New breast cancer drug being put to the test

Massachusetts General Hospital's Dr. Paul Goss normally treats patients sickened by breast cancer.

But soon he will begin administering a powerful new drug to women who face elevated cancer risks, but are otherwise healthy -- no cancer in sight.

The drug has some side effects, including sweating, hot flashes, fatigue, as well as a slight potential to cause high blood pressure and osteoporosis. But Goss believes the risk is worth it: Preliminary data shows the drug, part of a class called aromatase inhibitors, may reduce the chances of getting breast cancer by up to 80 percent for at-risk women, he said.

The international medical experiment he heads will put his theory to the test, with more than 2,000 healthy women around the world taking the drug for five years.

But where most preventative measures, such as vaccines and vitamins, involve little threat to the healthy, this new experiment employs a more controversial ethical calculus, trading one risk for another. Some women may well avoid death or ill health from breast cancer, but others will likely suffer discomfort and perhaps worse.

The experiment, which could soon involve dozens of Boston-area women, has generated controversy in the breast cancer world, where some activists question the wisdom of giving medicine to healthy people, particularly a medication that has only been studied for a handful of years.

''Our concern is that you would give healthy people these drugs without knowing what the side effects are, especially in the long term," said Barbara Brenner, a breast cancer survivor who is executive director of San Francisco-based Breast Cancer Action, a nonprofit advocacy group. ''We would rather see [researchers] use these kinds of resources to look into why people are getting sick in the first place, to look at what's causing breast cancer."

Attempting to prevent breast cancer has a controversial history, centered on the 40-year-old drug tamoxifen. In 1998, amid much publicity, the federal government approved tamoxifen based on data showing about a 40 percent risk reduction in high-risk women. But news of its side effects started spreading, and breast cancer advocates, a highly organized lobby, began sounding warnings.

Today, many women are wary of tamoxifen, still the only drug approved for breast cancer prevention. A study released yesterday found that only 17 percent of at-risk women over 50 were willing to take tamoxifen when told of its potential side effects, which include elevated risk of stroke, cataracts, lung blockages, and endometrial cancer.

The new trial seeks to supplant tamoxifen with aromatase inhibitors, a family of three drugs that lower estrogen levels. Estrogen stimulates the growth of many breast cancer tumors, and both tamoxifen and the new drugs disrupt this process, though through quite different mechanisms.

Goss uses a restaurant metaphor to explain: ''Think of cancer cells sitting at a table waiting for estrogen to eat. Tamoxifen blocks the door between the kitchen and the dining room," he explained. ''Aromatase inhibitors go into the kitchen and stop the preparation of estrogen in the first place."

Goss contends that concerns about aromatase inhibitors are overblown. The drug has only been studied for half as long as tamoxifen, but: ''We have literally tens of thousands of breast cancer patients going through five or more years of treatment with this drug. We feel fairly confident that we understand the side effects."

Three medical centers involved in Goss's trial have begun tests of the aromatase inhibitor exemestane. More than 30 other sites, in the United States, Canada, and Spain, are scheduled to start this spring, with a goal of testing the drug against a placebo in about 4,500 women over a five-year period. The trial includes a Boston wing, and researchers here are expected to enroll more than 100 women beginning in the next few weeks.

In Memphis, Brenda Vernon, a catering company owner, has joined the trial. Though her age alone, 64, places her at risk, Vernon's motives for volunteering go beyond her own health.

''My grandmother had breast cancer. I had lost two very dear friends to breast cancer. I have another one who's dying. And I have about 10 friends who are survivors. And I have two daughters and two granddaughters," she said. ''I am hoping that this trial helps people . . . this is my way of trying to give a little bit."

Vernon signed a consent form that outlined potential risks.

''At my age, I'm willing to take a chance. Had I been 35 or 40, I might not be as willing," she said.

The Dana-Farber Cancer Institute's Dr. Judy Garber, who is running the local wing of the trial, acknowledged that aromatase inhibitors' side effects have not been studied over the long term. But she said that the drugs' basic molecular mechanisms are well known, and researchers have a good idea of what to expect. Moreover, she said the potential benefits far outweigh the costs.

''We're talking about women shown to be at a higher risk of breast cancer," said Garber. ''It could be millions of women."

All the women in the trial will be postmenopausal, and most will have additional risk factors like a family history of breast cancer, a previous breast biopsy, a late-age first pregnancy, or just old age.

Breast cancer kills more than 40,000 women annually in the United States, according to government data. About 13 percent of women in this country will get breast cancer at some point in life, and the likelihood rises with each risk factor. Some women at very high risk elect to surgically remove their breasts. Others have opted for tamoxifen. But the notion of effectively and simply preventing breast cancer remains elusive.

Recent studies of aromatase inhibitors in breast cancer patients found that the drug reduced the chance of cancer spreading to the other breast by 60 percent to 80 percent, said Goss, convincing him and many researchers that a trial to test the drugs' preventative powers in at-risk women was necessary.

Goss said his experiment would not only test whether aromatase inhibitors reduce breast cancer risk, but also seek to determine which women, based on their genes, responded best to the drug. That way, the drugs could eventually be targeted to specific women.

''We're talking about a potential 60 to 80 percent reduction in risk," said Goss. ''That is very, very substantial."

Raja Mishra can be reached at rmishra@globe.com.

Breast cancer rates

Breast cancer is the third most common form of cancer, following skin and prostate cancer, but it's not as lethal as some, and most people live years with the disease. Nearly 90 percent of those diagnosed with breast cancer in 1995 were still alive in 2000, compared to only 15 percent of those diagnosed with lung cancer the same year.

In 2003:

New breast cancer cases diagnosed: 212,600

Deaths from breast cancer: 40,300

Average years of life lost from breast cancer: 19

New lung cancer cases diagnosed: 171,900

Deaths from lung cancer: 157,200

Average years of life lost: 15

SOURCE: National Cancer Institute