Breast Cancer’s New Controversy Recent Studies Question Assumptions About Mammograms by Gina Shaw included: Campaign to Bring Breast Cancer Programs to Romanian Women If you ask the average woman in most developed countries what disease most scares her, chances are good she’ll say "breast cancer." Even though heart attack and stroke are greater killers of women, some surveys have indicated that up to 61 percent of women think that breast cancer is their greatest health risk. But despite this high level of concern and awareness—despite years of pink ribbons and Races for the Cure—there’s still a lot that scientists don’t understand about this disease. And more often recently, what we think we understand is later questioned. What we know about prevention, diagnosis and treatment of breast cancer depends on whom you ask and when you ask them. Lately it seems that what’s accepted in breast cancer science, even more than with other troubling diseases, is changing almost daily. So how do women and their doctors know what treatments to choose, what tests to take, and what preventive strategies to pursue? Often the answers are complex and depend upon the particular woman and her case. The Mammography Muddle Although there’s always been some debate over just when screening mammograms should begin and how often women should have them, mammography has for quite some time been the gold standard of early breast cancer detection. Women who visited their obstetrician-gynecologist were taught to do monthly breast self-exams (and often given "shower cards" to remind them how to check for lumps) and were told to get regular mammograms once they reached the age of 40. Regular screening mammograms, the experts said, would reduce the risk of dying of breast cancer for women over 40 by some 30 percent and would also help them avoid radical mastectomies and other extremes of treatment that become necessary when a tumor isn’t discovered until it’s grown large and invasive. Leading experts disagreed over just how regularly women should have mammograms. The American Cancer Society and the American College of Obstetricians and Gynecologists recommend annual mammograms for women 40-plus, while the National Cancer Institute suggests that annual screening begin at age 50 and that women over 40 seek mammograms every one or two years, depending on risk factors. But recent studies have challenged these long-held assumptions about mammograms. In the fall of 2000, University of Toronto researchers working on the Canadian National Breast Screening Study-2 (CNBSS) reported that, according to their findings, annual mammograms did not lower breast cancer deaths in women age 50 to 59 who are also receiving professional breast physical examinations and have been taught how to do breast self-exams. "After an average follow-up of 13 years, comparing two groups of women aged 50-59—one group receiving annual mammograms and breast physical examinations and the other physical examinations alone—we’ve found that breast cancer mortality is almost identical in the two groups," said Dr. Anthony Miller, a professor emeritus in the university’s Department of Public Health Sciences, director of the CNBSS, and lead author of the study, which was published in the Journal of the National Cancer Institute. But what about the fact that breast cancer mortality has declined in the United States since the widespread adoption of mammography? There may be other factors involved, suggested Miller. "The recent reduction in mortality in North America is almost certainly attributable not to screening, but to the widespread adoption of adjuvant chemotherapy or tamoxifen for node-positive disease in the 1980s," he wrote in a letter published in The Lancet in February 2000. This past October, what we know about mammography was thrown into further question by a study published by Danish researchers in The Lancet. The study, a large-scale review of al l the major clinical trials of mammography’s effectiveness, in Copenhagen, Denmark, declared that mammography has not been demonstrated to reduce deaths from breast cancer or to prolong women’s lives. Women who have screening mammograms, concluded the review, die of breast cancer at the same rate as women who don’t. This study follows up and fine-tunes an earlier study by the same researchers that appeared in The Lancet in early 2000. Of course, both of these challenges to screening mammograms for women in their 40s and 50s have themselves been challenged and their methods criticized. For example, U.S. doctors called the Canadian study flawed because it included a number of low-quality mammograms. But the question remains—do mammograms really save lives? And when does it make sense to start them? The fact is, disagreement continues. A new pamphlet from the American Academy of Family Physicians details the risks and benefits of regular screening mammograms for women in their 40s—the age group about which there’s the most debate over mammography’s benefits. Women in this age group who have regular