David Ginsburg has conducted his own analysis of selected studies. The meta-analysis by the Early Breast Cancer Trialists' Collaborative Group, which included all the trials of chemotherapy plus tamoxifen versus tamoxifen alone in over 9000 postmenopausal women, demonstrated a statistically significant reduction in both breast cancer recurrence and mortality in favour of the combined chemohormonal therapy.1 Ginsburg points out that some of the trials that compared chemotherapy plus tamoxifen with tamoxifen alone included a small number of patients with estrogen receptor (ER)-negative tumours. Tamoxifen would not be expected to be of benefit in such patients. The implication is that the demonstrated benefit of combination therapy is driven by the effect of chemotherapy in the ER-negative patients. We believe that this is a spurious hypothesis for several reasons. First, the numbers of ER-negative patients were balanced between treatment arms in these trials and these patients comprised a relatively small subgroup. Second, chemotherapy is effective in women with ER-positive tumours as well as ER-negative tumours. Finally, in trials that included only postmenopausal women with ER-positive tumours, a benefit was detected in favour of the addition of chemotherapy to tamoxifen. For example, the Intergroup recently updated the results of their trial of anthracycline-containing chemotherapy plus tamoxifen versus tamoxifen alone.2 There was a statistically significant improvement in survival in favour of the addition of chemotherapy to tamoxifen.
We agree with Ginsburg that there were very few patients over 70 years of age in the trials of adjuvant chemotherapy. We alluded to this in our guideline3 and we feel that our recommendations were balanced and did not overstate the case.