Lodi Massimo, Voilquin Laetitia, Alpy Fabien, Molière Sébastien, Reix Nathalie, Mathelin Carole, Chenard Marie-Pierrette, Tomasetto Catherine-Laure
Department of Pathology, Strasbourg University Hospital, 67200 Strasbourg, France.
Surgical Oncology Department, Institut de cancérologie Strasbourg Europe (ICANS), 17 Rue Albert Calmette, 67200 Strasbourg, France.
Cancers (Basel). 2023 Jan 5;15(2):362. doi: 10.3390/cancers15020362.
Pathological complete response (pCR) after neoadjuvant systemic treatment (NST) is an important prognostic factor in HER2-positive breast cancer. The majority of HER2-positive breast cancers are amplified at the HER2 gene locus, several genes are co-amplified with HER2, and a subset of them are co-expressed. The STARD3 gene belongs to the HER2 amplicon, and its role as a predictive marker was never addressed. The objective of this study was to investigate the predictive value of STARD3 protein expression on NST pathological response in HER2-positive breast cancer. In addition, we studied the prognostic value of this marker.
We conducted a retrospective study between 2007 and 2020 on 112 patients with non-metastatic HER2-positive breast cancer treated by NST and then by surgery. We developed an immunohistochemistry assay for STARD3 expression and subcellular localization and determined a score for STARD3-positivity. As STARD3 is an endosomal protein, its expression was considered positive if the intracellular signal pattern was granular.
In this series, pCR was achieved in half of the patients. STARD3 was positive in 86.6% of cases and was significantly associated with pCR in univariate analysis ( = 0.013) and after adjustment on other known pathological parameters ( = 0.044). Performances on pCR prediction showed high sensitivity (96%) and negative predictive value (87%), while specificity was 23% and positive predictive value was 56%. Overall, specific, relapse-free, and distant metastasis-free survivals were similar among STARD3 positive and negative groups, independently of other prognosis factors.
NST is an opportunity for HER2-positive cancers. In this series of over a hundred HER2-positive and non-metastatic patients, a STARD3-negative score was associated with the absence of pathological complete response. This study suggests that determining STARD3 overexpression status on initial biopsies of HER2-positive tumors is an added value for the management of a subset of patients with high probability of no pathological response.
新辅助全身治疗（NST）后的病理完全缓解（pCR）是HER2阳性乳腺癌的一个重要预后因素。大多数HER2阳性乳腺癌在HER2基因位点发生扩增，有几个基因与HER2共同扩增，其中一部分基因共同表达。STARD3基因属于HER2扩增子，其作为预测标志物的作用从未被探讨过。本研究的目的是调查STARD3蛋白表达对HER2阳性乳腺癌NST病理反应的预测价值。此外，我们还研究了该标志物的预后价值。
我们对2007年至2020年间112例接受NST然后手术治疗的非转移性HER2阳性乳腺癌患者进行了一项回顾性研究。我们开发了一种用于检测STARD3表达和亚细胞定位的免疫组织化学检测方法，并确定了STARD3阳性的评分。由于STARD3是一种内体蛋白，如果细胞内信号模式呈颗粒状，则其表达被认为是阳性。
在本系列研究中，一半的患者实现了pCR。86.6%的病例中STARD3呈阳性，在单因素分析中与pCR显著相关（P = 0.013），在对其他已知病理参数进行调整后也显著相关（P = 0.044）。pCR预测的性能显示出高敏感性（96%）和阴性预测值（87%），而特异性为23%，阳性预测值为56%。总体而言，无论其他预后因素如何，STARD3阳性和阴性组之间的总生存、无病生存、无复发生存和无远处转移生存相似。
NST为HER2阳性癌症提供了一个机会。在这一系列超过一百例HER2阳性非转移性患者中，STARD3阴性评分与无病理完全缓解相关。本研究表明，在HER2阳性肿瘤的初始活检中确定STARD3过表达状态对于管理一部分无病理反应高概率患者具有附加价值。
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