Post-surgery chemotherapy questioned for certain breast cancer patients

July 16, 2002

BOSTON - Postmenopausal breast cancer patients with estrogen-sensitive tumors who undergo chemotherapy following surgery to increase their survival odds may not benefit from the regimen, which is often prescribed along with the hormone-blocking drug tamoxifen, according to an international study.

The research did show, however, that patients whose tumors were unresponsive to estrogen (known as ER-negative tumors) gained a decided benefit from chemotherapy. These patients were significantly less likely to relapse and less likely to die five years after treatment than those who didn't receive chemotherapy.

Published in the July 17 Journal of the National Cancer Institute, the findings question the value of the chemotherapy treatment following breast surgery in postmenopausal women who have relatively early tumors that haven't spread to their lymph nodes (node-negative), and which are responsive to the hormone estrogen (ER-positive).

The results, said Richard Gelber, PhD, a biostatistician at the Dana-Farber Cancer Institute who headed the statistical analysis of the trial data, indicate that cancer treatments need to be more finely "tailored" to the characteristics of patients and their tumors, in order to avoid unnecessary discomfort and expense.

"I'm hoping it will cause physicians and research investigators to examine more carefully whether or not these postmenopausal women with node-negative, ER-positive diseases should routinely be offered chemotherapy," Gelber said.

A total of 1,669 patients from many countries were recruited into the trial. All were postmenopausal and had node-negative cancer. About 75 percent had ER-positive tumors and 23 percent had tumors that were ER-negative: a small fraction were undetermined.

The women were randomly assigned to receive either chemotherapy followed by tamoxifen, or tamoxifen alone for five years.

Analysis showed that women with ER-negative tumors who received chemotherapy had a 15 percent increase in disease-free survival at five years (84 percent vs. 69 percent) compared to those not getting chemotherapy. The overall survival at five years was 89 percent in the chemotherapy group compared to 81 percent receiving tamoxifen alone.

But among women with ER-positive tumors, who have a better prognosis to begin with because they can be successfully treated with tamoxifen, addition of the chemotherapy provided no survival benefit. Their five-year disease-free survival rate was 85 percent without chemotherapy and 84 percent with it; and their overall survival rate at five years was 95 percent and 93 percent, respectively.

Postmenopausal women with ER+ and ER- tumors make up nearly half of all U.S. women who have surgery for non-metastatic breast cancer.

Women with ER-negative tumors have a higher risk of relapsing and tamoxifen is less effective in those patients, which may explain why the chemotherapy was relatively more beneficial in these women than in those whose tumors were ER-positive, said the investigators.

The issue of routinely prescribing chemotherapy for postmenopausal, lymph node-negative patients has long been controversial. While other studies have looked at certain aspects of the value of chemotherapy in this patient population, this is the first large study to compare the outcomes of chemotherapy in both ER-negative and ER-positive women who also are prescribed tamoxifen.

U.S. doctors have a greater tendency to offer chemotherapy to these patients than are their European counterparts, said Monica Castiglione-Gertsch, MD, at the coordinating center in Switzerland for the International Breast Cancer Study Group, which carried out the research. "In Europe we use much more endocrine treatment" to suppress production of estrogen in the patients' bodies, she said.

Even in the United States, she added, there has begun to be a shift away from routine chemotherapy use in the ER-positive patients.

The study found that patients who underwent chemotherapy felt more poorly and in some cases lost their hair, but that these and other "quality-of-life" symptoms largely disappeared afterward. "This means that they felt different during chemotherapy and it should not be used frivolously," said Gelber. "But on the other hand, this transient reduction in the quality of life should not be used as an excuse to deny chemotherapy when it can be helpful." Some physicians have been more reluctant to give chemotherapy to older women.

Women whose cancers haven't spread to the lymph nodes have a relatively low risk of relapse, but by 10 years after surgery the chance of metastasis (spreading) rise to about 25 percent. Since the 1970s, researchers have been studying the value of adding chemotherapy (so-called "adjuvant" chemotherapy) following breast cancer surgery to reduce this risk.

Meanwhile, measures that reduce the exposure of breast cancer cells to the body's estrogen have proved effective. Blocking the estrogen with tamoxifen is one such weapon. Removing the ovaries is another preventive treatment. The international study was designed to evaluate adjuvant chemotherapy in node-negative women and to compare the results in women with ER-positive to those with ER-negative tumors.

In an editorial accompanying the report, Drs. Antonio C. Wolff and Martin D. Abeloff of Johns Hopkins University said the study "clearly confirms the survival benefit" from a short course of chemotherapy in older women with lymph node-negative, ER-negative breast cancer. And it "reinforces the cautionary tone that already permeates the clinical practice guidelines" for chemotherapy used in similar patients but with ER-positive disease.
The study was supported by a variety of international governmental organizations, such as the Swiss Group for Clinical Cancer Research; the Australia-New Zealand Breast Cancer Study Group; Swedish Cancer Society and the National Cancer Institute.

Dana-Farber Cancer Institute ( is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

Dana-Farber Cancer Institute

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