title: Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial.
abstract: Trastuzumab and lapatinib are established treatments for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer with different mechanisms of action. The focus of this study is to investigate, whether altered expression levels of potentially relevant microRNAs (miRs) in serum are associated with response to trastuzumab or lapatinib. Circulating miR-21, miR-210, and miR-373 were quantified with TaqMan MicroRNA assays in serum of 127 HER2-postive breast cancer patients before and after neoadjuvant therapy and in 19 healthy controls. Patients received chemotherapy combined with either trastuzumab or lapatinib within the prospectively randomized Geparquinto trial. The association between miR levels and pathological response (pCR) to therapy and type of therapy was examined. Serum levels of miR-21 (p = 5.04e-08, p = 1.43e-10), miR-210 (p = 0.00151, p = 1.6e-05), and miR-373 (p = 7.87e-06, p = 1.75e-07) were significantly higher in patients before and after chemotherapy than in healthy women. Concentrations of miR-21 (p = 5.73e-08), miR-210 (p = 0.000724), and miR-373 (p = 0.00209) increased further after chemotherapy. A significant association of higher serum levels of miR-373 with advanced clinical tumor stage could be detected (p < 0.002). An association of miR-21 levels before (p = 0.0091) and after (p = 0.037) chemotherapy with overall survival of the patients could be detected, independent of type of anti-HER2 therapy. No association of circulating miRs with pCR was found. Our findings demonstrate a specific influence of neoadjuvant therapy on the serum levels of miR-21, miR-210, and miR-373 in breast cancer patients together with a prognostic value of miR-21.
authors.affiliation: Clinic of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.forename: Stephan
authors.initials: S
authors.lastname: Gade
authors.forename: Bettina
authors.initials: B
authors.lastname: Steinbach
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schwedler
authors.forename: Kristina
authors.initials: K
authors.lastname: Lübbe
authors.forename: Christian
authors.initials: C
authors.lastname: Schem
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Christine
authors.initials: C
authors.lastname: Mau
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Heidi
authors.initials: H
authors.lastname: Schwarzenbach
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D057170:Translational Research, Biomedical; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D035683:MicroRNAs; D011799:Quinazolines; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C524940:MIRN21 microRNA, human; C543800:MIRN210 microRNA, human; C527114:MIRN373 microRNA, human; C508053:ERBB2 protein, human