Prematurely aged (shortened) telomeres appears to be a common feature of iPS cells created by current pluripotency protocols. However, the spontaneous appearance of lines that express sufficient telomerase activity to extend telomere length may allow the reversal of developmental aging in human cells for use in regenerative medicine.
The prevalence and uniformity of FSIP1 expression in breast tumors, taken together with the highly restricted expression in normal tissues, suggests that FSIP1 may be an attractive target for breast cancer immunotherapy.
Background: Current breast cancer screening guidelines call for annual mammography for asymptomatic women age 45 to 54 and once every two years for women age 55 and older. Women with suspicious screening mammograms are recommended for a diagnostic mammogram and may also undergo MRI or ultrasound. Ultimately, suspicious findings unresolved by imaging typically result in the recommendation of a breast biopsy. Approximately 10% of suspicious diagnostic mammograms are recommended for breast biopsies and 67% to 95% of these biopsies yield negative results. With the goal of reducing the number of patients with benign pathology undergoing invasive biopsies, we conducted a screen for serum protein biomarkers and identified a novel panel for the non-invasive detection of breast cancer.
Methods: Serum samples were collected at two sites from women with suspicious diagnostic mammogram findings (primarily BI-RADS category 4) undergoing biopsy for the evaluation of a potential malignancy. Serum samples from 100-patients (50 benign pathology and 50 malignant pathology) were evaluated on the SOMAscan Assay 1.3k, which measures levels of 1,310 different protein analytes. Statistical screening methodologies, such as individual t-tests with control for false discovery, were used to identify markers with the potential to distinguish benign from malignant pathology. The candidate markers were further studied and combined using generalized linear modeling to develop three potential diagnostic models. K-fold cross validation was used to guard against over fitting of the models.
Results: A 15-marker model resulted in an AUC of 0.92 with a sensitivity of 90% and specificity of 76%. Two 6-marker models (with 4 markers in common) each resulted in AUC of 0.85, yielding a sensitivity of 90% with a specificity of 56% or 64%.
Conclusions: This study reveals a novel panel of serum protein biomarkers that may allow for the non-invasive and sensitive detection of breast cancer in BI-RADS category 4 patients. A multicenter study is underway to further refine and validate this panel in a larger set of prospectively collected patient samples.
Citation Format: Chapman KB, Copeland K, Kidd J, Qiu L, Sheibani N, Tam O, Friedman L, Korn R, Fiorica J, Lourenco A, Suthers S, Hesterberg L. Development of a panel of serum-based protein biomarkers for the non-invasive detection of breast cancer in BI-RADS category 4 patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-03-05.
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