No Heart Risk with Tamoxifen
An important new study was just published in the Journal of the American Medical Association. Dr. Steven Reis of the University of Pittsburgh Medical Center and colleagues reported that long-term treatment with tamoxifen does not appear to have any cardiovascular side-effects on the women taking the drug.
Using data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, the researchers followed 13,194 women for an average of 4 years and found no statistically significant difference in "cardiovascular events"-heart attacks, angina, etc.-between women taking tamoxifen and those taking a placebo.
The researchers concluded that tamoxifen was not associated with an increased risk of heart problems, even in women at high risk for heart disease. An accompanying editorial by Dr. V. Craig Jordan of Northwestern University Medical School went further, suggesting that additional studies with larger sample sizes and longer follow-up may show that tamoxifen actually has somewhat of a cardiovascular protective effect over time.
But Reis' team was more cautious, noting that their data showed no significant trend toward either a beneficial or a negative effect. Nonetheless, the fact that no increased risk of heart damage was associated with long-term tamoxifen use was singularly important.
Tamoxifen is a drug taken in pill form that interferes with the activity of estrogen, effectively countering that hormone's cancer-promoting effects. Tamoxifen has been used to treat both early and advanced stage breast cancers for more than 20 years.
In April 1992, the Breast Cancer Prevention Trial (BCPT) was launched to see if tamoxifen could also be effective in actually preventing the disease in high-risk women. But the BCPT was halted prematurely in March 1998 when interim results showed that tamoxifen had reduced breast cancer incidence by a remarkable 49 percent. In fact, the findings were so impressive that the lead investigators notified all of the 13,388 participants so that those women who had been taking the placebo could consider starting tamoxifen therapy.
In a totally unrelated study on osteoporosis-the Multiple Outcomes of Raloxifene Evaluation (MORE) trial-researchers were examining the use of another drug called raloxifene to prevent bone fractures in postmenopausal women.
But during the course of that study, the investigators noted an initial 74 percent reduction in the risk of breast cancer in women taking raloxifene compared with a placebo. After an average follow-up of just over three years, a 65 percent relative risk reduction was seen in the postmenopausal women studied.
The National Cancer Institute took notice, and in early 1999 launched a huge clinical trial to see which of these two major breast cancer drugs-tamoxifen or raloxifene-works better to actually prevent breast cancer. As many as 400 medical institutions nationwide are participating in the Study of Tamoxifen and Raloxifene (STAR) trial, which plans to eventually enroll more than 22,000 postmenopausal women over the next five years.
Women at increased risk for developing breast cancer, who have gone through menopause, and are at least 35 years old can participate in the STAR trial. Increased risk of breast cancer is determined in one of two ways. The risk for most women is determined by a computer calculation based on age, number of first-degree relatives with breast cancer, number of suspicious breast biopsies, and other factors. Also, women diagnosed as having lobular carcinoma in situ (LCIS), a condition that is not cancer but indicates an increased chance of developing invasive breast cancer, are eligible based on that diagnosis alone.
STAR is limited to postmenopausal women because the drug raloxifene has yet to be adequately tested for long-term safety in premenopausal women. The National Cancer Institute recently launched a separate study to evaluate the safety of raloxifene in premenopausal women.
Women who are interested in getting more information about the STAR trial can call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). To locate the nearest STAR center via the Internet, you can visit the NSABP's Web site at http://www.nsabp.pitt.edu or NCI's clinical trials Web site at http://cancertrials.nci.nih.gov.
Like most medications, tamoxifen and raloxifene can cause adverse effects in some women. The symptoms experienced most often include hot flashes and vaginal discharge, dryness or itching. It is possible that some women may experience leg cramps, constipation, pain with intercourse, sinus irritation or infection, or problems controlling the bladder upon exertion. Treatments are available to minimize or eliminate most of these side effects.
In the early Breast Cancer Prevention Trial, women taking tamoxifen were found to have an increased chance of developing three relatively rare conditions: endometrial cancer (cancer of the lining of the uterus), pulmonary embolism (blood clots in the lung), and deep vein thrombosis (blood clots in a major vein).
Women taking raloxifene in clinical trials demonstrated a similarly increased chance of developing a pulmonary embolism or deep vein thrombosis. However, the drug did not increase the risk of endometrial cancer as it did in women taking tamoxifen.
Finally, a number of recent studies have found that tamoxifen may have a limited time period of positive benefit-up to five years. Research initially undertaken by scientists at Duke University Medical Center found that taking tamoxifen for 10 years was no better than taking it for 5 years. In fact, subsequent studies have suggested that after 5 years tamoxifen can actually begin acting like estrogen rather than blocking it. A little is good, it appears, but more isn't necessarily better.
SOURCES:
Journal of the National Cancer Institute, January 3, 2001; 93:2-3, 16-21
National Surgical Adjuvant Breast and Bowel Project (http://www.nsabp.pitt.edu)
National Cancer Institute clinical trials Web site (http://cancertrials.nci.nih.gov)
American Cancer Society (www.cancer.org)
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