多基因检测时代遗传性乳腺癌的保乳治疗

Breast Conservation for Hereditary Breast Cancer in the Multigene Panel Era

摘要: 目的：梳理多基因检测背景下遗传性乳腺癌保乳治疗的证据，明确基因结果在局部治疗决策中的实际作用。方法：结合PubMed/MEDLINE检索至2026年6月的指南、系统评价、队列研究和临床实践资料，重点讨论BRCA1、BRCA2、PALB2、CHEK2、ATM及TP53。结果：近年指南和队列研究均达成相对稳定的共识：BRCA1/2携带者若符合常规保乳条件，胚系阳性本身不应排除保乳治疗。这类患者的总生存或乳腺癌特异性生存并未显示明确劣势，但同侧和对侧乳房事件会随随访延长而累积。在门诊沟通中，真正困难并非“能否保乳”这一单一问题，如何把初始肿瘤控制、未来新原发癌风险、放疗需求、影像随访负担和患者价值偏好同样重要。PALB2和CHEK2的局部治疗证据仍有限，尚不支持仅凭携带状态决定是否扩大手术范围。多数ATM杂合致病性变异携带者可接受有适应证的乳腺放疗。TP53相关乳腺癌需区别处理，因标准保乳治疗通常包含放疗，临床实践时更倾向全乳切除。此外，新辅助治疗效果及术后强化系统治疗的适应证应与基因型、肿瘤亚型应共同纳入局部治疗规划；治疗效果可扩大保乳机会，但不能消除遗传相关第二原发癌风险或基因特异性的放疗限制。结论：胚系检测结果应参与手术方案制定，但不应替代个体化判断。意义未明变异不应改变局部治疗。

Abstract: Objective: To review the evidence on breast-conserving therapy in hereditary breast cancer in the multigene panel era, and to clarify the practical role of germline results in local treatment decisions. Methods: Guidelines, systematic reviews, cohort studies, and clinically relevant reports indexed in PubMed/MEDLINE up to June 2026 were reviewed. The discussion focused on BRCA1, BRCA2, PALB2, CHEK2, ATM, and TP53. Results: Recent guidelines and cohort studies support a relatively consistent conclusion. For BRCA1/2 carriers who otherwise meet standard criteria for breast-conserving therapy, germline positivity alone should not exclude breast conservation. Overall survival and breast cancer-specific survival have not shown a clear disadvantage in selected carriers, although ipsilateral and contralateral breast events may accumulate with longer follow-up. In clinical consultation, the difficult issue is not the single question of whether breast conservation is technically possible. Surgeons also need to explain control of the primary tumor, future new primary cancer risk, radiotherapy requirements, imaging surveillance burden, and patient values. Evidence for PALB2 and CHEK2 remains limited and does not support routine escalation of surgery solely because of carrier status. Most heterozygous ATM pathogenic-variant carriers can receive indicated breast radiotherapy. TP53-associated breast cancer requires separate management because standard breast-conserving therapy usually includes radiotherapy; mastectomy is therefore generally favored in clinical practice when feasible. Neoadjuvant response and post-neoadjuvant systemic-treatment options should be integrated with genotype and tumor subtype; response may expand eligibility for breast conservation but does not erase hereditary second-primary risk or gene-specific radiotherapy constraints. Conclusion: Germline testing should inform surgical planning, but it should not replace individualized clinical judgment. Variants of uncertain significance should not alter local treatment.