Use of high-dose adjuvant chemotherapy and autologous stem-cell transplantation does not improve the chances of overall survival for a woman with high-risk breast cancer, according to two large, randomized trials of high-dose chemotherapy. However, the studies indicate that the more aggressive treatment may help reduce the risk of relapse.
Sjoerd Rodenhuis, M.D., of The Netherlands Cancer Institute in Amsterdam, and colleagues compared the outcomes of 885 women with high-risk breast cancers who were treated with either high-dose chemotherapy and stem cell transplantation or conventional-dose chemotherapy. High-dose chemotherapy was not associated with any improvement in overall survival. However, women treated with high-dose chemotherapy were less likely to relapse within 5 years.
In a second study, Martin S. Tallman, M.D., of the Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center in Chicago, and his colleagues examined outcomes of 540 women treated for high-risk breast cancer and found no difference in disease-free survival, overall survival, or time to recurrence between women treated with high-dose chemotherapy and those treated with conventional-dose chemotherapy. A subgroup analysis showed some improvement in relapse rates with high-dose chemotherapy. However, these benefits may be offset by the risks, the researchers said, noting that nine patients treated with high-dose chemotherapy died of complications and some patients developed subsequent cancers.
In an accompanying editorial, Gerald J. Elfenbein, M.D., of the Roger Williams Medical Center in Providence, R.I., said that despite the lack of benefit in overall survival, "there may be subgroups of women with high-risk breast cancer who can obtain a survival benefit from high-dose chemotherapy." He added that the findings are based on older forms of high-dose chemotherapy and are not representative of current high-dose chemotherapy regimens.
The studies appear in the July 3 issue of the New England Journal of Medicine.
See News, Vol. 92, No. 12, p. 961, "High-Dose Chemo For Breast Cancer: Does It Still Have a Chance?" and Vol. 91, No. 12, p. 992, "High-Dose Chemo and Breast Cancer: Early Results Spark Debate."
Cadmium Induces Estrogenic Effects in Rats
Cadmium appears to mimic the effects of estrogen in rats, suggesting that this naturally occurring metal may represent a new class of endocrine disruptors.
The new study builds on previous work that found that cadmium interacts with the estrogen receptor in cultured breast cancer cells. Compounds that mimic the effects of estrogen are believed to be associated in some cases with breast cancer risk.
Mary Beth Martin, Ph.D., of the Georgetown University Medical Center, Washington, D.C., and her colleagues found that exposure of ovariectomized rats to environmentally relevant doses of cadmium resulted in changes in the uterus and mammary gland consistent with changes induced by estrogen. Exposure to cadmium also affected unborn rats. Female offspring had a temporary increase in body weight, an earlier onset of puberty, and accelerated mammary gland development.
These effects on the mammary gland suggest that exposure to cadmium may be a potential risk factor for breast cancer, the researchers say. However, only one epidemiologic study in humans to date has found an association between cadmium exposure and breast cancer risk. The researchers say more studies are needed to substantiate these findings.
The study appears in the July 13 advanced online edition of Nature Medicine.
Linda Wang
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