Department of Neurosurgery, Semmelweis University, 57 Amerikai street, Budapest, Pest, 1145, Hungary.
National Institute of Clinical Neurosciences, 57 Amerikai street, Budapest, Pest, 1145, Hungary.
BMC Cancer. 2020 Jul 1;20(1):615. doi: 10.1186/s12885-020-07114-7.
Breast cancer is a global health problem - it is the most common malignancy among women. Triple negative breast cancers (TNBC) account for 10-20% of female breast cancer. Most TNBC cases confer poor prognosis. Brain metastasis appears in more than 15% in the triple negative breast cancer population, which causes serious decrease in survival. Changes of immunophenotype are not uncommon in breast cancer, offering new therapeutic options in cases where targetable proteins or pathways are being identified.
After five lines of chemotherapy and 82 months following the first diagnosis, our patient with brain metastatic triple negative breast cancer had human epidermal growth factor receptor 2 (HER2) genetic heterogeneity in the metastatic tissue sample interpreted as HER2 status conversion. After the removal of the metastasis, we started first line therapy for metastatic HER2 positive cancer with trastuzumab and paclitaxel. After the first cycle of trastuzumab, on day 8, she had a seizure, and neurosurgical examination showed an abscess-like lesion. The punctate proved to be sterile by microbiological and pathological examination, so we continued cytostatic therapy without the anti-HER2 antibody. 3 months later, we could not identify the previous abscess-like lesion in the control computer tomography (CT) scan, and our patient had no neurological deficits.
We emphasize the importance of regular tissue confirmation of predictive markers in progressive tumorous disease even if our presented case is not unequivocally a "conversion case". Tumor subtype is determined according to algorithms and definitions published in guidelines, nevertheless, use of different guidelines may lead to controversial interpretation in cases where HER2 genetic heterogeneity is present. Furthermore, we suggest that seronegative, aseptic intracranial fluid effusion after the removal of a brain metastasis may possibly be a side effect of trastuzumab.
乳腺癌是一个全球性的健康问题——它是女性中最常见的恶性肿瘤。三阴性乳腺癌（TNBC）占女性乳腺癌的 10-20%。大多数 TNBC 病例预后不良。脑转移在三阴性乳腺癌患者中超过 15%，导致生存严重下降。乳腺癌中免疫表型的变化并不少见，为在鉴定出靶向蛋白或途径的情况下提供了新的治疗选择。
在接受了五线化疗和首次诊断后 82 个月后，我们的脑转移三阴性乳腺癌患者的转移性组织样本中存在人表皮生长因子受体 2（HER2）基因异质性，该样本被解释为 HER2 状态转换。在转移灶切除后，我们开始对转移性 HER2 阳性癌症进行一线治疗，使用曲妥珠单抗和紫杉醇。在曲妥珠单抗的第一个周期后，第 8 天，她发生了癫痫，神经外科检查显示出脓肿样病变。通过微生物学和病理学检查，点状病变被证明是无菌的，因此我们继续进行细胞毒化疗，而不使用抗 HER2 抗体。3 个月后，在对照计算机断层扫描（CT）扫描中，我们无法识别以前的脓肿样病变，且患者没有神经功能缺损。
我们强调在进行性肿瘤疾病中定期对预测标志物进行组织确认的重要性，即使我们提出的病例并非明确的“转换病例”。肿瘤亚型根据指南中公布的算法和定义确定，但在存在 HER2 基因异质性的情况下，使用不同的指南可能导致有争议的解释。此外，我们建议脑转移切除后出现的无菌性颅内液性渗出可能是曲妥珠单抗的副作用。
