Powe Desmond G, Voss Melanie J, Zänker Kurt S, Habashy Hany O, Green Andrew R, Ellis Ian O, Entschladen Frank
Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK and The John van Geest Cancer Research Centre School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS UK.
Institute of Immunology, University of Witten/Herdecke, DE-58448, Witten, Germany.
Oncotarget. 2010 Nov;1(7):628-638. doi: 10.18632/oncotarget.197.
Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary.
实验室模型显示,β受体阻滞剂普萘洛尔可抑制去甲肾上腺素诱导的乳腺癌细胞迁移。我们推测,因高血压而接受β受体阻滞剂治疗的乳腺癌患者转移情况会减少,临床结局会得到改善。从466例连续的可手术乳腺癌女性患者(中位年龄57岁,范围28 - 71岁)的病历中确定了三个患者亚组,并进行随访(超过10年)。两个亚组分别包括43例和49例在癌症诊断前接受β受体阻滞剂或其他抗高血压药物治疗的高血压患者。374例患者组成非高血压对照组。对各组之间的转移发展、无病生存期、肿瘤复发和风险进行了统计学比较。采用Kaplan - Meier曲线来模拟生存率和远处转移情况。接受β受体阻滞剂治疗的患者转移发展显著减少(p = 0.026),肿瘤复发(p = 0.001),无病生存期更长(p = 0.01)。此外,转移风险降低了57%(风险比=0.430;95%置信区间=0.200 - 0.926,p = 0.031),10年后乳腺癌死亡率降低了71%(风险比=0.291;95%置信区间=0.119 - 0.715,p = 0.007)。这项原理验证研究表明,β受体阻滞剂治疗可显著降低乳腺癌患者的远处转移、癌症复发和癌症特异性死亡率,提示β受体阻滞剂治疗具有新的作用。对于乳腺癌以及包括结肠癌、前列腺癌和卵巢癌在内的其他癌症类型,需要进行更大规模的流行病学研究并开展随机临床试验。