The estrogen status of breast cancer tumors that have metastasized to lymph nodes is a factor in response to chemotherapy, according to an article in the April 12 issue of the Journal of the American Medical Association.

Analysis of data from three clinical trials with a total of 6,644 patients, researchers established that chemotherapy is more effective against estrogen receptor-negative disease than commonly thought and that chemotherapy is less effective against estrogen receptor-positive cancer than thought, according to study 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.

Berry said that the authors’ conclusion will surprise many oncologists. Women with node-positive breast cancer routinely are given chemotherapy regardless of receptor type. Women who have receptor-positive tumors are also given tamoxifen.

"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 estrogen receptor-positive tumors," Berry said.

"All in all, this is good news because it shows that the benefit of chemotherapy for estrogen receptor-negative tumors is surprisingly dramatic in the same way that tamoxifen's effect is substantial for estrogen receptor-positive tumors," Berry added.

The research team, which included investigators from top US cancer centers, studied outcomes from three large randomized clinical trials that tested optimal use of chemotherapy in node-positive breast cancer.

However, none of the trials 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.

Accumulated evidence indicates, however, that improvements in chemotherapy disproportionately benefit women with estrogen receptor-negative, 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 estrogen receptor-negative tumors compared with estrogen receptor-positive tumors. Specifically, 22.8 percent of receptor-negative patients were disease-free after five years if they received chemotherapy versus 7 percent of estrogen receptor-positive patients. The corresponding improvements for overall survival were 16.7 percent versus 4 percent.

The researchers also compared different chemotherapy regimens and found biweekly doxorubicin/cyclophosphamide plus paclitaxel lowered the rate of recurrence and death in estrogen receptor-negative patients by more than 50 percent compared with the low-dose regimen used in the first study.

"This tells us that breast oncology has made enormous strides in treating patients with estrogen receptor-negative 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 estrogen receptor-positive tumors," Berry said.