title: Insulin-like growth factor receptor-1 (IGF-1R) expression in normal breast, proliferative breast lesions, and breast carcinoma.
abstract: Insulin-like growth factor receptor 1 (IGF-1R) is a receptor protein tyrosine kinase that is activated by ligand (IGF-1) binding and promotes mitogenic, metastatic, and antiapoptotic phenotypes of breast cancer. There is a dearth of studies analyzing IGF-1R expression by immunohistochemistry in breast carcinoma. This biomarker analysis will be important for pharmacologic interventions that target the IGF system. IGF-1R expression pattern was first analyzed in normal breast tissue and a variety of breast lesions (71 diagnoses from 35 patients), followed by analysis in 191 consecutive invasive breast carcinomas. Furthermore, 86 carcinomas treated with neoadjuvant chemotherapy were also analyzed. The carcinomas were classified using immunohistochemical surrogate (to molecular classes) markers-estrogen receptors (ER), progesterone receptors, and human epidermal growth factor receptor 2. IGF-1R is expressed at moderate level in normal breast tissue which was considered as normal expression. Overexpression and lower expression were defined as higher than normal or lower than normal expression, respectively. Among the benign and noninvasive breast lesions, IGF-1R expression was slightly increased in lesions that are hormonally driven (such as atypical ductal hyperplasia and columnar cells changes) whereas it was significantly reduced in ER-negative lesions (such as apocrine metaplasia). Similarly, in 191 consecutive breast carcinomas, IGF-1R overexpression was predominantly seen in ER-positive+ tumors. The tumor group that consistently showed reduced expression was the ERBB2 group (ER negative/progesterone receptors negative/human epidermal growth factor receptor 2 positive). The expression was somewhat heterogeneous in the triple-negative group. IGF-1R expression was not predictive of pathologic complete response or tumor volume reduction in ER-negative tumors, but reduced IGF-1R was associated with pathologic complete response and significant tumor volume reduction in ER+ tumors. Therapies targeting IGF-1R will be useful in majority of ER+ and a subset of triple-negative tumors that express IGF-1R. The consistent presence of IGF-1R in ER+ tumors may explain the lower response rate to neoadjuvant chemotherapy in luminal tumors.
authors.affiliation: Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. rbhargava@mail.magee.edu
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhargava
authors.forename: Sushil
authors.initials: S
authors.lastname: Beriwal
authors.forename: Kim
authors.initials: K
authors.lastname: McManus
authors.forename: David J
authors.initials: DJ
authors.lastname: Dabbs
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D011230:Precancerous Conditions; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011960:Receptors, Estrogen