Prediction of response to neoadjuvant chemotherapy by MammaTyper® across breast cancer subtypes: A retrospective cross-sectional study

IF 5.7 2区医学 Q1 OBSTETRICS & GYNECOLOGY Breast Pub Date : 2024-05-25 DOI:10.1016/j.breast.2024.103753

Francesco Schettini , Silvana Saracchini , Anna Bassini , Wally Marus , Serena Corsetti , Ilaria Specogna , Manuela Bertola , Elvia Micheli , Ralph M. Wirtz , Mark Laible , Uğur Şahin , Carla Strina , Manuela Milani , Sergio Aguggini , Richard Tancredi , Elena Fiorio , Sandro Sulfaro , Daniele Generali

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Abstract

Background

Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or progesterone receptor (PR) positive/HER2-negative BC is questioned because of the low pathologic complete response (pCR) rates. This retrospective study assessed the mRNA-based MammaTyper® assay's capability of predicting pCR with NACT, and ER, PR, Ki67, and HER2 status at immunohistochemical (IHC) through transcriptomics.

Methods

Diagnostic biopsies from 76 BC patients treated at the Cremona Hospital between 2012-2018 were analyzed. Relative mRNA expression levels of ERBB2, ESR1, PGR, and MKI67 were measured using the MammaTyper® kit and integrated into a pCR score. Predicting capability of pCR and standard IHC biomarkers could be assessed with ROC curves in 75 and 76 patients, respectively.

Results

Overall, 68.0% patients obtained a MammaTyper® high-score and 32.0% a MammaTyper® low-score. Among high-score patients, 62.7% achieved pCR, compared to 16.7% in the low-score group (p = 0.0003). The binary MammaTyper® score showed good prediction of pCR in the overall cohort (area under curve [AUC] = 0.756) and in HR+/HER2-negative cases (AUC = 0.774). In cases with residual disease, the continuous MammaTyper® score correlated moderately with residual tumor size and decrease in tumor size. MammaTyper® showed substantial agreement with IHC for ESR1/ER and ERBB2/HER2, and moderate agreement for PGR/PR and MKI67/Ki67.

Conclusion

Overall, MammaTyper® pCR score may serve as a standardized tool for predicting NACT response in HR+/HER2-negative BC, potentially guiding treatment strategies. Additionally, it could provide a more standardized and reproducible assessment of ER, PR, HER2, and Ki67 status.

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通过 MammaTyper® 预测不同亚型乳腺癌对新辅助化疗的反应：回顾性横断面研究

背景：新辅助化疗（NACT）被广泛用于三阴性和HER2阳性乳腺癌（BC）的治疗，但由于病理完全反应（pCR）率较低，其在雌激素受体（ER）和/或孕激素受体（PR）阳性/HER2阴性BC中的应用受到质疑。这项回顾性研究通过转录组学评估了基于 mRNA 的 MammaTyper® 检测方法预测 NACT pCR 以及免疫组化（IHC）ER、PR、Ki67 和 HER2 状态的能力：分析了克雷莫纳医院 2012-2018 年间治疗的 76 例 BC 患者的诊断活检组织。使用MammaTyper®试剂盒测量了ERBB2、ESR1、PGR和MKI67的相对mRNA表达水平，并将其整合到pCR评分中。通过ROC曲线分别评估了75例和76例患者的pCR和标准IHC生物标志物的预测能力：总体而言，68.0%的患者获得了 MammaTyper® 高分，32.0%的患者获得了 MammaTyper® 低分。在高分患者中，62.7%获得了pCR，而在低分患者中，只有16.7%获得了pCR（p = 0.0003）。二元 MammaTyper® 评分对整个队列（曲线下面积 [AUC] = 0.756）和 HR+/HER2 阴性病例（AUC = 0.774）的 pCR 预测效果良好。在有残留病灶的病例中，MammaTyper®连续评分与残留肿瘤大小和肿瘤缩小程度呈中度相关。MammaTyper®与IHC在ESR1/ER和ERBB2/HER2方面显示出很大的一致性，在PGR/PR和MKI67/Ki67方面显示出中等程度的一致性：总体而言，MammaTyper® pCR 评分可作为预测 HR+/HER2 阴性 BC NACT 反应的标准化工具，为治疗策略提供潜在指导。此外，它还能对ER、PR、HER2和Ki67状态进行更标准化和可重复的评估。

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来源期刊

Breast 医学-妇产科学

CiteScore

8.70

自引率

2.60%

发文量

165

审稿时长

59 days

期刊介绍： The Breast is an international, multidisciplinary journal for researchers and clinicians, which focuses on translational and clinical research for the advancement of breast cancer prevention, diagnosis and treatment of all stages.