The cancer preventers many don't know about, or want

Few people are taking advantage of pills that have been proven to prevent a substantial number of common cancers.

If you didn't realize such pills exist, you are not unusual. Which is part of the problem.

This barely used arsenal in the war on cancer has grown to four drugs - two for the breast and two for the prostate gland. The first won federal approval in 1998; the fourth is now seeking approval.

Government researchers predicted cancer "chemoprevention" would be a public-health revolution, saving many lives.

In fact, studies show family doctors and the public still do not know much about the option, and even the well-informed usually reject it.

This is not totally surprising. The drugs aren't magic bullets. They reduce but don't eliminate the chance of cancer, and they can have dangerous side effects.

But the unpopularity of chemoprevention seems to have more to do with how individuals perceive health trade-offs than the actual statistical probabilities. The same medicine that men are leery of using to dodge prostate cancer is widely used in smaller doses to forestall a harmless condition: baldness. And some women would rather have their breasts removed than be on a drug to preserve them.

Narberth oncologist Marisa Weiss, founder of the educational website breastcancer.org, said that with chemoprevention, "the drop in breast cancer risk can easily be as high as 85 percent in high-risk women. Still, the idea of taking a medicine daily to reduce the theoretical, intangible risk of breast cancer - it's not enough to motivate most women."

Over the last two decades, government-funded researchers have spent hundreds of millions of dollars seeking a vitamin, mineral, or medicine that could prevent cancer.

Tamoxifen was the first success - or failure, depending on your viewpoint.

In 1998, the Breast Cancer Prevention Trial announced that tamoxifen - a drug long used to keep breast cancer from returning in women already treated for it - could prevent the disease in the first place. While not a sure thing, the protection was striking: Tamoxifen cut the five-year risk of cancer by half. And the benefit turned out to persist for a decade after women quit the drug.

Then, in 2003, came the results of the Prostate Cancer Prevention Study. Finasteride - a Merck & Co. drug sold as Proscar to treat enlarged prostate glands and as Propecia for balding - cut cancer risk by nearly 25 percent.

Next, raloxifene - better known as Evista, the Eli Lilly osteoporosis drug - went head-to-head with tamoxifen. The 2006 results suggested equal protection, but last month, updated data showed Evista was a bit less effective - a 38 percent reduction in breast cancer risk.

Also last month, GlaxoSmithKline announced that its prostate-shrinking drug Avodart, or dutasteride, reduced prostate cancer risk about as much as finasteride. Glaxo, the only drugmaker to fund a big prevention trial, is seeking approval for the new use.

The studies also revealed the downsides of the drugs.

Tamoxifen and raloxifene block the female hormone estrogen in some tissues, while imitating it in others. Both drugs increased the chance of rare but potentially life-threatening blood clots. Both fueled hot flashes. Tamoxifen also boosted the risk of uterine cancer, which is easy to detect and rarely fatal.

More perplexing for men was the serious side effect of finasteride and Avodart, which decrease production of a potent form of testosterone, the male hormone that stimulates the prostate. Although men on the drugs had fewer cancers, they were more likely to have aggressive, hard-to-cure malignancies.

No one can yet say whether these two drugs actually promote aggressive disease, but Patrick Walsh, the renowned Johns Hopkins University prostate cancer surgeon, concluded they were a bad gamble: "Dutasteride and finasteride do not prevent cancer, but merely temporarily shrink tumors that have a low potential for being lethal."

Some health activists, including Philadelphia's Fran Visco, leader of the National Breast Cancer Coalition, have been equally critical of tamoxifen and Evista, calling them "disease substitution," not disease prevention.

In any case, researchers' hope that chemoprevention would be embraced has not panned out.

A survey at the 2007 American Urological Association meeting suggested few members were prescribing finasteride for prevention.

A study published this year estimated that only 120,000 American women - less than one quarter of 1 percent of those over age 40 - were taking tamoxifen for prevention in 2000, and that fell to about 51,000 four years later.

Erika Waters, a social psychologist at the University of Washington School of Medicine who led that usage study, has found that the mere existence of side effects is enough to close most women's minds.

"What I don't want to say . . . is that people are irrational," Waters said. "It's more than just the risks and benefits. It's the qualitative and subjective value each woman places on those risks and benefits."

In 2007, National Cancer Institute director John E. Niederhuber canceled a study that would have compared Evista with another potential breast cancer prevention drug. Called letrozole, it blocks the formation of estrogen.

Barnett Kramer, associate director for disease prevention at the National Institutes of Health, said pragmatism had won out.

"These prevention trials are large, expensive, and take a long time," he said. "The argument was that [letrozole] would be on the same path" as the other drugs people are loath to take.

Judy Cahill, 68, doesn't understand the reluctance.

The retired Huntingdon Valley beautician, who has had six surgeries to evaluate suspicious breast cysts, participated in both breast cancer prevention trials. Although she was on the placebo in the first study, she was on Evista in the next - and enjoyed a five-year respite from false alarms. "I would say it was working," she said. "I had no cysts during the trial, but I've had two more since the trial stopped four years ago."

Side effects were minor. Still, she can't persuade friends: "They say, 'I'm a little nervous about taking a drug I don't need.' It stymies me."

It also troubles oncologists.

"The uptake of these drugs, given the benefit, is much less than we would expect," said Angela DeMichele, a University of Pennsylvania breast cancer specialist.

Age, ethnicity, race, and genetics can combine to make breast cancer more a question of "when" than "if." Even in such cases, chemoprevention is a hard sell.

In one study, 89 women who had undergone breast biopsies were encouraged to talk to their family doctors about chemoprevention. Only 48 women did so - and most were advised against it by their doctors. Just one woman went on tamoxifen; five began raloxifene, mostly because of low bone density.

Oncologist Weiss says she "regularly" sees high-risk women who opt for double mastectomies - which have permanent cosmetic and sexual side effects - rather than chemoprevention: "Women say to themselves: 'I'll make a deal. I'll get the mastectomies as long as I can avoid everything else.' "

For both men and women, "everything else" includes ongoing screening tests, biopsies, anxiety. Tamoxifen and raloxifene do nothing to prevent the one-third of breast cancers that are insensitive to estrogen, and there is no way to predict which women will have such tumors. The prostate drugs, meanwhile, suppress the level of a blood protein used to screen for the cancer, making vigilance even trickier than normal.

"What chemoprevention means is there's a possibility of near-term harms, but uncertain long-term benefits," said Stewart Justman, who examined the finasteride controversy in Do No Harm: How a Magic Bullet for Prostate Cancer Became a Medical Quandary. "And you're in a state of health . . . so the sense of urgency is not there."

Fox Chase Cancer Center oncologist Mary B. Daly believes education is needed to dispel misconceptions about chemoprevention.

"Do you remember when we put seat belts in cars and nobody used them? We could have said, 'Let's stop requiring them,' " she said. "Instead, we did a massive public education campaign . . . that seat belts save lives."

But a study published this year found that even when women were given a detailed "decision aid" quantifying their individual risks and benefits, only three out of 632 went on tamoxifen.