Tests Predict Breast Cancer Treatment Success
Two genetic tests may help predict how breast cancer patients will respond to chemotherapy or hormonal therapy, giving physicians a guide to help choose the best treatment.
Highly sensitive multiple-gene test predicted response to chemotherapy
Significance of results
Currently, physicians base predictions of how a patient will respond to chemotherapy on characteristics of the cancer. Knowing which patients might respond best to chemotherapy would be valuable in selecting treatment.
“This is important because if a physician knew in advance that a patient was unlikely to benefit from standard chemotherapy, a different treatment or an investigational drug might be a better choice,” says Lajos Pusztai, M.D., Ph.D., associate professor in MD Anderson’s Department of Breast Medical Oncology.
Researchers analyzed 82 women who received preoperative paclitaxel and fluorouracil-doxocrubicin-cyclophosphamide (T/FAC), one form of standard-of-care chemotherapy for breast cancer.
They analyzed 780 different gene combinations in this set of women, then applied 31 of the gene tests to 51 new patients who received identical T/FAC treatment.
The test accurately predicted 12 of the 13 patients who achieved complete response (no cancer after chemotherapy). Of the 28 patients the test predicted would have residual cancer, 27 had cancer after treatment.
Genomic index analyzed patients who received post-operative tamoxifen
Significance of results
About 70% of breast cancers express the estrogen receptor (ER), but tamoxifen and other anti-estrogen therapies benefit only about half of these patients. The challenge is to know exactly who will be helped and who should seek other treatment.
“We defined the 200 strongest ER-related genes and developed from those a Sensitivity to Endocrine Therapy (SET) index,” says W. Fraser Symmans, M.D., associate professor in the Department of Pathology.symmans photo
The ability of the SET index to predict the benefit of hormonal therapy was then tested in 267 patients who received tamoxifen for five years after surgery without chemotherapy.
Symmans says the SET index scores had a strong relationship to the probability of being disease-free 10 years later. Of the patients examined, those whose scores were in the:
- Top 35% had excellent relapse-free survival at 10 years
- Lower 50%:
- Derived little benefit from tamoxifen alone
- Benefited more often from chemotherapy
- Intermediate group (50% to 60%):
- Benefited initially from five years of tamoxifen
- Increased in relapse rates two years after treatment ended
At five years, patients with relapse-free survival included:
- 92% of the patients with high and intermediate SET index scores
- 70% of patients with low SET scores
At 10 years, patients with relapse-free survival included:
- 88% of high SET scorers
- 65% of patients with low SET scores
“We will soon start a clinical trial where these results are provided to the patient and her physician,” Pusztai says. “If an individual is predicted to be highly sensitive to the T/FAC chemotherapy, this treatment will be given preoperatively. Those who are predicted to be sensitive to endocrine therapy will receive preoperative endocrine therapy. If they are predicted to be resistant to both chemo- and endocrine therapies, we will recommend participation in a therapeutic study with novel agents.”
— From staff reports
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