Breast Cancer Study Offers Hope but No Easy Answers


Although the results of recent testing of the drug tamoxifen on women at high risk of breast cancer were startling, the findings will almost certainly lead to larger questions with no easy answers: Who should take the drug? And for how long?

The incidence of breast cancer among women at high risk of developing the disease was cut nearly by half among those who took the drug during the study.

“The results are so profound that I’m speechless,” said Sandy Kanicki, co-chair of an advisory panel to the National Surgical Adjuvant Breast and Bowel Project, the Pittsburgh-based research network that conducted the trial.

“This is a big deal,” said Dr. Harold Varmus, director of the National Institutes of Health, which sponsored the study through its National Cancer Institute.


As is the case in many drug breakthroughs, tamoxifen has side effects and potential risks, chief among them a higher-than-average chance of developing uterine cancer and blood clots.

Women at significant risk for breast cancer will have to decide which threat is greater--and whether it is worth the gamble to start taking the drug when they are still healthy. Breast cancer kills 43,500 American women a year.

Does tamoxifen prevent breast cancer? “The answer is an unequivocal yes,” said Dr. Richard Klausner, director of the National Cancer Institute.

But its adverse side effects “may make the very personal decision complex,” he added.


The institute “is feverishly working” to better define “what makes a woman at risk,” said Dr. Leslie Ford, associate director for early detection and community oncology at the cancer institute’s division of cancer prevention. “We’ll be trying to develop the tools to assist women in their decision-making.

“Even if a woman is at increased risk of breast cancer, tamoxifen therapy may not be appropriate for her,” she said. “As with any medical procedure or intervention, the decision to take tamoxifen is an individual one in which the benefits and risks must be considered.”


Factors that raise a woman’s risk of breast cancer include the number of first-degree relatives (mothers, daughters, sisters) who have had breast cancer, having no biological children, giving birth to a first child when older than 30, a history of noncancerous breast lumps and a history of lobular carcinoma in situ--a noninvasive, or localized, breast cancer--which makes a woman nine times more likely to develop invasive breast cancer.


Other risks include being older than 60, which makes a woman five times more likely to develop breast cancer than women 35 to 39, and beginning menstruation before age 12.

The study was launched before the discovery of breast cancer gene alterations, known as BRCA1 and BRCA2, which increase a woman’s risk of breast cancer. Researchers have begun analyzing blood samples from study participants to identify women with these alterations and to determine whether the drug has had the same effects on them.

“There are thousands of combinations of these factors that put women at risk and it’s important to take all these factors into consideration when making a decision to take [the drug],” Ford said.

Until now, women at high risk could opt for a mastectomy while still cancer-free to try to avoid the disease, or for “watchful waiting” to try to spot it early. They could also switch to a low-fat diet to reduce their risk. Tamoxifen has provided another option, researchers said.


Although noting that “the study results are good news,” Cynthia Pearson of the National Women’s Health Network cautioned that “it’s premature to break out the champagne.”

Breast cancer is the most commonly occurring cancer in women and the second leading cause of cancer deaths in women, after lung cancer. An estimated 178,700 new cases are predicted among women in 1998, according to the American Cancer Society.

The study, which began in 1992, involved 13,388 high-risk women who were divided into two groups, one put on tamoxifen, the second on a medically worthless placebo.

While there were 154 cases of invasive breast cancer among women randomly assigned to take the placebo, only 85 women taking tamoxifen developed the disease--a reduction of 45%.


The differences were seen among all age groups, researchers said.

The results were so compelling that researchers halted the trial 14 months early and began notifying women so that those taking the placebo could choose to take the drug.

However, the drug did increase the women’s chances of developing three rare but life-threatening health problems:

In the tamoxifen group there were 33 cases of uterine cancer, compared to 14 cases among women on the placebo; 17 cases of pulmonary embolism (blood clot in the lung), versus six in the placebo group; and 30 cases of deep vein thrombosis (blood clots in major veins), compared to 19 cases in women on the placebo.


These problems appeared only in women older than 50, researchers said.

Tamoxifen has been used for 25 years to treat women already diagnosed with breast cancer and is regarded as a potent weapon against the disease. Recommended use of the drug for these women is limited to five years. Studies have shown little benefit after that time and possible harm because of the uterine cancer risk.

Klausner acknowledged that in breast cancer prevention “we don’t know how long the protection will last and how long the drug can be taken,” but said that scientists are seeking the answer. Also, he said, future studies will compare the preventive effects of tamoxifen to other, newer drugs.

As a treatment, tamoxifen slows or stops the growth of cancer cells. Researchers first saw its potential as a preventive medication when it seemed to prevent the development of new cancers in a woman’s noncancerous breast.


The drug works in breast tissue by interfering with estrogen, a female hormone that promotes the growth of breast cancer cells. In other body systems, however, tamoxifen mimics estrogen--leading researchers to speculate that it could be effective against coronary heart disease and osteoporosis.

The drug did, in fact, result in fewer bone fractures of the hip, wrist and spine among study participants taking the drug, but it did not have an impact on heart attacks.

The study was conducted at 270 sites, including 22 in California.

“We are very pleased with the initial results and further analyses will help us define the groups of women who receive the maximal benefit,” said Dr. Lawrence D. Wagman, principal investigator for the participating City of Hope Cancer Center in Duarte, Calif.



Stages of Breast Cancer

Breast cancer develops in three stages. Survival odds are greatly increased with early detection.

STAGE 1. Cancer is found only in the breast tissue. Warning signs include lump of thickening in breast, bleeding from nipple.




STAGE 2. Cancer has spread to the surrounding tissue.




STATE 3. Cancer has spread to other parts of the body.