess risk as the cohort ages. Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36–1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37–32.42). Based on mothers' reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49–1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70–2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed. [ABSTRACT FROM AUTHOR]

Background: The breast, being a highly radiosensitive organ, is exposed to scattered radiation during brain computed tomography (CT) scans. This study aims to estimate the lifetime attributable risk (LAR) of female breast cancer resulting from brain CT scans. Method: 90 women participated in this cross-sectional study. The LAR of breast cancer incidence was estimated based on health risks associated with exposure to low levels of ionizing radiation, as per the BEIR VII Phase 2 guidelines. The absorbed dose to the breasts was measured using thermoluminescence dosimeters, and the effective dose was calculated from the dose length product. All brain CT scans were conducted using a 16-slice scanner (SOMATOM EMOTION). Statistical analysis involved the Mann-Whitney test to compare the means of breast dose, effective dose, and LAR at a significance level of 0.05. Results: The mean age of the participants was 40 ± 22 years, with an age range of 10 to 83 years. The average dose to the breasts without and with shielding was 0.26 ± 0.19 mGy and 0.096 ± 0.13 mGy, respectively (P < 0.05). The effective dose was 0.85 ± 0.35 mSv without shielding and 0.79 ± 0.32 mSv with shielding (P = 0.539). The maximum LAR was 5.41 cases per 100,000 persons aged 10-15 years without shielding. The average LARs were 1.16 and 0.41 breast cancer incidences per 100,000 persons with and without shielding, respectively (P < 0.05). Conclusion: The LAR of breast cancer in brain CT scans is significant and should not be overlooked. The use of breast shielding can substantially reduce this risk. Therefore, it is recommended to employ radioprotective shields to cover the breasts during this type of scan. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer worldwide and a leading cause of cancer-related deaths in women. Mammographic breast density, the relative amount of fibroglandular tissue as seen on a mammogram, is one of the strongest predictors of breast cancer risk, with higher breast density associated with greater risk. Breasts undergo extensive fibroglandular tissue proliferation in early life, making this a potential window of vulnerability for carcinogen exposures. Early-life growth (e.g., height and weight) is also associated with breast cancer risk. Research into the 'developmental origins of health and disease' paradigms investigate the pathways of risk for disease in later life from early-life exposures across developmental phases. However, little is known about the association between early-life growth and breast density. Further investigation into these risk pathways could increase knowledge of disease etiology and help identify women at increased risk at an earlier age and inform potential mediation of breast cancer risk. Breast density is a strong intermediate endpoint to investigate the association between early-life exposures and breast cancer risk. This study investigates the association between early-life growth and breast density in young adult women measured using Optical Breast Spectroscopy (OBS) and Dual X-ray Absorptiometry (DXA). OBS measurements were obtained for 536 female Raine Cohort Study participants at ages 27–28, with 268 completing DXA measurements. Participants with three or more height and weight measurements from ages 8 to 22 were used to generate linear growth curves for height, weight and body mass index (BMI) using SITAR modelling. Three growth parameters (size, velocity and timing) were examined for association with breast density measures, adjusting for potential confounders. Women who reached their peak height rapidly (velocity) and later in adolescence (timing) had lower OBS-breast density. Overall, women who were taller (size) had higher OBS-breast density. For weight, women who grew quickly (velocity) and later in adolescence (timing) had higher absolute DXA-breast density. Overall, weight (size) was also inversely associated with absolute DXA-breast density, as was BMI. These findings provide new evidence that adolescent growth is associated with breast density measures in young adult women, suggesting potential mediation pathways for breast cancer risk in later life. [ABSTRACT FROM AUTHOR]

