Faculty Bibliography

The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57-0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases.

BACKGROUND: Tissue engineering is often limited by the time required for culture expansion of cells necessary for scaffold seeding. Cell cycle regulators control entry and exit into the cell cycle and as such regulate cellular proliferation rates. The authors hypothesized that transient alteration in cell cycle regulators can be utilized as a means to accelerate stem cell proliferation. METHODS: Mesenchymal stem cells were harvested from wild-type mice and mice deficient in the cell cycle regulator p21. Wild-type cells were treated with small interfering RNA against p21 in two- or three-dimensional cultures in vitro. Cellular proliferation and the potential for cellular differentiation into the bone or fat lineage were assessed. RESULTS: Mesenchymal stem cells treated with small interfering RNA targeting p21 demonstrated a significant decrease in p21 protein and mRNA expression 96 hours after treatment. They also proliferated significantly faster than control cells (2.5 to three times) in both two- and three-dimensional culture. Similarly, cells harvested from p21-deficient mice demonstrated a significant acceleration in cellular proliferation. Inhibition of p21 expression was not associated with significant changes in spontaneous cellular differentiation. However, transient p21 inhibition promoted both osteoblastic and adipogenic differentiation when cells were exposed to differentiation medium. CONCLUSIONS: Transient inhibition of the cell cycle regulator p21 results in significant acceleration of mesenchymal stem cell proliferation without promoting spontaneous cellular differentiation. Exposure to differentiation medium results in increased cellular differentiation toward the osteoblast and fat lineage. Manipulation of cell cycle regulators may represent a novel means by which stem cell proliferation can be accelerated, thereby decreasing the time required for scaffold synthesis in tissue engineering.