查看“HER2阳性乳腺癌”的源代码

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            <strong>[[HER2阳性乳腺癌]]</strong>是一种由<strong>[[ERBB2]]</strong>（[[人表皮生长因子受体2]]）基因扩增或其编码蛋白过度表达驱动的乳腺癌亚型，约占所有乳腺癌病例的<strong>15%-20%</strong>。该亚型以生物学行为侵袭性强、细胞增殖快、早期易发生[[脑转移]]及[[内脏转移]]为特征。在靶向药物问世前，其预后显著劣于[[管腔型乳腺癌]]。随着<strong>[[曲妥珠单抗]]</strong>、<strong>[[帕妥珠单抗]]</strong>及新型<strong>[[ADC]]</strong>（如[[DS-8201]]）的临床应用，[[HER2阳性乳腺癌]]已从“高危亚型”转变为精准治疗获益最大的肿瘤类型之一，实现了从早期治愈到晚期长期生存的重大跨越。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[HER2阳性乳腺癌]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">HER2+ Breast Cancer · 点击展开</div>
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                    <div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">[[HER2]]受体二聚化及通路激活图示</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心驱动：[[ERBB2]]基因扩增</div>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">染色体定位</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">17q12</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">判定标准</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">IHC 3+ 或 FISH(+)</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">发病占比</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">~15%-20%</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关键靶点</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[HER2]] (ErbB2)</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">一线方案</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[曲帕双靶]]+[[紫杉类]]</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">高发转移位</th>
                    <td style="padding: 12px; color: #0f172a;">[[脑]]、[[肝]]、[[肺]]</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：HER2驱动的增殖风暴</h2>
    
    
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        [[HER2]]属于[[受体酪氨酸激酶]]家族。与其它成员不同，[[HER2]]无需配体结合即可处于“开放”构象：
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        <li style="margin-bottom: 12px;"><strong>受体二聚化：</strong>过度表达的[[HER2]]蛋白在细胞膜上发生自发[[同源二聚化]]或与[[HER3]]等形成[[异源二聚化]]，这是其致癌活性的核心起点。</li>
        <li style="margin-bottom: 12px;"><strong>信号级联激活：</strong>二聚化引发胞内结构域的[[自磷酸化]]，激活下游两条关键通路：<strong>[[PI3K/Akt]]</strong>（主导抗凋亡与细胞生存）和<strong>[[Ras/Raf/MAPK]]</strong>（主导细胞增殖与迁移）。</li>
        <li style="margin-bottom: 12px;"><strong>血管生成与浸润：</strong>[[HER2]]通路还通过上调[[VEGF]]促进肿瘤[[新生血管生成]]，并诱导[[上皮-间质转化]]（[[EMT]]），增加肿瘤细胞的远端播散能力。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床评价与分层治疗矩阵</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 20%;">疾病阶段</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">治疗核心策略</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">标准方案([[SOC]])</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[新辅助治疗]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">追求 [[pCR]] (病理学完全缓解)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[THP方案]] (多西他赛+曲妥珠单抗+帕妥珠单抗)</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[辅助治疗]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">Non-pCR患者的强化治疗</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[T-DM1]] (恩美曲妥珠单抗) 序贯治疗</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[晚期一线]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">最大化缓解深度</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[H+P+紫杉类]] (CLEOPATRA模式)</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[晚期二线]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">新型 [[ADC]] 突围</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[DS-8201]] (德曲妥珠单抗) 是目前的一致首选</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">诊疗策略：精准检测与靶向进化</h2>
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        [[HER2阳性乳腺癌]]的管理强调“全方位、全生命周期”的靶向封锁：
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        <li style="margin-bottom: 12px;"><strong>精准判读：</strong>根据[[ASCO/CAP]]指南，[[IHC 3+]]为阳性；[[IHC 2+]]需进一步行[[FISH]]检测，若[[HER2/CEP17]]比值 $\ge 2.0$ 且拷贝数 $\ge 4.0$ 则判定为阳性。</li>
        <li style="margin-bottom: 12px;"><strong>克服脑转移：</strong>针对HER2+极易发生的脑转移，小分子[[TKI]]（如[[吡咯替尼]]、[[图卡替尼]]）联合化疗展现出更强的血脑屏障穿透能力，是晚期管理的关键。</li>
        <li style="margin-bottom: 12px;"><strong>[[HER2低表达]]（HER2-low）：</strong>随着[[DS-8201]]的问世，[[IHC 1+]]或[[IHC 2+/FISH-]]的患者也被纳入精准治疗范畴，打破了传统的二分法。</li>
        <li style="margin-bottom: 12px;"><strong>心脏毒性监测：</strong>靶向治疗期间需定期（每3个月）通过[[心肌超声]]评估[[LVEF]]，预防可逆性心功能损伤。</li>
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            <li style="margin-bottom: 8px;"><strong>[[曲妥珠单抗]] (赫赛汀)：</strong>首个改变该亚型自然史的单克隆抗体，作用于HER2胞外IV区。</li>
            <li style="margin-bottom: 8px;"><strong>[[德曲妥珠单抗]] (DS-8201)：</strong>第三代 [[ADC]]，通过[[旁路杀伤效应]]彻底改变了耐药患者的结局。</li>
            <li style="margin-bottom: 8px;"><strong>[[pCR]]：</strong>新辅助治疗后手术标本无残留侵袭性癌。达到[[pCR]]的患者复发风险下降约60%。</li>
            <li style="margin-bottom: 8px;"><strong>[[PIK3CA突变]]：</strong>HER2+乳腺癌常见的耐药突变，常导致靶向治疗敏感性下降。</li>
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
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            [1] <strong>Slamon DJ, et al. (2001).</strong> <em>Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer.</em> <strong>[[The New England Journal of Medicine]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该研究奠定了曲妥珠单抗在HER2+乳腺癌中的基石地位。</span>
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            [2] <strong>Swain SM, et al. (2015).</strong> <em>Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer (CLEOPATRA trial).</em> <strong>[[NEJM]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：确立了“曲帕双靶”作为晚期一线治疗的国际标准方案。</span>
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            [3] <strong>Modi S, et al. (2020).</strong> <em>Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer (DESTINY-Breast01).</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：展示了新一代ADC在后线治疗中的颠覆性疗效，开启了HER2+治疗的新纪元。</span>
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            [[HER2阳性乳腺癌]] 诊疗生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[HER2]]•[[HER3]]•[[Akt]]•[[mTOR]]•[[PI3K]]•[[EGFR]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">治疗药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[曲妥珠单抗]]•[[帕妥珠单抗]]•[[DS-8201]]•[[吡咯替尼]]•[[T-DM1]]•[[拉帕替尼]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[NCCN]]•[[CSCO]]•[[圣安东尼奥乳腺癌会议]] (SABCS)•[[罗氏]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[抗HER2靶向联合免疫治疗]]•[[脑转移局部放疗联合TKI]]•[[去化疗方案的降阶治疗探索]]</td>
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