Health

An ounce of prevention

Tests show a drug can stop breast cancer from starting

MARK NICHOLS April 20 1998
Health

An ounce of prevention

Tests show a drug can stop breast cancer from starting

MARK NICHOLS April 20 1998

An ounce of prevention

Health

Tests show a drug can stop breast cancer from starting

MARK NICHOLS

Over the years, Patricia Vasko has seen a sister and a cousin die of breast cancer, and her mother and another sister were diagnosed with the disease. Now, doctors are monitoring two lumps in the breast of Vasko’s 35-year-old daughter. Because of her family history and age, Vasko,

62, a retired nurse who lives in Thunder Bay, Ont., knows she runs a high risk of contracting breast cancer herself—“The fear,” she admits, “is always there in the back of my mind.” It was there in 1992 when she heard reports of a massive study that was seeking to determine whether the drug tamoxifen—until then used to treat women who had already been stricken with breast cancer— could actually prevent the disease.

Now, with announcement last week of dramatic findings from the trial, it is almost certain the drug can do just that.

The results showed that, among women who took tamoxifen during the study, there were 45 per cent fewer cases of breast cancer, compared with those given a chemically inactive placebo. As it turned out, Vasko was one of the women taking a placebo—but that did not trouble here greatly. “I’m proud to have played a part in fighting this disease,” she said. “Please, God, let them find a cure.”

In fact, the benefits apparent in the study of 13,388 women in the United States and Canada were so great that health officials halted it 14 months early to let those on the placebo take advantage of tamoxifen’s effects. They say the drug appears to help women in all age groups, and predict that the findings could lead to drugs for preventing other kinds of cancer. “For the first time in history,” said Bernard Fisher, scientific director of the Philadelphia-based National Surgical Adjuvant Breast and Bowel Project, which conducted the $96-million study with funding from the National Cancer Institute in Bethesda, Md., “we have evidence that breast cancer cannot only be treated, but prevented.” Dr. Alan Lees of Edmonton’s Cross Cancer Institute—one of 15 Canadian centres that enrolled 1,762 women in the study—called the findings “really positive—a

landmark study.” The results, added Dr. Stephen Narod, a leading breast cancer researcher at Toronto’s Centre for Research in Women’s Health, constituted “a tremendous step forward—if it hadn’t shown a reduction in breast cancer, we’d have been back to Square 1.”

But experts cautioned that the study had not turned up a magic bullet capable of vanquishing breast cancer—and that it could be years before the long-term consequences of giving tamoxifen to healthy women are known. Nor, they said, did the findings justify giving tamoxifen to all women, only to those who had the same risk profile as study participants—women 60 or older, those with a family history of breast cancer, women who have had no children or gave birth later in life, those who began menstruating early or have been found to have abnormal breast cells. “It is important that doctors don’t start using this treatment without a meticulous assessment of the risks,” said Dr. H. S. Dhaliwal, head of the Northwestern Ontario Regional Cancer Centre in Thunder Bay, which enrolled 48 women in the study. “This treatment is not for everyone.”

The reason: while convincingly showing that tamoxifen can save lives, the controversial six-year study, temporarily halted in 1994 because of safety concerns, showed that taking tamoxifen also carries

risks. They include endometrial cancer (which can usually be treated successfully if caught in its early stages) and potentially deadly blood clots in the veins and lungs. During the study, 33 women who were taking tamoxifen developed cancers of the endometrius—the lining of the uterus—compared with 14 in the placebo group. And 47 of the women who took tamoxifen developed blood clots in their veins and lungs, compared with 25 women in the control group. Two women who used tamoxifen died of blood clots in their lungs.

Overall, however, the benefits of tamoxifen for high-risk women seemed to outweigh the risks. Besides sharply reducing the incidence of breast cancer among women who used the drug, it also appeared to prevent osteoporosis, a disease that weakens the bones of older people, especially common among women. In the « study, women who took tamoxg ifen experienced 47 bone fractures, compared with 71 among £ women in the placebo group, §

Study participant Shirley Nel| son, a Vancouver nursing home administrator, was ecstatic when =î she learned that the two white o pills that she took every day for ü five years were in fact tamoxifen | and not the placebo. “It was a | cause for celebration,” said Nel% son, 50, who has a family history ° of breast cancer. “I telephoned all my friends and relatives to tell them the news.” Doctors said women in the placebo group should weigh the potential benefits and risks before deciding to take tamoxifen.