Although breast cancer death rates have persistently declined over the last 3 decades, older women have not experienced the same degree in mortality reduction as younger women despite having more favorable breast cancer phenotypes. This occurrence can be partially attributed to less robust mammographic screening in older women, the propensity to undertreat with advancing age, and the presence of underlying comorbidities. With recent revisions to breast cancer screening guidelines, there has been a constructive shift toward more agreement in the need for routine mammographic screening to commence at age 40. Unfortunately, this shift in agreement has not occurred for cutoff guidelines, wherein the recommendations are blurred and open to interpretation. With increasing life expectancy and an aging population who is healthier now than any other time in history, it is important to revisit mammographic screening with advanced age and understand why older women who should undergo screening are not being screened as well as offer suggestions on how to improve screening mammogram attendance in this population. [ABSTRACT FROM AUTHOR]

In Brief: Patients with breast cancer continue to live longer, patient case volumes are increasing, and creative solutions are required to see all newly diagnosed patients quickly and subsequently for longer periods of time. Creation of advanced practice provider-led clinics—including breast health, high-risk, and survivorship facilities—can help offset some of this patient volume and expand capacity to absorb patients if providers leave or retire. This invited review presents the experience, including successes and challenges, at 1 breast center. [ABSTRACT FROM AUTHOR]

Background: Pathological nipple discharge (PND) commonly caused by benign diseases, but occasionally it signifies a major medical concern. Ultrasonography, in addition to mammography, is regarded as the standard imaging modality in the diagnosis of PND but their sensitivity in some cases are low, subsequently we used a contrast enhanced mammography (CEDM) as supplementary diagnostic modality in patients with PND. The purpose of our study was to investigate the diagnostic efficacy of CEDM in evaluating PND patients, added values of incorporating the CEDM in the diagnostic workup of patients with PND and to demonstrate its diagnostic significance as a predictor of malignancy in these patients as there have been few studies that have addressed the role of CEDM in the evaluation of PND. Results: Forty seven patients with PND were enrolled in this prospective study and underwent CEDM. The CEDM had high specificity (83.2%) compared to the combined sonomammography (SM) (59.3%), as there was a decrease in the number of false positive cases detected by the CEDM (6 cases) compared to the combined SM (11 cases). Combined (SM) had a moderate degree of agreement (55%, P = 0.01) with the final diagnosis, whereas CEDM had a strong degree of agreement (75%, P < 0.001). Additionally, the combined SM reported 76.6% accuracy with an area under the curve of 0.8, whereas the CEDM had 87.2% accuracy with an area under the curve of 0.89. Conclusions: CEDM had higher specificity, positive predictive value, and accuracy than SM in PND patients, along with its stronger agreement with the final pathology results, subsequently reduce the rate of false positive cases and the rate of recall back, making it a highly accurate malignancy predictor in those patients and can be an invaluable diagnostic imaging tool for identifying associated malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are high-risk lesions of the breast. These lesions are not routinely excised when diagnosed in isolation because they have low rates of upgrade to invasive cancer. When identified concurrently with invasive breast cancer, however, the upgrade rate is not well characterized. We sought to both characterize the upgrade rate for these lesions when diagnosed concurrently with invasive breast cancer, and to identify features of the high-risk lesions predictive of upgrade to cancer. In our cohort of 65 patients who were concurrently diagnosed with a high-risk breast lesion and an invasive cancer, 5 patients (7.7%) had an upgrade of their high-risk lesion to carcinoma. The rate of upgrade was higher for high-risk lesions that were ipsilateral to malignancy and within 5 cm of it, and lower for other lesions. High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series. [ABSTRACT FROM AUTHOR]

