Chemo Combo Fights Aggressive Breast Cancer
A common regimen works better against HER2-positive tumors, researchers find 
HealthDay
Wednesday, May 17, 2006
WEDNESDAY, May 17 (HealthDay News) -- Tailoring breast cancer chemotherapy by taking into account whether the tumor has a specific gene mutation can boost a patient's response to treatment, Canadian researchers report.
The finding builds on previous studies that have found similar improvements in patient results, experts say.
Women who have HER2-positive breast cancer -- in which the cancer cells produce an excess of HER2 (human epidermal growth factor receptor-2) -- responded better to a specific chemotherapy regimen compared to patients without HER-2 overexpression, said study lead researcher Dr. Kathleen I. Pritchard, a professor of medicine at the University of Toronto.
The regimen in question is called "CEF" for the three drugs used: cyclophosphamide, epirubicin and fluorouracil.
In the study, the CEF regimen reduced the 10-year risk of death for patients with HER2-positive cancers by 48 percent, compared to similar patients placed on another regimen, called CMF (cyclophosphamide, methotrexate and fluorouracil), Pritchard said.
The findings appear in the May 18 issue of the
New England Journal of Medicine.
According to the American Cancer Society, about one third of breast cancers have too much HER2, also called HER2/neu.
These cancers are generally more aggressive than other types and can be less responsive to hormone treatment. In recent years, experts have found that certain chemotherapy regimens, such as the ones Pritchard studied, along with Herceptin (trastuzumab), a medication that targets HER2, may slow cancer cell growth in these tumors.
In prior research, Pritchard's team showed that CEF outperformed CMF in women with node-positive breast cancer. So, the researchers went back to that study and analyzed 639 preserved specimens of the tumors obtained from 710 women, all pre-menopausal, who had received either one of the two chemotherapy regimens.
Then they compared 10-year treatment outcomes based on the women's HER2 status.
"HER2 [breast cancer] has a poor prognosis, but there is more benefit to giving CEF than CMF," Pritchard concluded. "While HER2 has a worse prognosis, they get more benefit from CEF than CMF." That finding was not replicated in patients without HER2 overexpression, she noted.
"We are suggesting that most of the benefit of these anthracycline-containing regimens seem to be in the HER2 over-expressing patients," Pritchard said.
The Toronto researchers used three laboratory methods rather than a single one to determine whether the HER2 tumors got a better benefit from CEF or CMF regimens, she added.
"We don't know where our observation fits together with Herceptin," said Pritchard, who explained that an answer to that question was beyond the scope of this study.
The study was praised by a Belgian physician who wrote an accompanying editorial in the journal.
"They managed to get a lot of tumor samples and they did a beautiful job," said Dr. Martine J. Piccart-Gebhart, head of the Medicine Department at the Jules Bordet Institute, Universite Libre de Bruxelles, Brussels. The fact that the team used a variety of laboratory methods to correlate the chemotherapy regimen with the outcome was good, she said.
But the study does have limitations, she said.
"Still, this is not the ideal way of doing this," Piccart-Gebhart said, pointing out that the Toronto study was a retrospective ("looking back") analysis rather than the "gold standard," a randomized, controlled prospective trial.
"The message from the study is, mostly likely HER2-positive tumors respond very well to anthracyclines. But it doesn't tell you in a definitive way that a HER2-negative tumor shouldn't be treated."
In her editorial, Piccart-Gebhart noted that another gene, topoisomerase II alpha or TOP2A, should also be looked at -- an observation that Pritchard also noted in her report. "Some people believe it could be the better marker" to predict the results of specific treatments, Piccart-Gebhart said.
As complicated as the decisions are, the new study offers help in making tough treatment decisions for women diagnosed with breast cancer. "One of the take-home points is that all women should have their HER2 measured in the tumor," Pritchard said. "Most centers in the U.S. and Canada should [already] be doing this."
"That [information] should be part of what their oncologist uses in deciding what chemo they get and whether they get Herceptin," she said.
"I think patients who are HER2-positive should all be considering Herceptin," she said.
Piccart-Gebhart added: "For women, the message is the data on molecular markers to direct the choice of chemo are still not good enough" to give definitive answers. "I think they should still at this time trust the clinical judgment of their physician."
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