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.

越来越多的证据表明，胃泌素释放肽受体（GRPR）可能是乳腺癌的重要靶标。为了了解哪些患者可能是基于GRPR的成像或靶向治疗的潜在候选者，我们通过免疫组织化学筛选了GRPR表达的存在和强度来筛查浸润性乳腺癌。方法：我们研究了2000年至2005年在Bergonié医院接受手术且未经新辅助治疗的患者中1,432例原发性乳腺肿瘤的组织芯片。我们研究了GRPR表达与临床，病理和生物学参数之间的关联。还检查了GRPR表达与远处无转移间隔之间的关系。结果：在1,432个肿瘤中，有75.8％的患者发现GRPR过表达，并且与雌激素受体（ER）的阳性率密切相关（在83.2％的ER阳性和12％的ER阴性的肿瘤中GRPR较高；P <0.00001）。当考虑乳腺癌的分子亚型时，GRPR在86.2％的管腔A样肿瘤，70.5％的管腔B样人表皮生长因子受体2（HER2）阴性肿瘤，82.8％的管腔B样HER2中过表达。 -阳性肿瘤，21.3％的富含HER2的肿瘤和7.8％的三阴性肿瘤。重要的是，当乳腺肿瘤过度表达GRPR时，在94.6％的转移淋巴结中也发现了高GRPR表达。在单因素分析中，GRPR高表达的原发性肿瘤与远处转移的风险较低相关（Log-rankP = 0.0084），但在多变量分析中却没有。因此，当在特定的分子亚型中检查时，GRPR的预后影响消失了。结论：由于GRPR在高比例的ER阳性肿瘤中过表达，因此GRPR靶向使用最近开发的放射性标记的GRPR配体为ER阳性乳腺癌患者的成像和治疗提供了广阔的前景。