Department of Medicine, Sunnybrook Odette Cancer Centre, 2075 Bayview Ave, Toronto, ON, M4N3M5, Canada.
Sunnybrook Research Institute, University of Toronto, Toronto, Canada.
Breast Cancer Res Treat. 2018 Oct;171(3):709-717. doi: 10.1007/s10549-018-4844-5. Epub 2018 Jun 18.
Preliminary data suggest that high expression of the TRβ1 tumor suppressor is associated with longer survival among women with early breast cancer. We undertook this study to validate these findings.
In this prospective cohort study, we analyzed the prognostic significance of TRβ1 protein expression in the breast tumors of 796 women who had undergone breast surgery in the Henrietta Banting Breast Cancer database. All women were recruited after undergoing primary surgical therapy at Women's College Hospital (Toronto, ON, Canada) between January 1987 and December 2000. Details regarding patient age at diagnosis, systemic, and local therapies, as well as pathological features of their tumor have been systematically recorded. Clinical outcomes including breast cancer recurrence and death have been updated at least once each year with a median follow-up of 9.6 years (range 0.1-21 years).
High TRβ1 expression (> 4 on the Allred score) was associated with a longer breast cancer-specific survival with a HR 0.45 (95% CI 0.33-0.61), p < 0.0001 in a univariable Cox regression model. This was maintained in a multivariable model adjusted for age, tumor size, nodal status, chemotherapy, hormone therapy, radiotherapy, surgery, and ER status with a HR of 0.61 (95% CI 0.44-0.85), p = 0.004.
High expression of TRβ1 is associated with longer breast cancer-specific survival independent of other prognostic factors. Given that low TRβ expression is associated with chemotherapy resistance in-vitro, TRβ1 may also serve as a predictive biomarker or even a therapeutic target given the availability of TRβ agonists.
初步数据表明，TRβ1 肿瘤抑制因子的高表达与早期乳腺癌患者的生存时间延长有关。我们进行这项研究是为了验证这些发现。
在这项前瞻性队列研究中，我们分析了 796 名在 Henrietta Banting 乳腺癌数据库中接受过乳房手术的女性乳房肿瘤中 TRβ1 蛋白表达的预后意义。所有女性均在 1987 年 1 月至 2000 年 12 月期间在加拿大安大略省多伦多的女子学院医院接受原发性手术治疗后被招募。患者诊断时的年龄、全身和局部治疗以及肿瘤的病理特征等详细信息已被系统记录。临床结果包括乳腺癌复发和死亡，至少每年更新一次，中位随访时间为 9.6 年（范围 0.1-21 年）。
在单变量 Cox 回归模型中，高 TRβ1 表达（Allred 评分>4）与乳腺癌特异性生存时间延长相关，HR 为 0.45（95%CI 0.33-0.61），p<0.0001。在多变量模型中，调整年龄、肿瘤大小、淋巴结状态、化疗、激素治疗、放疗、手术和 ER 状态后，HR 为 0.61（95%CI 0.44-0.85），p=0.004。
TRβ1 的高表达与其他预后因素无关，与乳腺癌特异性生存时间延长有关。鉴于 TRβ1 低表达与体外化疗耐药性有关，鉴于 TRβ1 激动剂的可用性，TRβ1 也可能作为预测生物标志物甚至治疗靶点。
