Tamoxifen for Breast Cancer Risk Reduction?

A drug can halve your risk of developing breast cancer. Or, in a small number of cases, it can have potentially fatal side effects. Is the risk worth it?
The Good, the Bad

Before Helene Wilson reached her 45th birthday she was warned in no uncertain terms about her chances of getting breast cancer. "You're a walking time bomb," her doctor told her.

Grim words, but hardly surprising. Helene's mother had died of breast cancer. So had her grandmother and two aunts. She discovered her first lump at age 29 and, though benign, it led to a parade of breast biopsies through the ensuing years. "I definitely had some red flags," she says.

Helene, from Blue Bell, Pennsylvania, is far from the only one with the same red flags: Ten million other American women are at high risk for breast cancer. And for many, it's like having a sword hanging over their heads. "It was nerve-racking going in for a biopsy every six months and always expecting them to find something," Helene recalls. "I got to the point I was willing to undergo a bilateral mastectomy just to have it over with."

Fortunately, she didn't have to go through such radical surgery. Instead, in the 1990s, Helene discovered tamoxifen. Also known by its brand name Nolvadex, tamoxifen was already a popular treatment for those with breast cancer because of its ability to keep the cancer from spreading. Then researchers decided to see whether tamoxifen could prevent the disease in the first place. Helene signed on as a study subject and took a pill every day for five years. "About a year into the tamoxifen trial, I stopped having any problems whatsoever," she says.

The Breast Cancer Prevention Trial, as it was called, was a watershed event. The study of 13,000 women concluded that tamoxifen reduces the chances of getting breast cancer by 49 percent among those at high risk for the disease.

In 1998, after the study results were released by the National Cancer Institute, the U.S. Food and Drug Administration (FDA) approved tamoxifen as a breast cancer preventive for women older than 35 who meet the high-risk requirement. That makes tamoxifen the only cancer-prevention drug in existence with FDA approval.

Think about that for a minute. There's a pill on the market that can drastically cut the number of cases of a cancer that's diagnosed more than 180,000 times a year in the U.S. and that caused 40,000 deaths in 2003.

However, after six years on the market, tamoxifen hasn't exactly set the world on fire in its preventive role. Existing data doesn't distinguish between prescriptions for tamoxifen for prevention or treatment, so no one is sure just how many women are using tamoxifen to fend off breast cancer. "But it's a very small percentage," says Andrew N. Freedman, PhD, an epidemiologist for the National Cancer Institute (NCI).

Lack of awareness may be one reason for the small number of women taking the drug as a preventive. "There's a need to educate women and physicians about the possibilities of tamoxifen," says Dr. Worta McCaskill-Stevens, an oncologist who conducts research on tamoxifen. "The existence of tamoxifen as a preventive is at least an opportunity for women to start the conversation with their doctor about breast cancer risk."

But the most important reason for tamoxifen's limited appeal as a preventive is that it has a dab of danger lurking within. Yes, tamoxifen reduces the risk of breast cancer. But in some cases it increases the risk of potential killers, including two kinds of cancer of the uterus, pulmonary embolism (an often-fatal blood clot in the lungs), and stroke. Because of these side effects, women can only stay on the drug for five years. After that, the drug stops working as well as a preventive yet the risks increase.

"Knowing about those risks, slight as they were, was a little scary," says Patricia Muir, a Pittsburgh schoolteacher who began taking tamoxifen at age 45. "But I decided to forge ahead because I really wanted to get that breast cancer risk under control."

Continued on page 2:  How Tamoxifen Works