Article(id=1322630871933371269, tenantId=1146029695717560320, journalId=1220038315760373764, issueId=1322630794611380728, articleNumber=null, orderNo=null, doi=10.12102/j.issn.1009-6493.2026.18.026, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1760544000000, receivedDateStr=2025-10-16, revisedDate=1782316800000, revisedDateStr=2026-06-25, acceptedDate=null, acceptedDateStr=null, onlineDate=1793269373161, onlineDateStr=2026-10-29, pubDate=1790265600000, pubDateStr=2026-09-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793269373161, onlineIssueDateStr=2026-10-29, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793269373161, creator=13701087609, updateTime=1793269373161, updator=13701087609, issue=Issue{id=1322630794611380728, tenantId=1146029695717560320, journalId=1220038315760373764, year='2026', volume='40', issue='18', pageStart='3153', pageEnd='3344', issueExtLink='null', onlineDate='null', pubDate='1790265600000', pubDateStr='2026-09-25', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1793269354727, creator='13701087609', updateTime=1793343080645, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322940023645011984, tenantId=1146029695717560320, journalId=1220038315760373764, issueId=1322630794611380728, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322940023645011985, tenantId=1146029695717560320, journalId=1220038315760373764, issueId=1322630794611380728, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3325, endPage=3331, ext={EN=ArticleExt(id=1322630872189223814, articleId=1322630871933371269, tenantId=1146029695717560320, journalId=1220038315760373764, language=EN, title=Research progress on the dual role of vitamin D in breast cancer, columnId=1220689485315101342, journalTitle=Chinese Nursing Research, columnName=Review Articles, runingTitle=null, highlight=null, articleAbstract=

The dual nature of the biological functions of vitamin D was summarized.The molecular mechanisms of vitamin D against breast cancer,the potential mechanisms by which vitamin D promotes breast cancer progression,the clinical associations with breast cancer,and the challenges in the prevention and treatment of breast cancer were reviewed.Future research directions were also proposed.

, authors=Jie ZHOU, Yanxia JIA, Xiaoli GENG, Feng GAO, Tengxin WANG, Zehua YANG, authorsList=Jie ZHOU, Yanxia JIA, Xiaoli GENG, Feng GAO, Tengxin WANG, Zehua YANG, authorCompany=null, correspAuthors=Zehua YANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322630873992774535, articleId=1322630871933371269, tenantId=1146029695717560320, journalId=1220038315760373764, language=CN, title=维生素D在乳腺癌中双重角色的研究进展, columnId=1220689485482873504, journalTitle=护理研究, columnName=科研综述, runingTitle=null, highlight=null, articleAbstract=

对维生素D生物学功能的双重性进行总结,对维生素D抗乳腺癌的分子机制、促乳腺癌进展的潜在机制、与乳腺癌的临床关联、在乳腺癌防治中的挑战进行综述,并提出未来研究方向。

, authors=周洁, 贾艳霞, 耿晓丽, 高峰, 王腾鑫, 杨泽华*, *, authorsList=周洁, 贾艳霞, 耿晓丽, 高峰, 王腾鑫, 杨泽华, authorCompany=null, correspAuthors=杨泽华, authorNote=

周洁,主管技师,硕士研究生在读

, correspAuthorsNote=
杨泽华,E-mail:
YANG Zehua, E-mail:
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周洁,主管技师,硕士研究生在读

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周洁,主管技师,硕士研究生在读

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维生素D在乳腺癌中双重角色的研究进展
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周洁 , 贾艳霞 , 耿晓丽 , 高峰 , 王腾鑫 , 杨泽华 *, *
护理研究 | 科研综述 2026,40(18): 3325-3331
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护理研究 |科研综述 2026 , 40 (18) : 3325 -3331
维生素D在乳腺癌中双重角色的研究进展
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周洁, 贾艳霞, 耿晓丽, 高峰, 王腾鑫, 杨泽华*, *
作者信息
  • 1山西医科大学第一医院,山西 030001
通讯作者:
杨泽华,E-mail:
YANG Zehua, E-mail:
作者简介:

周洁,主管技师,硕士研究生在读

Research progress on the dual role of vitamin D in breast cancer
Jie ZHOU, Yanxia JIA, Xiaoli GENG, Feng GAO, Tengxin WANG, Zehua YANG
Affiliations
  • 1First Hospital of Shanxi Medical University, Shanxi 030001 China
出版时间: 2026-09-25 doi: 10.12102/j.issn.1009-6493.2026.18.026
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对维生素D生物学功能的双重性进行总结,对维生素D抗乳腺癌的分子机制、促乳腺癌进展的潜在机制、与乳腺癌的临床关联、在乳腺癌防治中的挑战进行综述,并提出未来研究方向。

