CHICAGO, June 2, 2012 /PRNewswire/ --
--TLE3 Biomarker Over-expressed in HER2-positive, Hormone Receptor-positive, and Triple-negative Breast Cancers --
-- EGFR status May Facilitate Therapeutic Decision-making in Head and Neck Cancer --
Caris Life Sciences announced today the utility of the company's Caris Target Now evidence-based molecular profiling service in the characterization of breast and head and neck cancers. These data were presented today at the 2012 annual meeting of the American Society of Clinical Oncology (ASCO).
"By combining state-of-the-art genomic sequencing technology with a rigorous review of the clinical literature, Caris Target Now provides tumor-specific biomarker information, enabling physicians to make more informed, individualized treatment decisions for their patients," said Sandeep Reddy, MD, clinical professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). Loapracticing oncologist and clinical advisor to Caris Life Sciences. "The data presented today have potentially important predictive implications for patients with breast and head and neck cancers, as the molecular profiling information may point the way toward personalizing therapy based on tumor genetics."
Breast Cancer Data
In a poster presentation today, Gargi Basu, Ph.D., and colleagues at Caris Life Sciences, presented results from the first study providing a comprehensive review of transducin-like enhancer of split 3 (TLE3) expression in breast cancer subtypes. They described TLE3 as a transcriptional repressor that influences tumor growth and microtubule stability; its expression in epithelial tumor cells may reflect that these cells require the expression of TL3 to maintain their undifferentiated state. The expression of TLE3 is also associated with response to taxane therapy in patients with breast cancer.
Working with tumor cells collected from 978 breast cancer patients, the investigators employed two different technological platforms used in Caris Target Now -immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) - to gather information on four biomarkers: TLE3 (M-201), ER(1D5), PR(PgR636), and human epidermal growth factor receptor 2 (HER2)/neu (Polyclonal). IHC analysis of the four biomarkers was conducted at the protein level, and FISH was used to determine amplification of HER2/neu. Samples were then sub-classified as hormone receptor (HR)-positive (i.e., estrogen receptor [ER]-positive and/or progesterone receptor [PR]- positive), HER2-positive (either at the protein level or amplified by FISH), or triple-negative (i.e., lacking in ER, PR, and HER2/neu).
Overall, 351 (36%) of the patients were HR-positive, 150 (15%) were HER2-positive, and 477 (49%) were triple-negative. TLE3 was expressed in 82% of the HR-positive patients, 73% of the HER2-positive patients, and 61% of the triple-negative patients. To further investigate TLE3 expression in the patient subtypes, Dr. Basu and colleagues performed a pairwise Fisher's Exact Test between the various pairs; this analysis revealed that for all pairs, the ratios of TLE3-expressing individuals were significantly different. The largest difference was observed between the HR-positives and the triple-negatives (82% vs. 61%, respectively; p=2.509e-10), suggesting that the HR-positives have a higher likelihood of responding to taxane therapy. The HER2-positives, at 73%, had a ratio that was significantly higher than the triple-negatives and significantly lower than the HR-positives.
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