In the future, will all women take a pill to prevent breast cancer along with their daily vitamins?
An anti-breast cancer drug, tamoxifen, already exists. However, most medical experts say it’s a leap to go from tamoxifen to the prospect of a “one-size-fits-all” pill that every woman can take. No one is recommending tamoxifen for women in the general population. The drug, which has some dangerous side effects, is exclusively for women who have either had breast cancer or who are at a high risk of developing it. Furthermore, there is no guarantee that a woman taking a chemo-preventive drug will not get breast cancer.
What the latest breast cancer research does hold for the future, however, is more choices of anti-breast cancer drugs for more women.
New study compares two drugs
A nationwide study, sponsored by the National Cancer Institute, is under way to compare tamoxifen (Nolvadex®) with another drug, raloxifene (Evista®) that could cut a woman’s risk of breast cancer almost in half — if not more.
Risk factors for breast cancer include a strong family history of breast cancer or ovarian cancer, older age, breast lumps requiring biopsy, early menstruation (age 11 or younger) and either no full-term pregnancy or delivery of a first child after age 30.
Tamoxifen has been used for 20 years to treat breast cancer. It was approved two years ago as the first preventive drug after it was discovered that it reduced the incidence of developing breast cancer by 45 percent in women considered at high risk for the disease.
Raloxifene (Evista®), approved by the Food and Drug Administration (FDA) in 1997 to prevent bone loss in postmenopausal women, has not been approved as an anti-breast cancer drug. However, clinical studies have shown that it may be even more effective than tamoxifen. Studies showed that raloxifene reduced the incidence of breast cancer by almost 60 percent in women considered at normal risk.
The NCI study — known as the STAR trial (Study of Tamoxifen and Raloxifene) — is one of the largest breast cancer trials ever launched. It includes 22,000 postmenopausal women. The study, which began in 1999, is expected to determine not only which drug is more effective in preventing breast cancer, but also which is safer. The study may also answer another question. Will there ultimately be one anti-breast cancer drug for premenopausal women and another for postmenopausal?
The big debate over tamoxifen
Both tamoxifen and raloxifene are in a class of drugs called “selective estrogen receptor modulators”(SERMs). They’re synthetic hormones that have estrogen-like effects on some parts of the body and anti-estrogen-like effects elsewhere. SERMs act like estrogen on bone cells, thus preventing the bone thinning of osteoporosis. As anti-estrogens, they block estrogen from binding to estrogen receptors on cell surfaces, thus preventing the promotion of certain breast cancers.
Doctors clash over the use of tamoxifen to prevent breast cancer in healthy women defined as “at risk”. Some doctors believe it should not be routinely prescribed for women who don’t have cancer, because of the drug’s side effects.
Tamoxifen can triple the risk of developing dangerous blood clots in the lungs and double the risk of endometrial cancer in the uterine lining. Other side effects include hot flashes and vaginal discharge, similar to some of the symptoms of menopause, and cataracts.
However, a European study has shed some new light on tamoxifen. The study, published in the September 1999 issue of the Journal of Clinical Oncology, found that one quarter of the usual dose of tamoxifen may be just as effective as the regular dose.
Researchers at the European Institute of Oncology in Milan, Italy, concluded in their study of 105 women that the reduced dose may offer the same protection against cancer without causing many of the complications.
The researchers found that a reduced dose does not change tamoxifen’s effect on biomarkers — molecules that are affected when tamoxifen acts on estrogen receptors. They added the caveat, though, that the findings were not conclusive and that future clinical trials would be needed to compare the cancer-prevention ability of the normal dose of tamoxifen to a reduced dose of the drug.
In addition to the issue of side effects, there is also a question of how long a woman should take tamoxifen. The ideal length of treatment with tamoxifen is not known. Studies have suggested, though, that tamoxifen may behave more like an estrogen than an anti-estrogen if used longer than five years. Although it has never been proven, one concern is that prolonged use of tamoxifen may actually increase the risk of breast cancer.
What are the risks with raloxifene?
Less is known about raloxifene, because it is still relatively new. However, studies have shown that raloxifene can cause side effects similar to tamoxifen — with one major exception. It has not been shown to increase the risk of endometrial cancer. Unlike tamoxifen, raloxifene does not bind to the endometrial cell lining in addition to estrogen receptors in breast cells.
Different drugs, different age groups?
Is it possible that one drug will ultimately be used for postmenopausal women and another for premenopausal women? The answer may be “yes”.
Raloxifene is not approved by the FDA for any other use except to prevent osteoporosis in postmenopausal women. It’s not recommended in premenopausal women because it hasn’t been studied in this group and because it may carry an increased risk of ovarian cysts. It does not carry the same risk for postmenopausal women, however.
Tamoxifen is approved for both premenopausal and postmenopausal women. In the initial breast cancer trial, the risk of side effects was somewhat less for women under 50.
The STAR trial may provide more answers about which pill to prevent breast cancer is safer, and for what age group. For now, the only preventive measure available is tamoxifen.
How do you know if you’re at high risk for breast cancer? And what if you have just one close relative with breast cancer or you’ve had one benign breast biopsy?
If you have questions, sit down with your doctor so that he or she can assess your risk. Even if you don’t have risk factors, don’t forget that all-important monthly breast self-examination and, if you’re over 40, an annual mammogram, because the best ammunition in fighting breast cancer is early detection.
To learn more about the STAR trial, you can call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The number for deaf and hard-of-hearing callers with TTY equipment is 1-800-332-8615. Information on the NCI’s Cancer Trials is also available online.