Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients
Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients
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DOI：
10.1007/s10549-009-0318-0
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发表时间：
2010-01-01
影响因子：
3.8
通讯作者：
Nielsen, Torsten O.
中科院分区：
文献类型：
--
作者：
Liu, Shuzhen;Chia, Stephen K.;Nielsen, Torsten O.
乳腺癌雌激素受体状态与激素治疗反应和临床结果相关。孕激素受体（PR）的附加价值一直存在争议。我们研究了PR对预后的价值和对他莫昔芬对4,046例浸润性早期乳腺癌患者的反应。收集了研究队列的诊断年龄、分期、病理学、治疗和结局的临床信息;中位随访时间为12.4年。PR状态通过免疫组化使用兔单克隆抗体在从乳腺肿瘤手术切除建立的组织微阵列上确定。生存分析，Kaplan-Meier函数和考克斯比例风险回归模型被应用于评估PR和乳腺癌特异性生存之间的关联。在所有病例中，51%的患者为预后受体阳性，67%的患者为雌激素受体阳性（ER+）。对整个队列和接受他莫昔芬治疗的ER+病例的生存分析显示，与PR-患者相比，PR+肿瘤患者乳腺癌特异性生存的相对概率高24%，校正了ER、HER 2、诊断时年龄、分级、肿瘤大小、淋巴结状态和淋巴血管浸润协变量。较高的PR表达与患者生存率有较强的相关性。多变量考克斯比例风险回归模型的对数似然比检验表明，在整个队列和接受他莫昔芬治疗的ER+病例中，PR是乳腺癌特异性生存率的独立统计学显著因素。PR在乳腺癌中增加了显著的预后价值，超过了单独使用雌激素受体所获得的价值。
Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients. Clinical information for age at diagnosis, stage, pathology, treatment and outcome was assembled for the study cohort; the median follow-up was 12.4 years. PR status was determined by immunohistochemistry using a rabbit monoclonal antibody on tissue microarrays built from breast tumor surgical excisions. Survival analyses, Kaplan-Meier functions and Cox proportional hazards regression models were applied to assess the associations between PR and breast cancer specific survival. Progesterone receptor was positive in 51% of all cases and 67% of estrogen receptor positive (ER+) cases. Survival analyses for both the whole cohort and ER+ cases given tamoxifen therapy showed that patients with PR+ tumors had 24% higher relative probability for breast cancer specific survival as compared to PR- patients, adjusted for ER, HER2, age at diagnosis, grade, tumor size, lymph node status and lymphovascular invasion covariates. Higher PR expression showed stronger association with patient survival. Log-likelihood ratio tests of multivariate Cox proportional hazards regression models demonstrated that PR was an independent statistically significant factor for breast cancer specific survival in both the whole cohort and among ER+ cases treated with tamoxifen. PR adds significant prognostic value in breast cancer beyond that obtained with estrogen receptor alone.