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This version published online on November 22, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1967
A more recent version of this article appeared on February 1, 2006
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Submitted on September 1, 2005
Accepted on November 15, 2005

Estrogen-metabolizing enzymes in breast cancers from women over the age of 80

Naoko Honma*, Kaiyo Takubo, Motoji Sawabe, Tomio Arai, Futoshi Akiyama, Goi Sakamoto, Toshiaki Utsumi, Noriko Yoshimura, and Nobuhiro Harada

Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Tokyo; Department of Pathology, Tokyo Metropolitan Geriatric Medical Center, Tokyo; Department of Breast Pathology, Cancer Institute, Tokyo; Department of Surgery, Fujita Health University School of Medicine, Toyoake, Aichi; Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Aichi

* To whom correspondence should be addressed. E-mail: nhonma{at}tmig.or.jp.

Context. Aromatase, steroid sulfatase (STS), and 17{beta}-hydroxysteroid dehydrogenase type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase (EST) and 17{beta}-hydroxysteroid dehydrogenase type 2 (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) were compared with those from 39 controls (age 37-70), or compared according to estrogen (ER)/progesterone receptor (PR) status.

Results. Aromatase levels were higher in cancers of the elderly (EldCa) than normal tissue of the elderly (EldNorm, P = 0.0008) or cancers of controls (ContCa, P = 0.0033). In contrast, levels of STS and EST were higher in ContCa than normal tissue of controls (ContNorm, 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 ER/PR-negative carcinomas whereas EST and HSD-2 exhibited the 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.
Key words: breast cancer • elderly • aromatase • steroid sulfatase (STS) • estrogen sulfotransferase (EST) • 17{beta}-hydroxysteroid dehydrogenase type 1 (HSD-1) • 17{beta}-hydroxysteroid dehydrogenase type 2 (HSD-2) • apocrine carcinoma • mucinous carcinoma • estrogen receptor • progesterone receptor




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