Mutational landscape of triple-negative breast cancer in African American women.

African American (AA) women have the highest incidence of triple-negative breast cancer (TNBC) among all racial groups, but are underrepresented in cancer genomic studies. In 462 AA women with TNBC, we characterized the tumor mutational landscape by whole-exome sequencing and RNA sequencing. We unveiled a high-resolution mutational portrait of TNBC in AA women reminiscent of that in Asian and non-Hispanic white women, with no evidence of associations of mutational features with African ancestry.

Multi-Ancestry Transcriptome-wide Association Studies Uncover New Insights into Breast Cancer Genetics and Biology.

Genome-wide association studies (GWAS) have identified over 200 genetic risk loci for breast cancer, yet the target genes in these loci remain largely unknown. To address this knowledge gap, we conducted a series of multi-ancestry transcriptome-wide association studies (TWAS) to discover potential breast cancer susceptibility genes. We developed and validated ancestry-specific genetic models to predict levels of gene expression, alternative splicing, and 3' UTR alternative polyadenylation, using genomic and transcriptomic data from normal breast tissue samples of 652 females of African, Asian, or European ancestry.

Associations between social drivers of health and breast cancer stage at diagnosis among U.S. Black women.

U.S. Black women have disproportionately high breast cancer mortality, partly due to later-stage diagnoses.

The African-Specific Variant in the Duffy Antigen Receptor for Chemokines Gene, CD8+ T-Cell Density, and Aggressive Breast Cancer Subtypes in Black Women.

Background: Immune response in blood varies by ancestry, linked to an African-specific variant (rs2814778) in the Duffy Antigen Receptor for Chemokines (DARC/ACKR1) gene. We examined associations between rs2814778, CD8+ T-cell density in breast tumors, and breast cancer risk in African-American/Black women.

Methods: CD8+ T-cell density in tumors from 428 Black women were examined in relation to the rs2814778 variant.

Quantitative analysis of T cell subsets in a population of Black women with invasive breast cancer.

We compared T cell subpopulations in primary invasive breast tumors from Black and White women and investigated breast cancer subtype-specific associations of T cell abundance with survival in Black women. Multispectral immune staining was used to quantify helper, cytotoxic, and regulatory T cells in the tumor and stromal compartments of breast tissues. In fully adjusted models, breast tumors from Black women were significantly more likely than those from White women to have a higher abundance of cytotoxic T cells (IRR, 2.

Associations of DNA methylation in breast tumour subtypes with parity and breastfeeding in a cohort of 1459 Black women: implications for public health.

Objective: Having children reduces risk of breast cancer overall, but parity without breastfeeding, more prevalent among black women, increases risk of poor-prognosis oestrogen receptor negative (ER-) breast cancer. We investigated if relationships between parity, breastfeeding and ER subtypes result from epigenetic programming, potentially steering breast progenitor cells to a basal-like phenotype.

Methods And Analysis: The Illumina MethylationEPIC platform was used to assess genome-wide methylation in formalin-fixed, paraffin-embedded tumours from 1459 Black women with breast cancer.

Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification.

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS.

Plant-based diet, inflammation biomarkers and body composition among women with breast cancer: the Pathways Study.

The World Cancer Research Fund and the American Institute for Cancer Research recommend a plant-based diet to cancer survivors, which may reduce chronic inflammation and excess adiposity associated with worse survival. We investigated associations of plant-based dietary patterns with inflammation biomarkers and body composition in the Pathways Study, in which 3659 women with breast cancer provided validated food frequency questionnaires approximately 2 months after diagnosis. We derived three plant-based diet indices: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI).

Associations of Cruciferous Vegetable Intake with Breast Cancer Survival in a Diverse Population in the Pathways Study.

Background: Beneficial effects of cruciferous vegetable intake on breast cancer survival have long been postulated because they are primary sources of isothiocyanates, phytochemicals with multifaceted anticancer activities. However, observational studies have reported inconsistent results. We hypothesized that variations in vegetable types and polymorphisms in isothiocyanate-metabolizing genes across self-identified race and ethnicity contribute to such inconsistencies.

Associations between experiences of discrimination and quality of life in Black breast cancer survivors.

Background: Racial discrimination has been associated with decreased health-related quality of life (QOL) in the general population; however, its impact on QOL in cancer survivors is unclear. This study aims to examine how experiences of discrimination (EOD) impact QOL in breast cancer survivors and whether these associations vary by individual- and structural-level factors.

Methods: The association of EOD assessed at baseline (∼12 months post-diagnosis) was assessed in the Women's Circle of Health Follow-up Study, a population-based longitudinal cohort study of Black breast cancer survivors in New Jersey.

Neighborhood Disinvestment Predicts Shorter Cancer Survival Time among Black Women Diagnosed with Invasive Breast Cancer.

Background: Observed neighborhood disinvestment is a chronic social determinant that is understudied in relation to cancer outcomes. This study investigated associations between neighborhood disinvestment, stage at diagnosis, and breast cancer-specific survival (BCSS) time.

Methods: Individual-level data included 844 women, diagnosed 2013 to 2019, from the Women's Circle of Health Follow-up Study, a population-based cohort of breast cancer survivors self-identifying as Black or African American.

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.

Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.

Purpose: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

Experimental Design: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.

Under-Representation and Under-Reporting of Minoritized Racial and Ethnic Groups in Clinical Trials on Immune Checkpoint Inhibitors.

Purpose: Minoritized racial/ethnic groups are historically under-represented in cancer clinical trials, which may be exacerbated in recent trials on immune checkpoint inhibitors (ICIs). We examined the representation and reporting of the racial/ethnic composition of participants in clinical trials on ICIs.

Methods: We examined English full-text trials on ICIs published from 2007 to 2022.

A prospective study of vitamin D, proinflammatory cytokines, and risk of fragility fractures in women on aromatase inhibitors for breast cancer.

Background: Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs).

Methods: In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples.

Association of ESR1 Germline Variants with TP53 Somatic Variants in Breast Tumors in a Genome-wide Study.

Unlabelled: In breast tumors, somatic mutation frequencies in TP53 and PIK3CA vary by tumor subtype and ancestry. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somatic TP53 or PIK3CA mutation status in breast tumors.

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.