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  • Jirström, KarinLund University,Lunds universitet,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden (author)

Adverse effect of adjuvant tamoxifen in premenopausal breast cancer with cyclin D1 gene amplification

  • Article/chapterEnglish2005

Publisher, publication year, extent ...

  • 2005
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:liu-30238
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-30238URI
  • https://doi.org/10.1158/0008-5472.CAN-05-0746DOI
  • https://lup.lub.lu.se/record/143874URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • Cyclins D1 and A2 are cell cycle regulators that also have the ability to interact with the estrogen receptor (ER) and consequently interfere with antiestrogen treatment in breast cancer. Experimental data support this concept, but the clinical relevance needs to be further established. In this study, we evaluated cyclin D1 and A2 protein expression by immunohistochemistry and cyclin D1 gene (CCND1) amplification by fluorescence in situ hybridization in 500 primary breast cancers arranged in tissue microarrays. Patients had been randomized to 2 years of adjuvant tamoxifen or no treatment with a median follow-up of 14 years, allowing for subgroup analysis of treatment response defined by cyclin status. We found that both cyclin D1 and A2 protein overexpression was associated with an impaired tamoxifen response, although not significant in multivariate interaction analyses, whereas tamoxifen-treated patients with CCND1-amplified tumors had a substantially increased risk for disease recurrence after tamoxifen treatment in univariate analyses [relative risk (RR), 2.22; 95% confidence interval (95% CI), 0.94-5.26; P = 0.06] in contrast to nonamplified tumors (RR, 0.39; 95% CI, 0.23-0.65; P < 0.0001). Consequently, a highly significant interaction between tamoxifen treatment and CCND1 amplification could be shown regarding both recurrence-free survival (RR, 6.38; 95% CI, 2.29-17.78; P < 0.001) and overall survival (RR, 5.34; 95% CI, 1.84-15.51; P = 0.002), suggesting an agonistic effect of tamoxifen in ER-positive tumors. In node-positive patients, the disparate outcome according to gene amplification status was even more accentuated. In summary, our data implicate that despite a significant correlation to cyclin D1 protein expression, amplification status of the CCND1 gene seems a strong independent predictor of tamoxifen response, and possibly agonism, in premenopausal breast cancer.

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  • Stendahl, MariaLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups,Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden(Swepub:lu)pat-sma (author)
  • Rydén, LisaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden(Swepub:lu)pat-lry (author)
  • Kronblad, ÅsaLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups,Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden(Swepub:lu)pat-akr (author)
  • Bendahl, Pär-OlaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Oncology, University Hospital, Lund, Sweden(Swepub:lu)onk-pbe (author)
  • Stål, Olle,1952-Linköpings universitet,Onkologi,Hälsouniversitetet(Swepub:liu)ollst87 (author)
  • Landberg, GöranLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups,Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden(Swepub:lu)pat-gla (author)
  • Sektion VInstitutionen för kliniska vetenskaper, Lund (creator_code:org_t)

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  • In:Cancer Research65:17, s. 8009-80160008-54721538-7445

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By the author/editor
Jirström, Karin
Stendahl, Maria
Rydén, Lisa
Kronblad, Åsa
Bendahl, Pär-Ola
Stål, Olle, 1952 ...
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Landberg, Göran
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MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
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and Cancer and Oncol ...
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Cancer Research
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Linköping University
Lund University

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