Brasó-Maristany Fara, Sansó Miriam, Chic Nuria, Martínez Débora, González-Farré Blanca, Sanfeliu Esther, Ghiglione Lucio, Carcelero Esther, Garcia-Corbacho Javier, Sánchez Marcelo, Soy Dolors, Jares Pedro, Peg Vicente, Saura Cristina, Muñoz Montserrat, Prat Aleix, Vivancos Ana
Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain.
Front Oncol. 2021 Sep 20;11:710596. doi: 10.3389/fonc.2021.710596. eCollection 2021.
The immune checkpoint inhibitor atezolizumab is approved for PD-L1-positive triple-negative breast cancer (TNBC). However, no activity of atezolizumab in PD-L1-negative TNBC has been reported to date. Here, we present the case study of a woman with TNBC with low tumor infiltrating lymphocytes and PD-L1-negative disease, which achieved a significant response to atezolizumab monotherapy and durable response after the combination of atezolizumab and nab-paclitaxel. The comprehensive genomic analysis that we performed in her tumor and plasma samples revealed high tumor mutational burden (TMB), presence of the APOBEC genetic signatures, high expression of the tumor inflammation signature, and a HER2-enriched subtype by the PAM50 assay. Some of these biomarkers have been shown to independently predict response to immunotherapy in other tumors and may explain the durable response in our patient. Our work warrants further translational studies to identify biomarkers of response to immune checkpoint inhibitors in TNBC beyond PD-L1 expression and to better select patients that will benefit from immunotherapy.
免疫检查点抑制剂阿替利珠单抗已被批准用于治疗PD-L1阳性三阴性乳腺癌（TNBC）。然而，迄今为止，尚未有阿替利珠单抗在PD-L1阴性TNBC中具有活性的报道。在此，我们报告了一例TNBC女性患者的病例研究，该患者肿瘤浸润淋巴细胞数量低且疾病为PD-L1阴性，其对阿替利珠单抗单药治疗有显著反应，并且在阿替利珠单抗与白蛋白结合型紫杉醇联合治疗后有持久反应。我们对她的肿瘤和血浆样本进行的综合基因组分析显示，肿瘤突变负荷（TMB）高、存在APOBEC基因特征、肿瘤炎症特征高表达，且通过PAM50检测为HER2富集亚型。其中一些生物标志物已被证明可独立预测其他肿瘤对免疫治疗的反应，并可能解释我们患者的持久反应。我们的工作值得进一步开展转化研究，以确定除PD-L1表达之外TNBC中免疫检查点抑制剂反应的生物标志物，并更好地选择将从免疫治疗中获益的患者。
