Molecular diagnostic test for early-stage breast cancer

Researchers at Montefiore Medical Center are leading a nationwide clinical trial to determine whether a new genetic test can be used to personalize treatment for early-stage breast cancer.

"By using a molecular diagnostic test to assess whether a breast tumor will respond to chemotherapy, we're hoping to more precisely identify which patients can be adequately treated with hormonal therapy alone and which patients will truly benefit if chemotherapy is added to the treatment," said Joseph Sparano, MD, who directs the Breast Evaluation Center at the Montefiore-Einstein Cancer Center. "With better individualized treatment, we can spare women the side effects of chemotherapy where it is unnecessary."

Dr. Sparano is the lead investigator for the clinical trial, called TAILORx (an acronym for Trial Assigning Individualized Options for Treatment). The study, sponsored by the National Cancer Institute, will enroll about 10,000 women with breast cancer at more than 900 institutions throughout the United States and Canada.

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 235,000 new cases of invasive breast cancer expected in the United States and Canada in 2006. Nearly 140,000 of these women will have estrogen receptor-positive breast cancer that has not yet spread to the lymph nodes.

The standard treatment is surgery to remove the tumor, plus radiation and hormonal therapy, which cures about 80 to 85 percent of patients. Adding chemotherapy can further reduce the risk of recurrence by about 25 percent, but it benefits only a small proportion of women.

Currently, most women with early-stage breast cancer are advised to undergo chemotherapy, yet it's not clear that chemotherapy is worthwhile or even necessary in all these cases," Dr. Sparano said.

The researchers will use OncotypeDXTM, a modern diagnostic test developed by Genomic Health, Inc., in Redwood, Calif., in collaboration with the National Surgical Adjuvant Breast and Bowel Project, a network of cancer research professionals. The test identifies which of 21 specific genes are turned on or off in the tumor. This genetic assessment estimates a patient's risk of recurrence more precisely than standard clinical characteristics, such as tumor size and grade. It also helps predict whether a patient will benefit from chemotherapy.

"This test yields what is called a recurrence score. For about 55 percent of women, the recurrence score is greater than 25 or less than 11. In these cases, the test clearly indicates the most effective therapy: a combination of chemotherapy and hormones for women with high scores, and hormones alone for women with low scores," Dr. Sparano said. "But about 45 percent of women receive scores that range from 11 to 25, where the treatment path is not so clear. Our study is designed to resolve this uncertainty."

Women participating in the TAILORx trial will be assigned to one of three groups depending on their recurrence score. If the score is more than 25, women will receive chemotherapy plus hormonal therapy, the current standard of care. If it is less than 11, they will receive hormonal therapy alone. If the recurrence score is between 11 and 25, women will be randomized to receive either hormonal therapy or hormonal therapy together with chemotherapy.

"With this trial, we're taking a big leap forward in integrating modern molecular diagnostic testing into clinical decision-making in order to individualize cancer treatments," Dr. Sparano said.

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