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Factors Influencing Mutation at the hprt Locus in T-Lymphocytes: Women Treated for Breast Cancer¹

Genetics Laboratory, Department of Medicine, and the Vermont Regional Cancer Center, University of Vermont, Burlington, Vermont 05401

Forty-nine women with breast cancer were enrolled in a prospective, longitudinal study of the genetic damage caused by treatment. Assays of mutant frequency at the hprt locus in peripheral blood lymphocytes were performed at approximately 6-month intervals for 2 years. Treatment consisted of surgery alone or additional tamoxifen, radiotherapy, or chemotherapy in various combinations. At 6 months, there was an elevation of mean mutant frequency compared to initial values (P = 0.004) which persisted for as many as 2 years. A significant elevation at 6 months occurred only in the group of women who received combination chemotherapy (P = 0.005). Within this group, 5 of 15 patients had striking elevations of mutant frequency following chemotherapy (>3 SD). Three of these 5 women had serum folate levels in the deficient range, while only one of 9 patients with lesser responses to chemotherapy were folate deficient. The change in mutant frequency after chemotherapy was inversely related to serum folate levels (P = 0.05) and to the number of years of smoking cigarettes (P = 0.01). We conclude that of the various modalities used to treat breast cancer, only chemotherapy was accompanied by a high risk of somatic mutation. A subset of patients manifested substantial increases in mutant frequency, often in association with low serum folate levels.

¹ This work was supported by grants from the U.S. Environmental Protection Agency (Cooperative Agreement No. CR-812837), the American Institute for Cancer Research, and the National Cancer Institute (CA30688, CA41843, and P30 CA22435). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. This paper is the second in a series of studies.

² To whom requests for reprints should be addressed, at Genetics Laboratory, University of Vermont, 32 N. Prospect St., Burlington, VT 05401.

Received 7/24/91. Accepted 10/ 7/91.

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