Abiraterone, Olaparib, or Abiraterone + Olaparib in First-Line Metastatic Castration-Resistant Prostate Cancer with DNA Repair Defects (BRCAAway).

Purpose: Deleterious germline/somatic homologous recombination repair mutations (HRRm) are present in ∼25% of patients with metastatic castration-resistant prostate cancer (mCRPC). Preclinically, poly(ADP-ribose) polymerase (PARP) inhibition demonstrated synergism with androgen receptor pathway (ARP)-targeted therapy. This trial evaluated the efficacy of ARP inhibitor versus PARP inhibitor versus their combination as first-line therapy in patients with mCRPC with HRRms.

Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer.

Background: Studies have shown improved survival among individuals with cancer with higher levels of social support. Few studies have investigated social support and overall survival (OS) in individuals with advanced prostate cancer in an international cohort. We investigated the associations of marital status and living arrangements with OS among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer (IRONMAN).

Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States.

Unlabelled: Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.

A harmonized resource of integrated prostate cancer clinical, -omic, and signature features.

Genomic and transcriptomic data have been generated across a wide range of prostate cancer (PCa) study cohorts. These data can be used to better characterize the molecular features associated with clinical outcomes and to test hypotheses across multiple, independent patient cohorts. In addition, derived features, such as estimates of cell composition, risk scores, and androgen receptor (AR) scores, can be used to develop novel hypotheses leveraging existing multi-omic datasets.

curatedPCaData: Integration of clinical, genomic, and signature features in a curated and harmonized prostate cancer data resource.

Genomic and transcriptomic data have been generated across a wide range of prostate cancer (PCa) study cohorts. These data can be used to better characterize the molecular features associated with clinical outcomes and to test hypotheses across multiple, independent patient cohorts. In addition, derived features, such as estimates of cell composition, risk scores, and androgen receptor (AR) scores, can be used to develop novel hypotheses leveraging existing multi-omic datasets.

Effect of prior treatments on post-CDK 4/6 inhibitor survival in hormone receptor-positive breast cancer.

Purpose: Multiple treatment options exist for patients with metastatic breast cancer (MBC). However, limited information is available on the impact of prior treatment duration and class on survival outcome for novel therapies, such as cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ HER2-) MBC.

Methods: This study used a nationwide, de-identified electronic health record-derived database to identify women with HR+ HER2- MBC who received at least one CDK 4/6i between 2011 and 2020.

IRONMAN: A Novel International Registry of Men With Advanced Prostate Cancer.

Purpose: To describe a newly established international registry recruiting diverse patients with advanced prostate cancer across academic and community practices to address unmet needs in this population.

Patients And Methods: Initiated in 2017, IRONMAN (International Registry for Men with Advanced Prostate Cancer) is a prospective cohort of patients with advanced prostate cancer. The study will enroll 5,000 patients with metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC), recruited from Australia, the Bahamas, Barbados, Brazil, Canada, Ireland, Jamaica, Kenya, Nigeria, Norway, South Africa, Spain, Sweden, Switzerland, the United Kingdom, and the United States.

Tumor immune cell clustering and its association with survival in African American women with ovarian cancer.

New technologies, such as multiplex immunofluorescence microscopy (mIF), are being developed and used for the assessment and visualization of the tumor immune microenvironment (TIME). These assays produce not only an estimate of the abundance of immune cells in the TIME, but also their spatial locations. However, there are currently few approaches to analyze the spatial context of the TIME.

Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays.

Tissue microarrays (TMAs) have been used in thousands of cancer biomarker studies. To what extent batch effects, measurement error in biomarker levels between slides, affects TMA-based studies has not been assessed systematically. We evaluated 20 protein biomarkers on 14 TMAs with prospectively collected tumor tissue from 1448 primary prostate cancers.

Prognostic and therapeutic significance of COP9 signalosome subunit CSN5 in prostate cancer.

Chromosome 8q gain is associated with poor clinical outcomes in prostate cancer, but the underlying biological mechanisms remain to be clarified. CSN5, a putative androgen receptor (AR) partner that is located on chromosome 8q, is the key subunit of the COP9 signalosome, which deactivates ubiquitin ligases. Deregulation of CSN5 could affect diverse cellular functions that contribute to tumor development, but there has been no comprehensive study of its function in prostate cancer.

Dynamic expression of SNAI2 in prostate cancer predicts tumor progression and drug sensitivity.

Prostate cancer is a highly heterogeneous disease, understanding the crosstalk between complex genomic and epigenomic alterations will aid in developing targeted therapeutics. We demonstrate that, even though snail family transcriptional repressor 2 (SNAI2) is frequently amplified in prostate cancer, it is epigenetically silenced in this disease, with dynamic changes in SNAI2 levels showing distinct clinical relevance. Integrative clinical data from 18 prostate cancer cohorts and experimental evidence showed that gene fusion between transmembrane serine protease 2 (TMPRSS2) and ETS transcription factor ERG (ERG) (TMPRSS2-ERG fusion) is involved in the silencing of SNAI2.

A prospective study of inflammatory biomarkers and growth factors and risk of glioma in the UK Biobank.

