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Increased estrogen sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1(17β-HSD1) following neoadjuvant aromatase inhibitor therapy in breast cancer patients

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Abstract

Aromatase inhibitors (AIs) are considered the gold standard for endocrine therapy of estrogen receptor (ER) positive postmenopausal breast cancer patients. The therapy may enhance therapeutic response and stabilize disease but resistance and disease progression inevitably occur in the patients. These are considered at least partly due to an emergence of alternative intratumoral estrogen production pathways. Therefore, in this study we evaluated effects of exemestane (EXE) upon the enzymes involved in intratumoral estrogen production including estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), and estrogen sulfotransferase (EST) and correlated the findings with therapeutic responses including Ki67 labeling index (Ki67). 116 postmenopausal patients with invasive ductal carcinoma, stage II/IIIa, were enrolled in JFMC34-0601 clinical trials between March, 2006 and January, 2008. EXE of 25 mg/day was administered according to the protocol. Pre- and posttreatment specimens of 49 cases were available for this study. Status of STS, EST, 17β-HSD1, ER, progesterone receptor (PgR), human epidermal growth factor receptor type 2 (Her2), and Ki67 in pre- and post-specimens were evaluated. Specimens examined before the therapy demonstrated following features; ER+ (100%), PgR+ (85.7%), and Her2+ (77.6%). After treatment, the number of Ki67, PgR, and ER positive carcinoma cells demonstrated significant decrement in clinical response (CliR) and pathological response (PaR) groups. Significant increment of 17β-HSD1 and STS immunoreactivity was detected in all groups examined except for STS in PaR. EST showed significant increment in nonresponsive groups. Alterations of Ki67 of carcinoma cells before and after therapy were subclassified into three groups according to its degrees. Significant alterations of intratumoral enzymes, especially 17β-HSD1 and STS, were correlated with Ki67 reduction after neoadjuvant EXE therapy. This is the first study demonstrating significant increment of STS and 17β-HSD1 following AI neoadjuvant therapy of postmenopausal ER positive breast carcinoma patients. This increment may represent the compensatory response of breast carcinoma tissues to estrogen depletion.

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Acknowledgments

We thank the local hospital pathologists who performed tumor sample analysis and other clinicians who were not part of the research team, but took responsibility for patient management. Japanese Foundation for Multidisciplinary Treatment of Cancer was responsible for collating the data in a database. We also thank Kyowa medix co. Ltd Japan for providing a kit of STS antibody.

Disclosure/conflict of interest

Hironobu Sasano and Yasuhiro Miki received the educational research grant from Pfizer Japan Inc., Tokyo, Japan.

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Authors and Affiliations

  1. Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryou-machi, Aoba-Ku, Sendai, Miyagi, Japan, 980-8575

    Niramol Chanplakorn, Takashi Suzuki, Katsuhiko Ono, Monica S. M. Chan, Yasuhiro Miki & Hironobu Sasano

  2. Department of Orthopaedic, Tohoku University School of Medicine, Sendai, Japan

    Pongsthorn Chanplakorn

  3. Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Niramol Chanplakorn

  4. Department of Orthopaedic, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Pongsthorn Chanplakorn

  5. UNIMED Medical Institute, Hong Kong SAR, China

    Monica S. M. Chan

  6. Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan

    Shigetoyo Saji

  7. Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Takayuki Ueno

  8. Department of Surgery and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Masakazu Toi

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  1. Niramol Chanplakorn
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Correspondence to Hironobu Sasano.

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Chanplakorn, N., Chanplakorn, P., Suzuki, T. et al. Increased estrogen sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1(17β-HSD1) following neoadjuvant aromatase inhibitor therapy in breast cancer patients. Breast Cancer Res Treat 120, 639–648 (2010). https://doi.org/10.1007/s10549-010-0785-3

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  • DOI: https://doi.org/10.1007/s10549-010-0785-3

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