Ternary complex components responsible for rapid LDL internalization as biomarkers for breast cancer associated with proliferation and early recurrence.

The ternary complex of PGRMC1-σ2R/TMEM97-LDLR has recently been discovered and plays a role in cholesterol transport. This study investigated whether individual components of that complex are prognostic breast cancer biomarkers and defined expression in established molecular subtypes. 4,463 invasive breast cancers were analyzed as a function of molecular and phenotypic markers, estimates of cellular proliferation, and recurrence-free survival.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Spatial Clustering for Carolina Breast Cancer Study.

In the Carolina Breast Cancer Study (CBCS), clustering census tracts based on spatial location, demographic variables, and socioeconomic status is crucial for understanding how these factors influence health outcomes and cancer risk. This task, known as spatial clustering, involves identifying clusters of similar locations by considering both geographic and characteristic patterns. While standard clustering methods such as K-means, spectral clustering, and hierarchical clustering are well-studied, spatial clustering is less explored due to the inherent differences between spatial domains and their corresponding covariates.

A latent class assessment of healthcare access factors and disparities in breast cancer care timeliness.

Background: Delays in breast cancer diagnosis and treatment lead to worse survival and quality of life. Racial disparities in care timeliness have been reported, but few studies have examined access at multiple points along the care continuum (diagnosis, treatment initiation, treatment duration, and genomic testing).

Methods And Findings: The Carolina Breast Cancer Study (CBCS) Phase 3 is a population-based, case-only cohort (n = 2,998, 50% black) of patients with invasive breast cancer diagnoses (2008 to 2013).

Patient-reported persistent lymphedema and peripheral neuropathy among long-term breast cancer survivors in the Carolina Breast Cancer Study.

Background: Improved breast cancer treatment has lengthened survival but also has long-term impacts. Lymphedema and peripheral neuropathy are treatment-related sequelae that extend into survivorship. Co-occurrence of these conditions may further impair functional well-being.

DAB2IP loss in luminal a breast cancer leads to NF-κB-associated aggressive oncogenic phenotypes.

Despite proven therapy options for estrogen receptor-positive (ER+) breast tumors, a substantial number of patients with ER+ breast cancer exhibit relapse with associated metastasis. Loss of expression of RasGAPs leads to poor outcomes in several cancers, including breast cancer. Mining the The Cancer Genome Atlas (TCGA) breast cancer RNA-Seq dataset revealed that low expression of the RasGAP DAB2IP was associated with a significant decrease in relapse-free survival in patients with Luminal A breast cancer.

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.

Associations of Prostate Tumor Immune Landscape with Vigorous Physical Activity and Prostate Cancer Progression.

Background: Vigorous physical activity has been associated with lower risk of fatal prostate cancer. However, mechanisms contributing to this relationship are not understood.

Methods: We studied 117 men with prostate cancer in the University of North Carolina Cancer Survivorship Cohort (UNC CSC) who underwent radical prostatectomy and 101 radiation-treated patients with prostate cancer in FASTMAN.

Risk factors for breast cancer subtypes by race and ethnicity: A scoping review of the literature.

Background: Breast cancer is comprised of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated.

Methods: We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White.

Risk factors for breast cancer subtypes by race and ethnicity: a scoping review.

Background: Breast cancer consists of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated.

Methods: We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White.

Differences in 21-Gene and PAM50 Recurrence Scores in Younger and Black Women With Breast Cancer.

Purpose: Genomic tests, such as the Oncotype Dx 21-gene and Prosigna risk of recurrence (ROR-P) assay, are commonly used for breast cancer prognostication. Emerging data suggest variability between assays, but this has not been compared in diverse populations.

Materials And Methods: RNA sequencing was performed on 647 previously untreated stage I-III estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors in the Carolina Breast Cancer Study, which oversampled Black and younger women (age <50 years at diagnosis), using research versions of two common RNA-based prognostic assays: ROR-P and the 21-gene recurrence score (RS).

Assessing Etiologic Heterogeneity for Multinomial Outcome with Two-Phase Outcome-Dependent Sampling Design.

Etiologic heterogeneity occurs when distinct sets of events or exposures give rise to different subtypes of disease. Inference about subtype-specific exposure effects from two-phase outcome-dependent sampling data requires adjustment for both confounding and the sampling design. Common approaches to inference for these effects do not necessarily appropriately adjust for these sources of bias, or allow for formal comparisons of effects across different subtypes.

Visual Intratumor Heterogeneity and Breast Tumor Progression.

High intratumoral heterogeneity is thought to be a poor prognostic indicator. However, the source of heterogeneity may also be important, as genomic heterogeneity is not always reflected in histologic or 'visual' heterogeneity. We aimed to develop a predictor of histologic heterogeneity and evaluate its association with outcomes and molecular heterogeneity.

Geographic Access to Fertility Counseling among Adolescent and Young Adult Women with Cancer in North Carolina.

Background: Fertility counseling is recommended for adolescent and young adult women facing gonadotoxic cancer therapy. However, fertility care is subspecialized medical care offered at a limited number of institutions, making geographic access a potential barrier to guideline-concordant care. We assessed the relationship between geographic access and receipt of fertility counseling among adolescent and young adult women with cancer.

Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants That Confer Risk for Breast Cancer.

Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium.

Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes.

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls.

Emotional and functional well-being in long-term breast cancer survivorship.

Purpose: Emotional and functional well-being (EWB and FWB) are important components of mental health and quality of life. This study aims to evaluate long-term EWB and FWB in breast cancer (BC) survivors.

Methods: The Carolina Breast Cancer Study Phase 3 oversampled Black and younger (< 50 years in age) women so that they each represent approximately 50% of the study population and assessed participants' EWB and FWB with the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 5- (baseline), 25-, and 84-months post diagnosis.

BIRC5 expression by race, age and clinical factors in breast cancer patients.

Purpose: Survivin/BIRC5 is a proliferation marker that is associated with poor prognosis in breast cancer and an attractive therapeutic target. However, BIRC5 has not been well studied among racially diverse populations where aggressive breast cancers are prevalent.

Experimental Design: We studied BIRC5 expression in association with clinical and demographic variables and as a predictor of recurrence in 2174 participants in the Carolina Breast Cancer Study (CBCS), a population-based study that oversampled Black (n = 1113) and younger (< 50 years; n = 1137) participants with breast cancer.

Diffsig: Associating Risk Factors with Mutational Signatures.

Background: Somatic mutational signatures elucidate molecular vulnerabilities to therapy, and therefore detecting signatures and classifying tumors with respect to signatures has clinical value. However, identifying the etiology of the mutational signatures remains a statistical challenge, with both small sample sizes and high variability in classification algorithms posing barriers. As a result, few signatures have been strongly linked to particular risk factors.

Disparities in OncotypeDx Testing and Subsequent Chemotherapy Receipt by Geography and Socioeconomic Status.

Background: OncotypeDx is a prognostic and predictive genomic assay used in early-stage hormone receptor-positive, HER2- (HR+/HER2-) breast cancer. It is used to inform adjuvant chemotherapy decisions, but not all eligible women receive testing. We aimed to assess variation in testing by demographics and geography, and to determine whether testing was associated with chemotherapy.