Geometric tumor embolic budding characterizes inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) is characterized by numerous tumor emboli especially within dermal lymphatics. The explanation remains a mystery. METHODS: This study combines experimental studies with two different IBC xenografts with image algorithmic studies utilizing human tissue microarrays (TMAs) of IBC vs non-IBC cases to support a novel hypothesis to explain IBC's sina qua non signature of florid lymphovascular emboli. RESULTS: In the human TMAs, compared to tumor features like nuclear grade (size), mitosis and Ki-67 immunoreactivity which show that IBC is only modestly more proliferative with larger nuclei than non-IBC, what really sets IBC apart is the markedly greater number of tumor emboli and distinctly smaller emboli whose numbers indicate geometric or exponential differences between IBC and non-IBC. In the experimental xenograft studies, Mary-X gives rise to tight spheroids in vitro which exhibit dynamic budding into smaller daughter spheroids whereas Karen-X exhibits only loose non-budding aggregates. Furthermore Mary-X emboli also bud dramatically into smaller daughter emboli in vivo. The mechanism that regulates this involves the generation of E-cad/NTF1, a calpain-mediated cleavage 100 kDa product of 120 kDa full length membrane E-cadherin. Inhibiting this calpain-mediated cleavage of E-cadherin by blocking either the calpain site of cleavage (SC) or the site of binding (SB) with specific decapeptides that both penetrate the cell membrane and mimic either the cleavage site or the binding site on E-cadherin, inhibits the generation of E-cad/NTF1 in a dose-dependent manner, reduces spheroid compactness and decreases budding. CONCLUSION: Since E-cad/NFT1 retains the p120ctn binding site but loses the α-and ß-catenin sites, promoting its 360° distribution around the cell's membrane, the vacilating levels of this molecule trigger budding of both the spheroids as well as the emboli. Recurrent and geometric budding of parental emboli into daughter emboli then would account for the plethora of emboli seen in IBC.

Impact of Healthcare Access Disparities on Initial Diagnosis of Breast Cancer in the Emergency Department.

Breast cancer continues to be the second leading cause of cancer deaths in women in the United States. This is more noticeable in communities with pronounced healthcare disparities. The aim of this study was to investigate the different demographics that might play a role in the detection of breast cancer in a county hospital emergency department (ED). A retrospective study was conducted of female patients diagnosed with breast cancer over a five-year period (1/1/2015 to 12/31/2018). Patients with breast cancer as the primary or secondary diagnosis were identified. This study shows that 66 (73.3%) women diagnosed in the ED were Hispanic or African American. There was a significant delay (a median of 461 days) in the time between the diagnosis of suspected breast cancer in the ED to their follow-up visit with definitive diagnosis in a primary care clinic. These findings suggest that women with a suspected breast cancer diagnosis who are seen in a safety net hospital and have Medicaid funding may have significant delays before final diagnosis is made. Patient demographics could have an impact on the patients' access to screening and regular healthcare visits, hindering an early breast cancer diagnosis by a primary care provider.