FOXM1 Transcriptionally Co-Upregulates Centrosome Amplification and Clustering Genes and Is a Biomarker for Poor Prognosis in Androgen Receptor-Low Triple-Negative Breast Cancer.

There are currently no approved targeted treatments for quadruple-negative breast cancer [QNBC; ER/PR/HER2/androgen receptor (AR)], a subtype of triple-negative breast cancer (TNBC). AR-low TNBC is more proliferative and clinically aggressive than AR-high TNBC. Centrosome amplification (CA), a cancer hallmark, is rampant in TNBC, where it induces spindle multipolarity-mediated cell death unless centrosome clustering pathways are co-upregulated to avert these sequelae.

Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers.

Quadruple-negative breast cancer (QNBC) lacks traditional actionable targets, including androgen receptor (AR). QNBC disproportionately afflicts and impacts patients of African genetic ancestry. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from undergoing centrosome-amplification-induced apoptosis, has been reported to be upregulated in TNBCs and African-American (AA) TNBCs.

Molecular features of androgen-receptor low, estrogen receptor-negative breast cancers in the Carolina breast cancer study.

Purpose: Androgen receptor (AR) expression is absent in 40-90% of estrogen receptor (ER)-negative breast cancers. The prognostic value of AR in ER-negative patients and therapeutic targets for patients absent in AR remains poorly explored.

Methods: We used an RNA-based multigene classifier to identify AR-low and AR-high ER-negative participants in the Carolina Breast Cancer Study (CBCS; N = 669) and The Cancer Genome Atlas (TCGA; N = 237).

Molecular Features of Androgen-Receptor Low, Estrogen Receptor-Negative Breast Cancers in the Carolina Breast Cancer Study.

Purpose: Androgen receptor (AR) expression is absent in 40-90% of estrogen receptor (ER)-negative breast cancers. The prognostic value of AR in ER-negative patients and therapeutic targets for patients absent in AR remains poorly explored.

Methods: We used an RNA-based multigene classifier to identify AR-low and AR-high ER-negative participants in the Carolina Breast Cancer Study (CBCS; n=669) and The Cancer Genome Atlas (TCGA; n=237).

The DARC Side of Inflamm-Aging: Duffy Antigen Receptor for Chemokines (DARC/ACKR1) as a Potential Biomarker of Aging, Immunosenescence, and Breast Oncogenesis among High-Risk Subpopulations.

The proclivity of certain pre-malignant and pre-invasive breast lesions to progress while others do not continues to perplex clinicians. Clinicians remain at a crossroads with effectively managing the high-risk patient subpopulation owing to the paucity of biomarkers that can adequately risk-stratify and inform clinical decisions that circumvent unnecessary administration of cytotoxic and invasive treatments. The immune system mounts the most important line of defense against tumorigenesis and progression.

Racial Disparity in Quadruple Negative Breast Cancer: Aggressive Biology and Potential Therapeutic Targeting and Prevention.

Black/African-American (AA) women, relative to their White/European-American (EA) counterparts, experience disproportionately high breast cancer mortality. Central to this survival disparity, Black/AA women have an unequal burden of aggressive breast cancer subtypes, such as triple-negative breast cancer (ER/PR-, HER2-wild type; TNBC). While TNBC has been well characterized, recent studies have identified a highly aggressive androgen receptor (AR)-negative subtype of TNBC, quadruple-negative breast cancer (ER/PR-, HER2-wildtype, AR-; QNBC).

Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) surpasses other BC subtypes as the most challenging to treat due to its lack of traditional BC biomarkers. Nearly 30% of TNBC patients express the androgen receptor (AR), and the blockade of androgen production and AR signaling have been the cornerstones of therapies for AR-positive TNBC. However, the majority of women are resistant to AR-targeted therapy, which is a major impediment to improving outcomes for the AR-positive TNBC subpopulation.