TY - JOUR
T1 - Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer
AU - Berry, Donald A.
AU - Cirrincione, Constance
AU - Henderson, I. Craig
AU - Citron, Marc L.
AU - Budman, Daniel R.
AU - Goldstein, Lori J.
AU - Martino, Silvana
AU - Perez, Edith A.
AU - Muss, Hyman B.
AU - Norton, Larry
AU - Hudis, Clifford
AU - Winer, Eric P.
PY - 2006/4/12
Y1 - 2006/4/12
N2 - Context: Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. Objective: To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. Design, Setting, and Patients: Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 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 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. Main Outcome Measures: Disease-free and overall survival. Results: For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% 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%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%. Conclusion: Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.
AB - Context: Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. Objective: To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. Design, Setting, and Patients: Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 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 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. Main Outcome Measures: Disease-free and overall survival. Results: For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% 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%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%. Conclusion: Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.
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U2 - 10.1001/jama.295.14.1658
DO - 10.1001/jama.295.14.1658
M3 - Article
C2 - 16609087
AN - SCOPUS:33645729203
SN - 0098-7484
VL - 295
SP - 1658
EP - 1667
JO - JAMA
JF - JAMA
IS - 14
ER -