局部晚期乳腺癌~(18)F-FDG PET/CT显像和分子分型与预后相关性研究
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摘要
目的乳腺癌18F-脱氧葡萄糖(~(18)F-fluorodeoxy glucose,~(18)F-FDG)的摄取率反映了肿瘤代谢程度,本研究旨在探讨不同分子亚型局部晚期乳腺癌患者治疗前病灶~(18)F-FDG最大标准摄取值(maximum standardized uptake value,SUV_(max))与预后的相关性。方法选择2010-08-23-2014-10-31在佛山市第一人民医院行~(18)F-FDG正电子发射计算机断层扫描(positron emission tomography/computed tomography,PET/CT)的初治局部晚期乳腺癌患者119例,根据免疫组化结果将其分成Luminal A型、Luminal B/HER2+型、Luminal B/HER2-型、HER2+型和三阴性乳腺癌(tripe negative breast cancer,TNBC)5种分子亚型。结果入组患者术后总复发转移率为32.8%。根据是否发生术后局部复发或远处转移分为事件组(n=39)与无事件组(n=80),两组治疗前病灶SUV_(max)分别为9.68±3.83和7.71±4.39,差异有统计学意义,Z=2.681,P=0.007。单因素分析显示,3年无事件生存率(event free survival,EFS)与治疗前SUV_(max)、T分期、N分期及AJCC临床分期有关,P值分别为0.012、0.022、0.013和0.008;多因素分析显示,SUV_(max)是影响患者预后的独立因素。当SUV_(max)≥8.9时,患者转移复发率明显增高,无病生存时间缩短,SUV_(max)≥8.9组与SUV_(max)<8.9组生存曲线差异有统计学意义,χ~2=6.309,P=0.012。Luminal A型SUV_(max)≥8.9组EFS低于SUV_(max) <8.9组,χ~2=6.494,P=0.011,Luminal B/HER2-型SUV_(max)≥8.9组EFS低于SUV_(max)<8.9组,χ~2=3.962,P=0.047,而TNBC、HER2+型、LuminalB/HER2+分子亚型组SUV_(max)不同分组间EFS差异无统计学意义,χ~2值分别为0.767、0.057和0.271,P值分别为0.603、0.811和0.381。结论局部晚期乳腺癌治疗前~(18)F-FDG SUV_(max)较高是预测患者预后不良的重要因素之一,SUV_(max)≥8.9时Luminal A和Luminal B/HER2-分子亚型乳腺癌患者的无病生存期较短。
OBJECTIVE ~(18)F-fluorodeoxy glucose(~(18)F-FDG)uptake in breast cancer indicates the degree of tumor metabolism.This study aimed to explore the correlation between the ~(18)F-FDG maximum standardized uptake value(SUV_(max))of primary lesions before treatment and the prognosis in different molecular subtypes of locally advanced breast cancer patients.METHODS Totally 119 patients with locally advanced breast cancer underwent ~(18)F-FDG positron emission tomography/computed tomography scan(PET/CT)were recruited in this study from August 23 th,2010 to October31 th,2014.They were classified by immunohistochemical assays into five molecular subtypes as follows:Luminal A type,Luminal B/HER2+type,Luminal B/HER2-type,HER2 postive type and Triple-negative breast cancer(TNBC)type.RESULTS The total rate of recurrence or metastasis was 32.8%.After operation,patients were followed-up and they were divided into two groups(with and without recurrence events),SUV_(max)of primary lesions before treatment in two groups were 9.68±3.83(events group,n=39)and 7.71±4.39(no events group,n=80)respectively,and the difference was statistically significant(Z=2.681,P=0.007).In the univariate analysis,baseline SUV_(max),T staging,lymph node staging and clinical stage(according to American Joint Committee on Cancer staging system)were significant predictors for 3-year event free survival(EFS)(Pwere 0.012,0.022,0.013 and 0.008).Multivariate regression analysis showed that SUV_(max) was independent prognostic factors(P <0.001).While the cut-off point of SUV_(max) was set as 8.9,highSUV_(max)at baseline was associated with shorter EFS(χ~2=6.309,P=0.012).EFS was shorter in Luminal A and Luminal B/HER2-molecular subtypes breast cancer patients with baseline tumor SUV_(max)≥8.9(χ~2=6.494,P=0.011 for Luminal A,χ~2=3.962,P=0.047 for Luminal B/HER2-),but SUV_(max)could not predict the recurrence or metastasis in TNBC type,HER2 positive type,LuminalB/HER2+type molecular subtypes(P were 0.603,0.811 and 0.381).CONCLUSIONS A high ~(18)F-FDG SUV_(max)of primary lesions before treatment is one of the important predicting poor prognosis factors in locally advanced breast cancer.Luminal A,Luminal B/HER2-breast cancer with bigger SUV_(max)(SUV_(max)≥8.9)may have lower survival rate.
