Best for the Breast
Researchers are seeking and uncovering more reliable information that enables women to take an active part in reducing their breast cancer risk.
What could be better than survival to a woman who has endured the pain of a breast cancer diagnosis and treatment?
Maybe preventing the disease in the first place.
USC/Norris Comprehensive Cancer Center researchers are tracing their way back in the disease process, looking to uncover what can increase a woman’schances for developing breast cancer—and what women can do to whittle down their risk.
By studying lifestyle choices and cancer incidence in the population, scientists can gather information on aspects of diet, activity, family life, medications and other factors that affect risk.
Scientists make one thing clear: No woman today can make lifestyle choices that guarantee her protection against breast cancer. And when a woman develops breast cancer, no one can unequivocally blame it on the
fact that she weighs a few pounds too many or that she enjoys a martini on occasion. In most cases, scientists cannot know precisely why a specific woman develops or avoids breast cancer.
But women can make choices and decisions that decrease their risk over a lifetime. USC/Norris researchers are studying the complexities of some of those factors.
Exercising prevention
Leslie Bernstein, Ph.D., AFLAC Chair in Cancer Research and professor of preventive medicine at the Keck School of Medicine, is one of those Norris investigators studying breast cancer risk factors.
“We have wonderful potential opportunities in chemoprevention, vaccines and surgical interventions to reduce breast cancer risk, but they are expensive and require access to health care,” Bernstein says. “What is equally important, and mostly free, are the opportunities that lifestyle can offer in breast cancer prevention.”
Among other topics, Bernstein has been studying the importance of exercise as a way to reduce breast cancer risk.
A growing body of research suggests that exercising just a few hours a week can cut into the chances of developing the malignancy.
It all began with epidemiologists’ growing awareness over the past three decades that breast cancer risk is linked to ovarian hormones such as estrogen and progesterone. In population studies, breast cancers occur more often among women exposed to a greater dose of these ovarian hormones over a lifetime, such as women who begin menstruating early or begin menopause later in life.
As a former competitive swimmer, Bernstein recognized that ovarian hormone levels often plummet among women who exercise so intensely that they skip their periods. Even among recreational athletes, moderate exercise can decrease average hormone levels, lengthen menstrual cycles or prompt menstrual cycles in which no egg is released.
Bernstein and her colleagues wondered if those changes in ovarian hormone
levels might lower breast cancer risk, so they took their studies to adult
women to find out. 
Researchers recruited more than 500 women age 40 or younger who had breast cancer, and matched them to women without breast cancer for comparison. They asked the women about their exercise habits, looking at activities as varied as jogging and dancing.
Bernstein found that women who exercised at least four hours each week during their reproductive years cut their risk of breast cancer in half.
In a different study of nearly 1,900 women who developed breast cancer after menopause (comparing them to more than 1,600 cancer-free women), she and her colleagues found that women who exercised more than four hours a week for 12 or more years were 24 percent less likely to develop breast cancer than less-active women.
Most recently, Bernstein and her fellow investigators looked into relationships between early breast disease and exercise.
Publishing in the November 2003 journal Cancer, the team found that women who exercised had a 35 percent lower risk of developing breast carcinoma in situ (BCIS) than did inactive women.
Breast carcinoma in situ consists of clusters of abnormal cells confined either to breast ducts or lobules. Most BCIS cases are found through mammograms. Left untreated, some BCIS develops into invasive breast cancer.
Bernstein’s team interviewed nearly 600 women ranging in age from 35-64 years old who were diagnosed with BCIS and matched them to BCIS-free women based on race and age group.
The researchers found that among women with no family breast cancer history, the more hours they exercised every week, the more their BCIS risk dropped. Women who exercised more than four hours a week had a 47 percent lower risk of BCIS than inactive women—but even those who were active as little as one hour a week were somewhat protected.
Among women with a family history of breast cancer, though, physical activity did not reduce BCIS risk. Bernstein is not sure why, but suggests that women with a family history of breast cancer might have hereditary forms of the disease that develop differently.
Exercise during the teenage years might be particularly important to dropping ovarian hormone levels, with lifelong protective effects, Bernstein says. Cells in the breast ducts—where most breast cancers arise—grow fastest during adolescence, and scientists believe that lowering the cells’ exposure to ovarian hormones during that vulnerable time may be especially protective. In contrast, exercise later in life might reduce cancer risk indirectly, by helping to shrink body fat—where the body converts adrenal hormones to estrogens.
“Whether before or after menopause, physical activity, even a modest amount each week, appears to be helpful for reducing the risk of breast cancer,” Bernstein says, “and that is a powerful message.”
Hormones or health?
To millions of postmenopausal women, hormone replacement therapy means relief from the discomforts of night sweats and hot flashes. Yet to others, the therapy looms as a specter of breast cancer.
When part of the National Institutes of Health-funded Women’s Health Initiative study was halted early because women on hormone therapy in the study were developing breast cancer at increased rates, many women were alarmed and abandoned the therapy.
But what if hormone replacement therapy only raises the risk of breast cancer in certain women? And what if physicians could see in advance whether a woman would face higher risk from using the therapy?
That is the crux of recent work by Keck School and Norris researchers, who have found a genetic clue that scientists may eventually use to identify these women at risk.
