Kai Kazuharu, Nishimura Reiki, Arima Nobuyuki, Miyayama Haruhiko, Iwase Hirotaka
Breast and Endocrine Surgery, Faculty of Medical and Pharmaceutical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Int J Clin Oncol. 2006 Dec;11(6):426-33. doi: 10.1007/s10147-006-0601-6. Epub 2006 Dec 25.
Hormone receptor status has been one of the most important factors in predicting the response to endocrine therapy in breast cancer patients. However, half of those patients with estrogen receptor-positive tumors do not respond to endocrine therapy. There have been no universal factors for predicting resistance to endocrine therapy in this population. Recently, p53 status has been extensively used as a predictive factor for response to systemic therapy, because tumor cells lacking p53 function do not respond to systemic therapy due to a failure in apoptosis. We therefore studied the relationship between the efficacy of endocrine therapy and biological factors, including p53.
The expression of p53, Ki67, and human epidermal growth factor receptor (HER)2 was examined by immunostaining in the primary tumors of 53 patients who received endocrine therapy for recurrent or advanced breast cancer. The following clinical factors were also analyzed: site treated, disease-free interval, and response to first-line endocrine therapy. To evaluate the significance of these factors, time to endocrine therapy failure (TTEF), or the total duration of sequential endocrine therapies was adopted as representing the clinical outcome.
The median TTEF was 16.1 months (range, 2.5-89.9 months). Multivariate analysis showed significantly reduced TTEF associated with no response to first-line endocrine therapy (P = 0.006 and P = 0.002 in all patients and in recurrent patients, respectively) and associated with positive p53 expression (P = 0.066 and P = 0.004, respectively).
p53 expression status was a significant molecular marker as well as the response to first-line endocrine therapy for predicting TTEF in recurrent breast cancer with hormone-sensitive disease.
激素受体状态一直是预测乳腺癌患者内分泌治疗反应的最重要因素之一。然而,雌激素受体阳性肿瘤患者中有一半对内分泌治疗无反应。在这一人群中,尚无预测内分泌治疗耐药的通用因素。最近,p53状态已被广泛用作全身治疗反应的预测因素,因为缺乏p53功能的肿瘤细胞由于凋亡失败而对全身治疗无反应。因此,我们研究了内分泌治疗疗效与包括p53在内的生物学因素之间的关系。
通过免疫染色检测了53例接受复发性或晚期乳腺癌内分泌治疗患者原发肿瘤中p53、Ki67和人表皮生长因子受体(HER)2的表达。还分析了以下临床因素:治疗部位、无病间期和对一线内分泌治疗的反应。为了评估这些因素的意义,采用内分泌治疗失败时间(TTEF)或序贯内分泌治疗的总持续时间来代表临床结果。
TTEF的中位数为16.1个月(范围为2.5 - 89.9个月)。多变量分析显示,TTEF显著缩短与对一线内分泌治疗无反应相关(在所有患者和复发性患者中,P分别为0.006和0.002),且与p53表达阳性相关(P分别为0.066和0.004)。
p53表达状态是预测激素敏感型复发性乳腺癌TTEF的重要分子标志物,也是对一线内分泌治疗反应的重要指标。