Objective: This study sought to discern the differential impacts of communicating individualized breast cancer risk versus disseminating generic breast cancer information on women's proclivity towards breast cancer screenings. Method: A structured experimental design was used, including 300 female volunteers aged between 40-69, who had not previously been diagnosed with breast cancer, in Erzincan. Data collection entailed a face-to-face administration of a 22-item questionnaire complemented by the ASSISTS scale. Participants were randomized into two conditions: one receiving a standardized briefing on breast cancer screening modalities, and the other being apprised of their lifetime risk of breast cancer development based on the modified Gail model. Results: Post-intervention, 55.8% (n=72) of the risk-informed cohort and 40.5% (n=41) of the generic information cohort expressed a willingness to undergo screening (p=0.022). Notably, the group informed of their personalized risk exhibited a more pronounced uptick in requests for breast self-examination, clinical breast examination, and mammography screening compared to their counterparts. Conclusions: The communication of personalized breast cancer risk proves to be a more efficacious and time-efficient strategy than generic information dissemination in bolstering screening participation rates. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown an inverse association between the risk of breast cancer in women and physical activity. However, information on the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized test and the risk of developing breast cancer is limited. Purpose: To examine the CRF-breast cancer risk association in healthy females. Methods: This retrospective study was derived from the Exercise Testing and Health Outcomes Study cohort (n = 750,302). Female participants (n = 44,463; mean age ± SD; 55.1 ± 8.9 yr) who completed an exercise treadmill test evaluation (Bruce protocol) at the Veterans Affairs Medical Centers nationwide from 1999 to 2020 were studied. The cohort was stratified into four age-specific CRF categories (Least-fit, Low-fit, Moderate-fit, and Fit), based on the peak METs achieved during the exercise treadmill test. Results: During 438,613 person-years of observation, 994 women developed breast cancer. After controlling for covariates, the risk of breast cancer was inversely related to exercise capacity. For each 1-MET increase in CRF, the risk of cancer was 7% lower (HR, 0.93; 95% CI, 0.90-0.95; P < 0.001). When risk was assessed across CRF categories with the Least-fit group as the referent, the risk was 18% lower for Low-fit women (HR, 0.82; 95% CI, 0.70-0.96; P = 0.013), 31% for Moderate-fit (HR, 0.69; 95% CI, 0.58-0.82; P < 0.001), and 40% for Fit (HR, 0.60; 95% CI, 0.47-0.75; P < 0.001). Conclusions: We observed an inverse and graded association between CRF and breast cancer risk in women. Thus, encouraging women to improve CRF may help attenuate the risk of developing breast cancer. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the relative risk of risk factor in male and female breast cancer (BC) deaths in China and analyzed the changing trends in BC mortality rates from 1990 to 2019. Methods: Open data from the Global Burden of Disease database from 1990 to 2019 were analyzed to assess the number of BC deaths and age‐standardized mortality rates (ASMR) in China. The age‐period‐cohort model was employed to study age effects, period effects, cohort effects, as well as local drift and net drift of the data, determining the impact of changing risk factors on crude mortality rates and ASMR of BC. Results: In 2019, the number of BC deaths across all age groups in China increased by 130.38% compared to 1990, with an increase of 125.68% in females and 648.80% in males. The ASMR for BC and male BC increased in 2019, while female BC ASMR declined. Overall, alcohol consumption and smoking as risk factors contributed to increased mortality rates of BC with advancing age. Over the entire study period, the net drift of alcohol consumption in females for BC was 0.06% (95% confidence interval [CI]: −0.24% to 0.36%), while for smoking it was −0.64% (95% CI: −0.83% to −0.45%). For males, the net drift of alcohol consumption for BC was 6.75% (95% CI: 5.55% to 7.96%), and for smoking, it was 6.09% (95% CI: 2.66% to 9.64%). Conclusion: Hence, improving awareness of BC‐related risk factors and implementing prevention strategies are necessary to alleviate future BC burdens. [ABSTRACT FROM AUTHOR]

