Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.

Abstract

Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P < 0.0001) and intratumoral 17βHSD2 was inversely correlated with tumor size in ILC (P = 0.0075). These correlations suggest one protective mode of androgen action could be through modulation of estrogen metabolism. Results of our present study indicated that androgen-producing enzymes could play pivotal protective roles in AR-enriched ILC cases.

• Authors: Tomomi Yoda, Keely May McNamara, Yasuhiro Miki, Mayu Takagi, Yoshiaki Rai, Yasuyo Ohi, Yasuaki Sagara, Kentaro Tamaki, Hisashi Hirakawa, Takanori Ishida, Takashi Suzuki, Noriaki Ohuchi, Hironobu Sasano
• Journal: Cancer science (Cancer Sci) Vol. 105 Issue 11 Pg. 1503-9 (Nov 2014) ISSN: 1349-7006 [Electronic] England
• PMID: 25230018 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• Androgens
• Biomarkers, Tumor
• Estradiol Dehydrogenases
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Topics

• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (genetics, metabolism)
• Adult
• Aged
• Aged, 80 and over
• Androgens (metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Lobular (genetics, metabolism, pathology)
• Estradiol Dehydrogenases (genetics, metabolism)
• Female
• Humans
• Middle Aged
• Neoplasm Grading
• Neoplasm Invasiveness
• Neoplasm Staging
• Tumor Burden