mammograms reduce their risk of dying of breast cancer by about 16 percent, it says—much less than the mortality benefit for older women. Dr. Barron Lerner, associate professor of medicine and public health at Columbia University and author of "The Breast Cancer Wars: Hope, Fear, and the Pursuit of a Cure in Twentieth-Century America," recently considered the issue in an op-ed published in the New York Times. Until there is more definitive information, he said, women age 50 to 70 should continue to have yearly screening mammograms. "There has simply been too much supportive data for too long to abandon the test now," he wrote. He advises women in their 40s to talk carefully with their doctors, discussing the existing research in the context of their own family history and other risks. "At some point," he said, "we must be willing to challenge our most basic assumptions about how we fight breast cancer." The Genetics of Breast Cancer So far, scientists have identified two genes—dubbed BRCA1 and BRCA2—that, when they carry mutations, increase a woman’s risk of both breast and ovarian cancer. Women who carry a mutation in BRCA1 and BRCA2 have one normal copy of the gene and one mutated copy. Inherited risk factors, most of which result from mutations in BRCA1 and BRCA2, play a role in up to 10 percent of all breast cancers. Though it’s long been known that both BRCA1 and BRCA2 help regulate cell growth, scientists are now beginning to understand more specifically what at least one of these mutations does to bump up a woman’s cancer risk. The gene BRCA1, say researchers at the University of Texas at Austin, apparently plays a role in detecting and mending the damage to DNA that can take place when cells divide. If there’s a mutation on the gene, the scientists theorize, something can go wrong with the DNA repair process, which means that abnormal cells can grow out of control and lead to cancer. Scientists still aren’t sure why mutations in these genes seem tied only to breast and ovarian cancers and not to other types of cancer. Although they both predispose a woman to breast cancer, there are some key differences in how BRCA1 and BRCA2 mutations act in these women. About 80 percent of BRCA1 tumor cells lack the receptors that make them sensitive to estrogen, so they are what’s called "ER-negative." BRCA2 tumor cells, however, are exactly the opposite—about 80 percent of them are "ER-positive." This is important because at least one highly effective drug, recently shown not only to be effective in treating breast cancer but in helping to prevent it, targets estrogen receptors in breast tissue. If there are no estrogen receptors—if the cancer is "ER-negative," then there’s no target for the drug. New Developments The drug in question, tamoxifen, has become a standard treatment for women with breast cancer and has been shown to be effective in preventing recurrences of the disease. In late 2001, scientists released the results of a study that found that not only does tamoxifen help prevent breast cancer from coming back, it can also be of great benefit in preventing a first occurrence of breast cancer in women who are at high risk. The study, an analysis of 288 women over 35 who were taking the drug tamoxifen or a placebo and developed breast cancer during the Breast Cancer Prevention Trial (BCPT) between 1992 and 1998, found that tamoxifen reduced the incidence of breast cancer by 69 percent in women who carried the BRCA2 genetic mutation. The catch? Because most BRCA1 tumors are ER-negative, tamoxifen doesn’t appear to be effective in preventing them either from recurring or from developing in the first place. A new class of drugs, called aromatase inhibitors, heralded in a study released in December 2001 as possibly even more effective against early-stage breast cancer than tamoxifen, may well have the same limitations. Both anastrozole, the new drug, and tamoxifen, act as estrogen-blockers, although they operate in slightly different ways: Tamoxifen blocks estrogen from reaching cancer cells, while anastrozole reduces the levels of estrogen circulating in a woman’s body. (Although anastrozole looks promising, even the researchers studying this new drug don’t advocate switching patients to it from tamoxifen until they have further data.) "There’s a whole area of research that still needs to be done in ER-negative tumors, how to prevent them, and what their origins are," said Dr. Leslie Ford, of the National Cancer Institute, a co-author of the study. Women with the BRCA1 mutation, whose tumors are largely ER-negative, tend to develop cancer at a younger age than do other women. "We need a way of detecting those lesions when they’re so small that these women can retain the breast. We don’t have that yet," said Dr. Mary-Claire King, a geneticist with the University of Washington-Seattle. One new diagnostic tool that should soon be available to help women with a family history of breast cancer—including those with the BRCA1 mutation—is a technique that can detect tumors at