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Two Genes Provide Clues to Tamoxifen Success

Test could help predict who will benefit from breast cancer therapy

THURSDAY, June 3, 2004 (HealthDayNews) -- The activity of two genes may tell doctors who will succeed on tamoxifen therapy for breast cancer and, more importantly, who will fail.

That's the conclusion of a new study that found if high levels of a gene called HOXB13 or low levels of a gene known as IL17BR were expressed, tamoxifen therapy wasn't successful.

The simple gene test, researchers report in the June issue of Cancer Cell, was more than 80 percent accurate in predicting a recurrence of the cancer.

Tamoxifen is a breast cancer medication that blocks the effects of estrogen. This is important because, in many cases, breast cancer cells are fueled by estrogen. Estrogen-blocking drugs such as tamoxifen are often prescribed after a woman has surgery for breast cancer that is hormone-sensitive to try to keep the cancer from returning. Hormone-sensitive breast cancers are also known as hormone receptor positive.

"Thirty to 40 percent of women who are hormone receptor positive will recur even if taking tamoxifen," explained study co-author Dr. Dennis Sgroi, director of breast pathology at Massachusetts General Hospital in Boston. "Right now, we have no way of knowing who will do well. What we wanted to do was to find something that could identify the population that won't do well."

Sgroi and his colleagues from Massachusetts General Hospital, Harvard Medical School and Arcturus Bioscience Inc. examined frozen tumor samples from the initial biopsies of 60 women who had hormone receptor positive breast cancer. All had been treated with tamoxifen.

Thirty-two women from this sample remained disease-free up to 10 years later, while 28 women had a recurrence of cancer or their cancer spread to other areas of the body.

Sgroi said the researchers did detailed gene expression profiling and found two genes that were strongly associated with a recurrence of cancer -- HOXB13 and IL17BR.

Sgroi said the researchers don't know for sure what role these genes play in the development and spread of breast cancer. They suspect that HOXB13 may help cancer cells migrate and invade other cells. The role of IL17BR is less clear. Sgroi said other research has suggested this gene may play a role in inflammation and the immune system.

"Independently, each gene predicted recurrence, but when we looked at them together, we did even better. We were able to predict with 81 percent accuracy [by looking at the ratio of expression between the two genes]," Sgroi said.

To confirm these findings, the researchers validated the initial results on a smaller cohort of women who also had hormone receptor positive cancer and received tamoxifen therapy. The findings were similar.

"We are cautiously optimistic. These findings need to be validated in a population-based study, which we're in the process of doing," Sgroi said.

But, he added, it appears that "we've come up with a simple test that may assist an oncologist in deciding whether tamoxifen therapy alone is adequate."

"Not all breast cancers are alike," said Dr. Duane Superneau, chief of the section of medical genetics at Ochsner Clinic Foundation Hospital in New Orleans. "This could give clinicians a means to see what therapy would be most individually suited. Our strategies for treatment could be more directly applied for the individual and their individual disease."

Superneau said that any lab that currently does gene testing should be able to conduct these tests.

Both Sgroi and Superneau said that in addition to learning who will respond well to tamoxifen, the knowledge that a higher expression of HOXB13 and a lower expression of IL17BR occur in tamoxifen-resistant cancers could also help direct future research into treating those cancers.

More information

To learn more about tamoxifen, visit the National Cancer Institute.

SOURCES: Dennis Sgroi, M.D., director, breast pathology, Massachusetts General Hospital, and associate professor, Harvard Medical School, both in Boston; Duane Superneau, M.D., chief, section of medical genetics, Ochsner Clinic Foundation Hospital and Ochsner for Children, New Orleans; June 2004 Cancer Cell
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