title: Expression of Gastrin-Releasing Peptide Receptor in Breast Cancer and Its Association with Pathologic, Biologic, and Clinical Parameters: A Study of 1,432 Primary Tumors.
abstract: A growing body of evidence suggests that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer. To understand which patients can be potential candidates for GRPR-based imaging or targeted therapy, we screened invasive breast cancers by immunohistochemistry for the presence and intensity of GRPR expression.Methods:We explored a tissue microarray of 1,432 primary breast tumors from patients who underwent surgery between 2000 and 2005 at Institut Bergonié, without prior neoadjuvant treatment. We studied associations between GRPR expression and clinical, pathologic, and biologic parameters. The association between GRPR expression and distant metastasis-free interval was also examined.Results:GRPR overexpression was found in 75.8% of the 1,432 tumors and was most strongly associated with estrogen receptor (ER) positivity (GRPR was high in 83.2% of ER-positive and 12% of ER-negative tumors;P< 0.00001). When molecular subtypes of breast cancer were considered, GRPR was overexpressed in 86.2% of luminal A-like tumors, 70.5% of luminal B-like human epidermal growth factor receptor 2 (HER2)-negative tumors, 82.8% of luminal B-like HER2-positive tumors, 21.3% of HER2-enriched tumors, and 7.8% of triple-negative tumors. Importantly, when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic lymph nodes in 94.6% of cases. Primary tumors with high GRPR expression were associated with lower risk of distant metastases at follow-up in univariate analysis (Log-rankP= 0.0084) but not in multivariate analysis. Hence, the prognostic impact of GRPR was lost when examined within specific molecular subtypes.Conclusion:Because GRPR is overexpressed in a high percentage of ER-positive tumors, GRPR targeting offers wide perspectives for imaging and treatment in patients with ER-positive breast cancer, using recently developed radiolabeled GRPR ligands.
authors.affiliation: Nuclear Medicine Department, University Hospital of Bordeaux, F-33076 Bordeaux, France clement.morgat@chu-bordeaux.fr.|University Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.|CNRS, INCIA, UMR 5287, F-33400 Talence, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Morgat
authors.affiliation: Surgical Pathology Unit, Department of BioPathology, Institut Bergonié, F-33076 Bordeaux, France.|INSERM, ACTION U1218, F-33076 Bordeaux, France.
authors.forename: Gaétan
authors.initials: G
authors.lastname: MacGrogan
authors.affiliation: Clinical and Epidemiological Research Unit, Institut Bergonié, F-33076 Bordeaux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Brouste
authors.affiliation: Surgical Pathology Unit, Department of BioPathology, Institut Bergonié, F-33076 Bordeaux, France.|INSERM, ACTION U1218, F-33076 Bordeaux, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vélasco
authors.affiliation: INSERM, ACTION U1218, F-33076 Bordeaux, France.|Oncogenetics Unit, Department of BioPathology, Institut Bergonié, F-33076 Bordeaux, France; and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sévenet
authors.affiliation: INSERM, ACTION U1218, F-33076 Bordeaux, France.|Department of Medical Oncology, Institut Bergonié, F-33076 Bordeaux, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: Nuclear Medicine Department, University Hospital of Bordeaux, F-33076 Bordeaux, France.|University Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.|CNRS, INCIA, UMR 5287, F-33400 Talence, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fernandez
authors.affiliation: Department of Medical Oncology, Institut Bergonié, F-33076 Bordeaux, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Debled
authors.affiliation: Nuclear Medicine Department, University Hospital of Bordeaux, F-33076 Bordeaux, France.|University Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.|CNRS, INCIA, UMR 5287, F-33400 Talence, France.
authors.forename: Elif
authors.initials: E
authors.lastname: Hindié
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D011379:Prognosis; D018004:Receptors, Bombesin / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D018004:Receptors, Bombesin; D011960:Receptors, Estrogen
keywords: 177Lu; 68Ga; GRPR; PRRT; breast cancer; imaging