Background: Alcohol intake is associated with breast cancer (BC) risk, but estimates of greatest public health relevance have not been quantified in large studies with long duration. Materials and Methods: In this prospective cohort study of 39,811 women (median 25 years follow-up), we examined the association between alcohol consumption and BC incidence and mortality with adjusted hazard ratios (HRs), cubic splines, absolute risks, number needed to harm (NNH), and population-attributable fractions. Results: We documented 2,830 cases of BC, including 237 BC deaths. Each additional alcoholic drink/day was associated with a 10% higher rate (HR = 1.10, 95% confidence intervals [CIs]: 1.04–1.16) of total BC in a linear manner (p = 0.0004). The higher rate was apparent for estrogen receptor (ER)+ (HR = 1.12, 95% CI: 1.06–1.18) but not ER− tumors (HR = 0.95, 95% CI: 0.82–1.10), with a statistically significant difference between these associations (p = 0.03). We constructed models comparing BC incidence among 100,000 women followed for 10 years. Compared to a scenario where all women rarely or never consumed alcohol, we expect 63.79 (95% CI: 58.35–69.24) more cases (NNH = 1,567) had all women consumed alcohol at least monthly and 278.66 (95% CI: 268.70–288.62) more cases (NNH = 358) had all women consumed >1 drink/day. Approximately 4.1% of BC cases were attributable to consumption exceeding one drink/month. Conclusion: Alcohol consumption is associated with a linear dose–response increase in BC incidence even within recommended limits of up to one alcoholic drink/day, at least for ER+ tumors. Our estimates of risk differences, attributable fraction, and NNH quantify the burden that alcohol consumption imposes on women in the general population. ClinicalTrials.gov Identifier: NCT00000479. [ABSTRACT FROM AUTHOR]

Hormone replacement therapy (HRT) is considered the gold standard for management of vasomotor and vaginal symptoms of menopause. Vasomotor symptoms of menopause may include hot flashes and diaphoresis that vary in intensity and duration. Other symptoms of menopause can include vaginal atrophy and dryness, leading to dyspareunia and increased risk of infection. These symptoms can be impactful on a woman's life and HRT has data to support its efficacy, however, HRT carries significant risks that are generally well known, including risk of stroke, cardiovascular disease, breast cancer, and venous thromboembolism. These risks were most well characterized by several landmark trials published in the early 2000s. There are several nuances to prescribing HRT that can make doing so complex. These include consideration of cyclic vs continuous administration and of tapering therapy. Additionally, estrogen is available in a variety of dosage forms including injections and transdermal formulations. However, for women with an intact uterus, estrogen will need to be combined with progestin or bazedoxifene (a selective estrogen receptor modulator – SERM), both once daily oral formulations, in order to minimize malignancy risk. Though product preference and considerations of dosing may vary depending on practitioner preference, this brief report aims to clarify some nuances to prescribing or recommending HRT. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last few decades, studies have found many common genetic variants linked to breast cancer. Most of these variants are in non-coding regions or regions that do not directly affect gene function. This study aims to see if a polygenic risk score (PRS) based on functional variants could better predict breast cancer risk compared to an established 313-variant breast cancer PRS. Using publicly available summary data from GWASs, and Quantitative Trait Locus studies of gene expression and DNA methylation, we identified 149 variants potentially causally linked to the risk of developing breast cancer; the weighted sum of these variants was designated as the functional variant. The functional PRS was less effective at predicting breast cancer than the established PRS in 3560 breast cancer patients and 3383 non-breast cancer individuals. Combining both scores did not substantially enhance the prediction accuracy of the established PRS. Purpose: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer. Methods: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS). The two scores were evaluated in 3560 breast cancer cases and 3383 non-cancer controls and also in a prospective study (n = 10,213) comprising 418 cases. Results: We identified 149 variants showing pleiotropic association with breast cancer risk (eQTLHEIDI > 0.05 = 9, mQTLHEIDI > 0.05 = 165). The discriminatory ability of the functional PRS (AUCcontinuous [95% CI]: 0.540 [0.526 to 0.553]) was found to be lower than that of the GWAS PRS (AUCcontinuous [95% CI]: 0.609 [0.596 to 0.622]). Even when utilizing 457 distinct variants from both the functional and GWAS PRS, the combined discriminatory performance remained below that of the GWAS PRS (AUCcontinuous, combined [95% CI]: 0.561 [0.548 to 0.575]). A binary high/low-risk classification based on the 80th centile PRS in controls revealed a 6% increase in cases using the GWAS PRS compared to the functional PRS. The functional PRS identified an additional 12% of high-risk cases but also led to a 13% increase in high-risk classification among controls. Similar findings were observed in the SCHS prospective cohort, where the GWAS PRS outperformed the functional PRS, and the highest-performing PRS, a combined model, did not significantly improve over the GWAS PRS. Conclusions: While this study identified potentially functional variants associated with breast cancer risk, their inclusion did not substantially enhance the predictive accuracy of the GWAS PRS. [ABSTRACT FROM AUTHOR]

