title: miR-21 Expression in Cancer Cells may Not Predict Resistance to Adjuvant Trastuzumab in Primary Breast Cancer.
abstract: Trastuzumab is established as standard care for patients with HER2-positive breast cancer both in the adjuvant and metastatic setting. However, 50% of the patients do not respond to the trastuzumab therapy, and therefore new predictive biomarkers are highly warranted. MicroRNAs (miRs) constitute a new group of biomarkers and their cellular expression can be determined in tumor samples by in situ hybridization (ISH) analysis. miR-21 is highly prevalent and up-regulated in breast cancer and has been linked to drug resistance in clinical and in vitro settings. To determine expression patterns of miR-21 in high-grade breast cancers, we examined miR-21 expression in 22 HER2-positive tumors and 15 HER2-negative high-grade tumors by ISH. The histological examination indicated that patient samples could be divided into three major expression patterns: miR-21 predominantly in tumor stroma, predominantly in cancer cells, or in both stromal and cancer cells. There was no obvious difference between the HER2-positive and HER2-negative tumors in terms of the miR-21 expression patterns and intensities. To explore the possibility that miR-21 expression levels and/or cellular localization could predict resistance to adjuvant trastuzumab in HER2-positive breast cancer patients, we analyzed additional 16 HER2-positive tumors from patients who were treated with trastuzumab in the adjuvant setting. Eight of the 16 patients showed clinical recurrence and were considered resistant. Examination of the miR-21 expression patterns and intensities revealed no association between the miR-21 scores in the cancer cell population (p = 0.69) or the stromal cells population (p = 0.13) and recurrent disease after adjuvant trastuzumab. Thus, our findings show that elevated miR-21 expression does not predict resistance to adjuvant trastuzumab.
authors.affiliation: Bioneer A/S , Hørsholm , Denmark.
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.affiliation: Department of Pathology, Herlev Hospital, University of Copenhagen , Herlev , Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Balslev
authors.affiliation: Department of Pathology, Herlev Hospital, University of Copenhagen , Herlev , Denmark.
authors.forename: Tim Svenstrup
authors.initials: TS
authors.lastname: Poulsen
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen , Herlev , Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Nielsen
authors.affiliation: Bioneer A/S , Hørsholm , Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Møller
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen , Herlev , Denmark.
authors.forename: Christiane Ehlers
authors.initials: CE
authors.lastname: Mortensen
authors.affiliation: Bioneer A/S , Hørsholm , Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Holmstrøm
authors.affiliation: Department of Pathology, Herlev Hospital, University of Copenhagen , Herlev , Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
keywords: HER2; biomarker; breast cancer; miR-21; prediction; response; trastuzumab