Two important studies being published today challenge conventional thoughts about treating and avoiding breast cancer.
One suggests that doctors eventually may 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 is that there is as yet no reliable way to identify the women who may not need chemotherapy from those who would be helped by it.
Current guidelines call for women to get chemotherapy if their tumors are of a certain size.
“Virtually every woman with a tumor larger than a centimeter should get chemotherapy. Period. End of story,” said Dr. Eric Winer, an author of the paper and director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston.
But, Winer said, over the past couple of years, “That question has been reopened in a major way.”
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 if it was better to give chemotherapy drugs in low, moderate or high doses. The third asked 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 in Houston, 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 (chemotherapy) benefits were in the estrogen-receptor-negatives,” Berry said.
“Then I asked, 'What is going on here?' ” he said.
The answer, he and his colleagues report, is that hormone therapies with drugs like 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.
On average, the researchers report, a women whose cancer does not respond to estrogen has a 23 percent greater chance of surviving five years disease-free if she has chemotherapy.
For a woman whose cancer is fed by estrogen, chemotherapy increases her chance of surviving that long by 7 percent.
There are tests of how sensitive a tumor is to estrogen, but, Winer said, they “are not as reliable as we all would like.”
There also is a gene test, the Genomic Health/NSABP recurrence score, that looks at 21 genes and is correlated with a tumor's response to estrogen and response to chemotherapy. But, Winer said, “It, too, is not ready for general use” to determine which patients with estrogen-fueled cancer could actually forgo chemotherapy.
For now, said Dr. Clifford Hudis, a co-author of the paper and chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York, cancer treatment recommendations should not change. The results, Hudis said, are “hypothesis-generating” and call out for further research.
The second paper, also published today in JAMA, 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 report does not apply to most menopausal women, but only 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. 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. They did have more abnormal mammogram results, usually requiring that the test be repeated, and more breast biopsies.
The study ended early, at the end of February 2004, when the investigators found that estrogen increased the risk of strokes and of blood clots in the legs.
