Abstract
1026
Objectives: A growing body of evidence suggests that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer. In order 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 Micro-Array of 1432 primary breast tumors from previously untreated patients, who underwent surgery between 2000 and 2005 at Institut Bergonié. We correlated GRPR expression with clinical, pathological and biological parameters as well as molecular subtypes derived from these markers. Associations between GRPR expression and distant metastasis-free interval were also examined.
Results: GRPR expression was high in 75.8% of the 1432 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<.00001). When considering molecular subtypes, GRPR was overexpressed in 86.2% of luminal A-like, 70.5% of luminal B-like HER2-negative, 82.8% of luminal B-like HER2-positive, 21.3% of HER2-enriched and in 7.8% of triple-negative tumors. Primary tumors with high GRPR expression were associated with lower risk of distant metastases in univariate analysis (Log-rank p=.0084) but not in multivariate analysis. Hence, the prognostic impact of GRPR was lost when examined within specific molecular subtypes. Importantly, when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic lymph nodes in 94.6% of cases
Conclusion: Because GRPR is overexpressed in a high percentage of ER-positive tumors and metastatic lymph nodes, GRPR targeting offers wide perspectives for imaging and treatment of metastatic ER-positive breast cancer patients, using recently developed radiolabelled GRPR ligands. Research Support: This work was funded by the French Investment for the Future program within LabEx TRAIL ANR-10-LABX-57