Cancer Research：阿司匹林可减少乳腺癌复发

　　

生物通报道：科学家们发现，体重超标或肥胖的乳腺癌患者服用普通消炎药（例如阿司匹林或布洛芬），能够显著降低乳腺癌的复发率。这一成果发表在八月十四日的Cancer Research杂志上。

乳腺癌是目前全世界女性中最常见、也最严重的恶性肿瘤之一，其发病率正在不断增加。据资料统计，乳腺癌发病率占全身各种恶性肿瘤的7-10%。它的发病与遗传有关，以40-60岁之间、绝经期前后的妇女发病率较高，仅约1-2%的乳腺患者是男性。这种恶性肿瘤通常发生在乳腺上皮组织，严重影响了女性的身心健康乃至危及生命。乳腺癌远处转移是导致患者死亡的主要原因。

德克萨斯大学的肿瘤学家Andrew Brenner博士带领研究团队，对肥胖乳腺癌患者和体重正常乳腺癌患者的血样进行了检测。他们发现，与体重未超标的患者相比，肥胖患者的血液会增强癌细胞生长的侵袭性。

“肥胖乳腺癌患者的血液中前列腺素更多，而前列腺素在炎症中起到了一定的作用，” Dr. Brenner说。

研究人员指出，肥胖与乳腺癌预后差，以及机体炎症水平高有关，会引起COX-2活性的增加。COX-2的产物PGE2能刺激脂肪组织的芳香酶（Aromatase）表达和雌激素生成，在乳腺癌中起到推波助澜的作用。

在此基础上研究人员将乳腺癌患者分为两组，一组服用COX2抑制剂（阿司匹林或布洛芬），另一组作为对照。研究显示，每天服用非固醇类抗炎药物（NSAID）能够抑制COX-2活性，在肥胖患者中减少ERα阳性乳腺癌的复发。

“那些服用COX2抑制剂的患者，乳腺癌复发率更低，”Dr. Brenner 说。

ER阳性乳腺癌（应答雌激素）是最常见的一种乳腺癌，占到了乳腺癌诊断的75%。“与正常体重的女性相比，体重超标或肥胖的女性患上乳腺癌之后面临着更糟糕的预后，” 德克萨斯大学的癌症研究者Linda deGraffenried博士说。（延伸阅读：Nature子刊：同济研究员解析乳腺癌）

文章总结道，抗炎症药物将ERα阳性乳腺癌的复发率减少了50%，使患者的无症状期延长了两年多。不过研究人员也强调，这项研究还处于临床前期，相关成果转化到临床还需进行更多的实验。

“我们相信，肥胖女性的乳腺癌其实和正常人不同，这种疾病发生了分子水平上的改变。我们希望减少肥胖对乳腺癌的助推作用，”Dr. deGraffenried说。现在该研究团队已经启动了用抗炎症药物辅助治疗乳腺癌的临床试验。

 

生物通推荐原文：

NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions

Obesity is associated with a worse breast cancer prognosis and elevated levels of inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity in adipose-infiltrating macrophages. The product of this enzyme, the proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue aromatase expression and subsequent estrogen production, which could promote breast cancer progression. This study demonstrates that daily use of a nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is associated with reduced estrogen receptor α (ERα)–positive breast cancer recurrence in obese and overweight women. Retrospective review of data from ERα-positive patients with an average body mass index of >30 revealed that NSAID users had a 52% lower recurrence rate and a 28-month delay in time to recurrence. To examine the mechanisms that may be mediating this effect, we conducted in vitro studies that utilized sera from obese and normal-weight patients with breast cancer. Exposure to sera from obese patients stimulated greater macrophage COX-2 expression and PGE2 production. This was correlated with enhanced preadipocyte aromatase expression following incubation in conditioned media (CM) collected from the obese-patient, sera-exposed macrophages, an effect neutralized by COX-2 inhibition with celecoxib. In addition, CM from macrophage/preadipocyte cocultures exposed to sera from obese patients stimulated greater breast cancer cell ERα activity, proliferation, and migration compared with sera from normal-weight patients, and these differences were eliminated or reduced by the addition of an aromatase inhibitor during CM generation. Prospective studies designed to examine the clinical benefit of NSAID use in obese patients with breast cancer are warranted.