乳腺癌 (BC) 预防策略包括从改变生活方式（如增加体力活动和减轻体重）到预防药物（如他莫昔芬）（已知可降低高危女性的 BC 发病率）。性激素结合球蛋白 (SHBG) 与 BC 风险相关，因为它能够以高亲和力结合循环雌二醇并调节雌二醇的作用。基于对不同干预措施效果的评估提出了研究方案，例如每隔一天服用 10 毫克他莫昔芬 (LDT)、每周两天间歇性热量限制 (ICR)、生活方式干预（LI、计步器使用）及其干预措施结合调节性激素结合球蛋白 (SHBG) 和其他几种与 BC 相关的生物标志物。一项随机 II 期生物标志物研究将在 4 个意大利中心进行。年龄在 18 至 70 岁之间的未受影响女性、种系致病变异（BRCA1、BRCA2、PALB2 或其他中等外显率基因）携带者，或 10 年内 BC 风险 >5%（根据 Tyrer-Cuzick 或 Breast）癌症监测联盟风险模型）或先前诊断为上皮内瘤变的患者将符合资格。总共 200 名参与者将被随机分配到四个组之一：LDT； LDT ICR；李;李ICR。干预措施将持续六个月，包括基线和后续门诊就诊以及临时电话。该研究的目的是验证 6 个月后，无论有或没有 ICR，LDT 是否比 LI 更能增加循环性 SHBG。次要目标包括评估 HOMA 指数、炎症标志物、脂联素/瘦素比率、生活质量 (QoL)、安全性、毒性、乳房 X 光密度以及各组微生物组组成的变化。该研究的创新之处在于纳入了不同的乳腺癌风险类别，并结合了药物和行为干预措施，有可能增强干预效果，同时平衡他莫昔芬对生活质量（尤其是更年期症状）的副作用。EuCT编号：2023-503994-39-00；临床试验.gov NCT06033092。版权所有：© 2024 Guerrieri-Gonzaga 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Breast Cancer (BC) prevention strategies range from lifestyle changes such as increasing physical activity and reducing body weight to preventive drugs like tamoxifen, known to reduce BC incidence in high-risk women. Sex Hormone Binding Globulin (SHBG) is related to BC risk due to its ability to bind circulating estradiol at high affinity and to regulate estradiol action. A study protocol is presented based on the assessment of the effect of different interventions such as tamoxifen at 10 mg every other day (LDT), intermittent caloric restriction (ICR) two days per week, lifestyle intervention (LI, step counter use) and their combination on the modulation of SHBG and several other biomarkers associated to BC.A randomized phase II biomarker study will be conducted in 4 Italian centers. Unaffected women aged between 18 and 70 years, carriers of a germline pathogenetic variant (BRCA1, BRCA2, PALB2, or other moderate penetrance genes), or with a >5% BC risk at 10 years (according to the Tyrer-Cuzick or the Breast Cancer Surveillance Consortium Risk models) or with a previous diagnosis of intraepithelial neoplasia will be eligible. A total of 200 participants will be randomized to one of the four arms: LDT; LDT + ICR; LI; LI + ICR. Interventions will span six months, with baseline and follow-up clinic visits and interim phone calls.The aim of the study is to verify whether LDT increases circulating SHBG more than LI with or without ICR after 6 months. Secondary objectives include assessing HOMA-index, inflammatory markers, adiponectin/leptin ratio, quality of life (QoL), safety, toxicity, mammographic density, and changes in microbiome composition across groups. The study's innovation lies in its inclusion of diverse BC risk categories and combination of pharmaceutical and behavioral interventions, potentially enhancing intervention efficacy while balancing tamoxifen's side effects on QoL, especially menopausal symptoms.EuCT number:2023-503994-39-00; Clinical trials.gov NCT06033092.Copyright: © 2024 Guerrieri-Gonzaga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.