Push is on to tailor cancer care to

tumor's genes
By LAURAN NEERGAARD, AP Medical Writer Lauran Neergaard, Ap Medical
Writer – February 16, 2009

WASHINGTON – The days of one-size-fits-all cancer treatment are numbered: A rush of

new research is pointing the way to tailor chemotherapy and other care to what's written
in your tumor's genes.

Everyone with advanced colon cancer now is supposed to get a genetic test before
taking two of the leading treatments. It's a major change adopted by oncologists last
month after studies found that those pricey drugs, Erbitux and Vectibix, won't work in 40
percent of patients.

Scientists are furiously testing similar genetically tailored care in breast and lung cancer.
It's a flurry of work that reflects a huge problem: Most medications today benefit at best
about half of patients but it usually takes trial-and-error to tell.

That means a lot of people suffer side effects for nothing, and it's incredibly costly. When
the American Society of Clinical Oncology recommended giving colon cancer patients
that $300 test for a gene called KRAS, it estimated the move could save a stunning $600
million a year — by keeping drugs that cost up to $10,000 a month away from patients
who won't benefit.

Here's the critical consumer issue: As tantalizing as this personalized medicine is, gene
testing is like the Wild West. Laboratories often introduce new tests at the first clues they
might work, not waiting for final proof. Few tests so far have won the backing of major
medical groups like ASCO, the cancer specialists, making research studies a best bet
for many patients.

"A bad test is as dangerous to a patient as a bad drug," notes Dr. Richard Schilsky,
ASCO president and a University of Chicago oncologist. "The tricky part is to figure out
which of those (genetic differences) are clinically important and which are just variations
that exist."

This is not about testing if people carry so-called cancer genes that make them prone to
illness. Instead it's about finding a tumor's genetic signature — a pattern of gene and
protein activity that signals if the cancer will grow fast or slowly, be more or less likely to
recur, and whether it would be susceptible to treatment.

"We're getting into science fiction sort of, if now medicine is being able to analyze things
at the genome level," breast cancer patient Claire Weinberg of Oxford, N.C., says in
wonder.

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A community hospital initially dismissed Weinberg's breast lump but she fortunately
sought a second opinion at Duke University Medical Center — where, cancer confirmed,
she enrolled in a study of gene-directed chemotherapy.

"I felt it could only benefit me for them to know even more about me," she says.

The ultimate goal: "What's the right recipe for those patients?" explains Dr. Matthew Ellis
of Washington University in St. Louis, co-inventor of a different breast cancer genetic
approach.

Under study:

_A less precise test already can tell certain breast cancer patients if they're at high or
low risk of relapsing, helping the chemo-or-not decision. But which chemo? Duke's Dr.
Kelly Marcom is genetically profiling breast biopsy tissue from nearly 300 newly
diagnosed patients headed for pre-surgery chemo. Some are randomly assigned to one
of two standard chemotherapy cockails; the rest get the cocktail that matches their tumor
profile.

It's too early to tell if the gene-directed approach helps more tumors shrink.

But, "I can have no regrets," says Weinberg, who learned after surgery that she'd been
in the gene-tailored group and her tumor shrank enough to save her breast. She's also
getting post-surgery chemo in case any rogue cells remain.

_Instead of custom profiling, an experimental test unveiled last week examines 50 breast
cancer genes to determine which of four disease subtypes the woman has.

If it pans out — and much larger studies are planned — the Breast Bioclassifier could
change breast cancer's very names. When studied on stored samples of old tumors,
researchers found some women safely skipped chemo — their subtype responded
better to post-surgery tamoxifen, or hormone therapy. A more aggressive type was
sensitive to most chemo choices but not hormone treatment, the team reported in the
Journal of Clinical Oncology.

And still another group didn't respond well to either care, a group that desperately needs
new options, said Ellis, who co-developed the test with doctors at the University of Utah
and University of North Carolina, Chapel Hill.

_Next up, lung cancer. Hospitals nationwide are recruiting 1,200 lung cancer patients to
study who carries extra copies of the tumor-spurring gene EGFR. They'll get either of
two top treatments, Tarceva or Alimta, to see which is best for which genetic condition.

___

EDITOR's NOTE — Lauran Neergaard covers health and medical issues for The
Associated Press in Washington.

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