Neurotensin (NT) is a 13-amino acid peptide with trophic effects on some neoplasms. Its bioactivities are mainly mediated by neurotensin receptor 1 (NTSR1). Both NT and NTSR1 were found to be upregulated in breast can...Neurotensin (NT) is a 13-amino acid peptide with trophic effects on some neoplasms. Its bioactivities are mainly mediated by neurotensin receptor 1 (NTSR1). Both NT and NTSR1 were found to be upregulated in breast cancer. NT/NTSR1 thus becomes a potential therapeutic target. We studied whether any correlation exists between the expression of NTSR1 in breast carcinomas and the expression of ER, PR, and Her2. A total 85 cases of invasive ductal (62) and lobular (23) breast carcinomas were studied. Based on their ER/PR profiles, the ductal carcinomas (DCs) were subcategorized into ER+/PR+ (21), ER+/PR﹣ (20), and ER﹣/PR﹣ (21). All of the lobular carcinomas (LCs) were ER+/PR+. 21.57% of all DCs and 5.56% of LCs were Her2 positive. 77.78% of ER﹣/PR﹣ DCs were also Her2 negative (triple negative). The expression of NTSR1 was detected by immunohistochemistry and was semiquantitated (as negative, 1+, 2+, 3+). Both 2+ and 3+ were collectively defined as overexpression. The expression of NTSR1 was weak and focal in non-neoplastic mammary epithelial cells. It is increased in 74.19% of DCs (80.95% in ER+/PR+, 75% in ER+/PR﹣, and 66.67% in ER﹣/PR﹣ group), and in 95.65% of LCs. The overexpression of NTSR1 is similar between ER+ DCs and ER﹣ DCs (75% vs 66.67%, p > 0.05) as well as between PR+ DCs and PR﹣ DCs (80.95% in ER+/PR+ DCs vs 75% in ER+/PR﹣ DCs, p > 0.05). And it was seen in 77.78% of Her2+ DCs, 78.38% of Her2﹣ DCs, 94.12% of Her2﹣ LCs, and 78.57% of triple negative DCs. Overall, NTSR1 is commonly overexpressed in both ductal and lobular breast carcinomas and is independent of the ER/PR/Her2 profiles of the tumors. The present data supports the potential benefit of developing NTSR1 blockers in the adjuvant therapy of breast carcinomas, particularly for those “triple negative” tumors.展开更多
Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and...Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments.The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.展开更多
目的使用荧光原位杂交(fluorescence in situ hybridization,FISH)检测HER2基因扩增情况,并探讨影响HER2基因扩增的因素及其与临床病理特征的关系。方法收集新疆医科大学附属肿瘤医院2013年l月至2015年12月间IHC检测HER2(++)的乳腺癌病...目的使用荧光原位杂交(fluorescence in situ hybridization,FISH)检测HER2基因扩增情况,并探讨影响HER2基因扩增的因素及其与临床病理特征的关系。方法收集新疆医科大学附属肿瘤医院2013年l月至2015年12月间IHC检测HER2(++)的乳腺癌病例325份,均采用IHC和FISH两种方法分别检测所有患者的石蜡标本HER2表达和扩增情况,并分析HER2扩增状态与患者各临床病理特征的关系。结果全组患者经IHC检测HER2表达均为(++),FISH检测HER2扩增率为12.9%(42/325),对12项临床和病理指标进行单因素分析显示:HER2扩增状态与激素状态、肿瘤直径、P53显著相关(P<0.05),而与ki67表达、组织学分级、肿瘤个数等因素均无关(P>0.05)。结论雌孕激素表达均阴性、肿瘤直径>2 cm、P53表达阳性是预测FISH检测IHC HER2(++)扩增的独立因素。展开更多
文摘Neurotensin (NT) is a 13-amino acid peptide with trophic effects on some neoplasms. Its bioactivities are mainly mediated by neurotensin receptor 1 (NTSR1). Both NT and NTSR1 were found to be upregulated in breast cancer. NT/NTSR1 thus becomes a potential therapeutic target. We studied whether any correlation exists between the expression of NTSR1 in breast carcinomas and the expression of ER, PR, and Her2. A total 85 cases of invasive ductal (62) and lobular (23) breast carcinomas were studied. Based on their ER/PR profiles, the ductal carcinomas (DCs) were subcategorized into ER+/PR+ (21), ER+/PR﹣ (20), and ER﹣/PR﹣ (21). All of the lobular carcinomas (LCs) were ER+/PR+. 21.57% of all DCs and 5.56% of LCs were Her2 positive. 77.78% of ER﹣/PR﹣ DCs were also Her2 negative (triple negative). The expression of NTSR1 was detected by immunohistochemistry and was semiquantitated (as negative, 1+, 2+, 3+). Both 2+ and 3+ were collectively defined as overexpression. The expression of NTSR1 was weak and focal in non-neoplastic mammary epithelial cells. It is increased in 74.19% of DCs (80.95% in ER+/PR+, 75% in ER+/PR﹣, and 66.67% in ER﹣/PR﹣ group), and in 95.65% of LCs. The overexpression of NTSR1 is similar between ER+ DCs and ER﹣ DCs (75% vs 66.67%, p > 0.05) as well as between PR+ DCs and PR﹣ DCs (80.95% in ER+/PR+ DCs vs 75% in ER+/PR﹣ DCs, p > 0.05). And it was seen in 77.78% of Her2+ DCs, 78.38% of Her2﹣ DCs, 94.12% of Her2﹣ LCs, and 78.57% of triple negative DCs. Overall, NTSR1 is commonly overexpressed in both ductal and lobular breast carcinomas and is independent of the ER/PR/Her2 profiles of the tumors. The present data supports the potential benefit of developing NTSR1 blockers in the adjuvant therapy of breast carcinomas, particularly for those “triple negative” tumors.
基金Supported by Ricerca Sanitaria LILT 2015Beneficentia Foundation Stiftung,No.BEN2016/16 grants
文摘Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments.The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.
