【作者】 余科达； 狄根红； 吴炅； 陆劲松； 沈坤炜； 沈镇宙； 邵志敏；

【Author】 Yu Ke-Da Di Gen-Hong Wu Jiong Lu Jin-Song Shen Kun-Wei Shen Zhen-Zhou Shao Zhi-Min Department of Breast Surgery, Cancer Hospital, Fudan University, Shanghai, 200032, China.

【机构】 复旦大学附属肿瘤医院乳腺外科复旦大学上海医学院肿瘤学系；

【摘要】 目的:探讨雌激素受体阴性(ER-)孕激素受体阳性(PR+)乳腺癌的临床病理特性、对内分泌治疗的反应及预后。方法:回顾了1991年1月～2001年12月间就诊于复旦大学附属肿瘤医院的1863例ER／PR资料可用的可手术乳腺癌患者资料,ER、PR均采用免疫组化卵白素生物素复合物 (ABC)法检测,采用统一评定标准:细胞核出现棕黄色或棕褐色颗粒为阳性细胞,阳性细胞数≥10％为“阳性”。中位随访48个月(6月～141月),比较ER—PR+患者和ER+PR+ 患者接受内分泌治疗(特指服用三苯氧胺3～5年)后的无病生存(DFS)和总生存(OS)情况,以及不接受内分泌治疗的患者组间生存率差异。并分别对全部患者和ER—PR+患者进行单因素(Log Rank法)和多因素预后分析(Cox风险比例模型)。结果:ER+PR+患者、ER—PR+患者以及ER—PR- 患者分别占42．8％、11．0％和25．9％。ER—PR+患者的中位年龄49岁,肿块中位大小3．0cm。ER—PR+组中未绝经者比例高达63．9％。ER—PR+组较ER+PR+组而言,腋淋巴结转移数高、肿块大、分期晚,而与ER—PR-组基本可比。 ER+PR+组和ER—PR+组未行内分泌治疗时,组间生存无差别。虽然前者的5年DFS绝对值比后者高12％,但无统计学意义(P=0．141)。内分泌治疗后,两组的生存率均有所提高(ER+PR+组5年DFS从68．7％提高到79．0％,ER—PR+ 组从56．6％提高到70．9％,OS也有相似结果),但组间比较显示,ER+PR+组的预后比ER—PR+组更好,差别具有统计学意义(DFS P=0．016,OS P=0．007)。说明ER+PR+患者应用内分泌治疗后获得了更大的收益。多因素分析显示, 腋淋巴结转移状态、肿瘤分期、激素受体状态和内分泌治疗与否对全体患者DFS是独立的预后因素,ER+PR+组预后好于ER—PR+组(P=0．012),ER—PR+组和ER—PR-组预后相似(P=0．074)。多因素分析显示对ER—PR+患者,仅有腋淋巴结状态是独立的预后指标。结论:ER—PR+肿瘤占中国人乳腺癌中的10％左右,主要为绝经前患者,临床病理特性与ER—PR-肿瘤接近,恶性程度相对高。ER—PR+患者能从内分泌治疗中得到一定收益,但较有限。腋淋巴结转移数是ER—PR+肿瘤最重要的预后因子。因此,对ER—PR+ 患者在常规辅助内分泌治疗的前提下,宜结合腋窝淋巴结状态,加强化疗及其他可行的治疗,以期进一步降低复发,改善预后。更多还原

【Abstract】 Objective: To investigate the pathological characteristics, treatments response and prognosis of estrogen receptor negative (ER-) progesterone receptor positive (PR+) primary breast cancer. Methods: The expressions of ER and PR status in 1836 consecutive operable patients of primary breast cancer who admitted into Shanghai Cancer Hospital, China between Jan 1991 and Dec 2001 were reviewed . ER+PR+, ER-PR+, and ER-PR- patients accounted for 42.8%, 11.0% and 25.9% respectively. Median age was 50 years for all patients and 49 years for ER-PR+ group. The differences of DFS and OS between ER-PR+ group and ER+PR+ group with or without endocrine therapy were analyzed by following up to median 48 months(6 - 141 months). The survival curves were described by Kaplan-Meier and 5-year survivals were evaluated by Life Table estimates. Univariate and multi-variate prognostic analysis were done both for all patients and ER-PR+ patients respectively. Results: The proportion of premenopausal patients was higher in ER-PR+ group up to 63.9% than 3 other groups, while ER+PR-group had more postmenopausal patients. By comparing ER-PR+ group and ER+PR+ group, the former had more positive axillary lymph nodes, larger mass and higher stage. In contrast, ER-PR+ group and ER-PR- group were comparable. The DFS and OS were similar between ER+PR+ group and ER-PR+ group in the absence of endocrine therapy, however, the former had a significant better survival than later after receiving hormonal treatment (DFS:P=0.016, OS:P=0.007), although both groups had the 5-year survival increased (5-year DFS rate increased from 68.7% to 79.0% in ER+PR+ group, and from 56.6% to 70.9% in ER-PR+ group, similar results were found in OS.). The multivariate analysis showed that the prognosis of ER+PR- group was worse than ER+PR+ group (P=0.012) and similar to ER-PR- group (P=0.074). The status of axillary lymph nodes was important independent prognostic factor for ER-PR+ patients who had few other prognostic factors to predict prognosis. Conclusion: ER-PR+ tumor which frequently emerges in premenopausal patients accounts for low proportion in all breast cancer population. It is closer to ER-PR- tumor indicating its aggressive nature. ER-PR+ patients can get some benefits from endocrine therapy although the effect is less than ER+PR+ group. Thus, it is reasonable to perform additional therapies to ER-PR+ patients on the basis of endocrine therapy considering the status of axillary lymph nodes.更多还原