At USC’s Lee Breast Center, physicians are beginning to emphasize prevention along with early detection and less invasive treatment, in order to attack a disease that kills some 40,000 women a year.

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Bonnie Krull was certain she would get breast cancer. After all, her mother, sister, aunt and great aunt all had the disease. “When my sister got cancer it really hit home,” she says. “I thought: I’m next. It seemed like it was just a matter of time.”
But, six years later, the 55-year-old administrator and grandmother has not developed breast cancer. For this, she credits the drug tamoxifen, which she took as a participant in a national study supported by the National Cancer Institute. She learned about the study when her sister, Sandra Mascorro, 62, was being treated at the USC/Norris Comprehensive Cancer Center and Hospital, and joined it with a single hope ? that she would be the first female in her family to live her entire life without getting the disease.

Thus, Bonnie Krull became one of more than 13,000 women at high risk for breast cancer who were given either tamoxifen or a placebo for three and a half years. By this time, such dramatic protective results were shown by the women taking tamoxifen ? they cut their chances of developing the disease by about half ? that the study was halted early in order to give all women at high risk the opportunity to benefit.
Krull heard the news about the study results on her morning drive to work. “I remember raising my arm and saying ‘Yes!’ ” she says.
“Do I think that tamoxifen has saved me for my entire life? I don’t know,” she says. “Do I think that it saved me for quite a while? Absolutely.”
Today the two sisters ? one who has beaten cancer with the help of advances in treatment and the other who has beaten the specter of cancer ? are both happy, healthy and committed to stopping breast cancer.

The once-elusive goal of preventing breast cancer now seems increasingly attainable. Researchers are pursuing a number of strategies to stop breast cancer before it starts, their work spurred on by the fact that breast cancer rates continue to rise. According to the American Cancer Society, one in eight women are ex-pected to get breast cancer in their lifetime, up from one in 20 in 1940. Excluding cancers of the skin, breast cancer is the most common cancer among women, accounting for one out of every three cancer diagnoses in the United States. In 1998, scientists expected approximately 178,700 new cases of invasive breast cancer to be diagnosed, and 43,500 women to die from this disease. Only lung cancer causes more cancer deaths in women.
“Obviously we are intent on developing a cure for the disease and ways to detect it earlier,” says oncologist Christy A. Russell, who is co-director of the newly named Harold E. and Henrietta C. Lee Breast Center at the USC/Norris.
“But given the enormous toll breast cancer takes on women and their families, in recent years there has been significant effort exerted to find ways to better prevent it. It’s a difficult task, since the exact causes are elusive and seem to differ from woman to woman.”
At the Lee Breast Center, Russell works with a team of oncologists, breast surgeons, reconstructive surgeons, path-ologists, nurse specialists, radiologists and social workers to provide the best in multidisciplinary care for women with breast cancer. The USC/Norris, as one of 35 cancer centers nationwide designated “comprehensive” by the National Cancer Institute, is also home to a wide variety of research into new strategies for prevention, detection and treatment of the disease.


