Newer chemotherapies improve outcomes for some types of breast cancerCHICAGO – An updated analysis of findings from three major consecutive clinical trials of breast cancer treatment conducted over the past twenty years indicates that women who have breast cancer with lymph node involvement and estrogen-receptor negative tumors have a lower rate of recurrence and risk of death with treatment with newer chemotherapies, according to a study in the April 12 issue of JAMA.
Breast cancer estrogen-receptor status (ER – how cells respond to specific hormonal therapies) helps identify patients who benefit from endocrine therapy. With appropriate endocrine therapy, patients with ER–positive disease have substantially better prognoses as a group than do those with ER–negative disease. Evidence is accumulating that improvements in chemotherapy disproportionately benefit patients with ER–negative tumors.
Donald A. Berry, Ph.D., of the University of Texas M. D. Anderson Cancer Center, Houston, and colleagues examined whether breast cancer patients who have lymph node involvement and ER–negative tumors benefit more from recent improvements in supplemental chemotherapy than do women with ER–positive tumors treated with tamoxifen. The researchers compared disease-free and overall survival according to ER status among 6,644 patients enrolled in three consecutive randomized trials of chemotherapy conducted by the Cancer and Leukemia Group B and the U.S. Breast Cancer Intergroup. The trials compared (1): three regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) three doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also three-week vs. two-week cycles (September 1997 to March 1999).
The researchers found that for ER–negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21 percent, 25 percent, and 23 percent in the three studies, respectively, and 55 percent comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER–positive tumors treated with tamoxifen were 9 percent, 12 percent, and 8 percent in the three studies, and 26 percent overall. The overall death rate reductions associated with chemotherapy improvements were 55 percent and 23 percent among ER–negative and ER–positive patients, respectively. All individual ER–negative comparisons and no ER–positive comparisons were statistically significant.
The absolute improvement in five-year disease-free survival was 22.8 percent for ER–negative patients, as compared with 7.0 percent for ER–positive patients, and the difference for overall survival was an improvement of 16.7 percent for ER–negative patients vs. 4.0 percent for ER–positive patients.
"Our study has two substantive clinical implications. First, although patients with ER–positive breast tumors may reasonably opt for chemotherapy, they should recognize that the benefits are not great as compared with those for patients with ER–negative disease. The benefits of intensive and extensive chemotherapy for unselected patients who have ER–positive disease treated with tamoxifen are modest at best. Whether such patients should opt for chemotherapy will depend on their attitudes toward the associated negative sequelae. In the years ahead, it is likely that we will have better predictors that will allow clinicians to determine which patients with ER–positive disease truly benefit from the addition of chemotherapy."
"Second, with advances in chemotherapy, patients with ER–negative tumors have had sequentially improved outcomes and their prognoses now approach those of optimally treated patients with ER–positive disease. For patients with ER–negative disease, the overall disease-free survival and overall survival benefits of modern intensive and extensive chemotherapy considered in our study are substantial," the author conclude.
(JAMA. 2006;295:1658-1667. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This study was supported in part by a grant from the National Cancer Institute to the Cancer and Leukemia Group B. For the financial disclosures of the authors, please see the JAMA article.
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