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Biological profiles of endocrine breast cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0002-7498-7157
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university , 2015. , 82 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 123
Keyword [en]
Endocrine breast cancer, tamoxifen, Foxl2, Wwox, ErbB4, HER4, gene expression, randomized patients
National Category
Cancer and Oncology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-43963ISBN: 978-91-7529-071-3 (print)OAI: oai:DiVA.org:oru-43963DiVA: diva2:799253
Public defence
2015-05-29, Universitetssjukhuset, Wilandersalen, Södra Grev Rosengatan, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Cancer SocietyCancer and Allergy Foundation
Note

Funding: Magnus Bergvall Cancer Foundation; Percy Falk foundation for research in breast and prostate cancer; Nyckelfonden; Örebro University Hospital; Lions cancer research foundation, Region Uppsala-Örebro

Available from: 2015-03-30 Created: 2015-03-30 Last updated: 2015-12-21Bibliographically approved
List of papers
1. Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen
Open this publication in new window or tab >>Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen
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2011 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 38, no 4, 1145-1151 p.Article in journal (Refereed) Published
Abstract [en]

Aromatase is an important enzyme in the local synthesis of oestrogens and its expression has been shown to be increased in breast cancer through the activation of multiple promoters. However, the mechanisms behind this are not yet fully understood. A novel candidate in this context is the transcription factor forkhead box L2 (FOXL2), which has been recognised to be co-expressed with aromatase and transcriptionally active promoter 11 in developing goat and chicken ovaries. We propose that FOXL2 could be involved in the increased expression of aromatase in breast cancer. We examined FOXL2 and its relation to aromatase in 132 postmenopausal breast cancer patients by immunohistochemistry. Using in silico analysis, we further searched for FOXL2 binding-elements in the aromatase gene promoters. The results demonstrate that FOXL2 is expressed in breast cancer and influences clinical outcome with improved recurrence-free survival in cases with nuclear expression. In a multivariate Cox model, nuclear FOXL2 was a significant prognostic factor in ER-positive patients treated with tamoxifen (HR=0.18, 95% confidence interval (CI)=0.04-0.81, P=0.03). Tumours expressing nuclear FOXL2 were also more likely positive for stromal and/or cytoplasmic aromatase (P=0.03 and P=0.008, respectively). In silico analyses revealed binding elements of FOXL2 in promoters 1.3, 11 and 17 of the aromatase gene of which promoter 1.7 was most significant. In conclusion, this is the first study to report that FOXL2 is expressed in breast cancer and correlates with aromatase as well as with clinical outcome. The results further strengthen a possible binding of FOXL2 to aromatase promoter 1.7. Nevertheless, whether FOXL2 is a direct activator of aromatase requires further investigation.

Keyword
breast cancer, forkhead box L2, aromatase, tissue specific promoters, in silico
National Category
Cancer and Oncology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-16840 (URN)10.3892/ijo.2011.923 (DOI)000288581100027 ()21271216 (PubMedID)2-s2.0-79952329924 (Scopus ID)
Available from: 2011-09-02 Created: 2011-09-02 Last updated: 2017-03-26Bibliographically approved
2. Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients
Open this publication in new window or tab >>Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients
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2013 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 29, no 4, 1467-1474 p.Article in journal (Refereed) Published
Abstract [en]

Reduced or absent Wwox expression has recently been associated with tamoxifen resistance in breast cancer and has also been proposed as a candidate predictive marker for treatment. We aimed to investigate the correlation of Wwox expression with the outcome of tamoxifen treatment by examining tissues from 912 randomized breast cancer patients. Paraffin-embedded tissues from patient tumors were arranged on tissue microarray, and Wwox protein was stained using immunohistochemistry. After microscopic examination, the results were analyzed with Cox regression, Kaplan-Meier survival curves and the log-rank test. In the group of cases having a tumor absent for Wwox expression, there was no difference in recurrence-free survival between treated and untreated patients (P=0.81). For treated cases with a tumor expressing moderate or strong Wwox protein, recurrence-free survival was improved (P=0.001 and P=0.003, respectively). The test for interaction between Wwox and treatment response demonstrated a decreased risk of recurrence for treated patients with a moderate or strong Wwox expression (HR=0.31, 95% CI 0.10-0.98 and HR=0.28, 95% CI 0.08-0.97, respectively). Our results indicate that patients with high expression of Wwox may gain more benefit from treatment with tamoxifen.

Place, publisher, year, edition, pages
Athens, Greece: Spandidos Publications, 2013
Keyword
Wwox, breast cancer, tamoxifen, randomized patients
National Category
Cancer and Oncology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-41720 (URN)10.3892/or.2013.2261 (DOI)000316510600028 ()23381945 (PubMedID)2-s2.0-84874702740 (Scopus ID)
Available from: 2015-01-15 Created: 2015-01-15 Last updated: 2017-03-17Bibliographically approved
3. HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen
Open this publication in new window or tab >>HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen
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(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Keyword
Breast cancer, ErbB4, HER4, randomized patients, tamoxifen
National Category
Cancer and Oncology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-44646 (URN)
Available from: 2015-05-18 Created: 2015-05-18 Last updated: 2016-12-05Bibliographically approved
4. Gene expression profiles in breast tumors from tamoxifen treated patients with and without distant recurrence
Open this publication in new window or tab >>Gene expression profiles in breast tumors from tamoxifen treated patients with and without distant recurrence
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(English)Manuscript (preprint) (Other academic)
Keyword
Breast cancer, gene expression, microarray, tamoxifen
National Category
Cancer and Oncology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-44650 (URN)
Available from: 2015-05-18 Created: 2015-05-18 Last updated: 2016-12-08Bibliographically approved

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