Johnston Laura E, Randall Jamie, Chouraichi Safae, Luu Mary, Hunt Allison L, Mauro Lauren, Mueller Claudius, Davis Justin B, Petricoin Emanuel F, Conrads Thomas P, Cannon Timothy L, Huynh Jasmine
Inova Schar Cancer Institute, Inova Health System, 8081 Innovation Park Dr, Fairfax, VA, USA.
Women's Health Integrated Research Center, Women's Service Line, Inova Health System, 3289 Woodburn Rd, Annandale, VA, USA.
NPJ Precis Oncol. 2024 Sep 14;8(1):203. doi: 10.1038/s41698-024-00696-6.
Recent trials have shown the efficacy of trastuzumab deruxtecan (T-DXd) in HER2-negative patients, but there is not yet a way to identify which patients will best respond, especially with the inability of current HER2 IHC and FISH assays to accurately determine HER2 expression in the unamplified setting. Here, we present a heavily pre-treated patient with triple-negative breast cancer (HER2 IHC 0 who had a complete response to T-DXd. In this case, we used a CLIA-certified reverse-phase protein array-based proteomic assay (RPPA) to determine that the patient had moderate HER2 protein expression (HER2 2+, 42%) and activation (HER2 1+, 23%). Using these results, we determined that the patient may benefit from T-Dxd despite being traditionally qualified as HER2 IHC 0. These findings highlight the potential for proteomics-based assays that may more accurately quantitate HER2 and (its activation) in the HER2 unamplified/IHC 0 setting to better select patients whose tumors are classically molecularly defined as HER2 IHC 0, but still could respond to HER2-directed therapy, and give patients access to therapies which for which they otherwise would not be eligible.
近期试验已显示出曲妥珠单抗德鲁昔单抗（T-DXd）在HER2阴性患者中的疗效，但目前尚无办法确定哪些患者反应最佳，尤其是当前的HER2免疫组化（IHC）和荧光原位杂交（FISH）检测无法在未扩增情况下准确测定HER2表达。在此，我们介绍一名接受过大量治疗的三阴性乳腺癌患者（HER2 IHC 0），其对T-DXd完全缓解。在该病例中，我们使用经临床实验室改进修正案（CLIA）认证的基于反相蛋白质阵列的蛋白质组学检测（RPPA）来确定该患者有中等程度的HER2蛋白表达（HER2 2+，42%）和激活（HER2 1+，23%）。利用这些结果，我们确定该患者尽管传统上被判定为HER2 IHC 0，但可能从T-DXd中获益。这些发现凸显了基于蛋白质组学的检测方法的潜力，该方法可能在HER2未扩增/IHC 0情况下更准确地定量HER2及其激活情况，从而更好地选择那些肿瘤传统上分子定义为HER2 IHC 0但仍可能对HER2导向治疗有反应的患者，并使患者能够接受他们原本无资格接受的治疗。
