Oct. 30, 2000 -- The day that forever changed Bonnie McDonald's life started out like any other. It was a typically hectic Monday morning last spring when the 37-year-old decided to grab a quick shower. She'd gone for a run after dropping her son off at school and was about to rush off to her part-time catering job when she felt a pea-sized lump in her left breast. Tests later that week showed that she had found a cancerous tumor. "It was so frightening," she says. "I'd always been athletic and healthy. That was my first glimpse of mortality."
McDonald underwent a lumpectomy and eight weeks of radiation. Then her oncologist suggested she begin taking tamoxifen, an anticancer drug that has been playing a substantial role in the fight against the return of breast cancer. Tamoxifen works by blocking the estrogen that breast cancer cells need to grow. Her doctor explained that, as a side effect of the treatment, she might go through a temporary menopause and could experience hot flashes, mood swings, and all of the other symptoms associated with the change of life. He also said that taking tamoxifen could increase her risk of developing endometrial cancer -- cancer of the lining of the uterus or womb.
His prescription, he said, was based on a balance of risks and benefits and, like many other medical decisions these days, the choice was ultimately up to the patient. McDonald got on the Web and did her own research, talked to women in similar circumstances, and finally decided that she would take tamoxifen.
McDonald's choice is one that many women are making. About one million women worldwide take tamoxifen, according to a review article in the May 27 British Medical Journal, and medical research backs up the choice. In May, a Lancet article reported that breast cancer death rates in the United States and Britain have dropped dramatically -- between one quarter and one third -- in the past decade. Sir Richard Peto, a leader of the international Early Breast Cancer Trialists' Collaborative that produced this new report, calls this news "the best decrease in national death rates that has ever been seen with any common cancer." Surely earlier diagnosis, better surgery, chemotherapy, and radiotherapy all play a part in improved survival rates, Peto says, but he is convinced that the widespread and prolonged use of tamoxifen may be the most important factor. However, women on tamoxifen must cope with the side effects of taking the drug -- some of them quite severe.
How It Works
Originally developed as a fertility agent, tamoxifen is a selective estrogen receptor modulator (SERM). It affects the way estrogen reacts with cells. Breast cells have estrogen receptors on their surfaces that allow the hormone to lock onto them. While this is a perfectly normal process, over time the buildup of estrogen can promote breast cancer in some women. About 70% of breast cancers are estrogen receptor positive, meaning that estrogen fuels their growth. Tamoxifen blocks the absorption of estrogen by the breast cancer cell by locking onto these receptors first, thereby preventing metastasis, the growth of the cancer and its deadly migration to other parts of the body.
In 1998, Peto and associates published a report in The Lancet analyzing data from 55 clinical studies involving 37,000 women. They concluded that women who had estrogen receptor positive or estrogen receptor unknown tumors and took tamoxifen for five years reduced their risk of breast cancer recurrence from 42% to 26%, while women with all estrogen receptor status types lowered their risk of developing a new tumor in the other breast by 50%.
Not All Good News
This encouraging prognosis doesn't come without side effects, however. Research -- including a review article in the July 20 issue of The New England Journal of Medicine -- shows that tamoxifen can raise a woman's risks of developing uterine cancer, cataracts, and blood clots. The drug also induces menopause in many younger women. Coping with these side effects -- after dealing with breast cancer -- is more than some women are willing to do.
Like Bonnie McDonald, Katie Farrell, 42, had a lumpectomy and eight weeks of radiation after discovering a cancerous tumor in her breast. But, unlike McDonald, Farrell declined her doctor's prescription for tamoxifen. She was concerned about the risks and, because of her age, worried that she would go through early menopause, begin menstruating again after the five-year tamoxifen regimen, and then go through menopause naturally again. She did not want to do that. "You can't tell me that manipulating your hormones that way isn't going to affect other systems in your body," she says.
Indeed, though tamoxifen may ultimately help, coping with side effects such as hot flashes and night sweats can be daunting for women who are also recovering from breast cancer treatments. McDonald has swallowed the pills daily for more than a year now. It has not been an easy regimen. She suffers hot flashes and night sweats that can soak through her sheets. Her weight has ballooned from 126 to 146 pounds. And because her sleep is disrupted, she is tired most days. Her mood swings are testing her relationship with her husband, Alan, and her loss of libido doesn't help. "After all I've been through, you'd think that hot flashes would be a piece of cake, wouldn't you?" she says. "But the fatigue and the chronic PMS are a bad combination." Still, she intends to continue on tamoxifen for the five years recommended. "Every time I take that pill I feel like I'm killing another cancer cell," she says. "That's how I deal with it."
Coping with Side Effects
In an attempt to relieve some of the side effects, McDonald takes 400 IU of vitamin E daily. "At least one study has shown that vitamin E can help reduce the menopausal symptoms associated with tamoxifen," says Adriane Fugh-Berman, MD, a professor at the George Washington University School of Medicine and author of Alternative Medicine: What Works. Estrogen -- or the phyto-estrogens contained in soy products -- are not recommended, Fugh-Berman says, because they interfere with tamoxifen's antiestrogenic purpose. Some women swear by acupuncture, although there are no clinical studies showing that it helps reduce the side effects of tamoxifen treatment. "Relaxation therapy can help, too, with things like hot flashes and mood swings," she says.
In his new book Complementary Cancer Care, James S. Gordon, MD, clinical professor at Georgetown University School of Medicine and director of the Center for Mind-Body Medicine in Washington, D.C., reports case studies showing that supplements of the hormone melatonin may slow the growth of breast cancer cells and increase the effectiveness of tamoxifen. If so, women might be able to lower the dose they take and reduce side effects. However, as with other supplements, melatonin has not yet been tested in controlled trials.
Doctors also often prescribe Effexor, an antidepressant, to help women cope with hot flashes and night sweats. Other antidepressants, such as Paxil and Prozac, help some women modulate mood swings, and mild sedatives such as Ambien help others sleep through the night, Fugh-Berman says.
Little Research on Alternatives
But while some women may find these therapies effective, most have not been tested in controlled studies. "No research yet shows that diet, exercise, or other healthy habits, including taking herbs and vitamins, helps prevent the recurrence of breast cancer," says Fugh-Berman. Therefore, she does recommend tamoxifen as a treatment for early breast cancer -- when the cancer is restricted to the breast and can be removed surgically. "Studies show that it works," she says. "But I don't recommend taking it for longer than five years. There is no evidence that taking it longer helps, and some experts suspect it may actually increase breast cancer risk after that time period."
McDonald still has a few more years of her tamoxifen treatment. In the meantime, she copes by walking about two miles a day with Bea, her golden retriever, and hopes that this discipline will gradually help her lose the twenty pounds she's gained in the past year. These walks through the woods near her suburban Ohio home also help her maintain perspective. "I may be living with hot flashes and mood swings," she says, "but I'm living, and I want to keep on living."