维生素D  /  乳腺癌  /  分子机制  /  临床应用  /  综述

The dual nature of the biological functions of vitamin D was summarized.The molecular mechanisms of vitamin D against breast cancer,the potential mechanisms by which vitamin D promotes breast cancer progression,the clinical associations with breast cancer,and the challenges in the prevention and treatment of breast cancer were reviewed.Future research directions were also proposed.

vitamin D  /  breast cancer  /  molecular mechanism  /  clinical application  /  review
周洁, 贾艳霞, 耿晓丽, 高峰, 王腾鑫, 杨泽华. 维生素D在乳腺癌中双重角色的研究进展. 护理研究, 2026 , 40 (18) : 3325 -3331 . DOI: 10.12102/j.issn.1009-6493.2026.18.026
Jie ZHOU, Yanxia JIA, Xiaoli GENG, Feng GAO, Tengxin WANG, Zehua YANG. Research progress on the dual role of vitamin D in breast cancer[J]. Chinese Nursing Research, 2026 , 40 (18) : 3325 -3331 . DOI: 10.12102/j.issn.1009-6493.2026.18.026
乳腺癌在全球女性恶性肿瘤中发病率较高,疾病负荷逐年攀升,已成为严峻的公共卫生问题之一。现阶段该病仍存在复发转移风险高、化疗靶向治疗耐药多发、个体化辅助治疗体系不完善等临床痛点,挖掘安全可靠的抗肿瘤辅助靶点,对优化乳腺癌诊疗方案意义重大。活化维生素D可发挥抑癌作用,降低乳腺癌发病风险,抑制肿瘤进展,辅助提升临床治疗效果。但其作用效应受体内浓度、肿瘤分子分型、机体状态等多种因素调控,特定条件下可呈现促瘤趋势。现系统梳理维生素D在乳腺癌中的分子调控网络、免疫调节新视角及临床应用瓶颈等,旨在厘清争议、展望精准干预策略。
乳腺癌是全球女性最常见的恶性肿瘤,其疾病负担呈现持续增长趋势。已有数据显示,2020年,全球乳腺癌新发病例突破200万例,占女性癌症总发病数的24.5%,预计至2040年新发病例可能攀升至300万例[1-3]。值得注意的是,该疾病的流行病学特征存在显著的地域差异,高收入国家虽然发病率较高(如美国女性终生患病风险达1/8),但得益于完善的诊疗体系,其年龄标准化死亡率呈下降趋势;而中低收入国家由于医疗资源匮乏,死亡率较发达国家高17%,非洲和亚洲部分地区每千万人口仅有1台放疗设备,导致较少(20%~30%)病例能在I期确诊[4-7]。我国作为发展中国家,乳腺癌已跃居女性第五大癌症死因,发病率与死亡率均呈现持续上升趋势[8-9]。
乳腺癌的危险因素与可预防性特征值得关注。约30%的病例与可干预因素相关,包括肥胖、缺乏运动、激素替代疗法及乙醇摄入等[10-11]。环境因素研究结果显示,PM2.5暴露与乳腺癌发病率呈正相关,而绿地覆盖率可能通过减少污染物暴露发挥保护作用[12]。在病理分型方面,三阴性乳腺癌(triple negative breast cancer,TNBC)占比为15%~20%,其高度异质性导致治疗选择有限且预后较差,而绝经前病人的乳腺癌疾病负担在中低收入国家尤为突出[13-15]。