Keck School scientists looked at mammograms from more than 200 women and found that those with a particular marker in their genetic makeup developed denser breast tissue after using hormone replacement therapy than women without the marker. Mammographic density is a risk factor for breast cancer and has been proposed as a telltale signal for breast cancer risk.
“Our research is promising. We already know that only some women who use hormone replacement therapy with estrogen and progestin go on to develop breast cancer,” says Giske Ursin, M.D., Ph.D., associate professor of preventive medicine at the Keck School. “If we could pick out the subset of women who are at risk for breast cancer from using standard hormone replacement therapy, we could offer these women some other treatment for their postmenopausal complaints.”
At the heart of the research are genes and something called a polymorphism. Polymorphisms represent variants in the genetic blueprint. They may account for characteristics as obvious as differences in hair color or as complicated as the body’s ability to break down hormones.
In their first study, Keck School researchers aimed to find out which polymorphisms might link female hormones to increased breast density. They obtained mammograms and DNA from more than 200 postmenopausal women who were randomly assigned to take combination estrogen-and-progestin therapy, estrogen-only therapy or a placebo.
Scientists checked each participant’s DNA for the presence of several genetic polymorphisms associated with progesterone action or the body’s ability to break down estrogen or progesterone.
When scientists compared mammograms taken after 12 months on the trial to mammograms taken in the beginning, they saw something striking among women who were using combination therapy. Breast tissue had grown substantially denser among women with a certain polymorphism in one of the progesterone-breakdown genes compared to women who did not have that polymorphism.
Ursin thinks that this research is promising, but that there may be many different polymorphisms that can influence how effectively women break down progesterone and estrogen. She and a number of other investigators in her department are pursuing the role of a variety of genes that code for enzymes that could be important in the breakdown of these hormones.
Scientists do not yet know for sure whether increased breast density actually means increased breast cancer risk. Breast density, though, can be a measure of breast cell division. Researchers believe the more breast cells divide over a lifetime, the greater the breast cancer risk.
In young women, the estrogen and progesterone that naturally circulates through the body causes breast cells to divide; but as a woman enters menopause, hormone levels plummet and breast cell division slows down.
When a postmenopausal woman takes hormone replacement therapy, however, the therapy re-introduces hormones that are usually present only in very small amounts. That means additional breast cell division in these women—and potentially greater breast cancer risk.
If subsequent studies identify all the important polymorphisms for hormone therapy-related breast cancer risk, physicians may be able to one day test women to see if hormone replacement therapy would raise their risk of developing breast cancer. Those found to be at heightened risk could help protect themselves by avoiding the therapy—while women who could take it safely could once again benefit from the therapy.
| A Woman's Touch
When Gail Lebovic, M.D., sees a problem that keeps women from getting the most out of their health care, she does more than just complain: She invents a gadget, widget or gizmo to fix it. Sometimes these inventions, together with proven technology and screening guidelines, can head off breast cancer. According to Lebovic, a leading breast surgeon at USC/Norris Comprehensive Cancer Center, routine mammograms are a longstanding, critical tool available to women for finding breast disease early, when it is most curable. Although researchers argue about whether mammography truly saves lives, the imaging technology can detect changes in breast tissue as many as three years before a woman could feel a lump in her breast, tipping physicians off to cancer before a tumor could invade and spread. But mammography can only consistently find breast cancer early if women get annual mammograms faithfully. Lebovic knows that many women avoid the yearly screenings because they are, quite simply, a pain. Over the years, she has heard scores of women griping about the pinching and squeezing involved in getting a mammogram, so she set her mind on making the process softer and gentler. So began the Woman’s Touch MammoPad, a disposable cushion placed on mammography equipment before a woman has the test. The MammoPad cushions the breast during compression, reducing the pain. “This looks deceivingly simple, like a mousepad,” she says, holding up a thin, rectangular slice of foam. “But the foam is incredibly complex. The key was to develop a product that decreased pain, but didn’t affect the X-ray image. It took two years to create it.” Lebovic and the product’s maker, BioLucent Inc., took the MammoPad to Laszlo Tabar, M.D., at Falun Central Hospital in Sweden, to perform intense clinical trials. Almost 1,000 Swedish women had mammograms either with or without the MammoPad, and Tabar—whom Lebovic dubs the “granddaddy of mammography” for his pioneering work in the field—could not see any effects that interfered with the mammography results, even when examining the images with a magnifying glass. In the study, a majority of the women reported that the MammoPad cut the pain of mammography in half. “Our hope is that by decreasing pain, we can increase compliance with mammography screenings,” says Lebovic, associate director of the Harold E. and Henrietta C. Lee Breast Center at USC/Norris Comprehensive Cancer Center and Hospital, who came to USC from Stanford University in 2003. Today, USC/Norris and about 1,500 other mammography centers are using MammoPads, which cost about $4 each. Aside from her female-friendly inventions, Lebovic spreads the word to women about health in an understandable, friendly way. So friendly, in fact, the Web site Yahoo-Health! signed on Lebovic as its breast health expert. Lebovic has authored various columns on women’s health for popular magazines and has been featured on numerous television and radio shows, and she plans to keep going. She has a passion for community education, she says, and aims to arm women with the knowledge they need to protect and care for themselves. “It all starts by helping women understand what to look for.” |
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