title: Molecular changes in lobular breast cancers in response to endocrine therapy.
abstract: Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor-positive (ER(+)) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment.
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Arthur
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Arran K
authors.initials: AK
authors.lastname: Turnbull
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Webber
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Larionov
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Lorna
authors.initials: L
authors.lastname: Renshaw
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Charlene
authors.initials: C
authors.lastname: Kay
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Thomas
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom. andrew.sims@ed.ac.uk mike.dixon@ed.ac.uk.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Dixon
authors.affiliation: Edinburgh Breast Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom. andrew.sims@ed.ac.uk mike.dixon@ed.ac.uk.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Sims
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole