title: Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer.
abstract: The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor α (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the ErbB receptors or downstream effectors may repress ER expression. Here the authors investigated whether gefitinib, given neoadjuvant in combination with epirubicin and cyclophosphamide (EC), could restore ER expression. Eligible patients in the NICE trial were women with unilateral, primary operable, ER negative invasive breast cancer ≥ 2 cm. Material from patients randomized and completing treatment (four cycles of neoadjuvant EC plus 12 weeks of either gefitinib or placebo) in the NICE trial having available ER status both at baseline and after neoadjuvant treatment were eligible for this study. Tumors with indication of changed ER phenotype (based on collected pathology reports) were immunohistochemically reassessed centrally. 115 patients were eligible for this study; 59 patients in the gefitinib group and 56 patients in the placebo group. Five (4.3%) of 115 tumors changed ER phenotype from negative to positive. A change was seen in three patients in the gefitinib (5.1%) and in two patients in the placebo (3.6%) group with a difference of 1.51% (95% CI, -6.1-9.1). Results of the NICE trial have been reported previously. Post-operative reassessment of ER expression changed the assessment of ER status in a small but significant fraction of patients and should, whenever possible, be performed following neoadjuvant chemotherapy for ER negative breast cancer. Gefitinib did not affect the reversion rate of ER negative tumors.
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. mogenspetersen@gmail.com
authors.forename: Mogens
authors.initials: M
authors.lastname: Bernsdorf
authors.forename: Eva
authors.initials: E
authors.lastname: Balslev
authors.forename: Anne E
authors.initials: AE
authors.lastname: Lykkesfeldt
authors.forename: Niels
authors.initials: N
authors.lastname: Kroman
authors.forename: Eva
authors.initials: E
authors.lastname: Harder
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
authors.forename: Erik H
authors.initials: EH
authors.lastname: Jakobsen
authors.forename: Dorthe
authors.initials: D
authors.lastname: Grabau
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010641:Phenotype; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D000077156:Gefitinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human