Morgat Clément, MacGrogan Gaétan, Brouste Véronique, Vélasco Valérie, Sévenet Nicolas, Bonnefoi Hervé, Fernandez Philippe, Debled Marc, Hindié Elif
Nuclear Medicine Department, University Hospital of Bordeaux, F-33076 Bordeaux, France
University Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.
J Nucl Med. 2017 Sep;58(9):1401-1407. doi: 10.2967/jnumed.116.188011. Epub 2017 Mar 9.
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. 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. 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; < 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 = 0.0084) but not in multivariate analysis. Hence, the prognostic impact of GRPR was lost when examined within specific molecular subtypes. 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）可能是乳腺癌中有价值的靶点。为了了解哪些患者可能是基于GRPR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浸润性乳腺癌中GRPR表达的存在情况和强度。我们研究了来自2000年至2005年在贝戈涅研究所接受手术且未接受过新辅助治疗的患者的1432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表达与无远处转移生存期之间的关联。在1432例肿瘤中，75.8%发现GRPR过表达，且与雌激素受体（ER）阳性最密切相关（83.2%的ER阳性肿瘤和12%的ER阴性肿瘤中GRPR高表达；<0.00001）。当考虑乳腺癌的分子亚型时，GRPR在86.2%的管腔A型肿瘤、70.5%的管腔B型人表皮生长因子受体2（HER2）阴性肿瘤、82.8%的管腔B型HER2阳性肿瘤、21.3%的HER2富集型肿瘤和7.8%的三阴性肿瘤中过表达。重要的是，当乳腺肿瘤GRPR过表达时，94.6%的病例在转移淋巴结中也发现高GRPR表达。单因素分析中，GRPR高表达的原发性肿瘤在随访时远处转移风险较低（对数秩检验=0.0084），但多因素分析中并非如此。因此，在特定分子亚型中检查时，GRPR的预后影响消失。由于GRPR在高比例的ER阳性肿瘤中过表达，使用最近开发的放射性标记GRPR配体，GRPR靶向治疗为ER阳性乳腺癌患者的成像和治疗提供了广阔前景。
