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Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models

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Abstract

Objectives

To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC).

Methods

This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, αCTRW, βCTRW, DCTRW, βFROC, DFROC, μFROC, αSEM, and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability.

Results

The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW, DCTRW, βFROC, DFROC, μFROC, αSEM, and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877.

Conclusions

The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs.

Clinical relevance statement

Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue.

Key Points

• Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW, DCTRW, βFROC, DFROC, μFROC, αSEM, and DDCSEM values compared with HER2-overexpressing breast cancer.

• The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers.

• The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability.

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Abbreviations

ADC:

Apparent diffusion coefficient

AUC:

Area under the curve

BC:

Breast cancer

CI:

Confidence interval

CTRW:

Continuous-time random walk

DCE:

Dynamic contrast-enhanced

DTI:

Diffusion tensor imaging

DWI:

Diffusion-weighted imaging

ER:

Estrogen receptor

FISH:

Fluorescence in situ hybridization

FOV:

Field of view

FROC:

Fractional order calculus

HER2:

Human epidermal growth factor receptor 2

ICC:

Inter-class correlation coefficient

IHC:

Immunohistochemistry

MRI:

Magnetic resonance imaging

PR:

Progesterone receptor

QIBA:

Quantitative Imaging Biomarkers Alliance

ROC:

Receiver operating characteristic

ROI:

Region of interest

SE-EPI:

Spin-echo echo-planar imaging

SEM:

Stretched exponential model

T1WI:

T1-weighted imaging

T2WI:

T2-weighted imaging

TE:

Echo time

TR:

Repetition time

VOI:

Volume of interest

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Funding

This study was supported by the National Natural Science Foundation of China (82102130, 12126610), Guangdong Basic and Applied Basic Research Foundation (2021A1515010385, 2023A1515011305), Guangzhou Basic and Applied Basic Research Foundation (2023A04J2112), and SKY Imaging Research Fund Project of China International Medical Foundation (Z-2014-07-1912-21).

Author information

Author notes

  1. Chunping Mao, Lanxin Hu, and Wei Jiang have contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China

    Chunping Mao, Lanxin Hu, Wei Jiang, Ya Qiu, Zehong Yang, Dongye Wang, Yun Su, Jinru Lin, Zhaoxi Cai, Xiang Zhang & Jun Shen

  2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China

    Chunping Mao, Lanxin Hu, Wei Jiang, Ya Qiu, Zehong Yang, Yeqing Liu, Dongye Wang, Yun Su, Jinru Lin, Zhaoxi Cai, Xiang Zhang & Jun Shen

  3. Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China

    Yeqing Liu

  4. MR Scientific Marketing, Siemens Healthcare, Guangzhou, Guangdong, China

    Mengzhu Wang & Xu Yan

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  1. Chunping Mao
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Corresponding authors

Correspondence to Xiang Zhang or Jun Shen.

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Guarantor

The scientific guarantor of this publication is Jun Shen.

Conflict of interest

Two of the authors (Mengzhu Wang and Xu Yan) are employees of Siemens Healthcare.

The other authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

All participants provided written informed consent.

Ethical approval

Institutional Review Board approval was obtained from the Institutional Review Board of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University (Guangzhou, China) (SYSEC-KY-KS-2022-027).

Study subjects or cohorts overlap

No study subject or cohort has been previously reported in this study.

Methodology

• prospective

• diagnostic study

• single-center study

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Mao, C., Hu, L., Jiang, W. et al. Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models. Eur Radiol 34, 2546–2559 (2024). https://doi.org/10.1007/s00330-023-10198-x

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