Journal Article
. 2019 Aug;30(1).
doi: 10.1007/s00330-019-06383-6.

Diffusion-weighted MRI of estrogen receptor-positive, HER2-negative, node-negative breast cancer: association between intratumoral heterogeneity and recurrence risk

Jin You Kim 1 Jin Joo Kim 2 Lee Hwangbo 2 Ji Won Lee 2 Nam Kyung Lee 2 Kyung Jin Nam 3 Ki Seok Choo 3 Taewoo Kang 4 Heeseung Park 4 Yohan Son 5 Robert Grimm 6 
Affiliations
  • PMID: 31385051
  •     29 References
  •     2 citations

Abstract

Objectives: To investigate possible associations between quantitative apparent diffusion coefficient (ADC) metrics derived from whole-lesion histogram analysis and breast cancer recurrence risk in women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer who underwent the Oncotype DX assay.

Methods: This retrospective study was conducted on 105 women (median age, 48 years) with ER-positive, HER2-negative, node-negative breast cancer who underwent the Oncotype DX test and preoperative diffusion-weighted imaging (DWI). Histogram analysis of pixel-based ADC data of whole tumors was performed, and various ADC histogram parameters (mean, 5th, 25th, 50th, 75th, and 95th percentiles of ADCs) were extracted. The ADC difference value (defined as the difference between the 5th and 95th percentiles of ADCs) was calculated to assess intratumoral heterogeneity. Associations between quantitative ADC metrics and the recurrence risk, stratified using the Oncotype DX recurrence score (RS), were evaluated.

Results: Whole-lesion histogram analysis showed that the ADC difference value was different between the low-risk recurrence (RS < 18) and the non-low-risk recurrence (RS ≥ 18; intermediate to high risk of recurrence) groups (0.600 × 10-3 mm2/s vs. 0.746 × 10-3 mm2/s, p < 0.001). Multivariate regression analysis demonstrated that a lower ADC difference value (< 0.559 × 10-3 mm2/s; odds ratio [OR] = 5.998; p = 0.007) and a small tumor size (≤ 2 cm; OR = 3.866; p = 0.012) were associated with a low risk of recurrence after adjusting for clinicopathological factors.

Conclusions: The ADC difference value derived from whole-lesion histogram analysis might serve as a quantitative DWI biomarker of the recurrence risk in women with ER-positive, HER2-negative, node-negative invasive breast cancer.

Key Points: • A lower ADC difference value and a small tumor size were associated with a low risk of recurrence of breast cancer. • The ADC difference value could be a quantitative marker for intratumoral heterogeneity. • Whole-lesion histogram analysis of the ADC could be helpful for discriminating the low-risk from non-low-risk recurrence groups.

Keywords: Biomarkers; Breast neoplasms, Oncotype DX; Diffusion magnetic resonance imaging; Recurrence.

