Awareness of Breast Cancer Risk Factors in Women with vs. Without High Breast Density.

Purpose: Women with high breast density (HBD) carry an increased risk for breast cancer (BC). The aim of the study was to provide data on awareness and knowledge gaps among women with vs w/o HBD about BC risk factors (BCRFs), which is the basis for effective communication about screening. Patients and Methods: This was a web-based survey of 3000 women aged ≥30 and ≤70 from six countries. It comprised of 45 questions. T-tests and chi-square tests with False Discovery Rate adjustments were conducted as applicable, with significant differences reported at α=0.05. Results: Three-thousand women were included in the analysis, 733 (24.4%) had HBD. Overall, 39% of women were familiar with the concept of HBD in the context of BC. Thirty-one percent of women were aware of HBD as BCRF and for 24% of women HBD was personally applicable. A significantly higher proportion of women with HBD were aware of almost all BCRFs compared to women w/o HBD (p ≤ 0.05). Similarly, a significantly higher proportion of women with HBD have undergone screening procedures compared to women w/o HBD (p ≤ 0.05). Women with HBD were significantly better aware of basic facts about BC (p ≤ 0.05). A total of 1617 women underwent mammography, 904 ultrasound and 150 MRI during their last screening. The most relevant source of information about BC was the health care professional, as reported by 63% of women. Conclusion: Overall 39% of women were familiar with HBD as BCRF. Lack of BCRF awareness may contribute to delayed screenings, missed opportunities for early detection, and potentially poorer outcomes for individuals with dense breast tissue. Thus, this information should be communicated more widely.

Trends in breast density and other risk factors for breast cancer and associations with trends in the incidence of breast cancer in Korean women.

INTRODUCTION: This study investigated the trends in breast density in Korean women and their association with the incidence of breast cancer, incorporating the trends in the known risk factors for breast cancer from an ecological perspective. METHODS: The prevalence of risk factors for breast cancer from the National Health and Nutrition Survey, breast density from Korea's national breast cancer screening program, and breast cancer incidence from the Korea Central Cancer Registry during 2010-2018 were applied after age-standardization to the population at the middle of the year 2000. The association between the prevalence of risk factors for breast cancer, the prevalence of dense breast, and the incidence rate of breast cancer was estimated using linear regression. RESULTS: The proportion of age-standardized dense breasts steadily increased from 45.8 % in 2010 to 51.5 % in 2018. The increased prevalence of dense breasts in women was positively related to the prevalence of smoking, drinking, lack of exercise, early menarche age (<15 years old), premenopausal status, nulliparity, and no history of breastfeeding, and negatively related to the prevalence of obesity. The increased prevalence of the dense breast was associated with an increase in the incidence of breast cancer, and 96 % of the variation in breast cancer incidence could be explained by the variation in the prevalence of dense breast. The factors associated with dense breast and breast cancer incidence overlapped. CONCLUSIONS: Trends in breast cancer risk factors were associated with an increased prevalence of dense breast, which, in turn, was associated with an increased incidence of breast cancer in Korea.

A systematic review and meta-analysis of correlation of automated breast density measurement.

INTRODUCTION: Breast cancer is the most common cancer in women and a leading cause of mortality. This systematic review and meta-analysis aims to evaluate the correlation between breast density measurements obtained from various software and visual assessments by radiologists using full-field digital mammography (FFDM). METHODS: Following the PRISMA 2020 guidelines, five databases (Pubmed, Google Scholar, Science Direct, Cochrane Library, and MEDLINE) were searched for studies correlating volumetric breast density with breast cancer risk. The Newcastle-Ottawa Scale and the Joanna Briggs Institute Checklist were used to assess the quality of the included studies. Meta-analysis of correlation was applied to aggregate correlation coefficients using a random-effects model using MedCalc Statistical Software version 19.2.6. RESULTS: The review included 22 studies with a total of 58,491 women. The pooled correlation coefficient for volumetric breast density amongst Volpara™ and Quantra™ was found to be 0.755 (95% CI 0.496-0.890, p < 0.001), indicating a high positive correlation, albeit with a significant heterogeneity (I2 = 99.89%, p < 0.0001). Subgroup analyses based on study origin, quality, and methodology were performed but did not reveal the heterogeneity cause. Egger's and Begg's tests showed no significant publication bias. CONCLUSION: Volumetric breast density is strongly correlated with breast cancer risk, underscoring the importance of accurate breast density assessment in screening programs. Automated volumetric measurement tools like Volpara™ and Quantra™ provide reliable assessments, potentially improving breast cancer risk prediction and management. IMPLICATIONS FOR PRACTICE: Implementing fully automated breast density assessment tools could enhance consistency in clinical practice, minimizing observer variability and improving screening accuracy. These tools should be further validated against standardized criteria to ensure reliability in diverse clinical settings.