An Ounce of Prevention: the Role of Estrogen
Thanks to enormous leaps in research on the causes of breast cancer, physicians have a better handle on some of the factors that may contribute to the disease. Thus, for the first time ever, they are beginning to be able to offer practical advice to women like Bonnie Krull, who may know that they face a high risk but have had no guidance on how to keep the disease at bay.
But it’s not just women with a family history of breast cancer who will benefit, says Russell. While family history may play a significant causative role in some women who develop breast cancer, “these women are in the minority,” she says. “No woman is truly exempt.”
Determining why any one woman develops breast cancer is difficult, adds researcher Leslie Bernstein, a professor of preventive medicine. “Because we are talking about a disease where the web of causation is complex and encompasses many factors, most researchers prefer to speak in terms of risk reduction instead of prevention,” she says.
“All of our research is based on population statistics describing the usual characteristics we see among women with higher risk of breast cancer ? but there are always exceptions.”
A nationally known cancer researcher, Bernstein has focused on whether exercise can reduce the overall lifetime exposure to female hormones like estrogen. Estrogen has been shown to promote the growth of normal breast cells, and longer lifetime exposure (through late menopause, for example) has been linked to an increased risk of breast cancer. In an earlier study, Bernstein found that four hours or more per week of exercise in young women significantly reduced their risk of developing breast cancer.
In a new study of post-menopausal women (ages 55-64), Bernstein and her colleagues showed that women who maintain a high level of activity over their lives ? averaging about three hours per week of vigorous activity both before and after age 40 ? have about half the risk of breast cancer as women who are inactive throughout their lives. Also, women who exercised the equivalent of four hours per week over the past 10 years were also at approximately 30 percent lower risk of breast cancer. These protective effects were most pronounced among women who did not gain substantial weight during adulthood.
In addition to exercise, researchers are looking at other means of reducing overall exposure to estrogen to reduce risk. The breast cancer prevention study that Krull participated in, for example, tested tamoxifen, a drug which has long been used to treat breast cancer patients and blocks the action of estrogen on breast cells.
That study is now being followed by others to determine how long the “protection” lasts and whether similar drugs like the osteoporosis-prevention drug raloxifene will produce similar or even better results. One study suggested that post-menopausal women who take raloxifene reduce their risk of breast cancer 70 percent ? and without the increased risk of endometrial cancer that tamoxifen carries. Right now, physicians are recruiting women to participate in a national trial comparing raloxifene and tamoxifen.
While current versions of birth control pills reduce both ovarian and endometrial cancer, they do not decrease breast cancer risk. Physicians and scientists at the USC/ Norris have collaborated to create a “designer” hormonal contraceptive that may also protect against breast cancer, and they recently were awarded a grant from the National Cancer Institute to lead a multi-center trial of the method in young women at high risk.
Others at the USC/Norris are trying to uncover the genetic variations that translate into a greater lifetime exposure to estrogen and so predispose women to breast cancer. The hope is that early identification of those who face the highest risk and, possibly, therapy, might help prevent the disease. In collaboration with researchers at the Hawaii Cancer Center, USC/Norris scientists have put together one of the largest studies of its kind, the Multi-Ethnic Cohort Study. The study’s goal: to map differences across ethnicities in the ordinary genes that control hormones in all people, such as the series of genes that determine when a female begins to ovulate.
Diet, too, may play an important role in warding off breast cancer, although scientists are still trying to understand exactly what compounds in food may be protective. Phytoestrogens ? the plant chemicals found in whole grains, berries, fruits, vegetables and soy ? are under intense scrutiny for a possible role in reducing breast cancer risk. Both broccoli and garlic contain chemicals that may help the body break down carcinogens into harmless chemicals. Antioxidants, found in many foods including green tea, tomatoes, vitamin E, vitamin C and beta caro-tene, stop damage to genes that can lead to cancer.

Although researchers like Bernstein feel they are “nearly there” in terms of having concrete prevention strategies, they acknowledge that more work still needs to be done. “We need more clinical trials of prevention or risk-reduction strategies to test out different approaches,” she says. “We need to understand how risk varies by other attributes of women, including genetic attributes.”
In the meantime, women today can take many steps to reduce their risk of breast cancer, notes Russell. “As yet there is no one, sure-fire approach to preventing breast cancer,” she says. “But cumulatively, by reducing those factors that have been shown to in-crease the likelihood of getting the disease, women can take significant steps to make sure they and their families won’t be affected by this disease.”
The important thing, Russell says, is educating women and doctors that people can take action, whether it be exercise, using a drug like tamoxifen or a commitment to regular screening, to reduce their risk. “Prevention is still a new philosophy in cancer. I think that most people who haven’t had cancer assume they will never get it, which is not all bad. It only becomes a problem when that translates into people avoiding mammograms and other cancer screens.”

 

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Leslie Bernstein, Ph.D.
Researcher

“Because we are talking abut a disease where the web of causation is complex, most researchers prefer to speak in terms of risk reduction instead of prevention.”

Bonnie Krull (left) and Sandra Mascorro,
USC/Norris patients

“When my sister got cancer it really hit home, I thought: I’m next. It seemed like it was just a matter of time.”

Christy A. Russell, M.D.
Oncologist

“Cancer is frightening. There’s a fear of dying, a fear of losing a breast. Our culture places a lot of emphasis on breasts as a defining feature in sexuality.”

Russell Photo by Philip Channing

Bernstein Photo by Michael Chabaudo

Krull & Mascorro Photo by Philip Channing


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