News of the findings came just as health officials in Canada published grim new statistics on the growing incidence of cancer in an increasingly elderly population. The Toronto-based Canadian Cancer Society cited Statistics Canada figures showing a 30-per-cent increase in new cancer cases during the past decade —well ahead of a 12-per-cent population growth during the period—with nearly 130,000 new cases, and 62,700 deaths, expected this year. Moreover, the society warned that the number of new cancer cases could increase another 30 per cent by the year 2010. As for breast cancer—the secondbiggest killer of women after lung cancer—more than 19,000 new cases are expected to be diagnosed in Canada this year—and an estimated 5,300 women will die of the disease. Thanks to earlier detection and improved treatment, the breast cancer mortality rate has declined somewhat in recent decades, with about 28 women dying of the disease for every 100,000 in the population, compared with 31 deaths per 100,000 in 1969.

But breast cancer still claims far too many lives—which is why the evidence that tamoxifen can play a preventive role was greeted so rapturously. Developed more than 25 years ago by Britain’s Zeneca Group, tamoxifen was originally intended as a birth control drug, but flopped in that role. Since the mid-1970s, physicians have used it to prevent breast cancer from recurring in most cases involving post-menopausal women following surgery. The drug is believed to

act by occupying sites in breast cells that serve as gateways for the hormone estrogen—which, besides playing a key role in development of women’s reproductive systems, appears to fuel the growth of some cancers. By blocking breast receptors for estrogen, tamoxifen can either prevent cancers from starting, or from spreading once they have formed. But in the intricate chemistry of the human body, tamoxifen can have the opposite effect in the uterus, where it can help stimulate tumor growth.

An even better drug may be waiting in the wings. At a news conference in Philadelphia, officials involved in the tamoxifen study said the next step could be a trial that would compare tamoxifen with roloxaphene, a new drug from the U.S. pharmaceutical giant Eli Lilly & Co. Sold under the brand name Evista, roloxaphene is currently used to combat osteoporosis. But researchers say it probably has the same breast cancer-fighting qualities as tamoxifen—but with fewer side-effects. Officials said the new study, which could begin in the fall, would initially be limited to high-risk post-menopausal women. Because many women who now know they were taking placebos during the study want to switch to tamoxifen or roloxaphene, said Dr. Norman Wolmark, principal investigator in the study, “obviously we would like to have this trial available as quickly as possible.”

A key question left unanswered by the tamoxifen study is whether the drug can help women who carry two genes discovered after the study was underway. Researchers believe the genes BRCA1 and BRCA2 account for about four per cent of breast cancer cases. Toronto’s Narod, who played a major role in identifying the genes in 1994 and 1995, hopes to have a preliminary answer before the end of this year. Since 1991, Narod’s team has collected data on nearly 700 Canadian and American women who have one of the genes. About half of those women have already had cancer in one breast, and about onethird of those have been taking tamoxifen following surgery. Women with one of the genes who have had cancer in one breast have a high risk of developing it in the other—within 15 years in about 40 per cent of cases. If tamoxifen can prevent that from happening, says Narod, it may be possible to ward off cancer in the BRCAgene carriers by using the drug preventively. But, says Narod, in women with the genes, “the cancer risk begins at age 25, and by 40 almost half will have breast cancer. So you would have to start the treatment early.”

For now, the hopeful findings of the larger tamoxifen study seem to vindicate a project that, in the past, prompted some women’s organizations to accuse researchers of irresponsibility and a callous disregard for the risks involved. For women like Thunder Bay’s Vasko, the results offered hope of preventing a relentless and cruel disease. “Now I have a choice,” says Vasko. “I want to begin taking tamoxifen now—I’ve already talked to my doctor about it.” And she is more optimistic that her two young granddaughters may be able to escape the fate that has plagued her life—and the lives of so many other women. □

TRIAL AND SUCCESS

Incidence of breast cancer in 6,681 women taking the drug tamoxifen compared with 6,707 given a placebo

CASES OF BREAST CANCER

BREAKDOWN BY AGE

35-49 50-59 60 AND OVER

on tamoxifen 38 on tamoxifen 24 on tamoxifen 23

on placebo 59 on placebo 46 on placebo 49