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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2016

01-02-2016 | Preclinical study

Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas

Authors: Mayu Takagi, Yasuhiro Miki, Minoru Miyashita, Shuko Hata, Tomomi Yoda, Hisashi Hirakawa, Yasuaki Sagara, Yoshiaki Rai, Yasuyo Ohi, Kentaro Tamaki, Takanori Ishida, Takashi Suzuki, Noriaki Ouchi, Hironobu Sasano

Published in: Breast Cancer Research and Treatment | Issue 1/2016

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Abstract

The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.
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Metadata
Title
Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas
Authors
Mayu Takagi
Yasuhiro Miki
Minoru Miyashita
Shuko Hata
Tomomi Yoda
Hisashi Hirakawa
Yasuaki Sagara
Yoshiaki Rai
Yasuyo Ohi
Kentaro Tamaki
Takanori Ishida
Takashi Suzuki
Noriaki Ouchi
Hironobu Sasano
Publication date
01-02-2016
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-3739-6

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