Cardiovascular death and second non-breast cancer malignancy after postmastectomy radiation and doxorubicin-based chemotherapy

Abstract

Purpose: To assess the incidence of long-term toxicity after postmastectomy radiation and doxorubicin-based adjuvant chemotherapy.

Methods: Records of 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five institutional prospective trials were retrospectively reviewed. Actuarial toxicity rates were compared with those of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy who did not receive postmastectomy radiation. For those treated with radiation, the chest wall received a median dose of 55 Gy with Co-60 (42%) or electrons (51%). Adjuvant chemotherapy consisted of a doxorubicin-based regimen, often followed by 2 years of cyclophosphamide, methotrexate, and fluorouracil.

Results: Median follow-up was 10 years. The overall 10-year actuarial rates of RTOG toxicity Grade >1 and >or=3 after radiation were 4% and 2%, respectively. The overall 10- and 15-year actuarial rates of second non-breast cancer malignancy were 3.8% and 7%, respectively. There was no statistical difference between the rates of non-breast cancer second malignancy in the radiated and unirradiated cohorts (3.4% vs. 4.7% 10-year actuarial rates). Increasing age and treatment with >10 cycles of chemotherapy were associated with higher rates of second malignancy (p = 0.025, p = 0.016). The 10-year actuarial rate of death from myocardial infarction (MI) was 2.4% (eight events) and 0.5% (five events) in the radiated and unirradiated groups, respectively (p = 0.058). Of the 8 irradiated patients who died of MI, 2 patients had left-sided breast cancer.

Conclusions: We found very low rates of serious sequelae after postmastectomy radiation, including death from myocardial infarction and non-breast cancer second malignancy. The rate of second non-breast cancer malignancy was increased among patients treated with >10 cycles of cyclophosphamide-containing chemotherapy.