Idamakanti Muralidhar, Bijjam Rani Indrani, Kumar Manoj, Mukkamalla Shiva Kumar
Adult Inpatient Medical Services (AIMS), Presbyterian Healthcare Services (PHS), Albuquerque, NM, USA.
Adult Internal Medicine Services (AIMS), Presbyterian Healthcare Services (PHS), Albuquerque, NM, USA.
J Med Cases. 2025 Jun 16;16(6):212-221. doi: 10.14740/jmc5136. eCollection 2025 Jun.
The human epidermal growth factor receptor 2 (HER2)/erythroblastic oncogene B2 (ERBB2) is a tyrosine kinase receptor protein that plays an important role in the pathogenesis and aggressive nature of the tumors. It is well studied in various cancers, including breast, gastric, esophageal, ovarian, lung, and endometrial cancers. It is a well-known negative prognostic indicator in breast cancer associated with decreased disease-free survival and overall survival. Breast cancer treatment has been revolutionized with the invention of targeted monoclonal antibody therapies against the HER2 receptor, particularly trastuzumab and its antibody-drug conjugates (ADCs). HER2-targeted therapies have proven to improve progression-free survival and overall survival when added to chemotherapy in adjuvant, neoadjuvant, and metastatic settings in patients who are HER2-positive. ADCs approved for breast cancer include trastuzumab emtansine (Kadcyla, T-DM1) and trastuzumab deruxtecan (Enhertu, T-DXd). With enthusiasm and reported benefit, particularly in metastatic disease, HER2-targeted therapies are now widely used in breast cancer patients classified as HER2-negative based on binary classification but categorized as "HER2-low" with some degree of HER2 expression. HER2-targeted therapies are not approved for patients who have HER2 (ERBB2) mutation and have no HER2 expression of any degree (immunohistochemistry (IHC) 0+). We could not find any such reported cases, research studies, or clinical trials of HER2-targeted therapies being used in patients with HER2 mutation in our extensive search of the literature. We present a rare practice-changing case of a patient with triple negative metastatic breast cancer (estrogen receptor (ER), progesterone receptor (PR), and HER2 negative, HER2 0+ on IHC) and positive HER2 mutation, who achieved a disease-free survival of more than 2.5 years with trastuzumab deruxtecan monotherapy. This case makes a compelling argument for considering HER2-targeted therapies, mainly ADCs, in HER2-mutant breast cancer patients either as a monotherapy or in combination with other therapies, particularly in metastatic disease. This case report also indicates that further research and clinical trials looking into the efficacy and safety profile of anti-HER2 treatments in HER2-mutant breast cancers are warranted.
人表皮生长因子受体2（HER2）/成红细胞瘤基因B2（ERBB2）是一种酪氨酸激酶受体蛋白，在肿瘤的发病机制和侵袭性中起重要作用。它在包括乳腺癌、胃癌、食管癌、卵巢癌、肺癌和子宫内膜癌在内的多种癌症中都有深入研究。它是乳腺癌中一个众所周知的负面预后指标，与无病生存期和总生存期的降低有关。针对HER2受体的靶向单克隆抗体疗法的发明，特别是曲妥珠单抗及其抗体药物偶联物（ADC），彻底改变了乳腺癌的治疗方式。在HER2阳性患者的辅助、新辅助和转移环境中，HER2靶向疗法与化疗联合使用时，已被证明可改善无进展生存期和总生存期。批准用于乳腺癌的ADC包括曲妥珠单抗恩美曲妥珠单抗（赫赛莱，T-DM1）和曲妥珠单抗德曲妥珠单抗（优赫得，T-DXd）。鉴于其带来的热情和已报道的益处，特别是在转移性疾病中，HER2靶向疗法现在广泛应用于根据二元分类被归类为HER2阴性但有一定程度HER2表达而被归类为“HER2低表达”的乳腺癌患者。HER2靶向疗法未被批准用于有HER2（ERBB2）突变且无任何程度HER2表达（免疫组织化学（IHC）0+）的患者。在广泛检索文献时，我们未找到任何关于HER2靶向疗法用于HER2突变患者的此类报道病例、研究或临床试验。我们报告了一例罕见的改变治疗实践的病例，一名三阴性转移性乳腺癌患者（雌激素受体（ER）、孕激素受体（PR）和HER2均为阴性，IHC检测HER2为0+）且HER2突变阳性，接受曲妥珠单抗德曲妥珠单抗单药治疗后无病生存期超过2.5年。该病例有力地支持了在HER2突变的乳腺癌患者中考虑使用HER2靶向疗法，主要是ADC，作为单药治疗或与其他疗法联合使用，特别是在转移性疾病中。本病例报告还表明，有必要进一步开展研究和临床试验，以探究抗HER2治疗在HER2突变乳腺癌中的疗效和安全性。