Potential Role of Glyphosate, Glyphosate-Based Herbicides, and AMPA in Breast Cancer Development: A Review of Human and Human Cell-Based Studies.

The potential connection between exposure to glyphosate and glyphosate-based herbicides (GBHs) and breast cancer risk is a topic of research that is rapidly gaining the public's attention due to the conflicting reports surrounding glyphosate's potential carcinogenicity. In this review, we synthesize the current published biomedical literature works that have explored associations of glyphosate, its metabolite, aminomethylphosphonic acid (AMPA), and GBHs with breast cancer risk in humans and human cell-based models. Using PubMed as our search engine, we identified a total of 14 articles that were included in this review. In the four human studies, urinary glyphosate and/or AMPA were associated with breast cancer risk, endocrine disruption, oxidative stress biomarkers, and changes in DNA methylation patterns. Among most of the 10 human cell-based studies, glyphosate exhibited endocrine disruption, induced altered gene expression, increased DNA damage, and altered cell viability, while GBHs were more cytotoxic than glyphosate alone. In summary, numerous studies have shown glyphosate, AMPA, and GBHs to have potential carcinogenic, cytotoxic, or endocrine-disruptive properties. However, more human studies need to be conducted in order for more definitive and supported conclusions to be made on their potential effects on breast cancer risk.

Hair Dye and Relaxer Use among Cisgender Women in Embu and Nakuru Counties, Kenya: Associations with Perceived Risk of Breast Cancer and Other Health Effects.

Despite widespread use of hair products globally, little is known about the prevalence and patterns of use in populations outside the United States. As some hair products contain endocrine-disrupting chemicals (EDCs) and EDCs have been linked to breast cancer, which is increasing globally, in this study, we addressed key knowledge gaps about hair product use and practices, and perceptions of use among women in two counties in Kenya. Using community-engaged approaches in Embu and Nakuru, Kenya, we recruited women aged 15-50 years to complete a questionnaire that ascertained hair product use in the last 7-14 days, ever using hair dyes and chemical relaxers, and participants' perceptions or harm around hair product use. In multivariable-adjusted regression models, we evaluated associations between participants' sociodemographic characteristics and perceptions of hair product use in relation to if they have ever used hair dyes and relaxers. In our sample of 746 women (mean age, 30.4 ± 8.1 years), approximately one-third of participants reported ever using permanent and/or semi-permanent hair dyes, with approximately one-fifth reporting current use. Almost 60% reported ever using chemical relaxers, with a little over one-third reporting current use. Increasing age and having an occupation in the sales and service industry were statistically significant predictors of hair dye use (OR 1.04, 95% CI: 1.02-1.06 and OR 2.05, 95% CI: 1.38-3.03, respectively) and relaxer use (OR 1.03, 95% CI: 1.01-1.06 and OR 1.93, 95% CI: 1.30-2.87). On average, participants reported moderate-to-high levels of concern about exposures and general health effects from using hair products, and relatively high levels of perceived risk of breast cancer related to hair product use. However, in contrast to our hypotheses, we observed mixed evidence regarding whether higher levels of perceived risk were associated with lower odds of ever using hair dyes and relaxers. These findings add new knowledge to the extant literature on hair product use among women in Kenya, where breast cancer incidence rates are increasing. Improving the understanding of patterns of use of specific products and their chemical ingredients-which may be hormone disruptors or carcinogens-and exploring the role of environmental health literacy are critical for developing interventions to reduce potentially harmful exposures found in these products.

