雌激素受体阳性孕激素受体表达不同的乳腺癌患者肿瘤特征比较

目的探讨雌激素受体（ER）＋／孕激素受体（PR）-和ER＋／PR＋的两种类型乳腺癌患者肿瘤生物学特性的差异。方法回顾性研究3124例ER＋／PR-或ER＋／PR＋的乳腺癌患者,比较其临床病理及免疫组化法测定的分子生物学指标。结果ER＋／PR＋和ER＋／PR-的乳腺癌患者的年龄峰值均为50岁,显著高于ER-／PR-患者的年龄峰值48岁（P〈0．05）。且ER＋／PR-的乳腺癌较ER＋／PR＋者肿瘤直径大,淋巴结转移个数多、组织学分级低,ER表达水平低,c-erbB-2呈高表达（P〈0．05）,而Cathepsin D则呈现低表达（P〈0．05）;但两组间平均年龄差异无统计学意义（P〉0．05）。多因素分析显示影响两者不同表型的因子有：肿瘤ER表达水平（OR=1．792,95％CI=1．484-2．164,P=0．000）、Cathepsin D状态（OR=1．380,95％CI=1．023～1．862,P=0．035）及C-erbB-2表达状态（OR=0．639,95％CI=0．463～0．883,P=0．007）。结论ER＋／PR＋与ER＋／PR-的乳腺癌可能有相同的起病原因,但ER＋状态下PR表达与否可能有多方面的因素,导致二者的生物学行为不同,针对这些差异寻找新的治疗靶向可能更有助于改善ER＋／PR-患者的内分泌治疗效果及预后。

Clinico-pathological features of ER+/PR+ and ER+/PR- breast tumors: a comparative study of 5211 cases

OBJECTIVE: To compare the differences in the clinicopathological and molecular biological features between the breast cancer patients with estrogen receptor (ER)+/progesterone receptor (PR)+ or ER+/PR- tumors. METHODS: The clinicopathological data of 3124 female breast cancer patients with known ER/PR expression status, 2220 being ER+/PR+ and 904 being ER+/PR-, and 1484 being ER-/PR-, were analyzed retrospectively. Immunohistochemistry was used to detect the expression of c-erb and cathepsin D in the tumor specimens. RESULTS: The average peak onset age was 50 years in both the ER+/PR+ and ER+PR- patients, and the mean age of the ER+/PR+ patients was 52.40 years, not significantly different from that of the ER-/PR- patients (52.57 years, P = 0.709). The peak onset age of the ER+ patients was 50 years, significantly higher that that of the ER- patients (48 years, P = 0.001), and the mean age of the ER+ patients was 52.46 years, significantly higher than that of the ER- patients (51.42 years, P = 0.001). Univariate analysis showed that ER+/PR- tumors tended to be larger. 24.8% of the ER+/PR- patients had 4 or more metastatic lymph nodes, a rate significantly higher than that of the ER+/PR- patients (20.7%, P = 0.004). The tumors of 18% of the ER+/PR- patients were at the grade III, a rate significantly higher than that of the ER+/PR+ patients (13.5%, P = 0.008). The strong positivity rate of the ER+/PR+ tumors was 23.4%, ignorantly higher than hat of the ER+/PR- tumors (11.2%, P = 0.000). The c-erB-2 positive rate of the ER+/PR+ tumors was 19.7%, significantly lower than that of the ER+/PR- tumor group (28.7%, P = 0.000). The cathepsin D positive rate of the ER+/PR- group was 76.9%, significantly higher than that of the ER+/PR- group (71.9%, P = 0.005). Multivariate analysis indicated that positive PR expression was associated with the level of ER (OR = 1.792, 95% CI = 1.484 - 2.164, P = 0.000), cathepsin D (OR = 1.380, 95% CI = 1.023 - 1.862, P = 0.035) and c-erbB-2 (OR = 0.639, 95% CI = 0.463 - 0.883, P = 0.007). CONCLUSION: ER+/PR+ and ER+/PR- tumors may have identical etiology. The mechanism of whether PR is expressed in ER+ breast cancer may be caused by different factors, which causing many different aspects. According to these differences, new target of therapy may provide the possibility of improving the response and prognosis for patients with ER+/PR- tumors.