Biomarkers to distinguish subtypes in triple-Negative Breast Cancer (TNBC).
What is it about?
Breast cancer is the most commonly diagnosed cancer worldwide, and remains the second leading cause of cancer death in the United States. Triple-Negative Breast Cancer (TNBC), one of the most aggressive forms of breast cancer, defined by the lack of expression of estrogen receptor (ER), classic progesterone receptor (nPR), and epidermal growth factor receptor 2 (HER2), is a notoriously heterogeneous disease and yet the most poorly understood, exhibiting different histological and molecular subtypes, with much worse clinical outcomes. While breast cancer mortality has steadily declined over the past three decades through advances in medical care and technology, an alarming Black-White disparity in breast cancer mortality has emerged in the U.S. As compared to Caucasian women (CAW) with breast cancer, African American women (AAW) often face more aggressive forms of the disease, and experience a higher mortality rate. Overall, AAW face disproportionately higher breast cancer mortality than that of CAW; and the exact etiology of this racial disparity remains largely unknown. Evidence indicates the presence of intrinsic molecular factors that contribute to racial disparities in breast cancer mortality. AAW were independently associated with poorer survival and worse prognosis than age- and prognosis-matched CAW, suggesting that breast cancer is a more biologically aggressive disease in AAW under equal treatment. Overall, the high prevalence of TNBCs among younger AAW, along with poorer survival, supports possible genetic causes.
Why is it important?
Since poor prognosis in AAW-TNBCs is mostly due to aggressive TNBC phenotype and lack of biomarker-driven targeted therapies, therefore, identification of robust subtype-specific biomarkers of TNBCs is of the utmost importance for precision therapies for AAW-TNBCs. In this manuscript, we defined the novel CmP (CSC-mPRs-PRG) signaling network in nPR(-) TNBCs and systemically identified a set of AAW-TNBC biomarkers among various TNBC sample types. Our findings could provide invaluable insight into the molecular mechanisms involved in tumorigenesis of AAW-TNBCs, which might have a great impact on deciphering the molecular and cellular mechanisms underlying racial disparities in breast cancer mortality, through the CmP signaling network. More interestingly, the cellular mPRs were found to be distributed in both cytosol and nucleus, and act as nucleocytoplasmic shuttling proteins, under PRG actions, instead of previously reported PRG membrane receptors.