Breast Health |
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Gene Finding Provides Clues To Tamoxifen Success Scientists Enhance Understanding Of What Treatments Work Best The activity of two genes may tell physicians who will succeed on tamoxifen therapy for breast cancer and, more importantly, who will fail, according to a new report in the medical journal Cancer Cell. 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 was not successful. The simple gene test 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," explains 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," he says. "What we wanted to do was to find something that could identify the population that won't do well." Gene "Profiling" Aids ResearchersDr. Sgroi and his colleagues examined frozen tumor samples from the initial biopsies of 60 women who had hormone receptor positive breast cancer. All of the women 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. Dr. Sgroi says the researchers conducted detailed gene expression profiling and found two genes that were strongly associated with a recurrence of cancer - HOXB13 and IL17BR. Dr. Sgroi said the researchers do not 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. Dr. Sgroi says 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," he says. "We were able to predict with 81 percent accuracy [by looking at the ratio of expression between the two genes]." To confirm these findings, the researchers validated the initial results with a smaller group of women who also had hormone receptor positive cancer and received tamoxifen therapy. The findings were similar. "We are cautiously optimistic," Dr. Sgori reports. "These findings need to be validated in a population-based study, which we're in the process of doing." Study provides insight and raises additional questions"This study is important because it provides clues as to the mechanisms whereby tumors are resistant to tamoxifen," says Dr. Richard Santen, professor of Internal Medicine' s nationally-ranked Endocrinology Division and Associate Director of Clinical Research at UVa. "However, the current study does not distinguish between the two known types of resistance: primary and secondary," says Dr. Santen. "Primary resistance is the condition whereby the tumor is resistant to tamoxifen at the time tamoxifen is started. Secondary resistance is a condition in which the tumor develops resistance as a result of exposure to tamoxifen. Additional studies should be capable of distinquishing between these two types of resistance." UVa is one of only two NCI Cancer Centers in the state, and has very active clinical trials and research programs in cancer. Tailoring Treatment Looks Promising"Not all breast cancers are alike," says 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," Dr. Superneau says. "Our strategies for treatment could be more directly applied for the individual and their individual disease." Dr. Superneau says that any lab that currently does gene testing should be able to conduct these tests. Both Drs. Sgroi and Superneau say 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.
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July 2004Gene Finding Provides Clues To Tamoxifen Success Gene "Profiling" Aids Researchers Study provides insight and raises questions Tailoring Treatment Looks Promising Hormone Therapy DefinedHormone therapy is used to prevent the growth, spread, and recurrence of breast cancer. Hormones are chemicals produced by glands, such as the ovaries and testicles. Hormones help some types of cancer cells to grow, such as breast cancer and prostate cancer. The female hormone estrogen can increase the growth of breast cancer cells in some women. Hormone therapy may be considered for women whose breast cancers test positive for estrogen or progesterone receptors. A hormone receptor test measures the amount of certain proteins (called hormone receptors) in cancer tissue. Hormones (such as estrogen and progesterone that naturally occur in the body) can attach to these proteins. If the test is positive, it indicates that the hormone is probably helping the cancer cells to grow. In this case, hormone therapy may be given to block the way the hormone works and help keep the hormone away from the cancer cells (hormone receptors). If the test is negative, the hormone does not affect the growth of the cancer cells, and other effective cancer treatments may be given. Always discuss the results of the hormone receptor test with your physician. An antiestrogen drug frequently used, called tamoxifen (Nolvadex®), blocks the effects of estrogen on the growth of malignant cells in breast tissue. However, tamoxifen does not stop the production of estrogen. Side effects that may occur when taking tamoxifen include hot flashes, nausea or vomiting, vaginal spotting, fatigue, headaches, and skin rash. Taking tamoxifen also increases the risk of endometrial cancer (involves the lining of the uterus) and uterine sarcoma (involves the muscle tissue of the uterus), both cancers of the uterus. There is also a small risk of blood clots and stroke. Always consult your physician for more information. Online Resources(Our Organization is not responsible for the content of Internet sites.) American Society for Clinical Oncology Centers for Disease Control and Prevention (CDC) National Institutes of Health (NIH) |