OBJECTIVE ~(18)F-fluorodeoxy glucose(~(18)F-FDG)uptake in breast cancer indicates the degree of tumor metabolism.This study aimed to explore the correlation between the ~(18)F-FDG maximum standardized uptake value(SUV_(max))of primary lesions before treatment and the prognosis in different molecular subtypes of locally advanced breast cancer patients.METHODS Totally 119 patients with locally advanced breast cancer underwent ~(18)F-FDG positron emission tomography/computed tomography scan(PET/CT)were recruited in this study from August 23 th,2010 to October31 th,2014.They were classified by immunohistochemical assays into five molecular subtypes as follows:Luminal A type,Luminal B/HER2+type,Luminal B/HER2-type,HER2 postive type and Triple-negative breast cancer(TNBC)type.RESULTS The total rate of recurrence or metastasis was 32.8%.After operation,patients were followed-up and they were divided into two groups(with and without recurrence events),SUV_(max)of primary lesions before treatment in two groups were 9.68±3.83(events group,n=39)and 7.71±4.39(no events group,n=80)respectively,and the difference was statistically significant(Z=2.681,P=0.007).In the univariate analysis,baseline SUV_(max),T staging,lymph node staging and clinical stage(according to American Joint Committee on Cancer staging system)were significant predictors for 3-year event free survival(EFS)(Pwere 0.012,0.022,0.013 and 0.008).Multivariate regression analysis showed that SUV_(max) was independent prognostic factors(P <0.001).While the cut-off point of SUV_(max) was set as 8.9,highSUV_(max)at baseline was associated with shorter EFS(χ~2=6.309,P=0.012).EFS was shorter in Luminal A and Luminal B/HER2-molecular subtypes breast cancer patients with baseline tumor SUV_(max)≥8.9(χ~2=6.494,P=0.011 for Luminal A,χ~2=3.962,P=0.047 for Luminal B/HER2-),but SUV_(max)could not predict the recurrence or metastasis in TNBC type,HER2 positive type,LuminalB/HER2+type molecular subtypes(P were 0.603,0.811 and 0.381).CONCLUSIONS A high ~(18)F-FDG SUV_(max)of primary lesions before treatment is one of the important predicting poor prognosis factors in locally advanced breast cancer.Luminal A,Luminal B/HER2-breast cancer with bigger SUV_(max)(SUV_(max)≥8.9)may have lower survival rate.
引文
[1]陈万青,郑荣寿.中国女性乳腺癌发病死亡和生存状况[J].中国肿瘤临床,2015,42(13):668-674.
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[3]吴晖,欧阳取长,谢宁,等.乳腺癌患者术后胸壁复发及预后相关因素分析[J].中华肿瘤防治杂志,2016,23(22):1498-1502.
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[5]郭刚,张喜平,张俊晶,等.PET-CT评价乳腺癌新辅助化疗效果的研究[J].肿瘤研究与临床,2014,26(1):6-12.
[6]Leccisotti L,Gambacorta MA,De Waure C,et al.The predictive value of 18F-FDG PET/CT for assessing pathological response and survival in locally advanced rectal cancer after neoadjuvant radiochemotherapy[J].Eur J Nucl Med Mol Imaging,2015,42(5):657-666.
[7]刘德军,冯彦林,余丰文,等.乳腺癌腋窝淋巴结转移18 F-FDGPET/CT半定量分析预测阈值的临床研究[J].中华核医学杂志,2009,29(2):73-77.
[8]Governder P.An approach to the management of locally advanced breast cancer:part 1[J].S Afr Med J,2014,104(5):384.
[9]李雯,冯彦林.乳腺癌分子生物学指标与18F-FDG PET-CT SUVmax的相关性研究[J].中国现代医学杂志,2017,27(23):47-51.
[10]Jo JE,Kim JY,Lee SH,et al.Preoperative 18F-FDG PET/CT predicts disease-free survival in patients with primary invasive ductal breast cancer[J].Acta Radiol,2015,56(12):1463-1470.
