Noninvasive imaging signatures of HER2 and HR using ADC in invasive breast cancer: repeatability, reproducibility, and association with pathological complete response to neoadjuvant chemotherapy

Breast Cancer Research

Research

Xinyu Fan¹  Elaine Yuen Phin Lee²  Xinyu Zhang³  Jiang Zhang³  Ta Zhou³  Yu-hua Huang³  Lu Wang³  Xinzhi Teng³  Jing Cai⁴  Ruijie Yang⁵ 

[1] Department of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong, China;Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Y920, Lee Shau Kee Building, Hong Kong, China;Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China;Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China;The Hong Kong Polytechnic University Shenzhen Research Institute, Hong Kong, China;Research Institute for Smart Aging, The Hong Kong Polytechnic University, Hong Kong, China;Department of Radiation Oncology, Peking University Third Hospital, Beijing, China;

关键词: Immunohistochemistry;    HER2;    HR;    Image signatures;    ADC;   

DOI  :  10.1186/s13058-023-01674-9

 received in 2023-02-10, accepted in 2023-06-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe immunohistochemical test (IHC) of HER2 and HR can provide prognostic information and treatment guidance for invasive breast cancer patients. We aimed to develop noninvasive image signatures ISHER2 and ISHR of HER2 and HR, respectively. We independently evaluate their repeatability, reproducibility, and association with pathological complete response (pCR) to neoadjuvant chemotherapy.MethodsPre-treatment DWI, IHC receptor status HER2/HR, and pCR to neoadjuvant chemotherapy of 222 patients from the multi-institutional ACRIN 6698 trial were retrospectively collected. They were pre-separated for development, independent validation, and test–retest. 1316 image features were extracted from DWI-derived ADC maps within manual tumor segmentations. ISHER2 and ISHR were developed by RIDGE logistic regression using non-redundant and test–retest reproducible features relevant to IHC receptor status. We evaluated their association with pCR using area under receiver operating curve (AUC) and odds ratio (OR) after binarization. Their reproducibility was further evaluated using the test–retest set with intra-class coefficient of correlation (ICC).ResultsA 5-feature ISHER2 targeting HER2 was developed (AUC = 0.70, 95% CI 0.59 to 0.82) and validated (AUC = 0.72, 95% CI 0.58 to 0.86) with high perturbation repeatability (ICC = 0.92) and test–retest reproducibility (ICC = 0.83). ISHR was developed using 5 features with higher association with HR during development (AUC = 0.75, 95% CI 0.66 to 0.84) and validation (AUC = 0.74, 95% CI 0.61 to 0.86) and similar repeatability (ICC = 0.91) and reproducibility (ICC = 0.82). Both image signatures showed significant associations with pCR with AUC of 0.65 (95% CI 0.50 to 0.80) for ISHER2 and 0.64 (95% CI 0.50 to 0.78) for ISHER2 in the validation cohort. Patients with high ISHER2 were more likely to achieve pCR to neoadjuvant chemotherapy with validation OR of 4.73 (95% CI 1.64 to 13.65, P value = 0.006). Low ISHR patients had higher pCR with OR = 0.29 (95% CI 0.10 to 0.81, P value = 0.021). Molecular subtypes derived from the image signatures showed comparable pCR prediction values to IHC-based molecular subtypes (P value > 0.05).ConclusionRobust ADC-based image signatures were developed and validated for noninvasive evaluation of IHC receptors HER2 and HR. We also confirmed their value in predicting treatment response to neoadjuvant chemotherapy. Further evaluations in treatment guidance are warranted to fully validate their potential as IHC surrogates.

【 授权许可】

CC BY   
© The Author(s) 2023

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