The Prospective Association between Early Life Growth and Breast Density in Young Adult Women.

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.

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.

Participation in a High-Risk Program Is Associated with a Diagnosis of Earlier-Stage Disease Among Women at Increased Risk for Breast Cancer Development.

BACKGROUND: High-risk programs provide recommendations for surveillance/risk reduction for women at elevated risk for breast cancer development. This study evaluated the impact of high-risk surveillance program participation on clinicopathologic breast cancer features at the time of diagnosis. METHODS: Women followed in the authors' high-risk program (high-risk cohort [HRC]) with a diagnosis of breast cancer from January 2015 to June 2021 were identified and compared with the general population of women undergoing breast cancer surgery at Memorial Sloan Kettering Cancer Center (MSK; general cohort [GC]) during the same period. Patient and tumor factors were collected. Clinicopathologic features were compared between the two cohorts and in a subset of women with a family history of known BRCA mutation. RESULTS: The study compared 255 women in the HRC with 9342 women in the GC. The HRC patients were slightly older and more likely to be white and have family history than the GC patients. The HRC patients also were more likely to present with DCIS (41 % vs 23 %; p < 0.001), to have smaller invasive tumors (pT1: 100 % vs 77 %; p < 0.001), and to be pN0 (95 % vs 81 %; p < 0.001). The HRC patients had more invasive triple-negative tumors (p = 0.01) and underwent less axillary surgery (p < 0.001), systemic therapy (p < 0.001), and radiotherapy (p = 0.002). Among those with a known BRCA mutation, significantly more women in the HRC underwent screening mammography (75 % vs 40 %; p < 0.001) or magnetic resonance imaging (MRI: 82 % vs 9.9 %; p < 0.001) in the 12 months before diagnosis. CONCLUSIONS: Women followed in a high-risk screening program have disease diagnosed at an earlier stage and therefore require less-intensive breast cancer treatment than women presenting to a cancer center at the time of diagnosis. Identification of high-risk women and implementation of increased surveillance protocols are vital to improving outcomes.

A Mediation Analysis of Obesity and Adiponectin Association with Postmenopausal Breast Cancer Risk: A Nested Cohort Study in the International Breast Cancer Intervention Study II (IBIS-II) Prevention Trial.

Obesity is a risk factor for postmenopausal breast cancer (BC), and evidence suggests a role for adiponectin in the relationship between obesity and BC. We investigated whether adiponectin or other biomarkers mediate the effect of body mass index (BMI) on postmenopausal BC risk in a cohort study nested in the IBIS-II Prevention Trial. We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering baseline BMI as an exposure and the 12-month adiponectin increase as a mediator after adjustment for the Tyrer-Cuzick score and the lipid-lowering medications/supplements use. In the multivariable Cox model, both the 12-month adiponectin increase (HR, 0.60; 95%CI, 0.36-1.00) and BMI were associated with BC risk (HR, 1.05; 95%CI, 1.00-1.09), with a 40% reduction in women with a 12-month increase in adiponectin. A significantly higher cumulative hazard of BC events was observed in obese women (BMI > 30) with decreased adiponectin (p = 0.0087). No mediating effect of the adiponectin increase on the total effect of BMI on BC risk was observed (natural indirect effect: HR, 1.00; 95%CI, 0.98-1.02). Raising adiponectin levels might be an attractive target for postmenopausal BC prevention.

Association analysis of miRNA-146a and miRNA-196a polymorphism with breast cancer risk in Khyber Pakhtunkhwa, Pakistan: a preliminary study.

