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Is chemo best before or after surgery?

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[July 24, 2007]  WASHINGTON (AP) -- More breast cancer patients are being offered chemotherapy before surgery instead of afterward -- amid much debate about how to do it right and when it's a good option. Doctors have long known that having chemo first sometimes shrinks an advanced tumor enough that a woman can undergo smaller surgery and keep her breast.

What's new is the hope that it may help more women with earlier-stage cancer in a different way: by letting doctors switch drugs if the tumor doesn't respond right away. Wait until after surgery, and there's no way to measure the drugs' effect.

Does it really work? There's the rub: Studies show it doesn't endanger a woman to have chemo before surgery -- but so far, the hoped-for better survival hasn't been proven either.

That conundrum means whether a woman is offered pre-surgery chemo, and how, depends more on what doctor she chooses than on firm guidelines.

"I'm a fan of letting patients know what their choices are," says Dr. Minetta Liu of Georgetown University Hospital, a proponent who estimates that up to 10 percent of her patients who need chemo patients choose it pre-surgery. "You're not asking them to do something that's going to have a negative impact on their survival. It just may not help."

On the other side is Dr. Clifford Hudis of Memorial Sloan-Kettering Cancer Center, who wants more research to settle the issue before the fledgling trend becomes routine.

"It should not be used ... just because it exists," Hudis says.

With breast cancer deaths dropping since 1990, "the notion that we should move to a different strategy should be challenged, he adds. "We have uncharted territory."

More than 178,000 U.S. women will be diagnosed with breast cancer this year. Thanks to improvements in treatment and early detection, many will survive long-term. Still, breast cancer kills 40,000 a year.

Not every patient needs chemotherapy. It depends on the tumor's size and type, and whether the cancer has begun to spread, something determined with a check of lymph nodes under the arm.

There are no good statistics on how often women who need chemo choose it upfront. Most still have chemo after surgery, especially those treated in community hospitals.

But with more specialized cancer centers pushing upfront chemo for earlier-stage patients -- and dozens of clinical trials testing different methods -- the National Cancer Institute brought together experts last spring to debate the evidence behind what all agreed is a rising trend.

What's clear: If shrinking a tumor might save a woman's breast, or offer a markedly smaller lumpectomy, then pre-surgery chemo is a good option. Studies in the late 1990s proved that, and women with large tumors routinely are offered pre-surgery chemo -- including Elizabeth Edwards, wife of Democratic presidential hopeful John Edwards, who entered a chemo-first clinical trial when her breast cancer was first diagnosed in 2004. (Earlier this year, she learned her cancer had returned and spread to bone.)

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Where the NCI panel urged more study: Pre-surgery chemo in women with earlier-stage cancer, in case even small tumors have sent microscopic seedlings throughout the body.

Proponents contend that by using the intact breast tumor as a guide, they can tell when chemo's not working and try another drug -- and learn more about what subtypes of cancer are most dangerous and how to fight them.

About 25 percent of women who get upfront chemo have their initial tumor actually disappear, says Dr. Patrick Borgen of Maimonides Medical Center in Brooklyn. They don't avoid surgery: Doctors mark the spot before the chemo, and then cut it out anyway in case any cancer cells still lurk.

But those women do have a lower chance of relapse than their counterparts who don't respond as well.

That leads to some tough questions:

  • What to do with women who still have some tumor left to cut out after their chemo? There's no way to predict who will be fine and who will relapse, and no evidence that adding more chemo after surgery makes a difference. Doctors must make clear what to expect so these women don't feel like they flunked, stresses Georgetown's Liu.

  • What if doctors switched pre-surgery chemo several times in hopes of better shrinkage? Hudis warns that such women may never undergo a full standard treatment, just bits and pieces that actually might mean a worse outcome. What to do when tumors don't shrink right away is under study now.

  • How do doctors really know when a tumor's shrinking? Again, studies are tracking that. Surgeons sometimes find patients labeled hard-to-treat when scar tissue or a noninvasive type of cancer that doesn't respond to chemo in the first place was in the way.

Perhaps the biggest controversy: How to test and remove lymph nodes in women getting upfront chemo.

For now, specialists advise anyone considering pre-surgery chemo to get advanced testing, including a big enough biopsy, to make sure she's a good candidate.

Dr. Deborah Axelrod of New York University just had a woman seek pre-surgery chemo for a tumor way too small to need it. "The word is getting out," she says. "I'm not sure it's understood."

[Associated Press; by Lauran Neergaard]

Lauran Neergaard covers health and medical issues for The Associated Press in Washington.

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