A biomarker reflecting expression levels of two genes in tumor tissue may be able to predict which women treated for estrogen-receptor-positive (ER positive) breast cancer should receive a second estrogen-blocking medication after completing tamoxifen treatment. In their report published in the Journal of the National Cancer Institute, HMS researchers at the Massachusetts General Hospital Cancer Center describe finding 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, estrogen-receptor-positive breast cancer remain cancer-free after five years of tamoxifen treatment, but they remain at risk of recurrence for 15 years or longer after their initial treatment,” said Dennis Sgroi, HMS professor of pathology at Mass General and lead author of the report. “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.”
Previous research by Sgroi’s team, in collaboration with investigators from bioTheranostics Inc., discovered that the ratio between levels of expression of two genes—HOXB13 and IL17BR—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 MA.17, the highly successful clinical trial of letrozole, was designed to go further. It would evaluate the usefulness of the HOXB13/IL17BR ratio for predicting which tamoxifen-treated patients remained at risk of recurrence, but it also sought to identify who could benefit from continued treatment with letrozole.
To answer those questions, 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 who had received letrozole and 75 who got the placebo).
Analysis of the tumor samples revealed that a high HOXB13/IL17BR ratio—meaning the expression level of HOXB13 is greater than that of IL17BR—predicts an increased risk for tumor recurrence after tamoxifen therapy, but that elevated risk drops significantly if a patient receives letrozole.
“This discovery means that about 60 percent of women with the most common kind of breast cancer can be spared unnecessary treatment with the concomitant side effects and costs,” said Paul Goss, HMS professor of medicine, director of the Breast Cancer Research Program at the MGH Cancer Center and a co-author of the report. “But more important, the 40 percent 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.”
Goss and 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 MGH, and Novartis.
Adapted from a Mass General news release.
