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17 beta-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in premenopausal breast cancer

Kallstrom, Ann-Christine; Salme, Rebecka; Rydén, Lisa LU ; Nordenskjold, Bo; Jönsson, Per-Ebbe LU and Stal, Olle (2010) In European Journal of Cancer 46(5). p.892-900
Abstract
17 beta-Hydroxysteroid dehydrogenases (17HSDs) are involved in the local regulation of sex steroids. 17HSD1 converts oestrone (El) to the more potent oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these enzymes in premenopausal breast cancers and to analyse if they have any prognostic or tamoxifen predictive value. Premenopausal patients with invasive breast cancer, stage II (UICC), were randomised to either 2 years of adjuvant tamoxifen (n = 276) or no tamoxifen (n = 288). The median follow-up was 13.9 years (range 10.5-17.5). The expression of 17HSD1 and 17HSD2 was analysed with immunohistochemistry using tissue microarrays. The enzyme expression level (-/+/++/+++)... (More)
17 beta-Hydroxysteroid dehydrogenases (17HSDs) are involved in the local regulation of sex steroids. 17HSD1 converts oestrone (El) to the more potent oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these enzymes in premenopausal breast cancers and to analyse if they have any prognostic or tamoxifen predictive value. Premenopausal patients with invasive breast cancer, stage II (UICC), were randomised to either 2 years of adjuvant tamoxifen (n = 276) or no tamoxifen (n = 288). The median follow-up was 13.9 years (range 10.5-17.5). The expression of 17HSD1 and 17HSD2 was analysed with immunohistochemistry using tissue microarrays. The enzyme expression level (-/+/++/+++) was successfully determined in 396 and 373 tumours, respectively. Women with hormone-receptor positive tumours, with low levels (-/+/++) of 17HSD1, had a 43% reduced risk of recurrence, when treated with tamoxifen (Hazard Ratio (HR) = 0.57; 95% confidence interval (CI), 0.37-0.86; p = 0.0086). On the other hand high expression (+++) of 17HSD1 was associated with no significant difference between the two treatment arms (HR = 0.91; 95% CI, 0.43-1.95; p = 0.82). The interaction between 17HSD1 and tamoxifen was significant during the first 5 years of follow-up (p = 0.023). In the cohort of systemically untreated patients no prognostic importance was observed for 17HSD1. We found no predictive or prognostic value for 17HSD2. This is the first report of 17HSD1 in a cohort of premenopausal women with breast cancer randomised to tamoxifen. Our data suggest that 17HSD1 might be a predictive factor in this group of patients. (C) 2009 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Premenopausal women, Oestrogens, Treatment prediction, Predictive marker, Tamoxifen, HSD17B1, Breast cancer, 17 beta-Hydroxysteroid dehydrogenases
in
European Journal of Cancer
volume
46
issue
5
pages
892 - 900
publisher
IFAC & Elsevier Ltd.
external identifiers
  • wos:000276755800016
  • scopus:77349107688
ISSN
1879-0852
DOI
10.1016/j.ejca.2009.12.016
language
English
LU publication?
yes
id
e0809d59-6efa-4976-b664-fd2f5ff7ef5c (old id 1603105)
date added to LUP
2010-05-19 10:01:06
date last changed
2018-06-03 03:07:10
@article{e0809d59-6efa-4976-b664-fd2f5ff7ef5c,
  abstract     = {17 beta-Hydroxysteroid dehydrogenases (17HSDs) are involved in the local regulation of sex steroids. 17HSD1 converts oestrone (El) to the more potent oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these enzymes in premenopausal breast cancers and to analyse if they have any prognostic or tamoxifen predictive value. Premenopausal patients with invasive breast cancer, stage II (UICC), were randomised to either 2 years of adjuvant tamoxifen (n = 276) or no tamoxifen (n = 288). The median follow-up was 13.9 years (range 10.5-17.5). The expression of 17HSD1 and 17HSD2 was analysed with immunohistochemistry using tissue microarrays. The enzyme expression level (-/+/++/+++) was successfully determined in 396 and 373 tumours, respectively. Women with hormone-receptor positive tumours, with low levels (-/+/++) of 17HSD1, had a 43% reduced risk of recurrence, when treated with tamoxifen (Hazard Ratio (HR) = 0.57; 95% confidence interval (CI), 0.37-0.86; p = 0.0086). On the other hand high expression (+++) of 17HSD1 was associated with no significant difference between the two treatment arms (HR = 0.91; 95% CI, 0.43-1.95; p = 0.82). The interaction between 17HSD1 and tamoxifen was significant during the first 5 years of follow-up (p = 0.023). In the cohort of systemically untreated patients no prognostic importance was observed for 17HSD1. We found no predictive or prognostic value for 17HSD2. This is the first report of 17HSD1 in a cohort of premenopausal women with breast cancer randomised to tamoxifen. Our data suggest that 17HSD1 might be a predictive factor in this group of patients. (C) 2009 Elsevier Ltd. All rights reserved.},
  author       = {Kallstrom, Ann-Christine and Salme, Rebecka and Rydén, Lisa and Nordenskjold, Bo and Jönsson, Per-Ebbe and Stal, Olle},
  issn         = {1879-0852},
  keyword      = {Premenopausal women,Oestrogens,Treatment prediction,Predictive marker,Tamoxifen,HSD17B1,Breast cancer,17 beta-Hydroxysteroid dehydrogenases},
  language     = {eng},
  number       = {5},
  pages        = {892--900},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {17 beta-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in premenopausal breast cancer},
  url          = {http://dx.doi.org/10.1016/j.ejca.2009.12.016},
  volume       = {46},
  year         = {2010},
}