Biomarker Predicts Risk of Breast Cancer Recurrence after Tamoxifen Treatment
A biomarker reflecting expression levels of two genes in tumor tissue may be able to predict which women treated for estrogen receptor (ER)-positive breast cancer should receive a second estrogen-blocking medication after completing tamoxifen treatment. In a report published online in the Journal of the National Cancer Institute, investigators found that the HOXB13/IL17BR ratio can indicate which women are at risk for cancer recurrence after tamoxifen and which are most likely to benefit from continuing treatment with the aromatase inhibitor letrozole.
"Most patients with early-stage, ER-positive breast cancer remain cancer-free after 5 years of tamoxifen treatment, but they remain at risk of recurrence for 15 years or longer after their initial treatment," said lead author Dennis Sgroi, MD, of the Department of Pathology at Massachusetts General Hospital Cancer Center. "Our biomarker identifies the subgroup of patients who continue to be at risk of recurrence after tamoxifen treatment and who will benefit from extended therapy with letrozole, which should allow many women to avoid unnecessary extended treatment."
Study Details
Previous research by Dr. Sgroi's team discovered that the ratio between levels of expression of the HOXB13 and IL17BR genes in tumor tissue predicted the risk of recurrence of ER-positive, lymph node–negative breast cancer, whether or not the patient was treated with tamoxifen. The current study of patients from the MA.17 trial was designed to evaluate the usefulness of the HOXB13/IL17BR ratio both for prognosis and for identifying who could benefit from continued treatment with letrozole.
The investigators analyzed primary tumor samples and patient data from the placebo-controlled MA.17 trial, which confirmed the ability of extended letrozole therapy to improve survival after the completion of tamoxifen treatment. Tissue samples were available from 83 patients whose tumors recurred during the study period—31 who had received letrozole and 52 in the placebo group—and 166 patients with no recurrence, 91 of whom had received letrozole, with 75 getting the placebo.
Analysis of the tumor samples revealed that a high HOXB13/IL17BR ratio predicts an increased risk for tumor recurrence after tamoxifen therapy, but that elevated risk drops significantly if a patient receives letrozole (odds ratio = 0.35, 95% confidence interval = 0.16–0.75, P = .007). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with a high HOXB13/IL17BR ratio (P = .007), and the interaction between HOXB13/IL17BR and letrozole treatment was statistically significant (P = .03).
Biomarker May Identify Candidates for Continued Therapy
Paul E. Goss, MD, PhD, Director of the Breast Cancer Research Program at the Massachusetts General Hospital Cancer Center and a coauthor of the report, explained, "This discovery means that about 60% of women with the most common kind of breast cancer can be spared unnecessary treatment with the concommitant side effects and costs. But more importantly, the 40% of patients who are at risk of recurrence can now be identified as needing continued therapy with letrozole, and many will be spared death from breast cancer." He and Dr. Sgroi noted that their findings need to be validated by additional studies before they can be put into clinical practice.
The study was supported by National Institute of Health grant R01-CA112021, Department of Defense Breast Cancer Research Program grant W81XWH-04-1-0606, and grants from the Avon Foundation, the Breast Cancer Foundation, the NCI SPORE in breast cancer at Massachusetts General Hospital and Novartis. For full disclosures of the study authors, visit jnci.oxfordjournals.org.
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