title: Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer--results from the GeparQuattro study (GBG 40).
abstract: Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P = 0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2-0.9), P = 0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r = 0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r = 0.892) and after treatment (r = 0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P = 0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.
authors.affiliation: German Breast Group, c/o GBG Forschungs GmbH, Martin-Behaim-Straße 12, 63263 Neu-Isenburg, Germany. Gunter.vonMinckwitz@germanbreastgroup.de
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Hans
authors.initials: H
authors.lastname: Tesch
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.forename: Frank
authors.initials: F
authors.lastname: Holms
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Dietrich
authors.forename: Marianne
authors.initials: M
authors.lastname: Just
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clemens
authors.forename: Claus
authors.initials: C
authors.lastname: Hanusch
authors.forename: Iris
authors.initials: I
authors.lastname: Schrader
authors.forename: Stephan
authors.initials: S
authors.lastname: Henschen
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoffmann
authors.forename: Katharina
authors.initials: K
authors.lastname: Tiemann
authors.forename: Kurt
authors.initials: K
authors.lastname: Diebold
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000069287:Capecitabine; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human