Therapy for breast cancer questioned

Studies address merits of hormone, drug treatment


Two important studies being published today challenge conventional thought about treating and avoiding breast cancer.

One suggests that doctors might eventually be able to identify women who do not need chemotherapy. The other says that women who have had hysterectomies can take estrogen to relieve symptoms of menopause without increasing their risk of breast cancer.

The first study, published in the Journal of the American Medical Association, indicates that many of the 70 percent of women whose cancers are fed by estrogen get so much benefit from estrogen-blocking hormonal therapy that chemotherapy provides few, if any, additional advantages.

The caveat, though, is that there is as yet no reliable way to identify the women who might not need chemotherapy from those who would be helped by it.

Currently, guidelines call for women to get chemotherapy if their tumors are of a certain size. Dr. Eric P. Winer, an author of the paper, who is director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston, said: "Virtually every woman with a tumor larger than a centimeter should get chemotherapy. Period. End of story."

But, he said, over the past couple of years, "that question has been reopened in a major way." The new study, he said, is part of the re-examination.

The study involved an analysis of data from three large clinical trials that tested different chemotherapy regimens. One gave two standard drugs with or without a third chemotherapy drug, paclitaxel.

Another asked whether it was better to give chemotherapy drugs in low, moderate or high doses.

The third addressed whether it was better to give the drugs more intensely, in two-week cycles, or whether three-week cycles were best. The women also had surgery and radiation as appropriate, but the studies focused on the effects of chemotherapy.

The analysis, by a group of leading breast cancer researchers led by Dr. Donald Berry, a statistician at M.D. Anderson Cancer Center, looked at the studies' data and asked whether some women were more likely to benefit from chemotherapy than others.

The conclusion was that even though the studies involved very different chemotherapy regimens, one variable always stood out - whether a woman's cancer was estrogen-receptor-positive, meaning it was fed by estrogen, or estrogen-receptor-negative, meaning it was impervious to estrogen's effects.

"All the benefits were in the estrogen-receptor-negatives," Berry said. "Then I asked, `What is going on here?'"

The answer, he and his colleagues report in the new paper, is that hormone therapies with drugs such as tamoxifen that starve cancers of estrogen are so powerful - reducing the death rate by 30 percent in women with estrogen-receptor-positive tumors - that chemotherapy helps those women much less than it helps women with estrogen-receptor-negative tumors.

"For the estrogen-receptor-negatives, there is a very dramatic improvement with chemotherapy," Winer said. "The vast majority of those women, except for those with the tiniest tumors or those with other health problems who would be expected to live only a few more years, should receive a course of chemotherapy."

As for those with tumors that are fueled by estrogen, however, "we have a big challenge," Winer said. "We know that on average the benefit is less but there are clearly women who benefit" from chemotherapy. "The challenge is to identify them."

The second paper, also published in the Journal of the American Medical Association, involved a federal study of more than 10,700 healthy women whose uteruses had been removed. The question was, What are the health consequences of taking estrogen for the relief of menopausal symptoms?

The new report does not apply to most menopausal women, but to those who have had hysterectomies - the only women in the study. The difference is important because the two groups take different forms of hormone therapy. Women who have had hysterectomies can take estrogen alone. But other women cannot, because it can cause uterine cancer. For them, estrogen must be combined with another hormone, a form of progesterone, to counter the cancer-causing effect.

In this case, the study, the Women's Health Initiative, found that estrogen did not increase the women's risk of breast cancer. But they did have more abnormal mammogram results, usually requiring that the test be repeated, and more breast biopsies.

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