Simple Summary: Risk assessment in early breast cancer is critical for clinical decisions, but defining risk categories poses a significant challenge. The integration of conventional histopathology and biomarkers with artificial intelligence (AI) techniques, including machine learning and deep learning, has the potential to offer more precise information. AI applications extend beyond detection to histological subtyping, grading, and molecular feature identification. The successful integration of AI into clinical practice requires collaboration between histopathologists, molecular pathologists, computational pathologists, and oncologists to optimize patient outcomes. Effective risk assessment in early breast cancer is essential for informed clinical decision-making, yet consensus on defining risk categories remains challenging. This paper explores evolving approaches in risk stratification, encompassing histopathological, immunohistochemical, and molecular biomarkers alongside cutting-edge artificial intelligence (AI) techniques. Leveraging machine learning, deep learning, and convolutional neural networks, AI is reshaping predictive algorithms for recurrence risk, thereby revolutionizing diagnostic accuracy and treatment planning. Beyond detection, AI applications extend to histological subtyping, grading, lymph node assessment, and molecular feature identification, fostering personalized therapy decisions. With rising cancer rates, it is crucial to implement AI to accelerate breakthroughs in clinical practice, benefiting both patients and healthcare providers. However, it is important to recognize that while AI offers powerful automation and analysis tools, it lacks the nuanced understanding, clinical context, and ethical considerations inherent to human pathologists in patient care. Hence, the successful integration of AI into clinical practice demands collaborative efforts between medical experts and computational pathologists to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and causespecific cancers warrants investigation. OBJECTIVE: The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers METHODS: In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by CaCO3 concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors RESULTS: Over a median follow-up of 13.6 y (range: 12.7–14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed (푝 for nonlinearity <0.001). In comparison with individuals exposed to soft water (0–60 mg/L), the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause cancer were 1.00 (95% CI: 0.98, 1.02) for those exposed to moderate hard water (>60–120 mg/L), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water (>120–180 mg/L) and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water (>180 mg/L). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer DISCUSSION: Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. [ABSTRACT FROM AUTHOR]

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Background. Breast cancer ranks as the second most prevalent malignancy among women in Nepal. This cancer has a high likelihood of cure, if detected early. Therefore, it is imperative to emphasize awareness and screening for breast cancer in Nepal. It indeed underscores the importance of clinical breast examination. The study aims to find the disease burden, association of abnormal breast condition with sociodemographic variables, and the need for change in the breast cancer screening protocol. Methods. A cross-sectional study was conducted from July to September 2023 on 100 female participants who were older than 18 years. Data were collected through face-to-face interviews using a structured questionnaire. The chi-square test was used to compare nominal variables while the independent sample t-test and the paired sample t-test were used to compare nominal and continuous variables. Results. The findings of the study showed that 19% of all participants complained about abnormal breast, out of which 31.7% reported lumps, 26.31% reported discharge , another 26.31% reported pain, and the remaining 15.7% reported soreness. The upper outer quadrant and lower inner quadrant each individually accounted for 33.33% of the abnormal findings. The complaints of the participants in our study were significantly correlated with age at marriage, number of pregnancies, and use of contraception. Conclusion. Our study revealed considerable abnormal breast findings. This warrants the need for the change in breast cancer screening protocols which lead to early diagnosis and higher curability. [ABSTRACT FROM AUTHOR]