Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women.

IF 7.4 1区 医学 Q1 Medicine
Peter Lundberg, Annelie Abrahamsson, Johan Kihlberg, Jens Tellman, Ieva Tomkeviciene, Anette Karlsson, Maria Kristoffersen Wiberg, Marcel Warntjes, Charlotta Dabrosin
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引用次数: 0

Abstract

Purpose: One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts.

Methods: Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay.

Results: After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF.

Conclusions: ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted. Trial registration EudraCT: 2017-000317-22.

小剂量乙酰水杨酸可减少绝经后妇女致密乳腺组织的局部炎症和组织灌注。
目的:乳腺癌的一个主要风险因素是乳腺组织密度过高。据估计,致密乳腺组织占所有乳腺癌的 30%左右。针对致密乳腺组织的预防有可能改善乳腺癌的死亡率和发病率。抗雌激素可能会产生严重的副作用,但可用于高危妇女的乳腺癌预防。然而,目前还没有针对致密乳房的预防疗法。炎症是癌症的标志。虽然致密乳房罹患癌症风险增加的生物机制尚未完全明了,但高乳腺密度与炎症增加有关。我们研究了低剂量乙酰水杨酸(ASA)是否会影响致密乳房的局部乳腺组织炎症和/或结构及动态变化:方法:我们对定期接受乳腺 X 射线照相检查并发现乳房致密的绝经后妇女进行了鉴定。共有 53 名妇女被随机分配到接受 ASA 160 毫克/天或不接受治疗 6 个月。6个月前后分别进行磁共振成像(MRI)检查,通过计算瘦组织分数(LTF)对乳房密度进行精密、连续的测量。此外,还进行了包括组织灌注在内的动态量化。6 个月前后,对乳房和腹部皮下脂肪的蛋白质进行了微透析取样,以衡量其对全身的影响。使用邻近延伸测定法对微量透析液中的 92 种炎症蛋白进行了量化:结果:经误诊率校正后,92 种炎症蛋白中有 20 种在 ASA 治疗后的乳腺组织中明显减少,而未发现系统性影响。在未治疗组中,蛋白质水平未受影响。通过核磁共振成像(MRI)的LTF测量的乳腺密度在两组中均未受影响。ASA 能明显降低灌注率。灌注率与局部乳腺组织中血管内皮生长因子的浓度呈正相关:ASA可将局部乳腺组织微环境塑造成抗肿瘤状态。有必要进行试验,研究低剂量ASA对乳腺X线照相术中保持高密度的绝经后妇女原发性乳腺癌风险的影响。试验注册 EudraCT:2017-000317-22。
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来源期刊
CiteScore
12.00
自引率
0.00%
发文量
76
审稿时长
12 weeks
期刊介绍: Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.
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