Khoshnoud Mahmoud R, Fornander Tommy, Johansson Hemming, Rutqvist Lars-Erik
Department of oncology, Karolinska University Hospital, Söder Hospital, Stockholm, Sweden.
Breast Cancer Res Treat. 2008 Jan;107(1):71-8. doi: 10.1007/s10549-007-9520-0. Epub 2007 Feb 15.
Recent studies on the pattern of gene expression in estrogen receptor positive and negative tumours have revealed profound differences according to receptor status. However, it remains unclear if these differences reflect phenotypic traits in addition to sensitivity to endocrine therapy. This paper describes the long-term pattern of disease recurrence among ca. 2,600 pre- and post-menopausal patients with primary breast cancer according to estrogen receptor status.
The study was based on patients with an operable, invasive breast cancer entered in one of three controlled clinical trials conducted by the Stockholm Breast Cancer Group. We selected those 2,562 patients who had been randomly allocated between adjuvant tamoxifen and no adjuvant systemic therapy. These patients had a known estrogen receptor status.
Tamoxifen reduced locoregional (8.8% vs. 12.4%, hazard ratio (HR), 0.66; 95% CI, 0.52-0.83; P = 0.001, distant recurrences (17.2% vs. 20.2%, HR, 0.81; CI, 0.68-0.97; P = 0.018, as well as breast cancer death (18.7% vs. 23.7%, HR, 0.78; CI, 0.67-0.92; P = 0.002). Among patients not allocated to tamoxifen there was no significant differences in term of neither locoregional (12.4% vs. 12.4%, HR, 1; CI, 0.72-1.41; P = 0.98), nor distant metastases (18.5% vs. 20.7%, HR, 1.11;CI, 0.85-1.45; P = 0.46) according to ER status. The pattern of metastases was not different in ER positive comparison with ER negative.
The results showed that the mentioned substantial differences in terms of gene expression appeared mainly to be related to endocrine sensitivity and not to metastatic potential. However, a slight advantage during the first five years for the ER positive versus ER negative patients in terms of cumulative incidence of events, suggested that ER negativity in some cases is correlated with an increased tumour growth rate.
近期关于雌激素受体阳性和阴性肿瘤基因表达模式的研究显示,根据受体状态存在显著差异。然而,除了对内分泌治疗的敏感性外,这些差异是否反映表型特征仍不清楚。本文描述了约2600例绝经前和绝经后原发性乳腺癌患者根据雌激素受体状态的疾病复发长期模式。
该研究基于纳入斯德哥尔摩乳腺癌组进行的三项对照临床试验之一的可手术浸润性乳腺癌患者。我们选择了2562例随机分配接受辅助他莫昔芬治疗或不接受辅助全身治疗的患者。这些患者的雌激素受体状态已知。
他莫昔芬降低了局部区域复发(8.8%对12.4%,风险比(HR),0.66;95%置信区间,0.52 - 0.83;P = 0.001)、远处复发(17.2%对20.2%,HR,0.81;置信区间,0.68 - 0.97;P = 0.018)以及乳腺癌死亡(18.7%对23.7%,HR,0.78;置信区间,0.67 - 0.92;P = 0.002)。在未分配接受他莫昔芬治疗的患者中,根据雌激素受体状态,局部区域复发(12.4%对12.4%,HR,1;置信区间,0.72 - 1.41;P = 0.98)和远处转移(18.5%对20.7%,HR,1.11;置信区间,0.85 - 1.45;P = 0.46)方面均无显著差异。雌激素受体阳性与阴性患者的转移模式无差异。
结果表明,上述基因表达方面的显著差异主要与内分泌敏感性相关,而非转移潜能。然而,在事件累积发生率方面,雌激素受体阳性患者在最初五年相对于雌激素受体阴性患者有轻微优势,这表明在某些情况下雌激素受体阴性与肿瘤生长速度增加相关。