IHC-based Ki67 as response biomarker to tamoxifen in breast cancer window trials enrolling premenopausal women.
Autor: | Joosten SEP; Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Wellenstein M; WSK Medical B.V, Amsterdam, The Netherlands., Koornstra R; Department of Internal Medicine and Medical Oncology, Rijnstate hospital, Arnhem, The Netherlands., van Rossum A; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Sanders J; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van der Noort V; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Ferrandez MC; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Harkes R; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Mandjes IAM; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Rosing H; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Amsterdam, The Netherlands., Huitema A; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands., Beijnen JH; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Wesseling J; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., van Diest PJ; Department of Pathology, University Medical Centre, Utrecht, The Netherlands., Horlings HM; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. h.horlings@nki.nl., Linn SC; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. s.linn@nki.nl.; Department of Pathology, University Medical Centre, Utrecht, The Netherlands. s.linn@nki.nl.; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. s.linn@nki.nl., Zwart W; Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands. w.zwart@nki.nl.; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. w.zwart@nki.nl. |
---|---|
Jazyk: | angličtina |
Zdroj: | NPJ breast cancer [NPJ Breast Cancer] 2021 Oct 20; Vol. 7 (1), pp. 138. Date of Electronic Publication: 2021 Oct 20. |
DOI: | 10.1038/s41523-021-00344-3 |
Abstrakt: | Window studies are gaining traction to assess (molecular) changes in short timeframes. Decreased tumor cell positivity for the proliferation marker Ki67 is often used as a proxy for treatment response. Immunohistochemistry (IHC)-based Ki67 on tissue from neo-adjuvant trials was previously reported to be predictive for long-term response to endocrine therapy for breast cancer in postmenopausal women, but none of these trials enrolled premenopausal women. Nonetheless, the marker is being used on this subpopulation. We compared pathologist assessed IHC-based Ki67 in samples from pre- and postmenopausal women in a neo-adjuvant, endocrine therapy focused trial (NCT00738777), randomized between tamoxifen, anastrozole, or fulvestrant. These results were compared with (1) IHC-based Ki67 scoring by AI, (2) mitotic figures, (3) mRNA-based Ki67, (4) five independent gene expression signatures capturing proliferation, and (5) blood levels for tamoxifen and its metabolites as well as estradiol. Upon tamoxifen, IHC-based Ki67 levels were decreased in both pre- and postmenopausal breast cancer patients, which was confirmed using mRNA-based cell proliferation markers. The magnitude of decrease of Ki67 IHC was smaller in pre- versus postmenopausal women. We found a direct relationship between post-treatment estradiol levels and the magnitude of the Ki67 decrease in tumors. These data suggest IHC-based Ki67 may be an appropriate biomarker for tamoxifen response in premenopausal breast cancer patients, but anti-proliferative effect size depends on estradiol levels. (© 2021. The Author(s).) |
Databáze: | MEDLINE |
Externí odkaz: |