High-resolution microCT to assess breast microcalcification morphometry by histologic lesion subtype and radiologic classification.

Purpose: To assess associations of 3D morphometry of breast calcifications, determined using high-resolution microCT, with underlying histopathology and evaluate the potential for classifying tissue calcifications as an aid in optimizing identification and diagnosis of the most severe pathology in a biopsy.

Methods: We compared morphometry of calcifications in tissue blocks (n = 156) of benign breast disease (n = 74), ductal carcinoma in situ (n = 39), and ductal carcinoma in situ with invasive breast cancer (n = 43) using (10 µm) microCT. Matched sections were reviewed microscopically to define lesion(s) in which calcifications were embedded.

Genetic correlations of alcohol consumption and alcohol use disorder with sex hormone levels in females and males.

Background: Alcohol consumption behaviors and alcohol use disorder risk and presentation differ by sex, and are associated with blood concentrations of the steroid sex hormones, testosterone and estradiol, and their regulatory binding proteins, sex hormone binding globulin (SHBG) and albumin. Genetic variation is also associated with alcohol consumption, alcohol use disorder, and levels of these hormones and binding proteins.

Methods: To assess the contribution of genetic factors to previously described phenotypic associations between alcohol-use traits and sex-hormone levels, we estimated genetic correlations (r) using summary statistics from prior published, large sample size genome-wide association studies (GWAS) of alcohol consumption, alcohol dependence, testosterone, estradiol, SHBG, and albumin.

Habitual physical activity and sedentary behavior among women with and without premenopausal bilateral oophorectomy: an exploratory study.

Objective: To explore potential differences in physical activity and sedentary behavior volumes and patterns among postmenopausal women with and without premenopausal bilateral oophorectomy (PBO).

Methods: Women with a history of PBO (n = 50) and age-matched postmenopausal referent women (n = 50) were recruited. Participants wore accelerometers on both ankles for 7 days.

Bipolar disorder comorbidity in breast cancer: impact of genetic risk and lifestyle characteristic on breast cancer outcomes.

Background: Bipolar disorder (BD) is associated with increased risk of breast cancer (BC), yet its impact on BC features and outcomes is unclear. We compared BC-Only patients and those with BD comorbidity (BC+BD) regarding BC characteristics and investigated associations between polygenic risk for BD (PRS-BD), a score based on common genetic variants, and BC outcomes.

Methods: Female patients from the Mayo Clinic Breast Disease Registry (MCBDR), a longitudinal cohort study of patients seen at Mayo Clinic Rochester for BC, were included.

Associations of plasma sex-related hormone and protein levels and alcohol dependence.

Background And Aims: Sex-related hormones and proteins may underlie sex differences in alcohol use disorder characteristics and consequences. Previous reports suggest steroid sex hormones may influence alcohol consumption behaviors while proteins that regulate their circulation levels are rarely investigated. Following up on our earlier study of individual sex-related hormones' associations with alcohol dependence (AD), this study measured the associations between the combinations of sex-related hormones and proteins and AD in a larger sample.

Ovarian cancer risk and survival according to tumor sex hormone receptor expression: An ovarian Cancer association consortium and ovarian tumor tissue analysis consortium pooled analysis.

Objective: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

Method: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases).

Associations of social determinants of health on likelihood of systemic hormone therapy use in midlife women.

Objective: Social determinants of health (SDOH) can have a significant impact on women's health and quality of life. Little is known about the impact of SDOH during menopause, and whether certain SDOH impact the likelihood of using systemic hormone therapy (HT). Our objective was to evaluate the impact of SDOH on the likelihood of HT utilization among midlife women.

Radiomic Parenchymal Phenotypes of Breast Texture from Mammography and Association with Risk of Breast Cancer.

Background Parenchymal phenotypes reflect the intrinsic heterogeneity of both tissue structure and distribution on mammograms. Purpose To define parenchymal phenotypes on the basis of radiomic texture features derived from full-field digital mammography (FFDM) in breast screening populations and assess associations of parenchymal phenotypes with future risk of breast cancer and masking (false-negative [FN] findings or interval cancers), beyond breast density, and by race and ethnicity Materials and Methods A two-stage study design included a retrospective cross-sectional study of 30 000 randomly selected women with four-view FFDM (mean age, 57.4 years) and a nested case-control study of 1055 women with invasive breast cancer (151 Black and 893 White women) matched to 2764 women without breast cancer (411 Black and 2345 White women) (mean age, 60.

Evaluating cell type deconvolution in FFPE breast tissue: application to benign breast disease.

Transcriptome profiling using RNA sequencing (RNA-seq) of bulk formalin-fixed paraffin-embedded (FFPE) tissue blocks is a standard method in biomedical research. However, when used on tissues with diverse cell type compositions, it yields averaged gene expression profiles, complicating biomarker identification due to variations in cell proportions. To address the need for optimized strategies for defining individual cell type compositions from bulk FFPE samples, we constructed single-cell RNA-seq reference data for breast tissue and tested cell type deconvolution methods.

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer.

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls.

Changes in breast cancer risk associated with benign breast disease from 1967 to 2013.

Background: Benign breast disease (BBD) increases breast cancer (BC) risk progressively for women diagnosed with nonproliferative change, proliferative disease without atypia (PDWA), and atypical hyperplasia (AH). Leveraging data from 18 704 women in the Mayo BBD Cohort (1967-2013), we evaluated temporal trends in BBD diagnoses and how they have influenced associated BC risk over 4 decades.

Methods: BC risk trends associated with BBD were evaluated using standardized incidence ratios (SIRs) and age-period-cohort modeling across 4 eras-premammogram (1967-1981), precore needle biopsy (CNB) (1982-1992), transition to CNB (1993-2001), and CNB era (2002-2013).

The association between metabolic dysfunction-associated steatotic liver disease diagnosis and vasomotor symptoms in midlife women.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and vasomotor symptoms (VMS) are associated with increased cardiovascular disease risk. Although visceral adiposity has been linked to MASLD and VMS independently, this study aimed to evaluate associations between the two in midlife women.

Methods: A cross-sectional study of women aged 45-60 years receiving primary care at one of four sites was conducted from March 1 through June 30, 2021.

Polygenic risk scores stratify breast cancer risk among women with benign breast disease.

Background: Most breast biopsies are diagnosed as benign breast disease, with 1.5- to 4-fold increased breast cancer risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in breast cancer risk assessment of these patients.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10).

Exome sequencing identifies as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer.

Rare, germline loss-of-function variants in a handful of genes that encode DNA repair proteins have been shown to be associated with epithelial ovarian cancer with a stronger association for the high-grade serous hiostotype. The aim of this study was to collate exome sequencing data from multiple epithelial ovarian cancer case cohorts and controls in order to systematically evaluate the role of coding, loss-of-function variants across the genome in epithelial ovarian cancer risk. We assembled exome data for a total of 2,573 non-mucinous cases (1,876 high-grade serous and 697 non-high grade serous) and 13,925 controls.

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.