A Ton Of Prevention

The pros and cons of two drugs that may halve your risk of breast cancer

How many trade-offs would you make to halve your risk of developing breast cancer? That question is more than just a philosophical exercise. Results of a huge, government-run study published on June 21 proved that two drugs, tamoxifen and Evista, can cut risks in half. Other such treatments, known as chemopreventives, are now in the lab.

Cancer prevention is the holy grail of oncology research, and specialists are delighted that they have not one but two drugs that can actually keep breast cancer at bay. But the drug regimen is not an unqualified success. Taking a pill every day for at least five years to lower the odds of developing tumors can cause other sorts of troubles. Sorting out the pros and cons is a complicated task.

Although breast cancer mortality has declined dramatically in recent years, it is still second only to lung cancer as the deadliest cancer for women. An estimated 41,000 U.S. women will die of the disease this year, and 213,000 new cases will be diagnosed. The average American female has a 10% chance of developing breast cancer in her lifetime, and those odds can worsen depending on lifestyle, family history, and estrogen exposure. For some women with certain gene mutations, the risk can run as high as 60% to 80%.

Before worrying about prevention, every woman should figure out how likely she is to develop breast cancer in the first place. Doctors calculate the likelihood with the Gail model, a formula that combines various indicators, including the age of initial menstruation and menopause, the number of pregnancies, whether a close relative has developed breast cancer, and whether any biopsies have revealed abnormal breast cells. The Gail formula estimates both five-year and lifetime risk; a woman with a five-year score of 1.66% or greater is a candidate for chemoprevention.

A high Gail score doesn't doom you. It means that your chances are at least 16 to 17 in 1,000 of developing breast cancer over the next five years. A small percentage of breast cancer patients have an inherited form of the disease, however, usually related to mutations in the two BRCA genes associated with the breast. If you test positive for these mutations, your risk shoots through the roof, making the choice of chemoprevention an easy one.


A slightly elevated risk leaves women wrestling with the tamoxifen vs. Evista dilemma, if they decide to do anything at all. "This really is an issue each woman has to discuss carefully with her doctor," says Dr. Cheryl Perkins, senior clinical adviser for the Susan G. Komen Breast Cancer Foundation in Houston, a leader in breast cancer research. Specialists note that neither drug has been shown to keep women alive longer, suggesting that they may be arresting cancers that would have been curable in any case. "Of course you avoid the stress of cancer," says Dr. Elisa Port, a breast cancer specialist at Memorial Sloan-Kettering Cancer Center in New York, but she adds that, with early detection, breast cancer can be treated and even cured with minimal side effects.

Both tamoxifen and Evista block estrogen, a hormone that can promote tumor growth. Tamoxifen, a generic drug long used to treat breast cancer, was approved for prevention in 1998. But few women choose to take it, in part because it slightly increases the risk of ovarian and endometrial cancers, and of life-threatening blood clots in the lungs. Evista, also known by its generic name raloxifene, is an Eli Lilly & Co. (LLY ) drug widely used to prevent osteoporosis in post-menopausal women. It is not yet approved for breast cancer prevention, but the drug was tested against tamoxifen for that purpose by the National Cancer Institute in 20,000 high-risk women over seven years, the largest prevention study ever.

The final results, published in the Journal of the American Medical Assn., showed that both drugs reduced the risk of invasive breast tumors by 50%. Keep in mind that they did not prevent breast cancer altogether; there were 163 cases in the tamoxifen group and 167 in the Evista arm of the study. Without the drugs, specialists would have expected twice as many. Evista slightly elevated the risk of uterine cancers, but less so than tamoxifen. But Evista did not lower the chances of developing early-stage, noninvasive breast cancers found in the milk ducts. These cancers are curable if detected early but can turn deadly if they spread.


Women on the two drugs reported different experiences regarding quality of life. Although most said the side effects were mild, those on tamoxifen more often complained of hot flashes, vaginal bleeding, bladder control problems, and leg cramps, while Evista patients more often suffered from joint pain, pain during sexual intercourse, and vaginal dryness. As for cost, a daily tamoxifen pill runs about $100 per month, and Evista $75.

So, which course to choose? "I would advise that women should start on one drug and then reassess in three months," says Dr. Patricia Ganz of the Jonsson Comprehensive Cancer Center at the University of California at Los Angeles. She would probably start a woman who has not had her uterus removed on raloxifene. "Otherwise, it would depend on what is really important to her."

There are several other agents being studied as breast cancer chemopreventives, but none has proved effective so far. A new class of breast cancer treatments called aromatase inhibitors appear promising, in part because they can prevent cancer from recurring when taken after surgery or radiation. There are several current studies to see if the drugs can prevent breast cancer in the first place, but these will take some time. Cox-2 pain relievers, such as Celebrex, have also shown promise in some studies but can raise the risk of heart disease. "Keep in mind there is no free ride," cautions Port.

Actually, there is one free ride. Several studies have suggested that a healthy body weight and regular exercise not only lower the risk of developing cancer but also improve survival odds in women who do develop the disease. Unfortunately for older women, this natural approach is most effective -- and perhaps only effective -- if started early in life. A good reason to get our daughters to the gym.

By Catherine Arnst

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