EBCTCG Update of Adjuvant Treatment for Early Breast Cancer

FLORENCE—Long-term tamoxifen (Nolvadex) treatment and polychemother-apy prevent some 20,000 to 30,000 breast cancer deaths each year and, if more widely applied, could avert as many as 50,000 such deaths, according to the latest update from the 1995-1999 data cycle of the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

This optimistic conclusion is the result of “what happens when you put together all of the evidence in the world from randomized trials of adjuvant treatment for early breast cancer,” Professor Richard Peto, of the University of Oxford (UK), said at the First European Breast Cancer Conference.

Focusing on those trials that tested the value of 5 years of tamoxifen vs no treatment in 7,400 estrogen-receptor (ER)-positive women, Prof. Peto pointed out that hormonal therapy lowered the 10-year recurrence rate from 74% to 58% in women of all ages (P = .00001) and boosted 10-year overall survival from 66% to 74% (P < .00001). “These data are real because the study is based on such large numbers,” Prof. Peto said.

Long-term tamoxifen therapy reduced the 10-year recurrence rate from 79% to 64% in women with negative axillary nodes. For women with worse prognoses, Prof. Peto said, tamoxifen and chemotherapy are not either/or alternatives. Combining the two modalities slashed the recurrence rate from 61% to 40%, compared with chemotherapy alone, he reported.

“Starting 5 years of tamoxifen immediately in women with ER-positive disease prevents one in six women from relapsing and one in 12 from dying,” he said.

On balance, he maintained, the benefits are 30-fold greater than the risks, since adjuvant tamoxifen results in 80 per 1,000 fewer deaths from breast cancer while causing only 2 per 1,000 more deaths from endometrial cancer and 1 per 1,000 more deaths from pulmonary embolism.

Ovarian ablation yielded a highly significant absolute difference of 6% in overall survival in 12 trials involving 2,000 women under the age of 50. Assuming that about half of these women would have been ER positive if tested, Prof. Peto predicted that the real benefit of ovarian ablation would probably be twice as great for receptor-positive patients.

Chemotherapy Results

He went on to offer a wrap-up of 47 trials that studied the efficacy of adjuvant polychemotherapy in 18,000 women with early breast cancer. In women under age 50, polychemotherapy slashed the rate of recurrence by 35% and decreased mortality by 25%. In contrast, for women aged 50 to 69, the risk reductions, while still statistically significant, were only about half as great (20% and 11%, respectively).

Although the absolute benefit of polychemotherapy seemed to be twice as great in women with node-positive disease as in those with node-negative disease, improvements in survival were still observed among those with node-negative disease.

The EBCTCG analysis was unable to reliably demonstrate any differences between standard CMF (cyclophosphamide/methotrexate/fluorouracil) chemotherapy and CMF plus additional drugs.

Adjuvant Radiotherapy

Review of 41 trials involving 20,000 women showed that adjuvant radiotherapy caused the rate of isolated local recurrence to fall from 30% to 10%. This threefold risk reduction held across-the-board, Prof. Peto said, irrespective of age, nodal status, voltage, number of fields irradiated, radiation dose, chemotherapy status, trial nationality, and whether the trial was old or new.

He cautioned, however, that adjuvant radiotherapy may pose a late hazard 10 to 20 years down the road, especially in older women. Although radiotherapy significantly reduced the absolute risk of breast cancer death by 2.5% at 20 years, it increased the risk of death from other causes by 2% overall and by 3% in women over age 50.

Prof. Peto suggested that women under age 50 with node-positive disease are probably the group most likely to benefit from radiotherapy, although he cautioned that since these women are at risk for several decades, the balance could change.