Breast Cancer Advances Create New Dilemmas: The Vast Majority Of Women Don't Get Breast Cancer. So Which Women Should Take A New Drug That Can Prevent Breast Cancer In Some Women?< Providence, R.i. -- Every Woman Fears Breast Cancer. Even If You Can't Remember The Exact Numbers -- 175,000 New Cases And 43,000 Deaths Expected This Year -- You're Familiar With Their Dark Meaning...

By Felice J. Freyer The Providence Journal

But the fact is, while breast cancer strikes a significant number, the vast majority of women do escape it. Can you predict your chances of being one of the unlucky ones? And can you prevent breast cancer from happening in the first place?

Medical science is getting close to answering those questions. A computerized assessment tool can give individuals a rough estimate of their personal risk of getting breast cancer. And a drug -- tamoxifen -- can prevent breast cancer in about half the women who would otherwise get it.

But this is a bedeviling kind of good news, because the assessment tool is imperfect, the drug has some risks, and the questions continue to outnumber the answers.

''We're actually in a big transition period,'' says Dr. Robert Legare, director of the Cancer Risk Assessment and Prevention Program at Women & Infants Hospital, ''from thinking about cancer as only a disease we can treat to times when we're thinking intelligently about prevention. We're at the very infancy of cancer prevention.''

The possibilities and dilemmas came into the spotlight recently when the National Cancer Institute launched a nationwide study that will compare tamoxifen with raloxifene, a similar drug that may be safer.

Meanwhile, tamoxifen is already on the market, approved as a breast-cancer preventive in high-risk women. The availability of this promising medication leaves women in a quandary: how do you determine your risk and how do you know whether tamoxifen is a good choice for you?

Although no one knows exactly what causes breast cancer, over the years doctors have pieced together the factors that make one woman more likely to get it than another. (But many women with none of these risk factors have been stricken.)

The most important risk factor is age: most breast cancers occur after age 50.

Heredity also plays a key role. A small minority of women carry one of two genes -- called BRCA1 and BRCA2 -- that put them at extremely high risk of developing breast cancer. Genetic tests can determine whether someone carries the gene if she has many relatives with breast cancer.

But that's a rare situation. More commonly, if you have a mother, sister, or daughter who had breast cancer, you may have inherited a predisposition to develop it. You don't know for sure, though, whether you carry the same genes as your afflicted relative.

Another factor is how many years one's breast cells have been continuously exposed to the female hormone estrogen, which can promote tumor growth. Someone who started menstruating before age 12 has a slightly higher risk, because she started producing estrogen a few years earlier than average. For the same reason, women who had their first live birth after age 30 and women who have never had children have a higher risk, because pregnancy interrupts the flow of estrogen.

A history of certain breast abnormalities can also indicate a higher likelihood of developing cancer. If you have had breast biopsies, particularly if the biopsy revealed a change in breast tissue known as atypical hyperplasia, you are at greater risk of later developing breast cancer. Also, if you have been diagnosed with either of two precancerous conditions -- ductal carcinoma in situ or lobular carcinoma in situ -- you are more likely to later develop invasive breast cancer.

And finally, race also counts: white women are more likely to get breast cancer than black women.

Some of these factors are more important than others. The National Cancer Institute has devised a computerized assessment tool in which a patient enters her personal information, and the computer weights the data appropriately, coming up with an estimate of your risk.

Your gynecologist may have this tool available for you to use in the office. You can also request it directly from the NCI by calling 1-800-4-CANCER or by going to the institute's Web site

http://www.nci.nih.gov/ and ordering it on-line. The NCI will send you a disk so that you can run the program yourself.

The end result will be two percentages -- estimates of your risk over the next five years and over your lifetime. Someone with a 1.66 percent risk of breast cancer over the next five years is considered at high enough risk to qualify for the study comparing raloxifene and tamoxifen. But does that mean everyone with that risk level should take tamoxifen? What if your number is 1 percent? 1.2 percent? When do you panic?

''One should never panic,'' Legare says. ''All these numbers are so imperfect.

''Anything that empowers a woman to understand her situation better and gives her information is a good thing,'' Legare says. ''But this is an imperfect tool.'' It could underestimate the risk for some women, giving them a false sense of security, while overestimating for others, causing needless worry.

In other words, the assessment tool is not a crystal ball and the percentage you get is only one piece of information to consider in what must be a very individual decision.

''Generally, you should talk it over with your primary-care physician,'' said Dr. Theresa Graves, assistant professor of surgery at Brown University.

