Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA.
Agendia Inc, Irvine, CA, USA.
Mod Pathol. 2022 Aug;35(8):1075-1082. doi: 10.1038/s41379-022-01019-5. Epub 2022 Feb 19.
Recently, clinical trials have demonstrated promising efficacy for novel HER2-targeted therapies in HER2-low breast cancers, raising the prospect of including a HER2-low category (immunohistochemical [IHC] score of 1+, or 2+ with non-amplified in-situ hybridization [ISH]) in the HER2 evaluation of breast cancers. In order to better understand this newly-proposed HER2 category, we investigated the incidence, HER2 staining patterns, clinicopathologic features, and genomic profile of HER2-low breast cancers. HER2-stained slides of 281 consecutive breast cancers were re-reviewed and the clinicopathologic information, MammaPrint, and BluePrint results of these cases were retrospectively analyzed. HER2-low breast cancers were identified in 31% of cases and were more common in estrogen receptor (ER)-positive than ER-negative breast cancers (33.6% vs 15%, p = 0.017). HER2-low cancers were generally clinical stages I-II (79%), ER-positive (93.1%), had homogenous HER2 staining (59.2%), HER2 IHC score of 1+ (87.4%), ductal phenotype (81.6%), histologic grades of 1 or 2 (94.2%) and luminal molecular subtypes (94.3%). Three HER2-low patients received neoadjuvant chemotherapy and none of them achieved pathologic complete response. When compared to HER2-negative (IHC of 0+) and HER2-positive (IHC of 3+ or IHC of 2+ with amplified ISH) cancers, HER2-low breast cancers had significantly lower Ki-67 (p = 0.03 and p < 0.01, respectively) and higher ER positivity (p = 0.01 and p = 0.03, respectively). HER2-low breast cancers were less likely to be basal molecular subtype when compared to HER2-negative cancers (p < 0.01) and were less likely to have a HER2 molecular subtype when compared to HER2-positive cancers (p < 0.01). When adjusted for ER status, there was no significant difference on all the examined variables between HER2-low and HER2-negative groups. Our study provides valuable baseline characteristics of HER2-low breast cancers deriving from consecutive, real-world cases with a consensus confirmation of HER2 status, and would help to increase our understanding of this newly-proposed HER2 category in breast cancers.
最近，临床研究表明新型 HER2 靶向治疗在 HER2 低表达乳腺癌中具有良好的疗效，这使得将 HER2 低表达（免疫组化[IHC]评分为 1+或 2+且原位杂交[ISH]非扩增）纳入乳腺癌的 HER2 评估成为可能。为了更好地理解这一新提出的 HER2 类别，我们研究了 HER2 低表达乳腺癌的发生率、HER2 染色模式、临床病理特征和基因组特征。对 281 例连续乳腺癌的 HER2 染色切片进行了重新评估，并回顾性分析了这些病例的临床病理信息、MammaPrint 和 BluePrint 结果。在 31%的病例中发现了 HER2 低表达乳腺癌，并且在雌激素受体（ER）阳性乳腺癌中比 ER 阴性乳腺癌更常见（33.6%比 15%，p=0.017）。HER2 低表达乳腺癌通常为临床 I 期-II 期（79%）、ER 阳性（93.1%）、HER2 染色均匀（59.2%）、HER2 IHC 评分为 1+（87.4%）、导管表型（81.6%）、组织学分级 1 或 2 级（94.2%）和管腔分子亚型（94.3%）。3 例 HER2 低表达患者接受了新辅助化疗，但均未达到病理完全缓解。与 HER2 阴性（IHC 评分为 0+）和 HER2 阳性（IHC 评分为 3+或 IHC 评分为 2+且扩增 ISH）乳腺癌相比，HER2 低表达乳腺癌的 Ki-67 水平明显较低（p=0.03 和 p<0.01），ER 阳性率较高（p=0.01 和 p<0.01）。与 HER2 阴性乳腺癌相比，HER2 低表达乳腺癌更不可能为基底分子亚型（p<0.01），与 HER2 阳性乳腺癌相比，HER2 低表达乳腺癌更不可能为 HER2 分子亚型（p<0.01）。在调整 ER 状态后，HER2 低表达组和 HER2 阴性组在所有检查变量上均无显著差异。我们的研究提供了来自连续、真实世界病例的 HER2 低表达乳腺癌的有价值的基线特征，这些病例经过了 HER2 状态的共识确认，有助于增加我们对乳腺癌中这一新提出的 HER2 类别的理解。
