TIME: Almanac 1995

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<text id=94TT1289> <title> Sep. 26, 1994: Medicine:Cornering a Killer </title> <history> TIME--The Weekly Newsmagazine--1994 Sep. 26, 1994 Taking Over Haiti </history> <article> <source>Time Magazine</source> <hdr> MEDICINE, Page 70 Cornering a Killer </hdr> <body> After four years of searching, researchers pinpoint the location of a gene that causes breast cancer By J. Madeleine Nash/Chicago The errant gene that causes a hereditary form of breast cancer was an especially elusive quarry. Scientists knew that the gene--dubbed BRCA1--was somewhere on chromosome 17, but they couldn't pinpoint an exact location or identify the culprit's chemical makeup. Over the past four years, dozens of rival laboratories and hundreds of scientists took up the search, and rumors circled the globe that one group or another had found the damaging strand of DNA. Last week, finally, the rumors were true. An international team led by researchers at the University of Utah and Myriad Genetics, a Salt Lake City company, confirmed that the often fatal molecular flaw had in fact been tracked down. As reports of the achievement flashed across TV screens and the front pages of newspapers, Science magazine made the unusual concession of releasing articles that described the discovery three weeks in advance of the planned publication date. "When I heard the news on the car radio, I cried," says Judi Ellis of Richmond, Virginia. "It was the first time since my mother was diagnosed with breast cancer 30 years ago that anything so significant has happened." The discovery is indeed important: it is a major step toward understanding the origins of a disease that kills 46,000 women each year in the U.S. alone. But it is not the kind of breakthrough that will quickly reduce the death toll. For one thing, the inheritance of a defective brca1 gene is responsible for only about 5% of breast-cancer cases; most apparently result from cellular changes that take place after birth. Myriad Genetics expects to devise a clinical test to detect the gene, and that could be a boon to women whose families have a history of breast cancer. But a foolproof test will take time--perhaps years--to develop, because BRCA1 turns out to be an unusually long, complex gene that can be crippled by many different mutations. Scientists don't yet understand how the rogue gene causes breast cancer. The sequence of chemical components in this particular strand of DNA bears almost no resemblance to any other genetic message ever decoded. The one section that does remind researchers of other snippets of DNA they have studied contains a hint that BRCA1 could spell out the recipe for making a particularly potent protein--one that may serve as a master switch in the nucleus of breast cells, turning other genes on or off. Whatever BRCA1 does, it appears to be absolutely vital. For when one copy of the gene is inactivated by a mutation and the backup copy is damaged or lost, a breast cell takes a giant step toward malignancy. The proof: more than 80% of all women who inherit one bad copy of BRCA1 develop breast or ovarian cancer by the time they turn 70, and for many the onset of disease occurs three or four decades earlier. To women who have watched mothers or other relatives get breast cancer, a test for BRCA1 mutations could bring relief from a daily battle with nearly unbearable uncertainty. Already, Laurie Skelly is mentally steeling herself for the bad news that could come from such a test. "In my mind, I already know what I would do" says this 32-year-old Chicagoan, whose family history of breast cancer goes back three generations. "If it turns out that I have the gene, I would have a mastectomy. To me, my life is more important than my breasts." But physicians who counsel breast-cancer patients are worried that too little is known about the psychological and social effects of that kind of radical surgical intervention, or even its success in warding off cancer. The other options--watchful waiting and frequent medical exams--can also be nerve-racking, particularly for young women, whose dense breast tissue diminishes the chances that mammography will spot tiny tumors. For most breast-cancer patients, the discovery of BRCA1 will have very little immediate significance. At first scientists were hopeful that BRCA1 would shed light on the biological foundations of all types of breast cancer. In fact, many researchers expected to be able to detect mutations that were not inherited but happened later in life in the BRCA1 genes present in many different breast tumors. Yet when a team led by Donna Shattuck-Eidens and Mark Skolnick of Myriad Genetics and Roger Wiseman of the National Institutes of Health looked for these telltale changes in the tumors of randomly chosen breast-cancer patients, the researchers came up with only a few examples--and in the end it turned out that these people too had inherited the mutations. Still, it is far too early to write off BRCA1 as a bit player in the breast-cancer story. The complex interplay of DNA inside the nucleus of breast cells leaves open the possibility that BRCA1 will eventually lead scientists to genes that play a more central role in common forms of the disease. Scientists are working to locate BRCA2, a gene that appears to trigger breast cancer in males as well as females. It seems virtually certain that a BRCA3 also exists, and perhaps a still mysterious BRCA4. In a field where researchers have long been stymied, the prospect that not one but several genes related to breast cancer may shortly be discovered is downright exhilarating. "I'm excited," says Dr. Funmi Olopade, director of the Cancer Risk Clinic at the University of Chicago. "No, I'm delirious. Finally we are beginning to crack open the mystery." </body> </article> </text>