TIME: Almanac 1993/TIME Almanac 1993.iso/time/011491/0114353.000

Text File | 1992-08-28 | 5.3 KB | 114 lines

                ∙                                                              MEDICINE, Page 55

COVER STORIES

Tantalizing Clues to a Lethal Legacy


Research into the genetic factors is raising hopes of better
screening and treatment

By J. MADELEINE NASH/CHICAGO -- With reporting by James
Willwerth/ Los Angeles


    To most women, the notion of undergoing a mastectomy in
order to prevent breast cancer smacks of wild paranoia. But for
Maria Burkhardt of Covington, La., the unthinkable slowly
became the inevitable. Twenty years ago, an aunt was stricken
with the disease. Her mother died from it a decade later. In
1986 Maria's younger sister Jo Ann began fighting for her life.
Next her older sister Rose developed an aggressive tumor. Maria
consulted a doctor and was told she was "a ticking time bomb."
Ominously, her tissues were judged too dense for mammograms to
scan reliably.

    So last summer, at 47, Maria decided to have both breasts
removed. Her own graceful curves were replaced with silicone
implants that harbored no trace of her family's lethal legacy.
A short time later, Maria received a report that vindicated her
decision. A postoperative examination of her breast tissue had
found precancerous lesions. "I just broke down and cried," she
recalls. "I'd done this knowing I might never know if I'd made
the right choice."

    Families like Maria Burkhardt's are rare, accounting for a
tiny fraction of breast-cancer cases. But the malevolent genes
they pass down through the generations are beginning to yield
important clues to all breast malignancies. "Cancer," declares
celebrated molecular biologist James D. Watson, "is a disease
of the DNA," the master molecule that encodes the genetic
blueprint for every living cell. Tumors develop as the result
of rearrangements in DNA, specifically in the genes that govern
cell growth.

    In most cases, the changes that lead to breast cancer begin
accumulating after birth, perhaps triggered by some set of
environmental stresses, whether random cosmic rays or a dietary
factor. Some women, however, start out with the genetic deck
stacked against them. Like Burkhardt and her sisters, they
stand a greater risk of developing breast cancer, in both
breasts and at an earlier age, than other women.

    Recent months have brought a series of discoveries about the
genetic mutations involved in breast cancer. "Information is
accumulating at an astounding rate," says University of Utah
geneticist Mark Skolnick. Changes in at least two types of
genes play a role: those that direct cells to grow and divide;
and those that issue commands to halt growth. Much of the
research has focused on a growth-enhancing gene on chromosome
17, often referred to as the HER-2/neu oncogene. An estimated
30% of breast-cancer patients have somehow acquired abnormal
quantities of this gene -- as many as 50, as opposed to the
normal two.

    The extra copies are a bad omen. Patients that have them
suffer three times the rate of cancer recurrence of other
patients, says UCLA oncologist Dr. Dennis Slamon. Such
patients, he says, should "absolutely" get further treatment.
But one genetic abnormality is not enough to transform healthy,
law-abiding breast cells into anarchic tumors. "The genes
responsible for this disease are like pieces of a patchwork
quilt," says geneticist Mary-Claire King of the University of
California, Berkeley. The patchwork pattern may vary from one
woman to the next, but each case probably involves five or six
separate mutations occurring over a period of years.

    Researchers at the Cancer Institute in Tokyo have implicated
five genes on four different chromosomes. Dr. Yusuke Nakamura
speculates that the loss of a growth-suppressing gene on
chromosome 17 may be one of the earliest changes on the road
to malignancy. Other groups have also pointed to sites on
chromosome 17. Last November a team led by scientists at
Massachusetts General Hospital Cancer Center identified one
such gene as the likely cause of Li-Fraumeni syndrome, a rare
genetic disorder that increases susceptibility to breast cancer
and other malignancies. Since then, King and her colleagues
at Berkeley have identified another segment of chromosome 17
that is associated with familial breast cancer. Other
researchers, including a group in Strasbourg, France, are
unraveling the genetics behind the deadly process of
metastasis.

    The flood of insights into the genetics of breast cancer
will ultimately provide physicians with more effective weapons.
This year Dr. Slamon and his colleagues hope to begin clinical
trials of a genetically engineered antibody that locks onto the
protein made by the HER-2/neu oncogene, interfering with its
function. This antibody has already been shown to inhibit tumor
growth in mice.

    Researchers like Berkeley's King dream of diagnostic tools
powerful enough to identify abnormal genes in breast cells long
before they become fully cancerous. Such tools could begin to
lift the burden of uncertainty from women who, like Maria
Burkhardt, come from cancer-prone families and wonder if they
carry the dreaded trait. Someday, if King has her way, tests
for breast-cancer genes could become as commonplace as Pap
smears. And then, she says optimistically, "no one need die of
breast cancer anymore."