JNCI Journal of the National Cancer Institute

JNCI Journal of the National Cancer Institute 1993 85(23):1917-1920; doi:10.1093/jnci/85.23.1917
© 1993 by Oxford University Press

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Journal of the National Cancer Institute, Vol. 85, No. 23, 1917-1920, December 1, 1993
© 1993 Oxford University Press

Upregulation of Estradiol C16-hydroxylation in Human Breast Tissue: a Potential Biomarker of Breast Cancer Risk

Michael P. Osborne, H. Leon Bradlow, George Y. C. Wong, Nitin T. Telang^*

Strang-Cornell Cancer Research Laboratory, Strang Cancer Prevention Center, and Cornell University Medical College New York, N.Y.

Correspondence to: Nitin T. Telang, Ph.D., Division of Carcinogenesis & Prevention, Strang-Cornell Cancer Research Laboratory, 510 East 73rd St. (2nd Floor), New York, NY 10021.

BACKGROUND: The biotransformation of the natural estrogen 17-estradiol (E₂) via the C16-hydroxylation pathway is elevated in patients with breast cancer, in subjects at increased risk for developing breast cancer, and in c-Ha-ras-initiated mouse mammary epithelial cells.

PURPOSE: To determine Whether differences in the extent of E₂ C16-hydroxylation are related to the risk of developing breast cancer, we examined the extent of biotransformation of E₂ via the C16-hydroxylation pathway in the mamary terminal duct lobular units (TDLUs), epithelial organoids that are a presumptive taarget site of human breast carcinogenesis, and in nontarget component mammary fat tissue.

METHODS: Noninvolved mamary tissue was obtained from four patients undergoing reduction mamoplasty and from four undergoing mastectomy for breast cancer. A radiometric assay that measures ³H₂O formation caused by stoichiometric ³H exchange from [C16-³H]E₂ was utilized to compare the relative extent of C16-hydroxylation in explant cultures of TDLUs and mammary fat.

RESULTS: The extent of E₂ C16-hydroxylation was 1.83-fold higher (95% confidence interval [CI] = 1.71.1.97) in the TDLUs from reduction mammoplasty (i.e., "low-risk") patients and 7.96-fold higher (95% CI = 6.38.10.55) in the TDLUs from mastectomy (i.e., "high-risk") patients than in the correspondin values observed in the mammary fat. In the TDLUs obtained from the patients undergoing mastectomy for cancer, the extent of this metabolism was 4.56-fold higher (95% CI = 3.97-5.33) than that observed in TDLUs obtained from reduction mammoplasty patients who did not have cancer.

CONCLUSION: The increase in the extent of C16-hydroxylation of E₂ in the epithelial organoids of the human breast, TDLUs in particular, may be an important factor for breast cancer induction. This upregulation may represent an endocrine biomarker for the risk of developing breast cancer.

IMPLICATION: A large prospective study is required to confirm the clinical significance of this endocrine biomaarker. [J. Natl Cancer Inst 85:1971–1920, 1993]

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