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 non-proliferative (NP) 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 four decades.

Methods: BC risk trends associated with BBD were evaluated using standardized incidence ratios (SIRs) and age-period-cohort modeling across four eras-pre-mammogram (1967-1981), pre-core 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.

An examination of sexual function & distress among sexual minority & heterosexual women seeking care at menopause and sexual health specialty clinics.

Background: Sexual minority women (SMW) have worse mental and physical health outcomes compared to heterosexual women, but literature on sexual function in SMW compared to heterosexual women is lacking.

Aim: To evaluate sexual function and sexual distress in women across sexual orientations.

Method: Questionnaire data were analyzed for women aged 18 and older who presented to women's health clinics at Mayo Clinic in Minnesota, Arizona, and Florida from 2016 to 2023.

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

Purpose: Most breast biopsies are diagnosed as benign breast disease (BBD), with 1.5- to fourfold increased breast cancer (BC) risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in BC risk assessment of these patients.

Microcalcifications in benign breast biopsies: association with lesion type and risk.

Purpose: To characterize associations of microcalcifications (calcs) with benign breast disease lesion subtypes and assess whether tissue calcs affect risks of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).

Methods: We analyzed detailed histopathologic data for 4,819 BBD biopsies from a single institution cohort (2002-2013) followed for DCIS or IBC for a median of 7.4 years for cases (N = 338) and 11.

Multivariate testing and effect size measures for batch effect evaluation in radiomic features.

While precision medicine applications of radiomics analysis are promising, differences in image acquisition can cause "batch effects" that reduce reproducibility and affect downstream predictive analyses. Harmonization methods such as ComBat have been developed to correct these effects, but evaluation methods for quantifying batch effects are inconsistent. In this study, we propose the use of the multivariate statistical test PERMANOVA and the Robust Effect Size Index (RESI) to better quantify and characterize batch effects in radiomics data.

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.

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 these complex traits 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 associated with alcohol consumption and alcohol use disorder, as well as levels of steroid sex hormones and their 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.

Leveraging GWAS: Path to Prevention?

Developing novel cancer prevention medication strategies is important for reducing mortality. Identification of common genetic variants associated with cancer risk suggests the potential to leverage these discoveries to define causal targets for cancer interception. Although each risk variant confers small increases in risk, researchers propose that blocking those that produce causal carcinogenic effects might have large impacts on cancer prevention.

Benign Breast Disease and Breast Cancer Risk in the Percutaneous Biopsy Era.

Importance: Benign breast disease (BBD) comprises approximately 75% of breast biopsy diagnoses. Surgical biopsy specimens diagnosed as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH) are associated with increasing breast cancer (BC) risk; however, knowledge is limited on risk associated with percutaneously diagnosed BBD.

Objectives: To estimate BC risk associated with BBD in the percutaneous biopsy era irrespective of surgical biopsy.

Age-Dependent Sex Differences in the Prevalence of Selective Serotonin Reuptake Inhibitor Treatment: A Retrospective Cohort Analysis.

Antidepressants are among the most prescribed medications in the United States. The aim of this study was to explore the prevalence of antidepressant prescriptions and investigate sex differences and age-sex interactions in adults enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT) study. We conducted a retrospective analysis of the RIGHT study.

Long-term effects of premenopausal bilateral oophorectomy with or without hysterectomy on physical aging and chronic medical conditions.

Objective: We examined the long-term effects of premenopausal bilateral oophorectomy (PBO) with or without concurrent or preceding hysterectomy on physical and cognitive function and on odds of chronic conditions.

Methods: We enrolled 274 women with PBO with or without concurrent or preceding hysterectomy and 240 referents aged 55 years and older who were residents of Olmsted County, MN as of the PBO or index date. Chronic conditions were assessed via medical record abstraction.

Leadership Development in Early Career Scientists: Themes and Feedback from Executive Coaching and Mindful Leadership Training.

Career development is essential for all academic stages, but particularly critical for the growth and retention of early career scientists. In addition to scientific technical training, professional skill development is crucial for the upward transition from postdoctoral trainee to early faculty member and beyond. Building leadership skills, specifically, is an important component of professional development, and the evaluation and reporting of professional development are important to improve and enhance the impact of programs.