Baseline Screening MRI Uptake and Findings in Women with ≥ 20% Lifetime Risk of Breast Cancer.

BACKGROUND: The American Cancer Society recommends screening magnetic resonance imaging (MRI) for patients with a ≥ 20% lifetime breast cancer risk. This study assesses the outcomes of baseline MRI screens in women from a high-risk breast clinic (HRBC). METHODS: We retrospectively reviewed patients from our institution's HRBC, excluding those with prior breast cancer and predisposing genetic mutations. Screening MRI was recommended for a lifetime risk of ≥ 20% using the Tyrer-Cuzick model. We determined baseline MRI results, biopsy rates, and frequency of MRI-detected high-risk lesions (HRLs) and breast cancers. RESULTS: Overall, 319 women attended our HRBC; median age was 48 years and 4.7% had prior atypia/lobular carcinoma in situ. Screening MRI was recommended for 282 patients, of whom 196 (69.5%) completed a baseline screen. A Breast Imaging-Reporting and Data System (BIRADS) 3 or 4 finding occurred in 19.6% of patients; 23 (12.3%) required 6-month follow-up MRI, 16 (8.6%) underwent core biopsy, and 4 (2.1%) underwent excisional biopsy after initial core. An additional 7 (3.7%) patients had a non-breast incidental finding. An HRL was identified in 2 (1.1%) patients (atypical ductal and lobular hyperplasia, respectively), and 2 (1.1%) were diagnosed with T1N0 breast cancers. CONCLUSIONS: In the setting of an HRBC, 70% of women with a ≥ 20% lifetime risk of breast cancer pursued screening MRI when recommended. On baseline screen, the rate of MRI-detected breast cancer was low (1%); however, malignancies were mammographically occult and identified at an early stage. Despite a low cancer rate, nearly one in four women required additional diagnostic investigation. Prescreening counselling should include a discussion of this possibility, and longer-term follow-up of screening MRI is needed in this high-risk population.

Role of zyxin in differential cell spreading and proliferation of melanoma cells and melanocytes.

Cell spreading, proliferation, and survival are modulated by focal adhesions linking extracellular matrix proteins, integrins, and the cytoskeleton. Zyxin is a focal-adhesion-associated phosphoprotein with one domain involved in the control of actin assembly and three protein-protein adapter domains implicated in the regulation of cell growth and differentiation. We characterized zyxin expression in normal human melanocytes and six melanoma cell lines in relation to cell spreading, growth, and differentiation using Western immunoblotting techniques, image analysis, flow cytometry, and confocal microscopy. We found that zyxin, focal adhesion kinase, and paxillin were significantly upregulated in melanoma cells compared to melanocytes. Zyxin expression directly related to cell spreading and proliferation and inversely related to differentiation, whereas focal adhesion kinase correlated only to cell spreading and paxillin did not significantly correlate with any of the parameters. Treatment of melanoma cells with 12-O-tetradecanoylphorbol-13-acetate downregulated zyxin expression, inhibited cell spreading and proliferation, and promoted differentiation. In contrast, 12-O-tetradecanoylphorbol-13-acetate, a mitogen for melanocytes, induced upregulation of zyxin expression in melanocytes. These findings are consistent with a role of zyxin in modulation of cell spreading, proliferation, and differentiation. Therapies directed at the downregulation of this focal adhesion phosphoprotein in melanoma cells implicate a new approach for controlling melanoma cell growth.