Some women treated for ER-positive breast cancer are at higher risk for recurrence after completing tamoxifen treatment. Now a new US study suggests that by measuring a genetic biomarker, it may be possible to predict which women will have this higher risk, thus sparing a lot of women from treatment they don’t need.

Lead study author Dennis Sgroi, of the Cancer Center and Department of Pathology at Massachusetts General Hospital (MGH) in Boston, and colleagues, write about their findings in the 28 June online issue of the Journal of the National Cancer Institute.

In a statement, Sgroi says:

“Most patients with early-stage, ER-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.”

He goes on to explain how he and his colleagues have identified a biomarker that can identify which women will continue to have a higher risk of recurrence after tamoxifen treatment, and who will benefit from additional therapy with letrozole.

The biomarker measures the ratio of gene expression in the genes HOXB13 and IL17BR.

Co-author Paul E. Goss, director of the Breast Cancer Research Program at the MGH Cancer Center, says the finding means about 60% of women with the most common kind of breast cancer will be spared having extra treatment they don’t need. This will also reduce 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 adds.

However, both Goss and Sgroi note that more studies need to confirm these findings before they can be applied to patients.

ER-positive breast cancer is a breast cancer that is sensitive to the hormone estrogen. The cells from this type of cancer have proteins called estrogen receptors that get switched on when estrogen molecules bind to them. Once activated in this way, the estrogen receptors change the expression of certain genes, which can spur the growth of the tumor cells.

Drugs called selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene bind to estrogen receptors, blocking the estrogen. This either slows down or completely stops the growth of the tumor cells.

Letrozole is an aromatase inhibitor that blocks the activity of aromatase, an enzyme that is important for estrogen production.

Researchers have known for some time that the genes HOXB13 and IL17BR play a role in breast cancer.

For instance in 2006, Mayo clinic researchers reported in Clinical Cancer Research that expression of two novel genes, HOXB13 and IL17BR, within tumors may predict outcomes for breast cancer patients.

And in 2007, a study suggested that ER-positive breast cancer patients with a high ratio of HOXB13 to IL17BR expression did not benefit from extended endocrine therapy.

Before this latest study, Sgroi’s team worked on an earlier one that found the ratio of HOXB13 to IL17BR expression could predict the risk of recurrence of ER-positive, lymph-node-negative breast cancer, even in patients not treated with tamoxifen.

For the new study, the team analyzed tumor samples from a large placebo-controlled clinical trial of letrozole and determined the HOXB13/IL17BR gene expression ratio of each sample.

They were able to analyze tissue samples from 83 patients whose tumors recurred during the trial period, 31 patients who had received letrozole and 52 in the placebo group.

They also analyzed tissue samples from 166 patients whose cancer did not return during the trial period, 91 of whom had been treated with letrozole, and 75 in the placebo group.

They then compared these results against the trial data to see how useful the ratio might be both for prognosis (that is identifying which patients would still have a higher risk of recurrence after tamoxifen treatment), and for spotting which patients would most likely benefit from additional treatment with letrozole.

They found cancer was more likely to return after treatment with tamoxifen in patients with a high HOXB13 to IL17BR ratio, but that the risk fell significantly in those patients who received letrozole.

Written by Catharine Paddock PhD