Biomarker shows when letrozole may stop breast cancer recurrence

A biomarker reflecting expression levels of two genes in tumor tissue has been found to predict which patients may be at risk for late recurrence of estrogen receptor (ER)–positive breast cancer, and when adjuvant letrozole therapy may be of benefit.

In previous research, a team led by Dennis C. Sgroi, MD, of the Massachusetts General Hospital (MGH) Cancer Center and MGH's Department of Pathology in Boston, Massachusetts, discovered that the ratio between levels of expression of the HOXB13 and IL17BR (H/I) genes in tumor tissue predicted the risk for recurrence of ER-positive, lymph-node-negative breast cancer, whether or not the patient had undergone therapy with tamoxifen. As Sgroi noted in an MGH statement accompanying the release of his group's latest findings, most patients with early-stage, ER-positive breast cancer remain cancer-free after 5 years of tamoxifen treatment, but they are at risk for recurrence for 15 years or longer after initial therapy.

In their current work, Sgroi and fellow investigators evaluated the H/I biomarker for its effectiveness in identifying which women are at risk for cancer recurrence after tamoxifen treatment and which are most likely to benefit from continuing treatment with the aromatase inhibitor letrozole.

Sgroi and colleagues used primary-tumor samples and patient data from the placebo-controlled MA.17 study, which confirmed the ability of extended letrozole therapy to improve survival after tamoxifen treatment. Tissue samples were available from 83 patients whose tumors had recurred during the course of the MA.17 study (31 had received letrozole and 52 had received placebo), and from 166 patients with no recurrence (91 from the letrozole group and 75 from the placebo group).

An elevated H/I ratio, in which the expression level of HOXB13 was greater than that of IL17BR, predicted an increased risk for tumor recurrence after tamoxifen therapy, but that elevated risk fell significantly for patients receiving letrozole.

If these findings are validated by additional studies, approximately 60% of women with the most common kind of breast cancer can be spared unnecessary treatment with the concomitant side effects and costs, said Paul E. Goss, MD, PhD, in the MGH statement. “But more important,” affirmed Goss, who is the director of the Breast Cancer Research Program at the MGH Cancer Center and a coauthor of the study, which appears in Journal of the National Cancer Institute, “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.”
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