The Predictive Value of the Tumor-Stroma Ratio for Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive Breast Cancer

Sep 22, 2026

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Approximately 75% of breast cancers are hormone receptor-positive (HR+), and endocrine therapy can improve survival. Neoadjuvant endocrine therapy may allow breast- and axilla-conserving surgery, but predicting who benefits remains difficult. This study assesses whether the tumor-stroma ratio (TSR) predicts response to neoadjuvant endocrine therapy and evaluates MRI accuracy for (near) pathological complete response in women treated in two Dutch hospitals.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Study rationale and clinical background

Treatment goals in the neoadjuvant setting

International Journal of Cancer RESEARCH ARTICLE OPEN ACCESS Tumor Immunology and Microenvironment The Predictive Value of the Tumor-Stroma Ratio for Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive Breast Cancer Layla Andour1 | Sophie C. Hagenaars1 | Anne Florine de Groot2 | Elly M. M. Krol-Warmerdam1,2 | Judith R. Kroep2 | Hans Marten Hazelbag3 | Gerrit-Jan Liefers1 | Marieke E. Straver4 | Wilma E. Mesker1 1Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands | 2Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands | 3Department of Pathology, Haaglanden Medical Center, The Hague, the Netherlands | 4Department of Surgery, Medical Center Haaglanden, The Hague, the Netherlands Correspondence: Wilma E. Mesker ([w.e.mesker@lumc.nl](w.e.mesker@lumc.nl)) Received: 26 November 2025 | Revised: 13 March 2026 | Accepted: 31 March 2026 Keywords: breast cancer | endocrine therapy | magnetic imaging resonance | neoadjuvant systemic therapy | tumor-stroma ratio ABSTRACT Approximately 75% of breast cancers are hormone receptor-positive (HR+). Endocrine therapy may be administered to improve survival. Neoadjuvant therapy may enable breast-and axilla-conserving surgery, but identifying who will benefit remains challenging. This study evaluates the predictive value of the tumor-stroma ratio (TSR) for response to neoadjuvant endocrine therapy (NET) and examines the accuracy of MRI in predicting (near) pathological complete response (pCR). Women diagnosed between 2014 and 2024 with invasive HR+, human epidermal growth factor 2-negative breast cancer who received NET in two Dutch hospitals were included. A total of 208 women (215 tumors) were included, of whom 81 (37.7%) had a stroma-low tumor and 134 (62.3%) stroma-high. Almost 1 out of 4 stroma-low cases achieved (near) pCR after NET. In both univariable (OR 2.85, 95% CI 1.32–6.15, p = 0.008) and multivariable analysis (OR 3.70, 95% CI 1.54–8.90, p = 0.003), stroma-low tumors showed an increased likelihood of achieving (near) pCR compared to stroma-high tumors. In node-positive patients (n = 117), univariable analysis presented higher odds of pCR in the axilla after NET in the stroma-low group (OR 4.41, 95% CI 1.08–18.08, p = 0.039), although this was not significant in multivariable analysis (p = 0.060). The MRI correctly reported (near) pCR in 12 (75%) stroma-low cases and 8 (35%) stroma-high. Stroma-low patients significantly more often achieved (near) pCR of the tumor and axilla after NET compared to stroma-high patients. The accuracy of MRI to predict (near) pCR was higher in the stroma-low group compared to the stroma-high group. | Abbreviations: κ, Cohen's kappa; χ2, Pearson chi-square; ALND, axillary lymph node dissection; BCS, breast-conserving surgery; BOOG, Dutch Breast Cancer Research Group; CI, confidence interval; DCIS, ductal carcinoma in situ; ER, estrogen receptor; H&E, hematoxylin and eosin; HER2, human epidermal growth factor receptor 2; HMC, Medical Center Haaglanden; HR, hormone receptor; IHC, immunohistochemical; IKNL, The Netherlands Comprehensive Cancer Organization; LUMC, Leiden University Medical Center; MP, Miller-Payne; MRI, magnetic resonance imaging; MST, mastectomy; N, lymph node; NACT, neoadjuvant chemotherapy; NEOLBC, Tailoring NEOadjuvant Therapy in HR+/HER2 − , Luminal Breast Cancer; NET, neoadjuvant endocrine therapy; OR, odds ratio; pCR, pathological complete response; PR, progesterone receptor; RCB, residual cancer burden; rCR, radiological complete response; RCT, randomized controlled trial; RECIST, response evaluation criteria in solid tumors; T, tumor; TME, tumor microenvironment; TSR, tumor-stroma ratio. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2026 The Author(s). International

FAQs

What is the tumor-stroma ratio (TSR) used for in this study?

TSR is evaluated as a biomarker to predict response to neoadjuvant endocrine therapy in hormone receptor-positive breast cancer.

Which patients were included in the analysis?

Women diagnosed from 2014 to 2024 with invasive HR+, HER2-negative breast cancer who received neoadjuvant endocrine therapy in two Dutch hospitals.

How well did MRI predict (near) pathological complete response?

MRI correctly reported (near) pathological complete response more often in the stroma-low group than in the stroma-high group, indicating higher predictive accuracy in stroma-low cases.

Sep 22, 2026

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