Second malignancies after breast cancer: the impact of different treatment modalities

Treatment for non-metastatic breast cancer (BC) may be the cause of second malignancies in long-term survivors. Our aim was to investigate whether survivors present a higher risk of malignancy than the general population according to treatment received. We analysed data for 16 705 BC survivors treated at the Curie Institute (1981 - 1997) by either chemotherapy (various regimens), radiotherapy (high-energy photons from a 60 Co unit or linear accelerator) and/or hormone therapy (2 - 5 years of tamoxifen). We calculated age-standardized incidence ratios (SIRs) for each malignancy, using data for the general French population from five regional registries. At a median follow-up 10.5 years, 709 patients had developed a second malignancy. The greatest increases in risk were for leukaemia (SIR: 2.07 (1.52 - 2.75)), ovarian cancer (SIR: 1.6 (1.27 - 2.04)) and gynaecological (cervical/endometrial) cancer (SIR: 1.6 (1.34 - 1.89); P<0.0001). The SIR for gastrointestinal cancer, the most common malignancy, was 0.82 (0.70 - 0.95; P<0.007). The increase in leukaemia was most strongly related to chemotherapy and that in gynaecological cancers to hormone therapy. Radiotherapy alone also had a significant, although lesser, effect on leukaemia and gynaecological cancer incidence. The increased risk of sarcomas and lung cancer was attributed to radiotherapy. No increased risk was observed for malignant melanoma, lymphoma, genitourinary, thyroid or head and neck cancer. There is a significantly increased risk of several kinds of second malignancy in women treated for BC, compared with the general population. This increase may be related to adjuvant treatment in some cases. However, the absolute risk is small.