Developments in Breast Cancer Hormonal Treatment
The treatment of ]]>breast cancer]]> , the most common cancer in women except for ]]>skin cancers]]> , has come a long way in recent years. Breast cancer doctors are currently studying new biologic drugs and new hormonal treatments to block growth-stimulating receptors on the actual cancer cells. And results look promising. “It’s very exciting,” says Kellie Sprague, MD, an oncologist at Tufts-New England Medical Center in Boston, Massachusetts. “There are choices for women.”
Hormonal therapy, usually with tamoxifen (Nolvadex), has been long been advocated as standard treatment for breast cancer to block estrogen’s growth-promoting effects on breast cancer cells. However, recent scientific studies show that a newer drug, called anastrozole (Arimidex) may work better than tamoxifen and with fewer side effects.
Anastrozole was first tested against tamoxifen several years ago in women with advanced breast cancer. The results revealed less side effects and longer survival for the patients on anastrozole. The next logical step, says Anan Buzdar, MD, Professor of Medicine in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center, was to try it in patients with early breast cancer. “And we are seeing the same thing,” he says. “A higher fraction of patients are free of disease at two and a half years.”
“These findings show a modest but consistent improvement in disease-free survival among women who received an aromatase inhibitor compared to those who did not,” says Eric P. Winer, MD, Director of the Breast Oncology Center at the Dana Farber Cancer Institute in Boston, Massachusetts. “In women with hormone receptor-positive early breast cancer, hormones can influence the growth of the cancer. In post-menopausal women, aromatase inhibitors can block estrogen production and reduce estrogen levels by more than 90%,” Dr. Winer comments.
Based on results from multiple large randomized trials, aromatase inhibitors are appropriate either following a course of tamoxifen or used as initial treatment. Options include treatment with tamoxifen for 2-5 years, followed by treatment with aromatase inhibitors, or treatment for five years with an aromatase inhibitor alone. It’s not clear at this time which strategy is superior. Post-menopausal women who are currently taking tamoxifen may consider switching to an aromatase inhibitor after 2-5 years of tamoxifen therapy.
How Does It Work?
Tamoxifen works by blocking estrogen from binding to cancer cells. Anastrozole works by halting the production of estrogen in post-menopausal women, so there is essentially no estrogen available to promote the cancerous growths. Anastrozole is just one of a few drugs in a class called aromatase inhibitors, named after the way they stop estrogen production.
Although tamoxifen blocks estrogen from reaching the cancer cells, it also has some partial estrogen-like properties that account for its side effects. These include serious effects such as ]]>blood clots]]> , ]]>strokes]]> , and ]]>uterine cancers]]> , as well as more minor but often irritating side effects like hot flashes, weight gain, and mood swings. Since anastrozole works differently than tamoxifen, patients taking it have much less of these side effects. In the scientific studies, patients on anastrozole experienced more ]]>bone fractures]]> and musculoskeletal disorders than women taking tamoxifen.
Hope and Caution
Although the data on anastrozole looks good, the comparison studies have only followed its use in patients for an average of three years.
Many breast cancer specialists are wary that three years is not long enough to assess possible long-term side effects and not long enough to fairly compare it to the standard five years of tamoxifen. “Tamoxifen has been used routinely for twenty-five years,” says Dr. Jones. “We don’t want to suddenly replace tamoxifen. It is the gold standard. We understand about tamoxifen, we know how it works, and we know in whom it works.” Dr. Jones says that cancer specialists would feel more comfortable seeing what the results are after five or ten years.
“While researchers await more mature results and findings from additional trials using the aromatase inhibitors in the adjuvant setting, many patients and physicians have elected to use the third-generation aromatase inhibitors either as initial therapy in the adjuvant setting or following a course of tamoxifen,” Dr. Winer says. Women who switch to an aromatase inhibitor may continue this therapy for 2-3 more years, but no longer than five years. Women are advised that the result of treatment with an aromatase inhibitor for longer than five years has not been studied and should only be done in the context of a clinical trial.
Adjuvant therapy for post-menopausal women with hormone receptor-positive breast cancer should include an aromatase inhibitor in order to lower the risk of tumor recurrence, according to an updated technology assessment from the American Society of Clinical Oncology (ASCO). The three types of aromatase inhibitors are anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). The long-term side effects of aromatase inhibitors are not known. Early data suggest that when compared with tamoxifen, aromatase inhibitors may reduce the chance of blood clots and uterine cancer and may increase the risk of ]]>osteoporosis]]> and fractures.
Women who develop invasive hormone receptor-positive breast cancer while taking tamoxifen for breast cancer risk reduction, and women who cannot take tamoxifen because of high risk of severe side effects, or who have tried tamoxifen and had to stop because of severe side effects, might be advised to consider using an aromatase inhibitor.
American Cancer Society
American Society of Clinical Oncology
American Society of Clinical Oncology
People Living With Cancer
National Cancer Institute
Winer, P, Hudis C, Burstein HJ. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: Status report 2004. J Clin Oncol. 2005;23(3):619-629.
Buzdar AU, Cuzick J. Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. Clin Cancer Res. 2006;12:1037s-1048s.
Berry J. Are all aromastase inhibitors the same? A review of controlled clinical trials in breast cancer. Clin Ther. 2005;27:1671-1684.
Howell A. Pure oestrogen antagonists for the treatment of advanced breast cancer. Endocrine-Related Cancer. 2006;13:689-706.
Last reviewed February 2007 by ]]>David Juan, MD]]>
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