their earliest stages. Ductal lavage is a simple outpatient procedure that finds tiny tumors in the breast ducts (where milk is produced), the area where 99 percent of all breast cancers originate. After numbing the breast with an anesthetic cream, doctors insert a tiny catheter through the nipple into a milk duct, collect cells from the duct, and send them off for analysis. A study published last November in the Journal of the National Cancer Institute revealed that ductal lavage detected abnormal cells—the earliest signs of potential breast cancer—in 24 percent of the women participating, all of whom were at high risk for breast cancer and who had had normal mammograms and clinical exams just 12 months before the study. Though ductal lavage is very promising for women with a heightened risk of breast cancer, doctors warn that it doesn’t take the place of a mammogram because it can’t examine the entire breast in the same way a screening mammogram does. But some women who face an increased risk of breast cancer—women who have seen mothers, sisters and aunts struggle with and often die from the disease—choose a more radical option. Before tests show any signs of cancer, these women have both breasts removed. Prophylactic removal of both breasts is an extreme step, but it’s also effective, studies have shown. Most recently, researchers at the Mayo Clinic reported that prophylactic double mastectomy reduced the risk of subsequent breast cancer in women at the highest risk—those with the BRCA1 and BRCA2 mutations—by some 90 to 100 percent. The researchers followed 26 women, each of whom had one of the two mutations, for an average of 13.4 years after they’d had both breasts removed. They would have expected between six and nine breast cancers to develop among this group of women; but so far, none of them has developed breast cancer. "Our previous study had shown that prophylactic mastectomy reduced subsequent breast cancer risk substantially in women who had the procedure because of a strong family history," said oncologist Dr. Lynn Hartmann, a lead researcher on the study. "But a question remained: Would the procedure be able to reduce risk in the higher risk group—namely BRCA1 and BRCA2 carriers? Our current data support that it can, although ours is a relatively small group of carriers." Gina Shaw is the medical writer for The Washington Diplomat. Campaign to Bring Breast Cancer Programs to Romanian Women Daniela Nastase, wife of Romanian Prime Minister Adrian Nastase, is working to bring women’s health and social issues to the forefront of her country’s social agenda. A vocal advocate of breast cancer awareness, her support has been instrumental in gathering attention and badly needed funds to this often-overlooked health crisis. As part of her ongoing efforts to promote breast cancer awareness, Nastase recently participated in a black-tie ball in Bucharest to raise money for a clinic that would offer breast cancer screenings to low-income women. In an interview with The Washington Diplomat, Nastase said that it is absolutely crucial for businesses and private citizens to contribute their time and money to tackle this deadly disease. "You can’t always think of the government to solve problems. Everyone ought to give back," she said. She urges all Romanians to donate because "it’s important to give a part of your time for women, for children, for families." The event, the first of its kind, raised more than $70,000 and was a major step toward bringing women’s health issues out of the shadows in Romania. The goal of such clinics, Nastase said, would be to bring in doctor volunteers from other countries and provide women with annual checkups and the educational tools needed to not only prevent breast cancer, but also to boost the survival rate of women diagnosed with the disease. At this point, that rate stands at about 50 percent in Romania—far lower than the United States and most Western European nations. These clinics would primarily benefit women in major cities, but because most of Romania’s population is not concentrated in urban centers, Nastase also turned to alternative methods of extending health care services to women in sparsely populated rural pockets of the country. One novel approach is to bring the "clinic" to the patient. In October 2001, Nastase toured the George Washington University’s mobile mammography van, known as Mammovan, which she hopes to use as a model for a similar type of program in Romania. As director of social programs at the Foundation for Third Millennium Romania, Nastase has lent her time to a variety of issues ranging from curbing drug use to empowering young people. She continues to collaborate with U.S. breast cancer centers and has been a key player in establishing the grounds for a breast care program in her country, one that she hopes will only flourish in the future. "In 10 years I would like to see a new clinic and half the persons with breast cancer," she said. "We might even have a cure for breast cancer in 10 years." — Anna Gawel