乳腺癌的临床管理面临多重挑战。治疗相关并发症可影响病人生存质量,但化疗与放疗也可能诱发心脏毒性,已有研究结果显示,超过50%的生存者最终死于心血管疾病等非肿瘤原因[16-17]。在精准医疗下,循环肿瘤脱氧核糖核酸(ctDNA)检测虽能动态监测肿瘤负荷,但激素受体阳性/人表皮生长因子受体2(HER2)阴性亚型的ctDNA脱落量低于TNBC,限制了其复发监测效能[18]。肿瘤突变负荷可能预测免疫治疗响应,但其在乳腺癌中的临床应用仍需进一步验证[19]。医疗资源分配失衡可加剧治疗困境,新型靶向药物如细胞周期蛋白依赖性激酶(CDK)4/6抑制剂虽可提升疗效,但费用较高,可使美国病人年均治疗费用超过10万美元,高昂成本直接影响筛查策略的制定与推广[20-21]。以上挑战的协同作用,导致全球范围内乳腺癌防控仍面临诊断不及时、治疗不均衡和生存获益差异显著等问题。
维生素D作为关键的脂溶性信号分子,生物学功能在多个生理系统中呈现显著的“双刃剑”特征。在骨骼代谢与免疫调节领域,维生素D通过调控肠钙吸收(提升效率50%~80%)和肾钙重吸收维持骨骼稳态[22-23],同时借助广泛分布的维生素D受体(VDR)参与免疫微环境调控。其既能通过促进巨噬细胞抗菌肽cathelicidin分泌增强固有免疫[24],又可抑制Th17细胞活性调节获得性免疫,这种独特的“免疫开关”特性使其在感染防御与自身免疫性疾病防治中发挥着双向调节作用[25-27]。
在癌症生物学领域,维生素D展现出矛盾的双重效应,尽管其通过调控p21、p27等细胞周期蛋白及促凋亡基因显示出抗癌潜力[28],但大规模队列研究揭示其与结直肠癌风险的相关性存在显著个体差异[29]。这种异质性可能源于维生素D受体基因多态性,某些单核苷酸多态性(SNP)可完全逆转维生素D的肿瘤抑制作用[30]。代谢调控方面,维生素D在脂肪组织中的双向性尤为突出,其既能通过过氧化物酶体增殖物激活受体(PPAR)γ通路抑制脂肪生成改善代谢综合征[31],又能通过上调脂肪酸结合蛋白(FABP4)促进脂质储存,临床数据显示维生素D缺乏者补充维生素D后代谢改善显著,而正常水平者补充维生素D后可能产生负面效应[32-33]。
维生素D的免疫调节功能呈现显著的剂量依赖性,低浓度(<20 ng/mL)的维生素D可通过Toll样受体(TLR)4通路激活固有免疫[24],高浓度(>50 ng/mL)的维生素D则可通过抑制核因子-κB(NF-κB)发挥抗炎作用[34]。值得注意的是,维生素D2与D3的免疫调节效能存在差异,D3对白细胞介素(IL)-6的抑制效率为D2的3~5倍[35]。心血管系统中,维生素D通过抑制肾素-血管紧张素系统降低血压[36],但过度补充可能加速血管钙化,形成J型曲线效应,已有研究结果显示,慢性肾病病人血清25(OH)D在30~50 ng/mL时心血管获益最大,超过60 ng/mL时全因死亡率升高17%[37-38]。
维生素D在神经发育领域可显示出时空特异性双重作用,孕期缺乏维生素D可损害子代海马神经元突触可塑性[31],但出生后过量补充维生素D与孤独症谱系障碍风险增加相关,这可能与发育阶段特异性表观遗传修饰[如DNMT3A介导的脱氧核糖核酸(DNA)甲基化模式改变]有关[39-40]。这种广泛的功能双重性源于维生素D信号通路的组织特异性,同一维生素D受体在不同细胞中可激活差异化的基因表达程序,如在肠上皮细胞中主要调控钙转运基因,而在免疫细胞中优先调节细胞因子相关基因[41-42]。这种分子机制的多效性使维生素D成为连接营养代谢与系统生理的重要调控枢纽。
1)维生素D可通过其活性代谢物1,25-二羟基维生素D[1,25(OH)2D]与维生素D受体结合在乳腺癌中发挥多层次的抗肿瘤作用:细胞增殖与分化调控是其核心机制之一,即1,25(OH)2D可通过下调癌基因(如MYC)并上调细胞周期抑制蛋白(p21、p27),阻断细胞周期进程,同时激活维生素D受体信号通路,促进癌细胞向正常分化状态转变,从而降低恶性表型[43-44]。促凋亡效应则通过双重途径实现,其一方面可调控促凋亡蛋白Bax与抗凋亡蛋白Bcl-2的表达失衡;另一方面可直接激活线粒体凋亡通路,增强癌细胞对凋亡信号的敏感性[43-44]。2)维生素D在雌激素受体(ER)信号调控领域具有独特的治疗潜力:1,25(OH)2D可在ERα阴性乳腺癌中重新诱导ERα表达,恢复癌细胞对激素治疗的敏感性,其机制涉及抑制组蛋白去乙酰化酶(HDACs)以重塑ERα基因的染色质开放性[45]。这一过程与表观遗传调控密切相关,1,25(OH)2D通过抑制DNA甲基转移酶(DNMTs)降低BRCA1等抑癌基因的异常甲基化,同时调控转移核糖核酸(RNA)衍生小RNA(tsRNAs)的表达,抑制癌细胞的侵袭转移能力[28]。