Genomic Tests Predict Breast Cancer Treatment Response

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Main Category: Breast Cancer
Also Included In: Cancer / Oncology;  Endocrinology;  Genetics
Article Date: 15 Dec 2006 - 9:00 PDT


Predicting how well a breast cancer patient may respond to chemotherapy or hormonal therapy has been the dream of every doctor, and patient. Two new genomic tests, developed by scientists from the University of Texas M.D. Anderson Cancer Center, may help doctors do just that.

The researchers are presenting their findings at the San Antonio Beast Cancer Symposium.

Dr. Lajos Pusztai, team leader, said the tests will be moving towards clinical trials, where improvements in treatment response can be measured, as well as tracking how doctors and patients use the new data to make better decisions about treatment.

Multi-Gene Test Predicts Chemotherapy Response

One test is a multi-gene test, it can predict response to chemotherapy before surgery. The test analyzes 780 gene combinations, honing in on just a few sets of genes. Testing involved 51 patients who had breast cancer and received chemotherapy. It predicted 12 out of 13 patients who achieved a 'complete response' - there was no cancer after chemotherapy. The test also accurately predicted 27 out of 28 patients with residual cancer - cancer was still present after chemotherapy. This means the test has a high negative predictive value.

Pusztai said "That's important, because if you knew in advance that you were unlikely to benefit from this standard chemotherapy, then you might choose a different treatment or an investigational drug."

The chemotherapy findings were published in the Journal of Clinical Oncology (see link at the bottom of this article).

Predicting 10-Year Survival and Relapse Risk with Tamoxifen

The other test predicts survival rates over 10 years for patients receiving tamoxifen - a hormonal drug given after surgery. Only about half of patients, of the 70% who express the estrogen receptor (ER), can benefit from anti-estrogen therapies (tamoxifen). It has always been a challenge to identify these patients beforehand. If a doctor can know who benefits he/she can then decide whether a patient should have that treatment or some other.

W. Fraser Symmans, M.D., associate professor in the Department of Pathology, said "We defined the 200 strongest ER-related genes and developed from those a Sensitivity to Endocrine Therapy (SET) index to actually measure this activity of ER." The ability of the SET index to predict how well a patient might respond to hormonal therapy was tried out on 267 patients - they all received tamoxifen, and no chemotherapy, for five years after surgery. Symmans explained that there was a strong link between the patients' SET index scores and the chances of remaining cancer free for ten years or more.

Patients who scored in the top 35% of the index were much more likely to remain relapse free for ten years. However, those whose score was in the bottom 50% got little benefit from tamoxifen alone - these patients are more likely to derive benefit from chemotherapy.

Patients scoring in the 50th-65th percentile derived benefit from a five-year course of tamoxifen - but this benefit dropped significantly about two years after treatment stopped. Symmans said "The intermediate group may be very important, because recent clinical trials have indicated that there is a subset of patients who benefit from continuation of hormonal therapy with newer drugs after their five years of tamoxifen. This intermediate group might be showing us who those patients are."

"Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer"
Kenneth R. Hess, Keith Anderson, W. Fraser Symmans, Vicente Valero, Nuhad Ibrahim, Jaime A. Mejia, Daniel Booser, Richard L. Theriault, Aman U. Buzdar, Peter J. Dempsey, Roman Rouzier, Nour Sneige, Jeffrey S. Ross, Tatiana Vidaurre, Henry L. Gómez, Gabriel N. Hortobagyi, Lajos Pusztai
Journal of Clinical Oncology, Vol 24, No 26 2006: pp. 4236-4244
Click here to see abstract online

Nuvera Biosciences, a company set up by the University of Texas M.D. Anderson Cancer Center, is working in close collaboration with the researchers who developed the two tests.

Written by: Christian Nordqvist
Editor: Medical News Today
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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