Adoption of gene expression profile testing and association with use of chemotherapy among women with breast cancer.
Michael J Hassett, Samuel M Silver, +12 authors, Jane C Weeks.
J Clin Oncol, 2012 May 16; 30(18). PMID: 22585699    Free PMC article.
Rim sign and histogram analysis of apparent diffusion coefficient values on diffusion-weighted MRI in triple-negative breast cancer: Comparison with ER-positive subtype.
Yangsean Choi, Sung Hun Kim, +3 authors, Ahwon Lee.
PLoS One, 2017 May 26; 12(5). PMID: 28542297    Free PMC article.
Oncotype-DX recurrence score distribution in breast cancer patients with BRCA1/2 mutations.
R Lewin, A Sulkes, +11 authors, R Yerushalmi.
Breast Cancer Res Treat, 2016 May 27; 157(3). PMID: 27225387
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge.
N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349    Free PMC article.
Highly Cited.
Apparent diffusion coefficient in estrogen receptor-positive and lymph node-negative invasive breast cancers at 3.0T DW-MRI: A potential predictor for an oncotype Dx test recurrence score.
Sunitha B Thakur, Manuela Durando, +5 authors, Elizabeth A Morris.
J Magn Reson Imaging, 2017 Jun 24; 47(2). PMID: 28640531    Free PMC article.
Diffusion-weighted Imaging of Invasive Breast Cancer: Relationship to Distant Metastasis-free Survival.
Jin You Kim, Jin Joo Kim, +2 authors, Heeseung Park.
Radiology, 2019 Mar 13; 291(2). PMID: 30860453
Early-stage invasive ductal carcinoma: Association of tumor apparent diffusion coefficient values with axillary lymph node metastasis.
Jin You Kim, Hie Bum Seo, +5 authors, Young Tae Bae.
Eur J Radiol, 2015 Sep 01; 84(11). PMID: 26318821
Review.
Prognostic and predictive factors in breast cancer by immunohistochemical analysis.
D C Allred, J M Harvey, M Berardo, G M Clark.
Mod Pathol, 1998 Mar 21; 11(2). PMID: 9504686
Highly Cited. Review.
Random walks for image segmentation.
Leo Grady.
IEEE Trans Pattern Anal Mach Intell, 2006 Oct 27; 28(11). PMID: 17063682
Highly Cited.
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix.
M Hockel, K Schlenger, +3 authors, P Vaupel.
Cancer Res, 1996 Oct 01; 56(19). PMID: 8813149
Highly Cited.
Diffusion-weighted imaging of breast masses: comparison of diagnostic performance using various apparent diffusion coefficient parameters.
Maki Hirano, Hiroko Satake, +3 authors, Shinji Naganawa.
AJR Am J Roentgenol, 2012 Feb 24; 198(3). PMID: 22358015
Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix.
M Höckel, C Knoop, +5 authors, P Vaupel.
Radiother Oncol, 1993 Jan 01; 26(1). PMID: 8438086
Highly Cited.
Risk stratification of ductal carcinoma in situ using whole-lesion histogram analysis of the apparent diffusion coefficient.
Jin You Kim, Jin Joo Kim, +6 authors, Robert Grimm.
Eur Radiol, 2018 Aug 04; 29(2). PMID: 30073498
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Why does Oncotype DX recurrence score reduce adjuvant chemotherapy use?
Jeffrey G Schneider, Danny N Khalil.
Breast Cancer Res Treat, 2012 Jun 23; 134(3). PMID: 22723033    Free PMC article.
Prediction of Low versus High Recurrence Scores in Estrogen Receptor-Positive, Lymph Node-Negative Invasive Breast Cancer on the Basis of Radiologic-Pathologic Features: Comparison with Oncotype DX Test Recurrence Scores.
Vandana Dialani, Shantanu Gaur, +5 authors, Priscilla J Slanetz.
Radiology, 2016 Mar 05; 280(2). PMID: 26937802
Diffusion-weighted MRI characteristics associated with prognostic pathological factors and recurrence risk in invasive ER+/HER2- breast cancers.
Nita Amornsiripanitch, Vicky T Nguyen, +4 authors, Savannah C Partridge.
J Magn Reson Imaging, 2017 Nov 28; 48(1). PMID: 29178616    Free PMC article.
Invasive ductal carcinoma: correlation of apparent diffusion coefficient value with pathological prognostic factors.
Ahmed Abdel Khalek Abdel Razek, Gada Gaballa, Adel Denewer, Nadia Nada.
NMR Biomed, 2010 Mar 17; 23(6). PMID: 20232453
Breast Cancer Heterogeneity: MR Imaging Texture Analysis and Survival Outcomes.
Jae-Hun Kim, Eun Sook Ko, +5 authors, Seok Jin Nam.
Radiology, 2016 Oct 05; 282(3). PMID: 27700229
Highly Cited.
Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification.
Zhaohai Yang, Laura H Tang, David S Klimstra.
Am J Surg Pathol, 2011 May 14; 35(6). PMID: 21566513
Highly Cited.
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.
Lyndsay N Harris, Nofisat Ismaila, +11 authors, American Society of Clinical Oncology.
J Clin Oncol, 2016 Feb 10; 34(10). PMID: 26858339    Free PMC article.
Highly Cited. Review.
Histogram analysis of apparent diffusion coefficient at 3.0t: Correlation with prognostic factors and subtypes of invasive ductal carcinoma.
Eun Jeong Kim, Sung Hun Kim, +8 authors, Robert Grimm.
J Magn Reson Imaging, 2015 Apr 29; 42(6). PMID: 25919239
Interobserver reproducibility of diffusion-weighted MRI in monitoring tumor response to neoadjuvant therapy in esophageal cancer.
Robert M Kwee, Alexander K Dik, +7 authors, Roy F A Vliegen.
PLoS One, 2014 Apr 08; 9(4). PMID: 24704912    Free PMC article.
Differentiation of clinically benign and malignant breast lesions using diffusion-weighted imaging.
Yong Guo, You-Quan Cai, +5 authors, Jia-Hong Gao.
J Magn Reson Imaging, 2002 Aug 31; 16(2). PMID: 12203765
Highly Cited.
Quantitative justification of the change from 10% to 30% for human epidermal growth factor receptor 2 scoring in the American Society of Clinical Oncology/College of American Pathologists guidelines: tumor heterogeneity in breast cancer and its implications for tissue microarray based assessment of outcome.
Christopher B Moeder, Jennifer M Giltnane, +8 authors, College of American Pathologists.
J Clin Oncol, 2007 Dec 01; 25(34). PMID: 18048824
MR Imaging Radiomics Signatures for Predicting the Risk of Breast Cancer Recurrence as Given by Research Versions of MammaPrint, Oncotype DX, and PAM50 Gene Assays.
Hui Li, Yitan Zhu, +13 authors, Maryellen L Giger.
Radiology, 2016 Oct 19; 281(2). PMID: 27144536    Free PMC article.
Highly Cited.
Interobserver agreement of semi-automated and manual measurements of functional MRI metrics of treatment response in hepatocellular carcinoma.
David Bonekamp, Susanne Bonekamp, +5 authors, Ihab R Kamel.
Eur J Radiol, 2014 Jan 07; 83(3). PMID: 24387824    Free PMC article.
Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations.
N Lynn Henry, Mark R Somerfield, +6 authors, Ian E Krop.
J Clin Oncol, 2016 Mar 24; 34(19). PMID: 27001586
Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective.
Teresa W-M Fan, Richard M Higashi, Yelena Chernayavskaya, Andrew N Lane.
Metabolites, 2020 Jun 19; 10(6). PMID: 32549391    Free PMC article.
Review.
Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer.
Wen-Jie Tang, Zhe Jin, +8 authors, Xin-Qing Jiang.
Front Oncol, 2021 Jan 26; 10. PMID: 33489920    Free PMC article.