BACKGROUND: microRNAs (miRNAs) are small, noncoding RNA molecules, functioning either as oncogenes or tumor suppressor genes. SNPs in miRNAs might modify the expression of genes associated with miRNAs, enhancing susceptibility to breast cancer. Both miRNA-146a (rs2910164) and miRNA-196a (rs11614913) are identified and significantly associated with breast cancer risk in several ethnicities, but remains unexplored in Khyber Pakhtunkhwa population of Pakistan. METHODS: This study was aimed to check the relation of selected SNPs with breast cancer risk. The research cohort included 100 breast cancer patients and 100 healthy controls. All the participants were subjected for DNA extraction followed by T-ARMS PCR and gel electrophoresis. RESULTS: The results revealed a strong association between risk allele (G) of miRNA-146a and increased risk of breast cancer (OR = 2.04, P = 0.0006). Similarly, heterozygous and mutant genotypes also indicated high risk and significant association with breast cancer risk (CG; OR = 0.51, 9 P = 0.0001) (GG; OR = 3.76, P = 0.04). However, risk allele (T) of miRNA-196a (rs11614913) failed to exhibit significant association with breast cancer risk (OR = 0.92 P = 0.68). Similarly, the heterozygous and mutant genotype did not show significant association with breast cancer risk (CT; OR = 0.52, P = 0.125 (TT; OR = 0.88, P = 0.84). Furthermore, miRNA-146a (rs2910164) and miRNA-196a (rs11614913) polymorphisms exhibited non-significant associations with family history (P = 0.34, P = 0.77), PR status (P = 0.310, P = 0.397), ER status (P = 0.992, P = 0.981), nodal status (P = 0.86, P = 0.90), and menstrual status (P = 0.97, P = 0.09). Notably, miRNA-196a showed a significant association with the metastasis group (P = 0.010) and cancer stages (P = 0.047). CONCLUSIONS: In conclusion, this study highlights the association of miRNA-146a (rs2910164) polymorphism with breast cancer risk but suggested non-significant association of miRNA-196a (rs11614913) with breast cancer risk. However, these findings need to be confirmed through larger data set for more accurate result.

Characterizing the Relationship between Expression Quantitative Trait Loci (eQTLs), DNA Methylation Quantitative Trait Loci (mQTLs), and Breast Cancer Risk Variants.

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.

Beyond Milk and Nurture: Breastfeeding's Powerful Impact on Breast Cancer.

Breast cancer (BC) stands as a global concern, given its high incidence and impact on women's mortality. This complex disease has roots in various risk factors, some modifiable and others not. Understanding and identifying these factors can be instrumental in both preventing BC and improving survival rates. Remarkably, women's reproductive behaviors have emerged as critical determinants of BC susceptibility. Numerous studies have shed light on how aspects including age of menarche, first pregnancy and menopause along with number of pregnancies, hormone replacement therapies, can influence one's risk of developing BC. Furthermore, the act of breastfeeding and its duration have shown an inverse relationship with BC risk. This review delves into the biological and molecular mechanisms associated with breastfeeding that contribute to BC protection. It highlights the role of endocrine processes triggered by suckling stimulation, the gradual onset of lactational amenorrhea, delayed weaning, reduced lifetime menstrual cycles, chromosomal repair mechanisms, and immunological events throughout the lactation cycle. These insights provide a potential explanation for the protective effects conferred by breastfeeding against breast carcinomas.

Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry.

Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast tissue and how they associate with breast cancer risk factors remains unknown. N-glycans, a glucose metabolism-linked post-translational modification, has not been characterized in normal breast tissue. We hypothesized that normal female breast tissue with distinct Breast Imaging and Reporting Data Systems (BI-RADS) categories have unique microenvironments based on N-glycan signatures that varies with genetic ancestries. Profiles of N-glycans were characterized in normal breast tissue from BW (n = 20) and WW (n = 20) at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). A total of 176 N-glycans (32 core-fucosylated and 144 noncore-fucosylated) were identified in the NME. We found that certain core-fucosylated, outer-arm fucosylated and high-mannose N-glycan structures had specific intensity patterns and histological distributions in the breast NME dependent on BI-RADS densities and ancestry. Normal breast tissue from BW, and not WW, with heterogeneously dense breast densities followed high-mannose patterns as seen in invasive ductal and lobular carcinomas. Lastly, lifestyles factors (e.g. age, menopausal status, Gail score, BMI, BI-RADS) differentially associated with fucosylated and high-mannose N-glycans based on ancestry. This study aims to decipher the molecular signatures in the breast NME from distinct ancestries towards improving the overall disparities in breast cancer burden.

