NORMAL TISSUE RADIOSENSITIVITY IN BREAST-CANCER PATIENTS

Purpose: To investigate whether in vitro radiosensitivity of lymphocyt es derived from a blood sample will predict late effects from radiothe rapy in breast cancer patients. Methods and Materials: Blood samples w ere collect-ed from consenting patients who had received radiotherapy for breast cancer, Lymphocytes were extracted and transformed by the E pstein-Barr virus, The resulting lymphoblastoid cell lines (LCLs) were assessed for in vitro radiosensitivity using a tetrazolium-based colo rimetric assay (MTT), Survival curves were generated using doses of 0. 5 to 2 Gy, For each analysis an LCL derived from an individual with th e radiosensitive condition ataxia-telangiectasia (AT) was run as contr ol. Some patients also consented to give skin biopsies from which fibr oblast cultures were derived, Clonogenic assays were performed to gene rate survical curves using doses in the range of 0.5 to 4 Gy, Comparis on was made with the data obtained from LCLs. Late effects of radiothe rapy were assessed using the Radiation Therapy Oncology Group (RTOG) s coring scheme and compared with the in vitro radiosensitivity data. Re sults: LCLs from 56 breast cancer patients were assessed for in vitro radiosensitivity, Surviving fraction to 2 Gy (SF2) generated from surv ical curves ranged from 0.04-0.35 with coefficient of variation for th e whole group of 41%, None of the LCLs equalled the sensitivity of the AT line, but 16% showed equal or greater sensitivity to a line derive d from an AT heterozygote. Comparison of LCL and fibroblast radiosensi tivity showed reasonable correlation for 12 paired samples (r = 0.64), The majority of patients showed no or minimal effects after radiother apy (Grade 0,1 effects) but seven developed a Grade 2 reaction and fou r a Grade 3 or 4 reaction, Patients with a Grade 2-4 reaction were fou nd to be more sensitive in vitro than those with a Grade 0-1 reaction (p < 0.02). Conclusions: The use of the MTT assay to assess LCL radios ensitivity has demonstrated considerable heterogeneity amongst the bre ast cancer population, The presence of a proportion of patients showin g in vitro sensitivity but normal clinical response to radiotherapy wo uld limit the usefulness of the assay for predictive purposes.