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Genomic Predictors Report Likely Response to Multiple Treatments in Breast Cancer

Posted on: Monday, 16 April 2007, 18:00 CDT

Researchers at Nuvera Biosciences and The University of Texas M.D. Anderson Cancer Center have developed predictors of response to chemotherapy and hormonal treatments in breast cancer patients. Results of these studies will be announced at the Annual AACR Meeting in Los Angeles, CA.

"It is exciting that the tests can identify not only high responders to standard treatments but also which non-responders to hormonal treatment might benefit most from chemotherapy," said lead author Christos Hatzis, Ph.D., VP, Technology at Nuvera.

In previously described studies, a chemoresponse predictor was developed and validated from prospective samples of women who received standard paclitaxel-based chemotherapy (T/FAC) pre-operatively. The endocrine treatment predictor, developed from genes strongly associated with estrogen receptor (ER) activity, showed that high scorers had excellent 10-year survival whereas low scorers derived little benefit from tamoxifen. Hatzis and M.D. Anderson colleagues are further validating both predictors.

"There is a strong need to predict who will benefit from standard treatments, who will need combination treatments, and who may benefit from experimental therapies," says senior author Lajos Pusztai, MD, from the M.D. Anderson's Breast Medical Oncology.

In addition, the researchers have reported a quantitative measure of residual disease that has significant prognostic relevance. "It is critical to use measures of tumor response that most accurately predict patients' prognosis, so that predictive tests identify not only those who benefit from treatment, but also those whose tumor is intrinsically resistant" adds author Fraser Symmans, MD, from the M.D. Anderson's Pathology Department.

In the current study, ER-positive patients who had pre-operative T/FAC chemotherapy were analyzed for extent of residual disease and endocrine sensitivity (n=81). Of 19 patients observed to have high chemosensitivity, as indicated by pCR or minimal residual disease, 17 (90%) were predicted to have low endocrine sensitivity. Conversely, most patients who did not respond to chemotherapy (moderate or extensive residual disease) were predicted to have either high or moderate endocrine sensitivity.

The results show low responders to hormonal therapy to be good candidates for chemotherapy and vice versa. "Together, these predictors can make an integrated test to help triage and guide breast cancer treatment," adds Dr. Pusztai.

In addition, results show that 11 patients (14%) observed to have extensive disease after chemotherapy (resistance) may be non-responsive to hormonal treatment as well. Pusztai and Symmans believe that these patients might be candidates for investigational trials of new therapies since existing treatments offer little benefit.

Research is ongoing to extend the range of predictors to additional breast cancer treatments and to other cancers where correct treatment selection can create a significant impact on patient survival.

Nuvera Biosciences, a venture launched with M.D. Anderson Cancer Center, is developing novel molecular diagnostics that will significantly improve treatment selection. Using well-defined clinical studies, high-quality tissue access, and sophisticated bioinformatics, the Company is building a portfolio of tests directed at making personalized medicine a reality.

Source: Business Wire

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