Dept of Biology, Algoma University, Sault Ste Marie, Ontario, Canada.
Algoma District Cancer Program, Sault Area Hospital, Ontario, Canada; Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
Clin Breast Cancer. 2022 Jun;22(4):391-397. doi: 10.1016/j.clbc.2022.02.008. Epub 2022 Feb 26.
High expression of HER2 receptor in Immunohistochemistry (IHC) sections or amplification of its gene in In Situ Hybridization (ISH) assays define a subset of breast cancers that have an aggressive natural history but respond to treatments blocking HER2. In contrast, patients with lower HER2 expression, not meeting the criteria for clinical positivity, are currently treated similarly to completely HER2 negative patients. However, emerging data suggest that patients with low HER2 expression may benefit from newer, more potent antibody-drug conjugates. Thus, this investigation sought to clarify the characteristics of HER2 low expressors and compare them with patients with no HER2 expression.
We undertook a retrospective analysis of all breast cancer patients seen in our cancer center over a 6-year period and been classified as HER2 negative. Patients were categorized as HER2 negative when they had a score of 0 in IHC and as HER2 low if they had a score of 1 + or 2 + in IHC and no amplification by ISH. Characteristics of the patients and tumors in the 2 groups were compared.
A total of 391 HER2 negative and low patients have been included. Among them, 130 patients (33.2%) were HER2 negative (score 0 by IHC) and 261 patients (66.8%) were HER2 low (score 1 + and 2 + by IHC/ ISH non-amplified). There were no differences in age, menopause status, mode of detection of cancer (clinical or screening) and clinical stage at diagnosis between the 2 groups. Patients in the HER2 low group had less commonly high-grade cancers than HER2 negative patients (25.35 vs. 34.6%, xP = .04). In addition, The HER2 low group had higher ER Histoscore (> 240) in 88.1% of cases compared with 69.2% in the HER2 negative group (xP < .000). Similarly, a higher percentage of HER2 low cases than HER2 negative ones expressed the progesterone receptor (PR, xP < .000). HER2 low patients were rarely (3.8%) classified as triple negative, while this percentage was 21.5% in HER2 negative patients. The Overall Survival (OS) of patients with HER2 low cancers was longer than the OS of their HER2 negative counterparts (LogRank P =.001).
HER2 negative staining (IHC score 0) is associated with adverse tumor characteristics compared with clinically HER2 negative patients with low HER2 expression (score 1 + and 2 +/ ISH non-amplified).
免疫组织化学（IHC）切片中 HER2 受体的高表达或原位杂交（ISH）检测中其基因的扩增定义了一组具有侵袭性自然病史的乳腺癌，但对阻断 HER2 的治疗有反应。相比之下，HER2 表达较低、不符合临床阳性标准的患者目前与完全 HER2 阴性的患者接受类似的治疗。然而，新出现的数据表明，HER2 表达较低的患者可能受益于更新、更有效的抗体药物偶联物。因此，本研究旨在阐明 HER2 低表达者的特征，并将其与无 HER2 表达的患者进行比较。
我们对在我们癌症中心就诊的所有乳腺癌患者进行了一项回顾性分析，这些患者在 6 年内被归类为 HER2 阴性。HER2 阴性患者的 IHC 评分均为 0，HER2 低表达患者的 IHC 评分均为 1+或 2+，ISH 无扩增。比较两组患者和肿瘤的特征。
共纳入 391 例 HER2 阴性和低表达患者。其中，130 例（33.2%）为 HER2 阴性（IHC 评分 0），261 例（66.8%）为 HER2 低表达（IHC/ISH 非扩增评分 1+和 2+）。两组患者的年龄、绝经状态、癌症检出方式（临床或筛查）和诊断时临床分期均无差异。HER2 低表达组患者的高级别癌症发生率低于 HER2 阴性组（25.35%比 34.6%，xP=.04）。此外，HER2 低表达组患者的 ER Histoscore（>240）比例高于 HER2 阴性组（88.1%比 69.2%，xP<.000）。同样，HER2 低表达组中表达孕激素受体（PR）的比例高于 HER2 阴性组（xP<.000）。HER2 低表达患者很少（3.8%）被归类为三阴性，而 HER2 阴性患者的这一比例为 21.5%。HER2 低表达癌症患者的总生存（OS）长于 HER2 阴性患者（LogRank P=.001）。
与临床 HER2 阴性的 HER2 低表达（评分 1+和 2+/ISH 非扩增）患者相比，HER2 阴性染色（IHC 评分 0）与不良肿瘤特征相关。
