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.
"We found TLE3 to be over-expressed in the majority of patients with HER2-positive and hormone receptor-positive breast cancer," Dr. Basu observed. "Interestingly, the comparatively low over-expression of TLE3 in the triple-negative subtype makes it especially important to identify those patients in this group who are most likely to respond to taxane therapy. If physicians are provided with such knowledge prior to starting therapy, their chances of selecting appropriate regimens for patients with these subtypes of breast cancer may be greatly improved."
Head and Neck Cancer Data
In a separate presentation, a team of Caris Life Sciences researchers led by Rebecca Feldman, Ph.D., presented results from the first analysis of biomarker expression profiles in head and neck squamous cell carcinoma (HNSCC) based on p53 status. They noted that HPV positive patients tend to carry the wildtype p53 tumor suppressor and have an overall better prognosis compared to non-carriers of the virus who are more likely to be p53 mutated. Insight to this difference in prognosis was pursued by comparing the biomarker expression profiles of p53 wildtype and mutated patients.
The researchers performed TP53 gene sequencing on the DNA of 52 patients with HNSCC whose samples previously underwent IHC and FISH testing with Caris Target Now. Thirteen (25%) of the patients were found to have mutated copies of p53. Of the various biomarkers assayed and analyzed, only EGFR and HER2 (p=0.002 and p=0.004, respectively) were significantly differentially expressed in wildtype compared to mutated p53. Matched-pair analysis in the subgroup of patients with mutated p53 showed no significant trend in terms of EGFR status (p=0.763) , however half of the mutated patients with EGFR FISH data were EGFR FISH positive. In the 39 patients with wildtype p53, there was a strong association with EGFR non-amplification (n=28, 72%; p<0.001) and HER2 negativity (n=38, 97%; p<0.001).
"EGFR is an important growth-regulating signal-transduction molecule, playing a critical role in cell proliferation and survival. It is aberrantly overexpressed at the protein level or amplified at the gene level in many malignancies, and its amplification is typically associated with poor prognosis," explained Dr. Feldman. "The absence of EGFR amplification in the p53 wildtype cancers, as we saw in our study, may contribute to the improved prognosis observed in patients with HPV-positive head and neck squamous cell carcinoma. Additionally, the strong association between wildtype p53 and EGFR non-amplification suggests that EGFR-targeted therapies such as cetuximab would likely fail in patients carrying wildtype p53. However, EGFR IHC should also be analyzed before ruling out this treatment. Such patients may benefit instead from standard chemotherapy with 5-fluorouracil or platinum agents, or from radiation therapy, whereas the p53 mutated patients who have a tendency towards EGFR FISH positivity, are more likely candidates for EGFR-targeted treatment."
About Caris Life Sciences
Caris Life Sciences is a leading biosciences company focused on developing and delivering innovative molecular diagnostic, prognostic, and theranostic services. The company's evidence-based molecular profiling service, Caris Target Now™, matches molecular data generated from a patient's tumor with biomarker/drug associations derived from the world's leading clinical cancer literature. Caris Target Now uses the most advanced and clinically relevant technologies to provide physicians with information to aid in the selection of personalized cancer treatments more likely to work for each patient. Caris is also developing a series of blood tests based on the company's proprietary Carisome™ platform - a blood-based testing technology for diagnosis, prognosis, and theranosis of cancer and other complex diseases. Through the precise and personalized information provided by technologies like Caris Target Now and Carisome, the company believes that the quality of healthcare can be dramatically improved, while also significantly reducing costs. Headquartered in the Dallas metroplex, Caris Life Sciences offers services throughout the United States, Europe, and other international markets. To learn more, please visit www.carislifesciences.com or www.caristargetnow.com.
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