HER3 是 EGFR 受体家族的成员，在驱动乳腺癌中致癌细胞增殖方面发挥着核心作用。新型 HER3 疗法显示出有希望的结果，而最近开发的 HER3 PET 成像模式有助于预测和评估早期治疗反应。然而，基线 HER3 表达以及新辅助治疗期间表达的变化尚未得到充分表征。我们在新诊断的乳腺癌患者中进行了一项前瞻性临床研究，即新辅助/全身治疗前和后，以确定 HER3 表达，并确定通过 HER3 受体维持的可能耐药机制。该研究于 2018 年 5 月 25 日进行2019年10月12日。34名新诊断的任何亚型乳腺癌患者（ER ± 、PR ± 、HER2 ±）纳入该研究。诊断时从每位患者身上获取了两份核心活检标本。四名患者在开始新辅助/全身治疗或我们定义为新辅助治疗的全身治疗后接受了第二次研究活检。在治疗开始前和治疗后对 HER3 以及 PI3K/AKT 和 MAPK 通路的下游信号节点进行了分子表征。在外部数据集 (GSE122630) 中对 finings 进行了转录验证。在新诊断的乳腺癌中发现了可变的基线 HER3 表达，并且在各个亚型中与 pAKT 呈正相关 (r = 0.45)。在接受新辅助/全身治疗的患者中，HER3 表达的变化是可变的。在激素受体阳性（ER  /PR  /HER2-）患者中，新辅助治疗后 HER3 表达有统计学显着性增加，而 ER  /PR  /HER2 患者中 HER3 表达没有显着变化。然而，这两名患者的 PI3K/AKT 通路下游信号传导均有所增加。一名患有 ER  /PR -/HER2- 乳腺癌的受试者和另一名患有 ER  /PR  /HER2  乳腺癌的受试者显示 HER3 表达降低。转录组学研究结果揭示了治疗后 HER3 表达降低的患者存在免疫抑制环境。这项研究表明，不同乳腺癌亚型的 HER3 表达存在差异。 HER3 表达可以在新辅助治疗后的早期进行评估，为癌症生物学提供有价值的见解，并有可能作为预后生物标志物。使用 HER3 PET 成像可以实现新辅助治疗评估的临床转化，提供肿瘤生物学的实时信息并指导乳腺癌患者的个性化治疗。© 2024。作者。

HER3, a member of the EGFR receptor family, plays a central role in driving oncogenic cell proliferation in breast cancer. Novel HER3 therapeutics are showing promising results while recently developed HER3 PET imaging modalities aid in predicting and assessing early treatment response. However, baseline HER3 expression, as well as changes in expression while on neoadjuvant therapy, have not been well-characterized. We conducted a prospective clinical study, pre- and post-neoadjuvant/systemic therapy, in patients with newly diagnosed breast cancer to determine HER3 expression, and to identify possible resistance mechanisms maintained through the HER3 receptor.The study was conducted between May 25, 2018 and October 12, 2019. Thirty-four patients with newly diagnosed breast cancer of any subtype (ER ± , PR ± , HER2 ±) were enrolled in the study. Two core biopsy specimens were obtained from each patient at the time of diagnosis. Four patients underwent a second research biopsy following initiation of neoadjuvant/systemic therapy or systemic therapy which we define as neoadjuvant therapy. Molecular characterization of HER3 and downstream signaling nodes of the PI3K/AKT and MAPK pathways pre- and post-initiation of therapy was performed. Transcriptional validation of finings was performed in an external dataset (GSE122630).Variable baseline HER3 expression was found in newly diagnosed breast cancer and correlated positively with pAKT across subtypes (r = 0.45). In patients receiving neoadjuvant/systemic therapy, changes in HER3 expression were variable. In a hormone receptor-positive (ER +/PR +/HER2-) patient, there was a statistically significant increase in HER3 expression post neoadjuvant therapy, while there was no significant change in HER3 expression in a ER +/PR +/HER2+ patient. However, both of these patients showed increased downstream signaling in the PI3K/AKT pathway. One subject with ER +/PR -/HER2- breast cancer and another subject with ER +/PR +/HER2 + breast cancer showed decreased HER3 expression. Transcriptomic findings, revealed an immune suppressive environment in patients with decreased HER3 expression post therapy.This study demonstrates variable HER3 expression across breast cancer subtypes. HER3 expression can be assessed early, post-neoadjuvant therapy, providing valuable insight into cancer biology and potentially serving as a prognostic biomarker. Clinical translation of neoadjuvant therapy assessment can be achieved using HER3 PET imaging, offering real-time information on tumor biology and guiding personalized treatment for breast cancer patients.© 2024. The Author(s).