[11]Jiménez-BallvéA,García García-Esquinas M,Salsidua-Arroyo O,et al.Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging[J].Rev Esp Med Nucl Imagen Mol,2016,35(6):365-372.
[12]Groheux D,Martineau A,Teixeira L,et al.18 FDG-PET/CT for predicting the outcome in ER+/HER2-breast cancer patients:comparison of clinicopathological parameters and PET image-derived indices including tumor texture analysis[J].Breast Cancer Res,2017,19(1):3-12.
[13]庞琼,南昊成,马婕群,等.不同分子亚型乳腺浸润性导管癌的临床特征与预后分析[J].临床肿瘤学杂志,2015,20(2):132-136.
[14]王永南,王颀,张安秦,等.T1N0M0乳腺癌临床病理特征和预后分析[J].中华肿瘤防治杂志,2014,21(12):940-944.
[15]刘晓东,佟仲生,李淑芬,等.局部晚期乳腺癌1081例临床病理特征及预后分析[J].肿瘤,2011,31(10):918-923.
[16]Kitajima K,Fukushima K,Miyoshi Y,et al.Association between18F-FDG uptake and molecular subtype of breast cancer[J].Eur J Nucl Med Mol Imaging,2015,42(9):1371-1377.
[2]Garg PK,Prakash G.Current definition of locally advanced breast cancer[EB/OL].Curr Oncol,2015,22(5):e409-e410[2018-08-20].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608421/pdf/conc-22-e409.pdf.
[3]吴晖,欧阳取长,谢宁,等.乳腺癌患者术后胸壁复发及预后相关因素分析[J].中华肿瘤防治杂志,2016,23(22):1498-1502.
[4]Groheux D,HindiéE,Giacchetti S,et al.Early assessment with18F-fluorodeoxyglucose positron emission tomography/computed tomography can help predict the outcome of neoadjuvantchemotherapy in triple negative breast cancer[J].Eur J Cancer,2014,50(11):1864-1871.
[5]郭刚,张喜平,张俊晶,等.PET-CT评价乳腺癌新辅助化疗效果的研究[J].肿瘤研究与临床,2014,26(1):6-12.
[6]Leccisotti L,Gambacorta MA,De Waure C,et al.The predictive value of 18F-FDG PET/CT for assessing pathological response and survival in locally advanced rectal cancer after neoadjuvant radiochemotherapy[J].Eur J Nucl Med Mol Imaging,2015,42(5):657-666.
[7]刘德军,冯彦林,余丰文,等.乳腺癌腋窝淋巴结转移18 F-FDGPET/CT半定量分析预测阈值的临床研究[J].中华核医学杂志,2009,29(2):73-77.
[8]Governder P.An approach to the management of locally advanced breast cancer:part 1[J].S Afr Med J,2014,104(5):384.
[9]李雯,冯彦林.乳腺癌分子生物学指标与18F-FDG PET-CT SUVmax的相关性研究[J].中国现代医学杂志,2017,27(23):47-51.
[10]Jo JE,Kim JY,Lee SH,et al.Preoperative 18F-FDG PET/CT predicts disease-free survival in patients with primary invasive ductal breast cancer[J].Acta Radiol,2015,56(12):1463-1470.
[11]Jiménez-BallvéA,García García-Esquinas M,Salsidua-Arroyo O,et al.Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging[J].Rev Esp Med Nucl Imagen Mol,2016,35(6):365-372.
[12]Groheux D,Martineau A,Teixeira L,et al.18 FDG-PET/CT for predicting the outcome in ER+/HER2-breast cancer patients:comparison of clinicopathological parameters and PET image-derived indices including tumor texture analysis[J].Breast Cancer Res,2017,19(1):3-12.
[13]庞琼,南昊成,马婕群,等.不同分子亚型乳腺浸润性导管癌的临床特征与预后分析[J].临床肿瘤学杂志,2015,20(2):132-136.
[14]王永南,王颀,张安秦,等.T1N0M0乳腺癌临床病理特征和预后分析[J].中华肿瘤防治杂志,2014,21(12):940-944.
[15]刘晓东,佟仲生,李淑芬,等.局部晚期乳腺癌1081例临床病理特征及预后分析[J].肿瘤,2011,31(10):918-923.
[16]Kitajima K,Fukushima K,Miyoshi Y,et al.Association between18F-FDG uptake and molecular subtype of breast cancer[J].Eur J Nucl Med Mol Imaging,2015,42(9):1371-1377.