Aarnoutse Romy, Hillege Lars E, Ziemons Janine, De Vos-Geelen Judith, de Boer Maaike, Aerts Elvira M E R, Vriens Birgit E P J, van Riet Yvonne, Vincent Jeroen, van de Wouw Agnes J, Le Giang N, Venema Koen, Rensen Sander S, Penders John, Smidt Marjolein L
GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Department of Surgery, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
Cancers (Basel). 2021 Dec 9;13(24):6200. doi: 10.3390/cancers13246200.
Previous preclinical and clinical research has investigated the role of intestinal microbiota in carcinogenesis. Growing evidence exists that intestinal microbiota can influence breast cancer carcinogenesis. However, the role of intestinal microbiota in breast cancer needs to be further investigated. This study aimed to identify the microbiota differences between postmenopausal breast cancer patients and controls.
This prospective cohort study compared the intestinal microbiota richness, diversity, and composition in postmenopausal histologically proven ER+/HER2- breast cancer patients and postmenopausal controls. Patients scheduled for (neo)adjuvant adriamycin, cyclophosphamide (AC), and docetaxel (D), or endocrine therapy (tamoxifen) were prospectively enrolled in a multicentre cohort study in the Netherlands. Patients collected a faecal sample and completed a questionnaire before starting systemic cancer treatment. Controls, enrolled from the National Dutch Breast Cancer Screening Programme, also collected a faecal sample and completed a questionnaire. Intestinal microbiota was analysed by amplicon sequencing of the 16S rRNA V4 gene region.
In total, 81 postmenopausal ER+/HER2- breast cancer patients and 67 postmenopausal controls were included, resulting in 148 faecal samples. Observed species richness, Shannon index, and overall microbial community structure were not significantly different between breast cancer patients and controls. There was a significant difference in overall microbial community structure between breast cancer patients scheduled for adjuvant treatment, neoadjuvant treatment, and controls at the phylum ( = 0.042) and genus levels ( = 0.015). ( = 0.001) and its corresponding family Veillonellaceae ( = 0.001) were higher in patients scheduled for adjuvant treatment, compared to patients scheduled for neoadjuvant treatment. Additional sensitivity analysis to correct for the potential confounding effect of prophylactic antibiotic use, indicated no differences in microbial community structure between patients scheduled for neoadjuvant systemic treatment, adjuvant systemic treatment, and controls at the phylum ( = 0.471) and genus levels ( = 0.124).
Intestinal microbiota richness, diversity, and composition are not different between postmenopausal breast cancer patients and controls. The increased relative abundance of and Veillonellaceae was observed in breast cancer patients scheduled for adjuvant treatment, which might be caused by a relative decrease in other bacteria due to prophylactic antibiotic administration rather than an absolute increase.
既往的临床前和临床研究已经探讨了肠道微生物群在致癌过程中的作用。越来越多的证据表明，肠道微生物群可影响乳腺癌的发生。然而，肠道微生物群在乳腺癌中的作用仍需进一步研究。本研究旨在确定绝经后乳腺癌患者与对照组之间的微生物群差异。
这项前瞻性队列研究比较了绝经后经组织学证实的雌激素受体阳性/人表皮生长因子受体2阴性（ER+/HER2-）乳腺癌患者和绝经后对照组的肠道微生物群丰富度、多样性和组成。计划接受（新）辅助阿霉素、环磷酰胺（AC）和多西他赛（D）治疗或内分泌治疗（他莫昔芬）的患者前瞻性纳入荷兰的一项多中心队列研究。患者在开始全身癌症治疗前采集粪便样本并完成一份问卷。从荷兰国家乳腺癌筛查项目中招募的对照组也采集了粪便样本并完成了问卷。通过对16S rRNA V4基因区域进行扩增子测序分析肠道微生物群。
总共纳入了81例绝经后ER+/HER2-乳腺癌患者和67例绝经后对照组，共获得148份粪便样本。乳腺癌患者和对照组之间观察到的物种丰富度、香农指数和整体微生物群落结构无显著差异。计划接受辅助治疗、新辅助治疗的乳腺癌患者与对照组在门水平（P = 0.042）和属水平（P = 0.015）的整体微生物群落结构存在显著差异。与计划接受新辅助治疗的患者相比，计划接受辅助治疗患者中的韦荣球菌属（P = 0.001）及其相应的韦荣氏菌科（P = 0.001）丰度更高。为校正预防性抗生素使用的潜在混杂效应而进行的额外敏感性分析表明，计划接受新辅助全身治疗、辅助全身治疗的患者与对照组在门水平（P = 0.471）和属水平（P = 0.124）的微生物群落结构无差异。
绝经后乳腺癌患者与对照组之间的肠道微生物群丰富度、多样性和组成无差异。在计划接受辅助治疗的乳腺癌患者中观察到韦荣球菌属和韦荣氏菌科的相对丰度增加，这可能是由于预防性抗生素给药导致其他细菌相对减少而非绝对增加所致。
