在初次诊断时同时出现两种不同组织学的原发性乳腺癌是一种罕见的现象。在同一活检中发现这些病理上不同的群体更是罕见。在这里，我们报告了一名患者的病例，该患者被诊断患有明确界限的病理异质性三阴性乳腺癌 (TNBC) 和 HER2 乳腺癌，该患者接受了结合 Keynote-522 元素和标准 HER2 导向新辅助治疗方案的混合化学免疫治疗方案，产生了治疗效果手术时病理完全缓解，没有明显的不良事件。对组织学上不同的肿瘤群体的分子分析证实了 HER2 表达差异的分子证据，但也表明了基于突变谱的两个肿瘤群体的克隆相关性，表型差异可能是由 NF1 拷贝数改变引起的。总体而言，该病例凸显了一种罕见的组织学现象，通过结合 TNBC 和 HER2 定向新辅助疗法已成功治疗。© 2024。作者。

Simultaneous presentation of two separate primary breast cancers of differing histology at initial diagnosis is an uncommon phenomenon; it is even rarer to find these pathologically distinct populations within the same biopsy. Here we report the case of a patient diagnosed with clearly demarcated, pathologically heterogenous triple negative breast cancer (TNBC) and HER2+ breast cancer that was treated with a hybrid chemoimmunotherapy regimen combining elements of Keynote-522 and a standard HER2-directed neoadjuvant regimen, yielding apathologic complete response by the time of surgery with no notable adverse events. Molecular analysis of the histologically distinct tumor populations confirmed molecular evidence of differential HER2 expression but also suggested clonal relatedness of the two tumor populations based upon mutational profile, with phenotypic divergence potentially resulting from copy number alterations in NF1. Overall, this case highlights a rare histologic phenomenon that was successfully treated by combining both TNBC and HER2 directed neoadjuvant therapies.© 2024. The Author(s).