Identification of a Potentially Radiosensitive Subgroup Among Patients With Breast Cancer

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Abstract
The description of genes and genetic syndromes, such as ataxia-telangiectasia, that predispose some women to breast cancer will provide greater insight into the genetic basis of cancer susceptibility. Our goal was to establish cell lines from patients with breast and bladder cancers, to screen for enhanced levels of radiation-induced arrest in the G 2 phase of the cell cycle such as is observed in ataxia-telangiectasia heterozygotes, and to correlate G 2 arrest with other prognostic indicators of these cancers and in vivo radiosensitivity. Epstein-Barr virus-transformed lymphoblastoid cells were established from 108 female patients with breast cancer and 24 age-matched female control subjects, and from 45 patients with bladder cancer and 18 age-matched control subjects. Cells were exposed to 3 Gy of γy radiation, and the percentages of cells in G 1 , and G 2 phases were determined at 18 and 24 hours after irradiation by fluores cence-activated cell sorter analysis. Postirradiation delay in G 2 phase was determined by calculating the percentage of cells in G 2 and by using the ratio G 2 /G 1 . When we determined the percentage of cells in G 2 phase at 18 hours after irradiation in 108 lym phoblastoid cells from breast cancer patients, we observed an increase of be-tween 3% and 38% in the number of cells in G 2 phase in comparison with cells that were not irradiated. Comparison with previous G 2 -phase arrest data for ataxia-telangiectasia hetero zygotes using a cutoff point at 29% delay demonstrated that 20% and 8% of the breast cancer cell lines of the case patients and control subjects, respectively, fell into that category ( P <.001). At the same time after irradiation, it was not possible to distinguish between bladder cancer cell lines (7%) and those of the corresponding control group (6%). Assessment of radiation effects by G 2 /G 1 ratio showed that 18 of the breast cancer patients and 8% of the control subjects were in the high range. When G 2 arrest was correlated with other prognostic factors, we found that case patients with a greater G 2 block were more likely to have had a family history of breast cancer ( P <.006) and more aggressive tumors when assessed by number of involved lymph nodes ( P )<.002) and tumor size ( P <.05). Furthermore, an adverse response to radiotherapy was observed in a group of patients with high G 2 arrest. While the postirradiation increase in G 2 -phase arrest in cells from breast cancer patients observed in this study may indicate genetic heterozygosity for ataxia-telangiectasia, it might also reflect other genetic abnormalities im portant to breast cancer. [J Natl Cancer Inst 86:1627-1634, 1994]

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