This application, based on PreMD's existing colour measurement patents and patent applications, may facilitate more accurate and cost-effective detection of biomarkers in clinical specimens.

"With the news earlier this year of breast cancer patients being incorrectly diagnosed and treated based on erroneous interpretation of immunohistochemistry tests it immediately came to our minds that our existing intellectual property and expertise in colour measurement may be useful in improving this critical situation. Today I am pleased to say that we have made significant headway in developing this concept and have submitted a provisional patent application that may be used to improve the scoring of immunohistochemical reactions resulting in more accurate and cost-effective determination of test results" said Dr. Brent Norton, CEO of PreMD. "Biomarkers, detected in human tissue samples by immunohistochemistry, are playing an increasingly important role in prognosis and treatment decisions and the new methodology has the potential to be applicable to a broad range of such biomarkers. In the lab, with our limited budget, resources and test samples, we are getting accurate positive results in 90% of cases and full agreement in over 80% of all tests. To take this program to the next step we need to find a way, in these markets, to fund the development and testing," he added.

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The researchers found that if study participants eventually experienced disease progression on estrogen, they could go back to an aromatase inhibitor that they were previously resistant to and see a benefit - their tumors were once again inhibited by estrogen deprivation. That effect sometimes wore off after several months, but then the tumors might again be sensitive to estrogen therapy. In fact, some patients have cycled back and forth between estrogen and an aromatase inhibitor for several years, thereby managing their metastatic disease.

The researchers also found that PET (positron emission tomography) scans could predict whose tumors would respond to estrogen therapy. They measured tumor glucose uptake before starting the women on estrogen and again 24 hours later. The patients whose tumors showed an increased glucose uptake, called a PET flare, were the same patients who benefited from estrogen therapy.

It's too early to know why estrogen has a negative effect on metastatic breast cancer tumors. But Ellis has found one clue - estrogen reduces the amount of a tumor-promoting hormone called insulin-like growth factor-1 (IGF1).

"I think that in order for breast cancer cells to survive in the absence of estrogen (when patients are on aromatase inhibitors), the cells have to learn to alter their cellular programs to utilize alternative growth signals like IGF1," Ellis says. "In theory, when you give estrogen back, IGF1 decreases and cancer cells die as a consequence. But surviving cancer cells prefer to switch back to living on estrogen - to them it's like eating out at McDonald's every day instead of foraging on roots and berries. These cells eventually reappear as estrogen dependent tumors and the cycle starts over."

Ellis plans to continue to follow metastatic breast cancer patients to quantify the response rate to retreatment with aromatase inhibitors when estrogen therapy stops working.

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