Long-term effects of adjuvant chemotherapy in breast cancer.

Late effects of adjuvant chemotherapy (ACT) may include second malignant neoplasms (SMN), cardiotoxicity and ovarian suppression. Effects on the biology of residual tumour may be important in protocol design. Studies of SMN need large and reliable data sets. The leukaemia risk with current ACT is likely to be less than a five-fold increase. Leukaemia is predominantly a result of alkylating agents and peaks before 10 years. Solid SMN result also from radiotherapy and this risk continues after 10 years. Cardiotoxicity can be caused by anthracyclines but should not be a problem with current ACT regimens. It can be reduced by careful monitoring and by the cardioprotector ICRF-187. Amenorrhoea is a crude marker of ovarian suppression which may explain conflicting data on its relationship to outcome after ACT. Ovarian suppression following ACT is more likely and more permanent in older premenopausal women, but only explains a part of the ACT effects on outcome. Effects of early ACT on residual tumour are important for planning retreatments and combined modality protocols.