Lani
04-12-2006, 02:02 PM
when looking at all breast cancer patients as a whole group. Since her2+ patients constitute between 20 and 25% of breast cancer patients their statistics may be entirely different:
Benefit of chemotherapy in breast cancer depends on estrogen-receptor status [Eureka News Service]
HOUSTON - When it comes to chemotherapy treatment for women whose breast cancer has spread to their lymph nodes, the estrogen status of their tumors matters, says a team of researchers in the April 12 issue of the Journal of the American Medical Association.
Analyzing data from three clinical trials with a total of 6,644 patients, they determined that chemotherapy works much better in breast cancer that is estrogen receptor-negative (ER-) than many people think, and conversely, doesn't work as well in estrogen receptor-positive (ER+) cancer as believed, says the study's lead author Donald Berry, Ph.D., chair of the Department of Biostatistics and Applied Mathematics at The University of Texas M. D. Anderson Cancer Center.
This conclusion will come as a surprise to many oncologists, Berry says. Women with "node-positive" breast cancer routinely are given chemotherapy, regardless of their tumor type. Women who have ER+ tumors are also given tamoxifen, a drug which inhibits estrogen use by the cancer cells.
"Our analysis shows that tamoxifen works very well for a number of years and taken as a group, there is little or no benefit of even the cumulative effects of modern improvements in chemotherapy for women with ER+ tumors," he says.
"All in all, this is good news because it shows that the benefit of chemotherapy for ER- tumors is surprisingly dramatic in the same way that tamoxifen's effect is substantial for ER+ tumors," Berry says.
The research team, which includes investigators from top cancer centers nationwide, studied outcomes from three large randomized clinical trials which tested the optimal use of chemotherapy in node-positive breast cancer. But none of these trials, all of which were conducted by the Cancer and Leukemia Group B and the U.S. Breast Intergroup, considered estrogen status or whether women had received tamoxifen, largely because the diagnostic importance of estrogen status for chemotherapy was not recognized at the time the trials were designed, Berry says.
Accumulated evidence indicates, however, that improvements in chemotherapy disproportionately benefit women with ER- tumors, Berry says; so the research team decided to statistically model the relative contribution of chemotherapy treatment given estrogen receptor status.
They found the absolute benefits due to chemotherapy were greater for patients with ER- tumors compared to those with ER+ tumors. Specifically, 22.8 percent more ER- patients were disease-free after five years if they received chemotherapy versus 7 percent of ER+ patients. The corresponding improvements for overall survival were 16.7 percent versus 4 percent.
The researchers also compared the different chemotherapy regimens tested in the trials, and found the latest chemotherapy combination studied - biweekly doxorubicin/cyclophosphamide plus paclitaxel - lowered the rate of recurrence and death in ER- patients by more than 50 percent, compared to the low-dose regimen used in the first study.
"This tells us that breast oncology has made enormous strides in treating patients with ER- tumors, a finding which contradicts the prevailing wisdom that with the development of tamoxifen and newer selective estrogen receptor modulator drugs, the benefits of medical science have been primarily focused on ER+ tumors," Berry says.
"It is true that tamoxifen changed the landscape for ER+ tumors, but the playing field has now been leveled somewhat given the fact that ER- tumors respond well to modern improvements in chemotherapy regimens," he says.
ABSTRACT: Estrogen-Receptor Status and Outcomes of Modern Chemotherapy for Patients With Node-Positive Breast Cancer [Journal of the AMA; Subscribe]
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.
This stresses the needs to subdivide breast cancer patients and treat groups differently--no one-size-fits-all approach!
Benefit of chemotherapy in breast cancer depends on estrogen-receptor status [Eureka News Service]
HOUSTON - When it comes to chemotherapy treatment for women whose breast cancer has spread to their lymph nodes, the estrogen status of their tumors matters, says a team of researchers in the April 12 issue of the Journal of the American Medical Association.
Analyzing data from three clinical trials with a total of 6,644 patients, they determined that chemotherapy works much better in breast cancer that is estrogen receptor-negative (ER-) than many people think, and conversely, doesn't work as well in estrogen receptor-positive (ER+) cancer as believed, says the study's lead author Donald Berry, Ph.D., chair of the Department of Biostatistics and Applied Mathematics at The University of Texas M. D. Anderson Cancer Center.
This conclusion will come as a surprise to many oncologists, Berry says. Women with "node-positive" breast cancer routinely are given chemotherapy, regardless of their tumor type. Women who have ER+ tumors are also given tamoxifen, a drug which inhibits estrogen use by the cancer cells.
"Our analysis shows that tamoxifen works very well for a number of years and taken as a group, there is little or no benefit of even the cumulative effects of modern improvements in chemotherapy for women with ER+ tumors," he says.
"All in all, this is good news because it shows that the benefit of chemotherapy for ER- tumors is surprisingly dramatic in the same way that tamoxifen's effect is substantial for ER+ tumors," Berry says.
The research team, which includes investigators from top cancer centers nationwide, studied outcomes from three large randomized clinical trials which tested the optimal use of chemotherapy in node-positive breast cancer. But none of these trials, all of which were conducted by the Cancer and Leukemia Group B and the U.S. Breast Intergroup, considered estrogen status or whether women had received tamoxifen, largely because the diagnostic importance of estrogen status for chemotherapy was not recognized at the time the trials were designed, Berry says.
Accumulated evidence indicates, however, that improvements in chemotherapy disproportionately benefit women with ER- tumors, Berry says; so the research team decided to statistically model the relative contribution of chemotherapy treatment given estrogen receptor status.
They found the absolute benefits due to chemotherapy were greater for patients with ER- tumors compared to those with ER+ tumors. Specifically, 22.8 percent more ER- patients were disease-free after five years if they received chemotherapy versus 7 percent of ER+ patients. The corresponding improvements for overall survival were 16.7 percent versus 4 percent.
The researchers also compared the different chemotherapy regimens tested in the trials, and found the latest chemotherapy combination studied - biweekly doxorubicin/cyclophosphamide plus paclitaxel - lowered the rate of recurrence and death in ER- patients by more than 50 percent, compared to the low-dose regimen used in the first study.
"This tells us that breast oncology has made enormous strides in treating patients with ER- tumors, a finding which contradicts the prevailing wisdom that with the development of tamoxifen and newer selective estrogen receptor modulator drugs, the benefits of medical science have been primarily focused on ER+ tumors," Berry says.
"It is true that tamoxifen changed the landscape for ER+ tumors, but the playing field has now been leveled somewhat given the fact that ER- tumors respond well to modern improvements in chemotherapy regimens," he says.
ABSTRACT: Estrogen-Receptor Status and Outcomes of Modern Chemotherapy for Patients With Node-Positive Breast Cancer [Journal of the AMA; Subscribe]
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.
This stresses the needs to subdivide breast cancer patients and treat groups differently--no one-size-fits-all approach!