USAN DENTZER: Like many sisters, Barbara Guttman and Lisa Greaves have a lot in common. But much to their shock and grief, they discovered several years ago that they also shared a deadly trait, an inherited predisposition to breast cancer.
BARBARA GUTTMAN: My grandmother died of breast cancer a long time ago, in 1941, and her sister had had cancer. And in the meantime two of my aunts got ovarian cancer. These are my father's - they're actually his half-sisters. And then Lisa got breast cancer, and that just changed everything.
SUSAN DENTZER: Lisa is now 35 years old. She was diagnosed unexpectedly with breast cancer in 1994.
LISA GREAVES: I had just turned 31, and that was treated locally with lumpectomy, and really in the time that I was evaluating whether that was all the treatment I would need, I was diagnosed with a much more major malignant tumor in the other breast, and following that diagnosis, I had bilateral mastectomies in January of 1995.
SUSAN DENTZER: Lisa's illness prompted Barbara to take a drastic move that more women may have to contemplate. First she and Lisa got blood tests that showed that they both had a genetic mutation linked to breast cancer. Then, in 1997, when Barbara was 35, she had both of her healthy breasts removed to stave off the disease.
BARBARA GUTTMAN: I feel lucky that I found out the easy way as opposed to the hard way. I've both reduced my risk a lot and I didn't have to suffer that much to do it.
SUSAN DENTZER: For years many women like Barbara have had preventative mastectomies without knowing how much they would reduce their cancer risk. But now there's hard evidence that the procedure is in fact a potent weapon against breast cancer. Dr. Lynn Hartmann of the famed Mayo Clinic is lead author of a study published recently in The New England Journal of Medicine.
DR. LYNN HARTMANN: This study really provides the first solid evidence that the procedure does reduce the risk of breast cancer by about 90 percent.
SUSAN DENTZER: That is stunning news for the estimated 1 in 9 American women who stand to develop breast cancer over their lifetimes -- and especially for the 5 to 10 percent of those women who have an inherited risk for the disease. Dr. Claudine Isaacs is a leading breast cancer specialist at Georgetown University.
DR. CLAUDINE ISAACS: If somebody comes from a family where they've witnessed their mothers, sisters, aunts, cousins, die of breast cancer, they don't view their breasts in the same way as the general population does. What they view them as is sort of a ticking time bomb, as the eventual cause of their demise.
SUSAN DENTZER: And that propels many to follow the same route as Barbara Guttman -- undergoing a difficult and disfiguring operation in pursuit of peace of mind.
BARBARA GUTTMAN: I was not keen to face cancer. A lot of the evidence was completely anecdotal. You know, some doctor who has been involved in the field for 50 years says well, people who have had prophylactic mastectomies, I don't know of any occurrences, they were very, very anecdotal but eventually I decided that that would significantly reduce my risk.
DR. CLAUDINE ISAACS: It is a very difficult decision. I mean, obviously, we now have good reconstructive surgery and the cosmetic result is very good following reconstructive surgery. But that is a reconstruction. That is not normal breast tissue. So these women will never -- it will clearly change their body, and for some will change their body image as well.
SUSAN DENTZER: Because even a preventative mastectomy doesn't necessarily remove all potentially cancerous breast cells. As a result, the effectiveness of the procedure at deterring breast cancer had long been questioned. So the Mayo study examined the case histories of 639 women who underwent the procedure at the clinic from 1960 to 1993. Based on their family history of breast or ovarian cancer, the women were classified as having been at either moderate or high risk of developing breast cancer themselves.
DR. LYNN HARTMANN: Two procedures were performed - mainly a subcutaneous mastectomy, which removes 90 to 95% of the breast tissue but preserves the nipple and the aureolar complex. That was done because we really didn't have other ways to do nipple reconstruction. Today with advanced reconstructive techniques, the procedure of choice for these high risk women is a total mastectomy.
SUSAN DENTZER: Retracing what had happened to these women years later, the researchers unearthed some startling results. Of 214 high risk women who had preventive mastectomies, only three later developed breast cancer -- a rate of just 1.4 percent. To get a sense of how much the surgery itself was responsible, the researchers compared these results with the experience of the women's sisters. In stark contrast, almost 39 percent of these untreated sisters had gone on to develop breast cancer.
DR. CLAUDINE ISAACS: This is really the best type of information that we can have this. This is as good as it gets, but I think the important thing is to realize you have to look very carefully at the characteristics of the women who had the surgery to know how to apply it to the general population.