3)维生素D的免疫调节功能可通过激活肿瘤微环境中的免疫监视发挥作用:维生素D可上调主要组织相容性复合体I类(MHC-I)抗原呈递分子和IL-12等促炎细胞因子,增强T细胞介导的肿瘤杀伤作用,并与免疫检查点抑制剂产生协同效应[46]。此外,维生素D还可通过激活核因子E2相关因子2(Nrf2)抗氧化通路和抑制NF-κB炎症信号,减少活性氧(ROS)积累与慢性炎症,形成抑制肿瘤发生的保护屏障[47-48]。4)维生素D可在信号通路调控层面抑制Wnt/β-catenin通路以减少β-catenin核转位,从而阻断Cyclin D1等下游靶基因表达,抑制乳腺癌干细胞自我更新[49]。同时,维生素D还可通过下调富含组氨酸钙结合蛋白(HRC)干扰细胞内钙稳态,在肺癌模型中可抑制肿瘤生长和转移,提示该机制在乳腺癌中具有潜在适用性[50]。化疗协同作用则表现为增强吉西他滨等药物的疗效,机制包括下调BRCA1/2等DNA修复蛋白,导致化疗诱导的DNA损伤持续积累[44,51]。
维生素D的潜在促癌机制存在争议且证据有限。当前研究主要聚焦于特定条件下维生素D信号通路异常或与其他生物学过程的交互作用可能产生的间接效应。1)已有研究结果显示,维生素D受体功能异常是维生素D促乳腺癌进展的重要机制之一,维生素D受体基因多态性(如rs2228570)可导致信号通路失调,增加乳腺癌发生风险[52],而ER阴性乳腺癌中维生素D诱导ERα重新表达后,若缺乏有效调控可能激活激素依赖性生长信号,但目前临床研究尚未观察到此类负面效应[45,53],提示维生素D受体功能状态可能决定维生素D作用的双向性。2)肿瘤微环境代谢互作是维生素D促进乳腺癌进展的另一潜在机制。维生素D活性形式[1,25(OH)2D3]在免疫抑制性微环境中可能产生复杂效应,其虽能通过促进T细胞功能增强抗肿瘤免疫[46],但在程序性细胞死亡蛋白1(PD-1)/细胞毒性T淋巴细胞相关抗原4(CTLA-4)高表达的微环境中可能异常调节免疫检查点分子,导致免疫逃逸风险[54]。此外,钙信号调控的双向性值得关注,虽然维生素D可通过抑制HRC蛋白减少肺癌转移[50],但在乳腺癌中异常激活的钙信号可能通过促进细胞迁移间接影响乳腺癌进展。3)在化疗耐药性领域,维生素D的剂量依赖性效应具有复杂性,与顺铂、多柔比星联用时,维生素D3可通过降低乙醛脱氢酶1(ALDH-1)水平抑制乳腺癌干细胞活性[55],但剂量不足或代谢异常时,可能无法有效清除耐药干细胞群,反而可能导致残留细胞增殖。同时,人群异质性会进一步增加机制的复杂性,已有研究结果显示,非西班牙裔白人女性中维生素D水平与乳腺癌发生风险无显著关联,而黑人和西班牙裔女性中低维生素D水平与乳腺癌发生风险升高相关[56-57],提示遗传背景或代谢差异可能使特定亚群对维生素D状态更敏感,间接促进肿瘤进展。4)维生素D与其他信号通路的交叉调控网络可能产生不可预见的效应,其虽通过抑制Wnt/β-catenin通路抑制癌细胞增殖[53],但在ER阳性乳腺癌病人中,异常激活的ER信号可能拮抗维生素D的抗癌作用。此外,慢性炎症状态下维生素D代谢受损可能削弱其抗炎保护效应,形成促肿瘤微环境[58]。以上机制提示,维生素D的生物学效应高度依赖细胞背景与环境稳态的平衡。
维生素D与乳腺癌的临床关联研究近年来在流行病学、干预效果及分子机制层面取得了阶段性进展,但其应用价值仍存在争议。
流行病学关联的矛盾性首先体现在种族差异方面,尽管实验室研究证实维生素D可以通过调控细胞增殖、凋亡及免疫调节发挥抗癌作用[43,53],但人群研究却呈现异质性结果。有研究显示,维生素D浓度与乳腺癌风险呈负相关,尤其在拉丁裔人群中保护效应更显著[56]。但一项涵盖17个国际队列研究的汇总分析(纳入10 484例浸润性乳腺癌病人)发现,经季节校正后的循环25(OH)D水平与乳腺癌总体发病率无统计学关联[57]。这种矛盾可能与肿瘤分子亚型异质性相关,低维生素D水平与ER阴性乳腺癌风险升高相关,而对ER阳性肿瘤影响不明显[59],机制研究进一步揭示维生素D可诱导ER阴性细胞重新表达ERα,恢复对内分泌治疗的反应性,为精准干预提供理论依据[45]。
