Chemoprevention of breast cancer applies to only a few

Asking a woman about her age and her breast cancer risk can pinpoint who fits into the small percentage for whom taking the drug tamoxifen for the primary prevention of breast cancer is a realistic option.

The drug is also only cost effective for those in their 40s who are at high risk of the disease, according to two studies published last month. The authors hope their findings will enable physicians to target the extensive discussion required before initiating chemoprevention of breast cancer to those who need it the most.

"I hope this saves doctors some time," said Russell Harris, MD, MPH, associate professor of medicine at the University of North Carolina at Chapel Hill School of Medicine. "It may help focus discussions where they need to go. Tamoxifen can prevent breast cancer, but it can do some bad things, too."

Dr. Harris's study, published in the Sept. 27 Archives of Internal Medicine, found that asking about breast cancer family history and previous breast biopsies was enough to exclude the majority of women from long, complicated talks about the risks and benefits of this type of breast cancer chemoprevention.

The other study, appearing in the September issue of Obstetrics & Gynecology, found that the drug was cost effective for women ages 40 to 50 who were at significant risk for breast cancer. It also could be cost effective for older women depending on their fear of breast cancer, level of risk and whether they had a uterus.

"We're saying almost the same thing," said Sam Cykert, MD, lead author on that paper and chief of the internal medicine program at Moses H. Cone Memorial Hospital in Greensboro, N.C. "For certain women, doctors ought to mention tamoxifen and have the talk."

But at least for now, the authors said, very few primary care physicians are sold on tamoxifen's benefits for primary prevention, and several doctors said these papers still did not sell them on the merits of offering this drug to their patients. The number of patients who would benefit is small, and the subset of those who would be willing to take it for years, particularly with the various side effects, is even smaller.

"I haven't been pushing it," said Julie Fagan, MD, associate professor of medicine at the University of Wisconsin women's health center in Madison. "Women who have breast cancer will put up with the side effects, but I haven't had a lot of people clamoring to take it primarily for breast cancer prevention. The benefits are pretty slim at this point unless they're extremely motivated."

Pinpointing the promise

Some who support the increased use of tamoxifen for primary prevention, however, said these papers were crucial work toward getting pharmacological primary prevention of cancer out of the specialist setting and into primary care -- where most believe it belongs. Specialists have long been familiar with tamoxifen and use it widely for secondary prevention, but they say it will not reach enough people to achieve its full promise until it becomes a part of general practice.

"A lot of this information has been out in the medical oncology literature," said Claudine Isaacs, MD, associate professor of medicine and oncology at Georgetown University in Washington, D.C. "But obviously, the group that it applies to and the people who need to think about talking to patients about this are the primary care physicians."

Experts argue that, although the number of women for whom tamoxifen is worth its risks is small, these women do benefit significantly.

They also say, as a result, that this concept makes it worthwhile for physicians to screen their patients to detect appropriate candidates for this drug therapy.

"There are relatively few women who would benefit from the drug, but for women who would benefit, it's a big benefit." said Jennifer Haas, MD, MPH, associate professor of internal medicine at Brigham and Women's Hospital in Boston. "To not screen women is a disservice."

Experts also acknowledged, though, that an urgent need continues for better methods to determine who will most benefit from this intervention.

"I get asked all the time: How many women do you need to treat in order to prevent one breast cancer?" said Lawrence Wickerham, MD, associate chair of the National Surgical Adjuvant Breast and Bowel Project which has run many of the tamoxifen trials. "The answer is two -- because it reduces the risk by 50%. The challenge is to find the right two."

Nonetheless, tamoxifen's supporters also recognize that while the drug has tentatively started the era of primary prevention of cancer, this era probably will not blossom until newer agents with fewer side effects come on the market. For example, the study in the Archives found that the drug would probably prevent only 6% to 8% of breast cancers if everyone eligible agreed to take it, a significant but not very large reduction.

"[Tamoxifen] is not the answer to breast cancer," Dr. Harris said. "It does mean that it's a promising approach. If we were able to come up with a pill like tamoxifen that didn't have the side effects and we could give it to a larger number of women, maybe we'd be on to something."

Most expect a big step in this direction with the release of the results of the Study of Tamoxifen and Raloxifene -- the STAR trial -- expected at the end of next year.

"If the STAR study shows definite benefit, that may change everything," Dr. Fagan said. "I think everyone's waiting for that before they go whole hog into chemoprevention."