Frequency of sister chromatid exchanges and micronuclei monitored over time in patients with early-stage breast cancer: results of an observational study.

Spontaneous chromosomal instability correlates with a high risk of cancer. The frequency of spontaneous sister chromatid exchanges (SCE) and micronuclei (MN) in peripheral blood lymphocytes was used for evaluation of spontaneous chromosomal instability in early-stage breast cancer patients to determine whether SCE and MN frequencies are biomarkers of damage from chemotherapy and radiotherapy. In 20 stage I-II breast cancer patients, SCE and MN were measured before surgery and at 4 weeks after. In patients who received adjuvant chemotherapy (CTx), they were also determined before starting radiotherapy (RTx). Other assessments were done 2, 6, and 12 months after RTx in almost all patients and at 18 months in 4 patients. Generalized estimating equations (GEE) were used to estimate population averaged effects at the different treatment and follow-up time points. Moreover, SCE and MN baseline values in patients were compared with those of a control group of 12 healthy women. A significant difference emerged between patients and healthy controls (P<0.0001 for SCE and P<0.0003 for MN; Mann-Whitney test); SCE increased significantly after CTx and MN increased significantly after RTx. In the GEE model, the smoking habit was associated with increased SCE in patients treated with CTx; age significantly affected MN frequencies. Both MN and SCE frequencies are increased in breast cancer patients and are indicators of CTx and RTx damage, respectively. The increased SCE levels in patients treated with CTx may be due to a synergic effect of smoking and chemotherapy.