The Steering Committee's original guideline had recommended either doxorubicin (Adriamycin) plus cyclophosphamide (AC) chemotherapy or cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy in premenopausal women with node-positive breast cancer. It also made a preliminary recommendation for a more aggressive regimen with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) on the basis of results from a trial conducted by the National Cancer Institute of Canada Clinical Trials Group. After an extended follow-up, the updated results of that trial have now been published.⁴ Compared with CMF, CEF resulted in improved disease-free survival (63% v. 53%) and overall survival (76% v. 70%) at 5 years.

In addition, a new chemotherapeutic agent, paclitaxel, was evaluated. Paclitaxel is a member of a class of drugs known as taxanes. These drugs act by interfering with microtubules, thereby disrupting the normal mitotic process. Thus they can potentially be used together with anthracycline compounds (doxorubicin, epirubicin), which act by interfering with DNA replication. A number of clinical trials are investigating the incorporation of taxanes with anthracycline-based chemotherapy regimens in the adjuvant setting. A large multicentre trial involving women with node-positive breast cancer showed that adding paclitaxel after AC chemotherapy provided a better result than AC alone.⁵ At a median follow-up of 30 months, there was a 22% reduction in the risk of recurrence and a 26% reduction in the risk of death. The benefit was confined to women with estrogen receptor (ER)-negative tumours. For women with ER-positive tumours who were taking tamoxifen, no statistically significant difference was detected in the risk of recurrence or death. A second large multicentre trial, however, failed to detect a statistically significant difference between AC alone and AC followed by paclitaxel.⁶ The data are therefore inconclusive at present and require longer follow-up. In the above studies, both the CEF regimen and the AC regimen followed by paclitaxel were associated with an increased incidence of side effects.

The Steering Committee's updated guideline recommends the AC, CMF or CEF regimen for node-positive breast cancer. A firm recommendation for AC followed by paclitaxel is not made. The committee felt that the data were preliminary based on a relatively short follow-up. However, a highly informed and motivated patient may wish to receive this regimen. Participation in clinical trials is encouraged. As before, the choice of chemotherapy regimen depends on the individual woman's preference.

In the original guideline no recommendations could be made concerning high-dose chemotherapy plus stem-cell support. The results of 2 randomized trials published since then do not support this form of treatment. In one trial, conducted in the United States and Canada, women with disease involving 10 or more axillary lymph nodes were randomly assigned to receive either high-dose chemotherapy consisting of cyclophosphamide, cisplatin and BCNU (bis-chloronitrosourea) plus stem-cell support or intermediate doses of these drugs.⁷ No difference in breast cancer recurrence and mortality was detected between the 2 groups. In a Scandinavian trial, women with high-risk primary breast cancer were randomly assigned to receive either a dose-intensive regimen consisting of 9 cycles of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) or 3 cycles of FEC followed by high-dose chemotherapy with stem-cell support.⁸ No difference in overall survival was detected between the groups.

In the original guideline ovarian ablation was recommended for premenopausal women who refused chemotherapy. In the 1990 meta-analysis by the Early Breast Cancer Trialists' Collaborative Group, data on the use of tamoxifen in premenopausal women were inconclusive. In the group's 1995 analysis, there was a 45% proportional reduction in recurrence among women with ER-positive tumours receiving tamoxifen for 5 years.³ In the updated guideline, the Steering Committee now recommends the use of tamoxifen in premenopausal women who refuse chemotherapy or ovarian ablation.

The original guideline recommended the use of tamoxifen in postmenopausal women with ER-positive tumours. It was suggested that patients might benefit further by the addition of chemotherapy. In the recent meta-analysis by the Early Breast Cancer Trialists' Collaborative Group, there was a 19% proportional reduction in recurrence and an 11% proportional reduction in mortality among women who received chemotherapy plus tamoxifen compared with those given tamoxifen alone.^2,3 The additional benefit of tamoxifen plus chemotherapy over tamoxifen alone in this group of women is supported by several other recent trials, which are discussed in the updated guideline. Given these findings, the Steering Committee now recommends the addition of chemotherapy to tamoxifen therapy in postmenopausal women with ER-positive tumours. Personal preference and quality of life also influence the choice of chemotherapy.

The Steering Committee's original recommendation for AC or CMF chemotherapy in postmenopausal women with ER-negative tumours who are fit to receive chemotherapy is unchanged.

Previously, it was suggested that tamoxifen could be used in women over 70 years of age with ER-negative tumours. More recent data do not support the use of tamoxifen in any women with ER-negative tumours, regardless of age.^3,9