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Estrogen-Metabolizing Enzymes in Breast Cancers from Women over the Age of 80 Years

Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology (N.H., K.T.), Tokyo 173-0015, Japan; Department of Pathology, Tokyo Metropolitan Geriatric Medical Center (M.S., T.A.), Tokyo 173-0015, Japan; Department of Breast Pathology, Cancer Institute (F.A., G.S.), Tokyo 135-8550, Japan; and Departments of Surgery (T.U.) and Biochemistry (N.Y., N.H.), Fujita Health University School of Medicine, Toyoake 470-1192, Japan

Address all correspondence and requests for reprints to: Dr. Naoko Honma, Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Sakaecho 35-2, Itabashi-ku, Tokyo 173-0015, Japan. E-mail: nhonma{at}tmig.or.jp.

Context: Aromatase, steroid sulfatase, and 17ß-hydroxysteroid dehydrogenase type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase (EST) and HSD-2 down-regulate, the synthesis of active and more potent estrogens. These estrogen-metabolizing enzymes (EMEs) are important in postmenopausal breast cancers, but have never been systematically examined in breast cancers of the elderly.

Objective and Design: mRNA levels of EMEs in cancerous and normal breast tissues from 39 elderly patients (age, 80–99 yr) were compared with those from 39 controls (age, 37–70 yr) or compared according to estrogen (ER)/progesterone (PR) receptor status.

Results: Aromatase levels were higher in cancers of the elderly (EldCa) than in normal tissue of the elderly (P = 0.0008) or cancers of controls (P = 0.0033). In contrast, levels of steroid sulfatase and EST were higher in cancers of controls than normal tissue of controls (P = 0.0046 and P < 0.0001, respectively) or EldCa (P = 0.0001 and P < 0.0001, respectively). Levels of HSD-1 and HSD-2 did not differ significantly between any two of the categories. Among EldCa, HSD-1 levels were higher in ER/PR-positive than in ER/PR-negative carcinomas, whereas EST and HSD-2 exhibited opposite results.

Conclusions: The importance of aromatase is relatively increased in EldCa. ER/PR-positive EldCa exhibited a pattern of EMEs more beneficial to the production of estrogen than did ER/PR-negative EldCa. The specific pattern exhibited in EldCa may elucidate the role of EMEs in the absence of ovarian estrogens in the pathogenesis of breast cancer.

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