临床干预效果的争议聚焦于剂量效应与代谢干扰。相关研究结果表明,补充维生素D可使总体癌症死亡率降低13%[60-61],但对乳腺癌特异性死亡率的影响尚未明确[62]。剂量选择成为关键分歧点,部分随机试验结果显示,将每日≥2 000 IU的高剂量维生素D3应用于基线维生素D3不足人群效果较好[63-64],而其他研究未观察到剂量依赖性关联[65]。此外,肥胖导致的代谢干扰可影响疗效,这可能与维生素D的脂溶性特性使其在肥胖人群中的生物利用度降低有关,随机试验亚组分析结果显示,使用维生素D后仅在正常体重女性中观察到乳腺癌风险降低,而超重/肥胖人群效应不明显[63]。提示需基于代谢状态制定个体化维生素D补充策略。
机制研究的新进展为突破争议提供了潜在方向。表观遗传调控领域发现,维生素D通过激活维生素D受体诱导DNA甲基化重塑和染色质构象改变,抑制MYC等促癌基因表达并激活抑癌通路[44,53],动物实验证实其可抑制肺癌转移并增强化疗敏感性[50],但乳腺癌中的等效机制仍需验证。当前的免疫微环境调节研究已取得一定突破,小鼠模型显示维生素D可提高移植瘤对PD-1/CTLA-4抑制剂的响应率,人类队列数据揭示维生素D相关基因特征与免疫治疗疗效呈正相关,提示维生素D具有作为免疫治疗增敏剂的潜力[46,53]。
维生素D在乳腺癌防治中的临床应用面临多种挑战,其转化潜力受限于生物学复杂性、人群异质性及临床证据的不确定性。尽管实验室研究证实维生素D可以通过调控细胞增殖、诱导凋亡及免疫调节发挥抗癌作用[53,57],但流行病学研究结果却存在不一致性,一项纳入17个国际队列研究的研究结果显示,循环25(OH)D水平与侵袭性乳腺癌发病率关联不明显,即使在维生素D充足的人群中亦如此[57]。这种差异可能源于人群遗传背景、代谢特征及研究设计(如季节校正不足)的异质性[51,66]。生物标志物开发的困境会进一步加剧应用难度,虽然维生素D可能通过调节ER表达影响治疗反应,但预处理维生素D水平与新辅助化疗疗效及生存结局的关联尚未明确,且维生素D受体基因多态性(如rs2228570)对个体敏感性的影响仍需进行机制验证[43,52,67]。
高剂量维生素D(≥4 000 IU/d)补充策略在增强抗癌效应的同时也可能引发高钙血症等毒性反应;而低剂量维生素D(<2 000 IU/d)补充策略在肥胖人群中因生物利用度降低往往难以达到有效浓度[68-69]。现有临床试验因剂量、频率及疗程缺乏标准化,导致疗效评估困难,维生素D有利于降低转移性癌症风险的结果还需更大规模研究予以验证[63,70-71]。这一挑战与人群异质性深度交织,已有研究结果显示,维生素D与乳腺癌发生风险的负相关性仅在拉丁裔女性中显著[56],而肥胖、肿瘤分子亚型(如ER状态)等因素可进一步调节维生素D效应,亟须开发基于代谢特征和分子分型的个体化方案[63,66,72]。
维生素D通过表观遗传重塑(如DNA甲基化调控)、免疫微环境调节及与p53、HRC等通路交互作用发挥效应[44,53,73],但人体中这些机制的实际贡献尚未明晰。已有研究结果显示,维生素D通过抑制ALDH-1增强化疗敏感性的现象在小鼠模型中显著[55],但其与免疫检查点抑制剂的协同作用仍需临床验证[46]。临床指南的缺失反映了证据等级不足,目前缺乏针对癌症病人的维生素D补充共识,现有推荐多基于观察性研究结果,维生素D对三阴性乳腺癌或转移性乳腺癌病人的潜在益处尚未形成临床规范[45,51,61,72]。
传统口服维生素D制剂因首过效应和脂溶性限制,难以维持在肿瘤微环境中的有效浓度,而纳米载体(如脂质体包裹)虽能提高靶向性,但其安全性和成本效益尚未明确[69,74]。此外,长期安全性考量要求权衡风险收益,高剂量维生素D补充策略可能增加血管钙化及代谢紊乱风险[36,66],而普遍筛查补充策略在低风险人群中成本效益不佳,需通过生物标志物(如p53突变状态[73])筛选潜在获益亚群以提高精准性[75]。
维生素D与乳腺癌的关联研究已从基础机制探索逐步转向临床转化,但仍存在关键科学问题亟待突破。
需深入阐明维生素D在不同种族/族裔中的效应差异,结合遗传背景(如维生素D受体基因多态性、维生素D代谢酶CYP27B1变异)与生活方式(日晒时长、饮食结构)的交互作用,建立基于多组学数据的精准预防模型[43,56]。针对维生素D普遍缺乏的高危群体(如肥胖、深肤色人群),需开发区域性补充策略并评估其公共卫生成本效益[72,75]。
