NEW YORK (Reuters Health) - The expression ratio of two genes -- HOXB13 and IL17BR -- in breast cancer tissue can accurately identify women with estrogen receptor-positive (ER+) tumors who are at high risk for recurrence after adjuvant tamoxifen therapy, new research shows.
“We know that 30% to 40% of women with ER+ breast tumors will fail to respond to adjuvant tamoxifen,” Dr. Dennis C. Sgroi, director of breast pathology at Massachusetts General Hospital in Boston said in a telephone interview with Reuters Health. “But until now, we haven’t been able to identify which of these women would be at risk for recurrence in the setting of adjuvant tamoxifen.”
Knowing which women are most likely to fail adjuvant tamoxifen would allow earlier use of alternative therapies, such as aromatase inhibitors, that might be more effective.
Dr. Sgroi and colleagues used microarray technology to analyze gene expression patterns in 60 archived ER+ breast tumor tissue samples. All 60 patients were uniformly treated exclusively with systemic adjuvant tamoxifen after surgery. According to the medical records, 32 women remained free of breast cancer for an average of 8 years, while 28 had a recurrence of their tumor or metastasis.
In multivariate analysis, the expression ratio of HOXB13 to IL17BR was a strong independent predictor of treatment outcome in the setting of adjuvant tamoxifen therapy, they report in the June issue of the journal Cancer Cell. Women who had a higher level of expression of HOXB13 over IL17BR, and a low level of expression of IL17BR, had a significantly higher risk of recurrence (odds ratio 7.3) compared with women without this expression pattern.
“The positive predictive value was 87.5% and the negative predictive power was 75%,” Dr. Sgroi told Reuters Health. The results from an independent validation sample of 20 tamoxifen-treated tumors confirmed the predictive power of the two-gene expression ratio.
The HOXB13 gene may also play a role in tumor development. In separate experiments, the researchers found high levels of expression of HOXB13 in both pre-invasive and invasive breast carcinoma compared with normal breast tissue. This suggests that the pathway controlled by HOXB13 might be a new therapeutic target for breast cancer, Dr. Sgroi said.
Source: Cancer Cell 2004;5:00-00. [ Google search on this article ]
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