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
J Nucl Med. 2017-03-09; 58(9): 1401-1407
DOI: 10.2967/jnumed.116.188011
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1. J Nucl Med. 2017 Sep;58(9):1401-1407. doi: 10.2967/jnumed.116.188011. Epub 2017
Mar 9.
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.
Morgat C(1)(2)(3), MacGrogan G(4)(5), Brouste V(6), Vélasco V(4)(5), Sévenet
N(5)(7), Bonnefoi H(5)(8), Fernandez P(9)(2)(3), Debled M(8), Hindié E(9)(2)(3).
Author information:
(1)Nuclear Medicine Department, University Hospital of Bordeaux, F-33076
Bordeaux, France .
(2)University Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.
(3)CNRS, INCIA, UMR 5287, F-33400 Talence, France.
(4)Surgical Pathology Unit, Department of BioPathology, Institut Bergonié,
F-33076 Bordeaux, France.
(5)INSERM, ACTION U1218, F-33076 Bordeaux, France.
(6)Clinical and Epidemiological Research Unit, Institut Bergonié, F-33076
Bordeaux, France.
(7)Oncogenetics Unit, Department of BioPathology, Institut Bergonié, F-33076
Bordeaux, France; and.
(8)Department of Medical Oncology, Institut Bergonié, F-33076 Bordeaux, France.
(9)Nuclear Medicine Department, University Hospital of Bordeaux, F-33076
Bordeaux, France.
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-rank P = 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.
© 2017 by the Society of Nuclear Medicine and Molecular Imaging.
DOI: 10.2967/jnumed.116.188011
PMID: 28280221 [Indexed for MEDLINE]