Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancer

To assess the frequency and type of cardiac effects in women treated with adjuvant chemotherapy with or without breast irradiation for operable breast cancer.

Retrospective analysis of a series of 825 women taking part in prospectively randomized trials on adjuvant chemotherapy with or without adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) for operable breast cancer at high risk of new disease manifestations. A total of 360 patients (44%) also received breast irradiation because of conservative surgery. Median follow-up in first clinical complete remission from end of all adjuvant treatments was 80 months. According to the protocol requirements, electrocardiograms were obtained before breast cancer surgery, before starting therapy with adriamycin and at the end of all adjuvant treatments. During the follow-up observation, electrocardiograms were systematically obtained at least once a year. In the presence of suspicious findings as well as of clinical symptoms and signs of cardiovascular disease, additional cardiac investigations were undertaken. However, percutaneous endomyocardial biopsies were never performed.

Congestive heart failure occurred in a total of 4 women (0.5% of all patients; 0.8% following adriamycin-containing chemotherapy; 2.6% after both adriamycin and irradiation to the left breast), in two of whom it was fatal. ST-segment and T-wave abnormalities in the absence of other symptoms and signs were detected in 3.4% of the case series. Other cardiac events were documented in 6.8% of all patients Overall, cardiac effects were more frequently detected in women who received irradiation to the left breast. In addition, age greater than 55 years at surgery and history of risk factors were important risk modifiers in the occurrence of cardiac events.

The addition of full-dose adriamycin to alkylating-containing adjuvant chemotherapy, as given in our studies, failed per se to increase the frequency of cardiac effects. Thus anthracyclines, which have the potential to improve current treatment results, deserve a proper place in the design of future adjuvant studies.