Faculty of Medicine, Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Division of Medical Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
JCO Precis Oncol. 2024 Mar;8:e2300487. doi: 10.1200/PO.23.00487.
Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM).
Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied. Estrogen receptor, progesterone receptor, and HER2 status were assessed on the basis of ASCO/College of American Pathologists (CAP) guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH)-negative status. HER2-positive (HER2+) was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathologic features were recorded. We also assessed the prognostic association between extent of HER2 expression and (1) brain-specific progression-free survival (bsPFS), as well as (2) overall survival (OS).
In this retrospective cohort of 102 patients with resected BC BrM, 53% (n = 54) were HER2+, 29.4% (n = 30) were HER2-low, and 17.6% (n = 18) had HER2-zero status. Among BrM that were triple-negative on the basis of ASCO/CAP guidelines, 63.6% (n = 14/22) were reclassified as being HER2-low. Sixty percent (n = 15/25) of BrM that were hormone receptor-positive/HER2-negative (HR+/HER2-) were reclassified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low, and HER2+ were concordant in 82.3% (n = 42/51) of cases (Cohen's kappa, 0.58; = .07). There was no significant association between HER2-zero, HER2-low, and HER2+ status in BrM and either bsPFS or OS.
Among patients with surgically resected BrM, a high proportion of those with metastatic triple-negative BC and HR+/HER2- disease have HER2-low BrM with potential to benefit from HER2-targeted therapy.
曲妥珠单抗 deruxtecan 是一种治疗晚期人表皮生长因子受体 2（HER2）低水平乳腺癌（BC）患者的新选择。尽管早期和晚期 BC 中已经对 HER2 低水平状态进行了特征描述，但在脑转移瘤（BrM）中尚未完全描述。
对在 Sunnybrook 健康科学中心接受 BC BrM 手术且切除的 BrM 上可获得 HER2 状态的患者进行了研究。根据 ASCO/美国病理学家学院（CAP）指南评估雌激素受体、孕激素受体和 HER2 状态。HER2-0 定义为免疫组化（IHC）0；HER2-低水平定义为 IHC 1+或 IHC 2+，荧光原位杂交（FISH）阴性。HER2-阳性（HER2+）定义为 IHC 3+或 IHC 2+，FISH 阳性。记录临床病理特征。我们还评估了 HER2 表达程度与（1）脑特异性无进展生存期（bsPFS）以及（2）总生存期（OS）之间的预后相关性。
在这项回顾性队列研究中，纳入了 102 例接受手术治疗的 BC BrM 患者，其中 53%（n=54）为 HER2+，29.4%（n=30）为 HER2-低水平，17.6%（n=18）为 HER2-0。在基于 ASCO/CAP 指南的三阴性 BrM 中，63.6%（n=14/22）重新分类为 HER2-低水平。60%（n=15/25）激素受体阳性/HER2-阴性（HR+/HER2-）的 BrM 重新分类为 HER2-低水平。共有 51 例患者的原发性乳腺和 BrM 组织标本可供匹配；当按照 HER2-0、HER2-低水平和 HER2+进行分类时，HER2 状态的结果在 82.3%（n=42/51）的病例中是一致的（Cohen's kappa，0.58；P=.07）。在 BrM 中，HER2-0、HER2-低水平和 HER2+状态与 bsPFS 或 OS 之间无显著相关性。
在接受手术切除的 BrM 患者中，相当一部分转移性三阴性 BC 和 HR+/HER2-疾病的患者存在 HER2-低水平 BrM，有潜在获益于 HER2 靶向治疗。
