Trinity College, University of Dublin, Dublin, Ireland.
J Clin Oncol. 2011 Jul 1;29(19):2635-44. doi: 10.1200/JCO.2010.33.5422. Epub 2011 May 31.
Preclinical studies have demonstrated that antagonism of β₂-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality.
Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β₁/β₂ antagonist; n = 70) or atenolol (β₁ antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed.
Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers.
The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.
临床前研究表明,β₂-肾上腺素能信号的拮抗作用抑制了乳腺癌进展和转移所必需的几种途径。进行了一系列基于人群的观察性研究,以检查β受体阻滞剂的使用与诊断时的乳腺肿瘤特征或乳腺癌特异性死亡率之间的关联。
利用国家癌症登记处和处方配发数据,确定 2001 年 1 月 1 日至 2006 年 12 月 31 日期间诊断为 I 期至 IV 期浸润性乳腺癌的女性。在乳腺癌诊断前一年使用普萘洛尔(β₁/β₂拮抗剂;n=70)或阿替洛尔(β₁拮抗剂;n=525)的女性与未使用β受体阻滞剂的女性(n=4738)进行 1:2 匹配。评估普萘洛尔或阿替洛尔的使用与诊断时局部肿瘤侵袭(T4 肿瘤)、淋巴结或远处转移受累(N2/N3/M1 肿瘤)以及乳腺癌特异性死亡率的时间之间的关系。
与匹配的非使用者相比,普萘洛尔使用者出现 T4(优势比 [OR],0.24,95%置信区间,0.07 至 0.85)或 N2/N3/M1(OR,0.20;95%置信区间,0.04 至 0.88)肿瘤的可能性显著降低。与匹配的非使用者相比,普萘洛尔使用者的乳腺癌特异性死亡率的累积概率明显较低(风险比,0.19;95%置信区间,0.06 至 0.60)。阿替洛尔使用者与匹配的非使用者在 T4 或 N2/N3/M1 肿瘤发生率或乳腺癌特异性死亡率方面没有差异。
这些结果为临床前观察提供了证据,表明抑制β₂-肾上腺素能信号通路可以减少乳腺癌的进展和死亡率。