WUNRN
BREAST CANCER - STUDY DIVIDES INTO 4
DISTINCT TYPES
By Gina Kolata - September 23, 2012
Dr.
Charles Perou is the lead author of the study, part of a federal project.
Dr.
Matthew Ellis was a researcher for the study.
These discoveries, published online on Sunday in the
journal Nature,
are expected to lead to new treatments with drugs already approved for cancers
in other parts of the body and new ideas for more precise treatments aimed at
genetic aberrations that now have no known treatment.
The study is the first comprehensive genetic analysis
of breast cancer, which kills more than 35,000 women a year in the United
States. The new paper, and several smaller recent studies, are electrifying the
field.
“This is the road map for how we might cure breast
cancer in the future,” said Dr. Matthew Ellis of Washington University, a
researcher for the study.
Researchers and patient advocates caution that it will
still take years to translate the new insights into transformative new
treatments. Even within the four major types of breast cancer, individual tumors appear to
be driven by their own sets of genetic changes. A wide variety of drugs will
most likely need to be developed to tailor medicines to individual tumors.
“There are a lot of steps that turn basic science into
clinically meaningful results,” said Karuna Jaggar, executive director of Breast
Cancer Action, an advocacy group. “It is the ‘stay tuned’ story.”
The study is part of a large federal project, the Cancer
Genome Atlas, to build maps of genetic changes in common cancers. Reports
on similar studies of lung and colon cancer have been published recently. The
breast cancer study was based on an analysis of tumors from 825 patients.
“There has never been a breast cancer genomics project
on this scale,” said the atlas’s program director, Brad Ozenberger of the National Institutes
of Health.
The investigators identified at least 40 genetic
alterations that might be attacked by drugs. Many of them are already being
developed for other types of cancer that have the same mutations. “We now have
a good view of what goes wrong in breast cancer,” said Joe Gray, a genetic
expert at Oregon
Health & Science University, who was not involved in the study. “We
haven’t had that before.”
The study focused on the most common types of breast
cancer that are thought to arise in the milk duct. It concentrated on early
breast cancers that had not yet spread to other parts of the body in order to
find genetic changes that could be attacked, stopping a cancer before it
metastasized.
The study’s biggest surprise involved a particularly
deadly breast cancer whose tumor cells
resemble basal cells of the skin and sweat glands, which are in the deepest
layer of the skin. These breast cells form a scaffolding for milk duct cells.
This type of cancer is often called triple negative and accounts for a small
percentage of breast cancer.
But researchers found that this cancer was entirely
different from the other types of breast cancer and much more resembles ovarian
cancer and a type of lung cancer.
“It’s incredible,” said Dr. James Ingle of the Mayo
Clinic, one of the study’s 348 authors, of the ovarian cancer connection. “It raises
the possibility that there may be a common cause.”
There are immediate therapeutic implications. The study
gives a biologic reason to try some routine treatments for ovarian cancer
instead of a common class of drugs used in breast cancer known as anthracyclines.
Anthracyclines, Dr. Ellis said, “are the drugs most breast cancer patients
dread because they are associated with heart damage and leukemia.”
A new type of drug, PARP inhibitors, that seems to help
squelch ovarian cancers, should also be tried in basal-like breast cancer, Dr.
Ellis said.
Basal-like cancers are most prevalent in younger women,
in African-Americans and in women with breast cancer genes BRCA1 and BRCA2.
Two other types of breast cancer, accounting for most
cases of the disease, arise from the luminal cells that line milk ducts. These
cancers have proteins on their surfaces that grab estrogen, fueling
their growth. Just about everyone with estrogen-fueled cancer gets the same
treatment. Some do well. Others do not.
The genetic analysis divided these cancers into two distinct
types. Patients with luminal A cancer had good prognoses while those with
luminal B did not, suggesting that perhaps patients with the first kind of
tumor might do well with just hormonal therapy to block estrogen from spurring
their cancers while those with the second kind might do better with chemotherapy in
addition to hormonal therapy.
In some cases, genetic aberrations were so strongly
associated with one or the other luminal subtype that they appeared to be the
actual cause of the cancer, said Dr. Charles Perou of the University of North
Carolina, who is the lead author of the study. And he called that “a stunning
finding.”
“We are really getting at the roots of these cancers,”
he said.
After basal-like cancers, and luminal A and B cancers,
the fourth type of breast cancer is what the researchers called HER2-enriched.
Breast cancers often have extra copies of a gene, HER2, that drives their
growth. A drug, Herceptin, can block the gene and has changed the prognosis for
these patients from one of the worst in breast cancer to one of the best.
Yet although Herceptin is approved for every breast
cancer patient whose tumor makes too much HER2, the new analysis finds that not
all of these tumors are alike. The HER2-enriched should respond readily to
Herceptin; the other type might not.
The only way to know is to do a clinical trial, and one
is already being planned. Herceptin is expensive and can occasionally damage
the heart. “We absolutely only want to give it to patients who can benefit,”
Dr. Perou said.
For now, despite the tantalizing possibilities, patients
will have to wait for clinical trials to see whether drugs that block the
genetic aberrations can stop the cancers. And it could be a vast undertaking to
get all the drug testing done. Because there are so many different ways a
breast cancer cell can go awry, there may have to be dozens of drug studies,
each focusing on a different genetic change.
One of Dr. Ellis’s patients, Elizabeth Stark, 48, has a
basal-type breast cancer. She has gone through three rounds of chemotherapy,
surgery and radiation over the past four years. Her disease is stable now and
Dr. Stark, a biochemist at Pfizer, says she knows it will take time for the
explosion of genetic data to produce new treatments that might help her.
“In 10 years it will be different,” she said, adding emphatically, “I know I will be here in 10 years.”