SUSAN DENTZER: In fact, advances in genetic research and testing might now make these findings even more useful for certain high-risk women. They can be tested to determine whether they carry one of two known mutations in the genes BRCA-1 and BRCA-2. Doctors believe that these mutations account for almost half of inherited cases of breast cancer -- while as-yet undiscovered mutations may explain many of the rest.
SUSAN DENTZER: How did you feel, Lisa, when Barbara found that she did have the mutation in the gene?
LISA GREAVES: I was horrified. I hoped that she would be in the pool of all other women who have a significant risk of cancer but that don't have this elevated risk, and in particular because this information was so new, and there were no -- there really were not many guidelines about the implications. So it was horrifying, and scary.
SUSAN DENTZER: Barbara, a computer security analyst by training, plunged into a round of consultations with physicians and conducted her own research on the Internet. That led her to conclude that preventative mastectomy was the best option.
BARBARA GUTTMAN: So, eventually I found a wonderful oncologist and scheduled the surgery, and the surgery went really well.
LISA GREAVES: And I'm glad that she was at a time in her life when she could make those decisions without certain other, you know, emotional repercussions or difficulties, which I think is a very important factor in decision making, as where are you in your life, and, you know, particularly in terms of dating, and having children, and --
SUSAN DENTZER: But as confident as Barbara is that she made the right choice, preventative mastectomy may not be for every high-risk woman. Thanks to recent advances in breast cancer detection and care, other options are now proving to be remarkably effective. One is close surveillance with highly sophisticated mammography to detect cancer at its earliest and most treatable stages. Another is the new drug Tamoxifen.
DR. CLAUDINE ISAACS: In women who are at increased risk of developing breast cancer, we have a drug, Tamoxifen, which can reduce the risk of developing breast cancer by about 45 percent.
SUSAN DENTZER: Tamoxifen works by counteracting the effects of the female hormone estrogen in promoting the growth of breast cancer cells. A newer, related drug, Raloxifene, works much the same way but is thought to be free of Tamoxifen's side effects, such as blood clots and uterine cancer. Tamoxifen has been shown to be effective in reducing the incidence of breast cancer in high risk women, and thus represents another treatment option for such women. Raloxifene's efficacy in reducing the incidence of breast cancer is so far unproven, but is about to be studied in a large clinical trial.* Dr. Isaacs says that a woman's choice of any of these options -- surveillance, drug treatment, or mastectomy - should depend on her individual circumstances.
DR. CLAUDINE ISAACS: So I think what I've learned is how incredibly personal this decision is; that given the same facts, that I don't think any one woman or any two women will react in the same way.
SUSAN DENTZER: The differing responses of Lisa and Barbara to their mastectomies underscores a point. For Lisa, who also underwent aggressive chemotherapy and a bone marrow transplant, losing both breasts was --
LISA GREAVES: It's like a rape. I mean it really is. I lost my breasts. I never thought of myself as, you know, somebody who was particularly attached to my own breasts or who regarded my breasts as a particular symbol of my own womanhood, femininity, any of that. You know, having had cancer in both breasts, I just wanted to get rid of that cancer. But I find now that -- and I had a wonderful reconstructive surgeon -- I have the appearance of normalcy but I don't find at all that I look at my breasts now -- the reconstruction as instead of wearing some other type of prosthetic. they to me are other -
BARBARA GUTTMAN: And my experience was completely different. I feel my reconstructed breasts are me, and I suspect that a lot of that is I had so much control over the decision. It happened on my terms, at my time.
SUSAN DENTZER: Even more groundbreaking advances in the detection and treatment of breast cancer almost certainly lie ahead, so the sisters emphasize that if you should find yourself faced with a difficult decision -
BARBARA GUTTMAN: Prepare yourself that the data that comes in tomorrow may counteract the decision you made that you acted on. So, you can't make yourself crazy, as Lisa says, by letting future data make you think you were stupid to have made that choice. It was still a good choice at the time, even if it doesn't work out the best in the long run.
SUSAN DENTZER: And in the long run, women like Barbara and Lisa will benefit from our growing knowledge about breast cancer -- in part that will come from additional work on the Mayo study, ongoing research into breast cancer's genetic roots, and a massive clinical trial comparing Raloxifene to Tamoxifen scheduled to begin soon.