瓦特乳头癌（ampullary cancers，ACs）占所有胃肠肿瘤的不到1％。ACs通常在晚期被诊断出来，预后不良，治疗选择有限。在ACs中发现BRCA2突变的比例高达14％，与其他肿瘤类型不同，治疗方案仍需要定义。在此，我们报告了一位转移性AC患者的临床案例，其BRCA2生殖系突变的发现推动了个性化的多模态方法，具有治愈意图。一名42岁的女性被诊断为IV期BRCA2生殖系突变AC，接受了铂类首线治疗，实现了重要的肿瘤反应，但也出现了威胁生命的毒性反应。基于此，以及分子学结果和可用系统性治疗选择的预期低影响，患者接受了原发肿瘤和转移病灶的根治性完全手术切除。在经历孤立的腹膜后淋巴结复发后，考虑到BRCA2突变癌症在放疗方面的预期敏感性更高，患者接受了影像引导下的放疗，导致长时间的完全肿瘤缓解。经过两年多，该疾病仍无法在影像学和生化学上检测到。患者参加了BRCA2生殖系突变携带者的专门筛查计划，并接受了预防性双侧卵巢切除。即使考虑到单个临床报告的内在限制，我们建议应考虑在ACs中发现BRCA生殖系突变的情况，以及其他临床变量，因为它们与可能伴有增强毒性的细胞毒化疗有显著的反应关联。因此，BRCA1/2突变可能提供进一步个性化治疗的机会，超越PARP抑制剂，选择具有治愈意图的多模态方法。 © 2023年。作者（们）。

Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent.A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy.Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent.© 2023. The Author(s).