Exposure to Pesticides and Breast Cancer in an Agricultural Region in Brazil.

Rural workers are disproportionally exposed to pesticides and might be at an increased risk of developing chronic diseases. Here, we investigated the impact of pesticide exposure on breast cancer (BC) risk and disease profile in rural female workers. This is a case-control study that prospectively included 758 individuals. The study was conducted in the Southwest region of Paraná state in Brazil, a region characterized by family-based agriculture and intensive use of pesticides. We found that this region has a 41% higher BC diagnosis rate and 14% higher BC mortality rate than the mean rates in Brazil, as well as a pesticide trade volume about 6 times higher than the national average. We showed substantial exposure in this population and found that even women who did not work in the fields but performed equipment decontamination and clothes washing of male partners who worked in the fields had urine samples positive for glyphosate, atrazine, and/or 2,4-D. The crude association showed a significantly higher risk of BC among women exposed to pesticides (OR: 1.58, 95% CI 1.18-2.13). Adjusted analyses showed a lower and nonstatistically significant association (OR: 1.30, 95% CI 41 0.87-1.95). Stratification on disease profile showed a significantly higher risk of lymph node metastasis (adjusted OR: 2.19, 95% CI 1.31-3.72) in women exposed to pesticides. Our findings suggest that female populations exposed to pesticides are at a higher risk of developing BC with a more aggressive profile and draw attention to the need to monitor rural populations potentially exposed to pesticides in the field or at home.

Explainable Precision Medicine in Breast MRI: A Combined Radiomics and Deep Learning Approach for the Classification of Contrast Agent Uptake.

In DCE-MRI, the degree of contrast uptake in normal fibroglandular tissue, i.e., background parenchymal enhancement (BPE), is a crucial biomarker linked to breast cancer risk and treatment outcome. In accordance with the Breast Imaging Reporting & Data System (BI-RADS), it should be visually classified into four classes. The susceptibility of such an assessment to inter-reader variability highlights the urgent need for a standardized classification algorithm. In this retrospective study, the first post-contrast subtraction images for 27 healthy female subjects were included. The BPE was classified slice-wise by two expert radiologists. The extraction of radiomic features from segmented BPE was followed by dataset splitting and dimensionality reduction. The latent representations were then utilized as inputs to a deep neural network classifying BPE into BI-RADS classes. The network's predictions were elucidated at the radiomic feature level with Shapley values. The deep neural network achieved a BPE classification accuracy of 84 ± 2% (p-value < 0.00001). Most of the misclassifications involved adjacent classes. Different radiomic features were decisive for the prediction of each BPE class underlying the complexity of the decision boundaries. A highly precise and explainable pipeline for BPE classification was achieved without user- or algorithm-dependent radiomic feature selection.

Effects of Endocrine Interventions Targeting ERα or PR on Breast Cancer Risk in the General Population and Carriers of BRCA1/2 Pathogenic Variants.

There is evidence suggesting that endocrine interventions such as hormone replacement therapy and hormonal contraception can increase breast cancer (BC) risk. Sexual steroid hormones like estrogens have long been known for their adverse effects on BC development and progression via binding to estrogen receptor (ER) α. Thus, in recent years, endocrine interventions that include estrogens have been discussed more and more critically, and their impact on different BC subgroups has increasingly gained interest. Carriers of pathogenic variants in BRCA1/2 genes are known to have a high risk of developing BC and ovarian cancer. However, there remain open questions to what extent endocrine interventions targeting ERα or the progesterone receptor further increase cancer risk in this subgroup. This review article aims to provide an overview and update on the effects of endocrine interventions on breast cancer risk in the general population in comparison to BRCA1/2 mutation carriers. Finally, future directions of research are addressed, to further improve the understanding of the effects of endocrine interventions on high-risk pathogenic variant carriers.

