ER(-)/PR(+)乳腺癌的临床病理特点及预后分析

Clinicopathological characteristics and prognosis analysis of ER(-)/PR( +) breast cancer

目的探讨ER(-)/PR(+)乳腺癌的临床病理特点及预后。方法回顾性分析2005年1月至2008年12月郑州大学附属肿瘤医院乳腺科收治的762例乳腺癌患者的临床病理资料。根据ER、PR表达情况将患者分为3组,即ER(-)/PR(+)组179例,ER(-)/PR(-)组300例,ER(+)/PR(+)组283例。分析3组患者的年龄、月经状态、肿瘤大小、组织学分级、脉管侵犯、淋巴结状态、HER-2状态及组织学类型等临床指标。其中,年龄、月经状态、脉管侵犯、HER-2状态和组织学类型等计数资料比较,采用χ~2检验,组间两两比较采用χ~2分割法;肿瘤大小、组织学分级等级资料比较,采用Kruskal-Wallis H检验。并用Kaplan-Meier法进行生存分析,用Log-rank法进行组间比较。结果 ER(-)/PR(+)组、ER(-)/PR(-)组及ER(+)/PR(+)组中,发病年龄<50岁者分别占56.4%(101/179),62.7%(188/300)和35.0%(99/283),3组相比,差异有统计学意义(χ~2=47.497,P<0.001),其中,ER(-)/PR(+)组患者发病年龄比ER(+)/PR(+)组患者明显年轻(χ~2=20.535,P<0.017),而与ER(-)/PR(-)组相比,差异无统计学意义(χ~2=1.825,P>0.017);并且,3组肿瘤组织学分级差异也有统计学意义(χ~2=30.362,P<0.001),其中,ER(-)/PR(+)组肿瘤的组织学分级比ER(+)/PR(+)组高(P=0.017),而与ER(-)/PR(-)组相比,差异无统计学意义(P=0.126);3组间HER-2阳性表达差异也有统计学意义(χ~2=56.518,P<0.001),其中,ER(-)/PR(+)组HER-2阳性比例明显高于ER(-)/PR(-)组和ER(+)/PR(+)组(χ~2=6.298、51.044,P均<0.017)。中位随访62个月(17~94个月),ER(-)/PR(+)组、ER(-)/PR(-)组及ER(+)/PR(+)组患者5年DFS率分别为44%、40%和74%,5年OS率分别为87%、77%和95%,3组相比,差异均有统计学意义(5年DFS率比较,χ~2=95.269,P<0.001;5年OS率比较,χ~2=45.768,P<0.001),其中,ER(-)/PR(+)组5年DFS率和OS率均低于ER(+)/PR(+)组(χ~2=56.276,P<0.001;χ~2=17.454,P<0.001),而与ER(-)/PR(-)组相比,5年DFS率的差异无统计学意义(χ~2=3.010,P=0.083),5年OS率高于ER(-)/PR(-)组(χ~2=5.549,P=0.018)。结论 ER(-)/PR(+)乳腺癌具有发病年龄早、组织学分级高、HER-2阳性率高等特点,与ER(+)/PR(+)乳腺癌相比有更强的侵袭性和更差的预后,临床病理特征及预后与ER(-)/PR(-)乳腺癌更类似,值得深入探索。

Objective To investigate the clinicopathological characteristics of ER（-）/PR（＋） breast cancer and patients＇ prognosis. Methods We retrospectively analyzed the clinicopathological data of 762 breast cancer patients in the Affiliated Cancer Hospital of Zhengzhou University between January 2005 and December 2008. According to their ER and PR status, they were divided into three groups： ER（-）/PR（＋） group （n = 179）, ER （ - ）/PR （ - ） group （ n = 300 ）, and ER （ ＋ ）/PR （ ＋ ） group （ n = 283 ）. Clinicopathological parameters including age, menstruation, tumor size, histological grade, lymphatic or vascular invasion, lymph node status, HER-2 status and histological grade were evaluated. The numeration data including age, menstruation, lymphatic or vascular invasion, HER-2 status and histological type were compared among groups using X2 test, Pairwise comparison was conducted using X2 segmentation. The ranked data including tumor size and histological grade were compared using Kruskal-Wallis H test. Kaplan-Meier method was used for survival analysis and log-rank test was used for group comparison. Results The proportion of the patients〈50 years was 56.4% （101/179） in ER （-）/PR （＋） group, 62. 7% （188/300） in ER （-）/PR （-） group and 35.0% （99/283） in ER（＋）/PR（＋） group, indicating a significant difference （X2 =47. 497, P〈0. 001 ）. The onset age in ER（-）/PR（＋） group were significantly younger than that in ER（＋）/PR（＋） group （ Х^2 = 20. 535, P〈 0. 017） while there was no significant difference between ER（-）/PR（-） group and ER（-）/PR（＋） group （Х^2= 1. 825,P〉0. 017）. There was a significant difference in histological grade among three groups （X2= 30. 362,P〈0. 001 ）. ER（-）/PR（＋） group had a higher histological grade compared with ER（ ＋）/PR（＋） group （P=0. 017） while no significant difference was found between ER（ -）/PR（＋） group and ER（-）/PR（-） group （P = 0. 126）. There was a significant difference in HER-2 expression among three groups （Х^2 = 56. 518, P〈0. 001 ）,and HER-2 positive rate in ER（-）/PR（＋） group was significantly higher than that in the other two groups（ Х^2= 6. 298, 51. 044 ,both P〈0. 017 ）. The patients were followed up for median 62 months （17- 94 months）. The 5-year DFS was 44%, 40% and 74% in ER（ -）/PR（＋） group, ER（ -）/PR（ -）group and ER（＋）/PR（＋） group, respectively, and the 5-year OS was 87%, 77% and 95% in ER（-）/PR（＋） group, ER（-）/PR（-） group and ER（＋）/PR（＋） group, respectively. The 5-year DFS and OS both presented significant differences （ the 5-year DFS： X2 = 95. 269, P〈0. 001 ; the 5-year OS ： Х^2 = 45.768, P〈0. 001 ）. The 5-year DFS and OS in ER（-）/PR（＋） group were significantly lower than those in ER（＋）/PR（＋） group （Х^2 =56. 276, P〈0. 001; Х^2= 17. 454, P〈0. 001 ）, while no significant difference was noted in the 5-year DFS between ER （-）/PR （＋） group and ER （-）/PR （-） group （ Х^2 = 3.010, P = 0. 083 ）, and the 5-year OS inER（-）/PR（＋） group was higher than that in ER（-）/PR（-） group（x2=5.549, P=0.018）. Conclusions ER（ -）/PR（＋） breast cancer has young age of onset, advanced histological grade and high rate of HER-2 positive. It has clinicopathological characteristics and prognosis similar to ER （-）/PR （-） tumor, but stronger invasion and worse prognosis compared with ER （＋）/PR （＋） tumor, which requires further research.