通过单细胞测序等技术解析维生素D通过维生素D受体介导的表观遗传重塑(如BRCA1去甲基化、非编码RNA调控)及免疫微环境重编程机制(如增强CD8+T细胞浸润、抑制Treg活性),重点验证其对ER阴性及三阴性乳腺癌的靶向治疗潜力[44-46,53,55]。同时,需借助类器官与人源化小鼠模型系统评估维生素D与化疗(如吉西他滨)、免疫检查点抑制剂(如PD-1单抗)的协同效应及剂量优化策略[55,70]。
需开展多中心随机对照试验,明确维生素D在辅助治疗(如新辅助化疗周期同步补充)及维持治疗(预防复发)中的作用,建立动态监测循环25(OH)D水平、肿瘤突变负荷(TMB)等生物标志物的疗效预测体系[44,67]。标准化研究设计是核心挑战之一,需统一维生素D检测方法(液相色谱-质谱法)并实施季节校正,以减少数据异质性[29,57]。此外,需构建大规模前瞻性队列,追踪维生素D水平动态变化与乳腺癌发病率、无病生存期的长期关联[60]。
借鉴结直肠癌病人维生素D与肠道菌群互作、头颈癌病人氧化应激调控等成果,探索维生素D在乳腺癌微环境中的特异性通路(如HRC介导的钙信号异常)[51-52,55]。同时,需评估维生素D与维生素K(增强抗钙化)、维生素C(协同抗氧化)的联合干预效果,揭示营养素协同作用的分子基础[76]。可运用家庭护士饮食处方通过抗氧化、抗炎症、调节代谢辅助治疗慢性病。日常膳食通过护士开具饮食处方或农产品处方,运用到癌症预防、治疗、康复的各个阶段,对癌症的控制、治疗、预后有积极意义[77-78]。未来需整合计算生物学、纳米药物递送系统等前沿技术,推动维生素D从基础研究向临床实践的跨越式转化。
维生素D在乳腺癌中的作用具有复杂性,其双重性源于剂量依赖性、遗传背景及微环境互作的动态平衡。尽管基础研究揭示了其通过维生素D受体介导的多维抗肿瘤网络,临床转化仍面临多重挑战,如人群异质性导致流行病学数据矛盾、剂量策略缺乏标准化、生物标志物开发滞后以及长期补充的安全性风险(如高钙血症)。当前争议焦点集中于维生素D在特定亚群(如ER-乳腺癌、非西班牙裔黑人女性)中的精准应用潜力及与现有疗法(化疗、免疫治疗)的协同效应。未来研究应聚焦机制深化、临床转化、技术创新、公共卫生策略等。通过跨学科合作与精准医学策略,使维生素D从争议性分子转化为乳腺癌防治的突破性工具,但其临床应用需严格遵循“个体化阈值”,平衡抗癌获益与代谢风险。

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doi: 10.12102/j.issn.1009-6493.2026.18.026
  • 接收时间:2025-10-16
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  • 出版时间:2026-09-25
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  • 收稿日期:2025-10-16
  • 修回日期:2026-06-25
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    1山西医科大学第一医院,山西 030001

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2种不同金属材料的力学参数
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species
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total species (%)
属
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species
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species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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