Factors influencing U.S. women's interest and preferences for breast cancer risk communication: a cross-sectional study from a large tertiary care breast imaging center.

BACKGROUND: Breast imaging clinics in the United States (U.S.) are increasingly implementing breast cancer risk assessment (BCRA) to align with evolving guideline recommendations but with limited uptake of risk-reduction care. Effectively communicating risk information to women is central to implementation efforts, but remains understudied in the U.S. This study aims to characterize, and identify factors associated with women's interest in and preferences for breast cancer risk communication. METHODS: This is a cross-sectional survey study of U.S. women presenting for a mammogram between January and March of 2021 at a large, tertiary breast imaging clinic. Survey items assessed women's interest in knowing their risk and preferences for risk communication if considered to be at high risk in hypothetical situations. Multivariable logistic regression modeling assessed factors associated with women's interest in knowing their personal risk and preferences for details around exact risk estimates. RESULTS: Among 1119 women, 72.7% were interested in knowing their breast cancer risk. If at high risk, 77% preferred to receive their exact risk estimate and preferred verbal (52.9% phone/47% in-person) vs. written (26.5% online/19.5% letter) communications. Adjusted regression analyses found that those with a primary family history of breast cancer were significantly more interested in knowing their risk (OR 1.5, 95% CI 1.0, 2.1, p = 0.04), while those categorized as "more than one race or other" were significantly less interested in knowing their risk (OR 0.4, 95% CI 0.2, 0.9, p = 0.02). Women 60 + years of age were significantly less likely to prefer exact estimates of their risk (OR 0.6, 95% CI 0.5, 0.98, p < 0.01), while women with greater than a high school education were significantly more likely to prefer exact risk estimates (OR 2.5, 95% CI 1.5, 4.2, p < 0.001). CONCLUSION: U.S. women in this study expressed strong interest in knowing their risk and preferred to receive exact risk estimates verbally if found to be at high risk. Sociodemographic and family history influenced women's interest and preferences for risk communication. Breast imaging centers implementing risk assessment should consider strategies tailored to women's preferences to increase interest in risk estimates and improve risk communication.

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.

The characteristics and risk factors of breast cancer patients trend distinctive regional differences: a cross-sectional study.

OBJECTIVE: To determine the characteristics and risk factors of breast cancer patients in a tertiary care setting. METHODS: The retrospective, cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, and comprised data of all patients diagnosed with breast cancer from March 2017 to December 2021. Demographic characteristics, clinical presentation, stage of the disease and histopathological characteristics were noted. Data related to all the variables was not available in all cases. Data was analysed using SPSS 23. RESULTS: Of the 690 patients, 683(99%) were females and 7(1%) were males. The mean age at presentation was 49.3±13.5 years, while the mean duration of symptoms was 10.24±17.64) months. Most of the females were married 642(93%) and multiparous 484(70.9%), while 293(42.5%) had breastfed their children for >1 year, and 412(59.7%) had no history of contraception use. The most common stage at presentation was stage II (48.6%), and most patients had grade II 395(57.2%) invasive ductal carcinoma, with Luminal A molecular subtype noted in 287(41.6%) cases. CONCLUSIONS: The characteristics of breast cancer in the sample had certain distinctions compared to other populations. It is important to integrate all datasets and develop guidelines appropriate to Pakistani population.

Role of Breast Cancer Risk Estimation Models to Identify Women Eligible for Genetic Testing and Risk-Reducing Surgery.

Hereditary breast and ovarian cancer (HBOC) syndrome is responsible for approximately 10% of breast cancers (BCs). The HBOC gene panel includes both high-risk genes, i.e., a four times higher risk of BC (BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11 and TP53), and moderate-risk genes, i.e., a two to four times higher risk of BC (BARD1, CHEK2, RAD51C, RAD51D and ATM). Pathogenic germline variants (PGVs) in HBOC genes confer an absolute risk of BC that changes according to the gene considered. We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies.