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Class of Chemotherapy Drugs Helps Certain Breast Cancer Patients

Anthracyclines increase survival for HER2-positive tumors, but not negative ones, analysis finds,,

WEDNESDAY, Dec. 26 (HealthDay News)-- Chemotherapy drugs known as anthracyclines help boost survival for women with HER2-positive breast cancer who have undergone surgery, but they may not offer any survival benefit for those with HER2-negative tumors.

That's the conclusion of a wide-ranging analysis that pooled the results of eight randomized trials that compared the drugs with non-anthracyclines and took into account the women's HER2 status.

HER2-positive cancers test positive for a protein called human epidermal growth factor receptor 2 (HER2) and tend to grow quickly, the researchers said.

Since anthracyclines (such as doxorubicin and epirubicin) were introduced in the 1980s, they have been widely used as supplementary chemotherapy for breast cancer, said Dr. Alessandra Gennari, a medical oncologist at the National Cancer Research Institute in Genoa, Italy, and lead author of the study.

But the new analysis may change that, Gennari said. "Our study provides convincing statistical evidence that the added benefit of adjuvant chemotherapy with anthracyclines is confined to women who have breast tumors in which HER2 is overexpressed or amplified," she said.

"Since only about 25 to 30 percent of all breast cancers are HER2-positive, the vast majority of patients, with HER2-negative disease, may be spared unnecessary toxicities related to the use of this class of agents," she added.

The study findings were published online Dec. 25 in the Journal of the National Cancer Institute.

Anthracyclines have been associated with an increased risk of heart damage in some patients -- a risk doctors have known about for some time. An increased risk of leukemia, which can strike years later, is also associated with use of the drugs.

But, Gennari said, anthracyclines came into widespread use despite these risks, because a previous meta-analysis found they improved overall survival. "As a result, anthracyclines-based regimens have been long regarded as the standard therapeutic option in the vast majority of early breast cancer patients. However, when individual trials are taken into account, the absolute magnitude of this benefit is not consistent across studies," she added.

The new study suggests the drugs work best for those women whose tumors are HER2-positive. Of the 6,564 patients reviewed, 5,354 had HER2 status information available. In those women with tumors that were HER2-positive, the anthracyclines produced a greater reduction in risk of relapse or death than non-anthracycline regimens, the study found.

For women with HER2-negative tumors, however, there was no difference in survival between the chemotherapy regimens.

But, in an accompanying editorial in the journal, Dr. Charles Geyer Jr. and his colleagues from the National Surgical Adjuvant Breast and Bowel Project in Pittsburgh, said that it may not be as simple as determining who should get anthracyclines based just on HER2 status.

That's because other research has suggested that the overexpression of another gene called topoisomerase II alpha (or topo2) may also play a role in how well anthracyclines work. "The topo2 gene is thought to be the real target of the anthracyclines," said Geyer, director of medical affairs for the NSABB project. And it may or may not be overexpressed along with the HER2 gene, he said.

The new study's conclusions, Geyer added, provide another example of therapies becoming more and more tailored to the specific type of breast cancer.

In another study in the same issue of the journal, researchers reported that women with breast cancer getting chemotherapy and tamoxifen had reduced risk of getting cancer in the healthy breast. Chemotherapy reduced the risk for at least 10 years and tamoxifen for five years, the study said.

More information

To learn more about anthracyclines and other chemotherapy drugs, visit the American Cancer Society.

SOURCES: Alessandra Gennari, M.D., Ph.D., medical oncologist, National Cancer Research Institute, Genoa, Italy; Charles E. Geyer Jr., M.D., director of medical affairs, National Surgical Adjuvant Breast and Bowel Project, director of the Cancer Center, Allegheny General Hospital, Pittsburgh; Dec. 25, 2007, Journal of the National Cancer Institute, online

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