HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers.

IF 7.1 2区医学 Q1 ONCOLOGY ESMO Open Pub Date : 2025-01-17 DOI:10.1016/j.esmoop.2024.104100

F Lynce, O Martínez-Sáez, B Walbaum, F Brasó-Maristany, A G Waks, P Villagrasa, G Villacampa Javierre, E Sanfeliu, P Galván, L Paré, L M Anderson, C M Perou, J S Parker, A Vivancos, M K DiLullo, S Pernas, E P Winer, B Overmoyer, E A Mittendorf, C Bueno-Muiño, M Martín, A Prat, S M Tolaney

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Abstract

Background: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).

Patients and methods: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts. Comparative analyses included HER2DX scores, gene signatures, and expression of individual genes between patients with IBC and non-IBC.

Results: Notable differences in clinicopathological characteristics included higher pertuzumab and chemotherapy usage and lower axillary burden in patients with IBC compared with non-IBC. In the combined cohort (n = 179), HER2DX pCR score and pertuzumab use were significant predictors of pCR, but not IBC status. The pCR rates in patients treated with trastuzumab-based chemotherapy (including IBC and non-IBC) were 68.9%, 58.5%, and 16.3% in the HER2DX pCR-high, -medium, and -low groups, respectively. Comparative gene expression analysis indicated minor differences between IBC and non-IBC affecting individual HER2, immune, and proliferation genes.

Conclusions: The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified.

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her2阳性炎症性乳腺癌中的HER2DX：与非炎症性乳腺癌的相关见解和比较分析

背景：HER2DX检测可预测接受新辅助全身治疗的早期人表皮生长因子受体2 （HER2）阳性乳腺癌患者的长期预后和病理完全缓解（pCR），但尚未在炎症性乳腺癌（IBC）中进行评估。患者和方法：在一项接受新辅助曲妥珠单抗、帕妥珠单抗和紫杉醇（THP）治疗的II期试验（NCT01796197）中，对23例III期her2阳性IBC患者的基线活检组织进行了HER2DX分析。为了评估pCR对IBC的预测准确性，将该IBC队列的临床病理特征和结果与来自四个不同队列的156例III期her2阳性非IBC患者进行了比较。比较分析包括HER2DX评分、基因特征和个体基因表达在IBC和非IBC患者之间。结果：与非IBC患者相比，IBC患者在临床病理特征上的显著差异包括更高的pertuzumab和化疗使用以及更低的腋窝负担。在联合队列（n = 179）中，HER2DX pCR评分和帕妥珠单抗使用是pCR的重要预测因子，但不是IBC状态的重要预测因子。在接受曲妥珠单抗化疗的患者（包括IBC和非IBC）中，HER2DX pCR高、中、低组的pCR率分别为68.9%、58.5%和16.3%。比较基因表达分析显示，IBC和非IBC影响个体HER2、免疫和增殖基因的差异较小。结论：HER2DX pCR评分可以预测经降级新辅助全身治疗后的III期her2阳性IBC和III期her2阳性非IBC的pCR。在HER2DX pCR评分较高的her2阳性IBC中，pCR率升高表明在这些患者中可能存在治疗降级的作用，并且证实性研究是合理的。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.