Will biomarkers help ID women with TNBC who benefit from taxanes?

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CHICAGO, June 2, 2012 /PRNewswire via COMTEX/ -- TLE3 Biomarker Over-expressed in HER2-positive, Hormone Receptor-positive, and Triple-negative Breast Cancers --

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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."