Purpose: The role of growth factors and inflammation in the onset of glioma is poorly understood, and conflicting reports of associations of circulating IGF-1 and inflammatory biomarkers with glioma risk exist in the literature. We examined associations between C-reactive protein (CRP), white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and insulin-like growth factor-1 (IGF-1) and glioma risk in the UK Biobank cohort.

Methods: Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to circulating biomarkers concentrations were calculated using Cox proportional hazards regression, adjusted for age, sex, race, and education.

Prostate Cancer Racial Disparities: A Systematic Review by the Prostate Cancer Foundation Panel.

Context: Prostate cancer (PCa) is a complex disease that disproportionately impacts Black men in the USA. The structural factors that drive heterogeneous outcomes for patients of differing backgrounds are probably the same ones that result in population-level disparities. The relative contribution of drivers along the PCa disease continuum is an active area of investigation and debate.

Enabling Precision Medicine in Cancer Care Through a Molecular Data Warehouse: The Moffitt Experience.

Purpose: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose.

Distribution of Estimated Lifetime Breast Cancer Risk Among Women Undergoing Screening Mammography.

Supplemental screening breast MRI is recommended for women with an estimated lifetime risk of breast cancer of greater than 20-25%. The performance of risk prediction models varies for each individual and across groups of women. The present study investigates the concordance of three breast cancer risk prediction models among women presenting for screening mammography.

A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.

Background: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer).

Methods: Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer.

KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.

Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium.

Tackling Diversity in Prostate Cancer Clinical Trials: A Report From the Diversity Working Group of the IRONMAN Registry.

Prostate cancer disproportionately affects racial and ethnic minority populations. Reasons for disparate outcomes among minority patients are multifaceted and complex, involving factors at the patient, provider, and system levels. Although advancements in our understanding of disease biology have led to novel therapeutics for men with advanced prostate cancer, including the introduction of biomarker-driven therapeutics, pivotal translational studies and clinical trials are underrepresented by minority populations.

Circulating lipids and glioma risk: results from the UK Biobank, Nurses' Health Study, and Health Professionals Follow-Up Study.

Purpose: Evidence is mixed on whether cholesterol plays a role in the pathogenesis of glioma. We explored the associations between circulating lipids and glioma risk in three prospective cohorts.

Methods: Using prospective data from the UK Biobank, we examined the associations of total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides (TG) with glioma risk in multivariable (MV)-adjusted Cox proportional hazards models.

Novel Transcriptomic Interactions Between Immune Content and Genomic Classifier Predict Lethal Outcomes in High-grade Prostate Cancer.

Grade group 4 and 5 (GG-45) prostate cancer (PCa) patients are at the highest risk of lethal outcomes, yet lack genomic risk stratification for prognosis and treatment selection. Here, we assess whether transcriptomic interactions between tumor immune content score (ICS) and the Decipher genomic classifier can identify most lethal subsets of GG-45 PCa. We utilized whole transcriptome data from 8071 tumor tissue (6071 prostatectomy and 2000 treatment-naïve biopsy samples) to derive four immunogenomic subtypes using ICS and Decipher.

TMPRSS2-ERG fusion impacts anterior tumor location in men with prostate cancer.

Background: In prostate cancer (PCa), lack of androgen receptor (AR) regulated TMPRSS2-ETS-related gene (ERG) gene fusion (ERG ) status has been associated with African American race; however, the implications of ERG status for the location of dominant tumors within the prostate remains understudied.

Methods: An African American-enriched multiinstitutional cohort of 726 PCa patients consisting of both African American men (AAM; n = 254) and European American men (EAM; n = 472) was used in the analyses. Methods of categorical analysis were used.

Accessible Pipeline for Translational Research Using TCGA: Examples of Relating Gene Mechanism to Disease-Specific Outcomes.

Bioinformatic scientists are often asked to do widespread analyses of publicly available datasets in order to identify genetic alterations in cancer for genes of interest; therefore, we sought to create a set of tools to conduct common statistical analyses of The Cancer Genome Atlas (TCGA) data. These tools have been developed in response to requests from our collaborators to ask questions, validate findings, and better understand the function of their gene of interest. We describe here what data we have used, how to obtain it, and what figures we have found useful.

Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell-Level PI3K Pathway Activation.

Purpose: Identifying cancers with high PI3K pathway activity is critical for treatment selection and eligibility into clinical trials of PI3K inhibitors. Assessments of tumor signaling pathway activity need to consider intratumoral heterogeneity and multiple regulatory nodes.

Experimental Design: We established a novel, mechanistically informed approach to assessing tumor signaling pathways by quantifying single-cell-level multiplex immunofluorescence using custom algorithms.

Molecular Determinants of Thyroid Nodules with Indeterminate Cytology and Mutations.

gene family mutations are the most prevalent in thyroid nodules with indeterminate cytology and are present in a wide spectrum of histological diagnoses. We evaluated differentially expressed genes and signaling pathways across the histological/clinical spectrum of -mutant nodules to determine key molecular determinants associated with a high risk of malignancy. Sixty-one thyroid nodules with mutations were identified.