''If you feel, based on some of these factors -- particularly if you have many relatives with breast cancer -- you should consider the possibility of chemoprevention, speak with your physician. Look at the risk-benefit ratio, the upside and the downside.''

Tamoxifen, manufactured by Zeneca Pharmaceuticals under the trade name Nolvadex, is one of a class of drugs known as selective estrogen receptor modulators or SERMs. They're also called ''designer estrogens'' because they're tailored to do exactly what you want: they mimic estrogen when estrogen does good, such as promoting bone strength and preventing heart disease, and they block estrogen when estrogen does harm, such as promoting breast cancer.

In a major study of 13,000 high-risk women completed a year ago, tamoxifen was shown to dramatically lower the odds of getting breast cancer. Half as many women taking tamoxifen were afflicted as women who took the placebo. The study also noted that the women taking tamoxifen were less likely to get hip and wrist fractures, suggesting that the drug works against osteoporosis. Tamoxifen also appears to lower cholesterol, suggesting that it can be a hedge against heart disease.

But tamoxifen also had negative side effects. Women on tamoxifen were far more likely to develop cancer of the uterine lining than women on a placebo. In both groups the number of women affected was minuscule, but the risk was still twice as great for women taking tamoxifen. Women on tamoxifen were also more likely to develop blood clots in major veins or in the lungs, a condition that can be fatal. But again, very few women suffered this side effect -- many fewer than were spared breast cancer.

Unlike raloxifene, another SERM that is being studied as a possible breast cancer preventive, tamoxifen is a well-known, well-studied drug. Women have been taking it for 30 years, either to treat breast cancer or to prevent a recurrence of breast cancer. Last October, the U.S. Food and Drug Administration approved tamoxifen for use in healthy women at high risk of breast cancer.

In so doing, the FDA ruled that tamoxifen is sufficiently safe and beneficial to give to healthy women -- most of whom are not destined to get breast cancer anyway.

In the study, 89 of 6,600 women taking tamoxifen did get invasive breast cancer (as did 175 of the 6,600 taking placebo). Taking tamoxifen does not guarantee that you won't get cancer -- it merely lowers your risk, and in doing so exposes you to some other health risks. So decision-making becomes a game of odds.

For example, if you no longer have a uterus, you don't need to worry about uterine cancer as a hazard of tamoxifen, making it a more attractive option for you. But if you have had a blood clot in the past, it may not be worth the risk.

Graves says that the other positive effects of tamoxifen -- its possible cardiac and bone-building benefits -- should also enter the equation in women at risk for heart disease or osteoporosis.

For women who have had lobular carcinoma in situ or hyperplasia, Graves says she tends to be more aggressive in recommending tamoxifen. With such conditions, she says, ''they have evidence in their own body. They are creating cells that are atypical: their own body has the potential to create cancer.''

On the other hand, Graves remembers one patient of hers who'd had lobular carcinoma in situ and decided that tamoxifen made sense for her. But because it works like a hormone, tamoxifen made this woman feel like she had permanent premenstrual syndrome, and she decided it wasn't worth the stress.

''You have to look at each person as an individual,'' Graves said.

''It comes down to an individual choice based on a woman translating the information that exists to her own personal circumstances and desires,'' Legare says.

If you do decide to take tamoxifen, you also need to decide when. It's considered safest to limit tamoxifen use to five years. But which five years?

''The ultimate answer is: we don't know,'' Legare says. In the tamoxifen study, the dangerous side effects were more common in women over 50, so either around or right before menopause might be the best time.

For many women, a reasonable response is simply to wait for research to bring the risks and benefits into clearer focus -- or until newer, better drugs become available. Several promising new SERMs are in the pipeline.

Meanwhile, Legare advises, don't forget the simple measures that have already been shown to make a difference: monthly breast self-exams, annual breast exams by a health professional, and annual mammograms starting at age 40. Obviously these steps don't prevent breast cancer, but enable you to detect tumors when still small and curable.

Lifestyle changes may also prevent breast cancer, although the evidence is cloudy. In particular, women should limit their alcohol consumption, Legare advises; studies have found that having two or more drinks a day can increase your risk of breast cancer. There is also some evidence, although it's not as strong, that a healthy diet and regular exercise can lower the risk of breast cancer. Even if it doesn't, such changes have so many other benefits that they're well worth it, he says.

''I hope we get smarter,'' Legare says, ''and that 10 years from now there will be whole lot more information.''

If you are interested in participating in the Study of Tamoxifen and Raloxifene, call 1-877-788-6667 to reach a consortium of four hospitals working with Brown University, or 456-2230 to reach Roger Williams Medical Center, which is affiliated with Boston University.