Risk of new primaries after chemotherapy and/or tamoxifen treatment for early breast cancer.

BACKGROUND

Both chemotherapy and tamoxifen are widely used either alone or in combination as adjuvant treatment following mastectomy. Despite the fact that both of them exhibit carcinogenic properties in experimental models, detailed reports on the incidence of new primaries following chemotherapy and/or tamoxifen in patients with early breast cancer are limited.

PURPOSE

To investigate the incidence of new primaries (including opposite breast tumors and skin cancers) in untreated patients and in patients treated with either tamoxifen or chemotherapy or with both modalities.

PATIENTS AND METHODS

A total of 1696 patients with early breast cancer, 1286 of whom were treated with either CMF-based adjuvant chemotherapy (n = 410), tamoxifen (n = 656) or with a combination of the two (n = 220) were considered for the present analysis. Patients were operated on between November 1983 and December 1991 and were followed up to June 1994. Detailed information about second malignancies were available for all patients.

RESULTS

Overall, 53 new primaries, 19 of them opposite breast tumors, occurred in 53 patients. The actuarial cumulative incidence rates at 5 years were: 3.1% (95% CI: 1.4%-4.8%) in untreated patients; 1.7% (95% CI: 0.0%-3.5%) in tamoxifen-treated patients; 4.2% (95% CI: 1.3%-7.1%) in chemotherapy-treated patients and 2.6% (95% CI: 0.0%-5.2%) in the chemo-tamoxifen group (all groups: P = n.s.; chemotherapy-treated versus tamoxifen-treated: P = 0.01). The corresponding figures, after exclusion of the patients with opposite-breast and skin tumors, were: untreated patients: 2% (95% CI: 0.6%-3.4%); tamoxifen-treated patients: 0.95% (95% CI: 0.0%-2.4%); chemotherapy-treated patients: 2.6% (95% CI: 0.4%-4.8%); chemotherapy plus tamoxifen: 1.65% (95% CI: 0.4%-3.8%); (all groups: P = n.s.; CT versus TAM P = 0.05). Chemotherapy-treated patients showed a risk that was about two-fold that of the one to be expected in the general population. By contrast, a decrease in the total risk was observed in patients treated with tamoxifen. Patients who received chemotherapy and tamoxifen as well as those in the no-treatment group showed a risk which was comparable to that of the general population.

CONCLUSIONS

Adjuvant chemotherapy appears to increase the risk of second malignancies. By contrast, tamoxifen seems to exert an overall protective effect in this regard, and it also appears to counteract, at least partially, the carcinogenic effect of chemotherapy.

IMPLICATIONS

While there is plenty of evidence that the benefit achieved by adjuvant chemotherapy considerably exceeds the risk of second malignancies, the indiscriminate use of chemotherapy should be avoided, particularly in patients with a low risk of relapse. Moreover, it seems reasonable to prefer tamoxifen over chemotherapy for patients likely to obtain comparable therapeutic benefit from antiestrogenic treatment.