A Practical Immunohistochemistry-Based Model for Predicting Pathologic Complete Response in Estrogen Receptor-Strong Positive and HER2-Negative Breast Cancer

Sep 22, 2026

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Purpose: Neoadjuvant chemotherapy benefit is established in HER2-positive and triple-negative breast cancers, but patient selection and pCR achievement in estrogen receptor (ER)-strong positive/HER2-negative disease remain insufficiently defined. Methods: A prospective cohort was retrospectively analyzed, including 522 patients receiving NAC followed by surgery (2008–2021). Immunohistochemistry markers (PR, Ki-67, EGFR, CK5/6, p53) informed multivariable modeling to build a weighted four-point score. Results: PR-negative status, basal-like positivity (EGFR or CK5/6), and Ki-67≥50% independently predicted pCR, with AUC=0.754. Higher scores showed stepwise pCR increases and improved survival in the high group. Conclusion: The IHC-based model predicts pCR and identifies subgroups where pCR links to meaningful survival benefit after NAC in ER-positive/HER2-negative breast cancer.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Purpose

Methods

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J Breast Cancer. 2026 Apr;29(2):128-140 [https://doi.org/10.4048/jbc.2025.0242](https://doi.org/10.4048/jbc.2025.0242)[ ](https://doi.org/10.4048/jbc.2025.0242)pISSN 1738-6756·eISSN 2092-9900 Original Article Received: Sep 29, 2025 Revised: Nov 23, 2025 Accepted: Dec 15, 2025 Published online: Jan 28, 2026 Correspondence to Hyunwoo Lee Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. Email: [hwpatho.lee@samsung.com](hwpatho.lee@samsung.com) Woong Ki Park Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. [Email: woongki.park@samsung.com](Email: woongki.park@samsung.com) *These authors contributed equally to this work as co-first authors. © The Authors 2026 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0/](creativecommons.org/licenses/by-nc/4.0/)) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID iDs Su Min Lee [https://orcid.org/0009-0004-8537-7874](https://orcid.org/0009-0004-8537-7874)[ ](https://orcid.org/0009-0004-8537-7874)Jeong Eon Lee [https://orcid.org/0000-0003-0037-2456](https://orcid.org/0000-0003-0037-2456)[ ](https://orcid.org/0000-0003-0037-2456)Seok Jin Nam [https://orcid.org/0000-0003-1072-8954](https://orcid.org/0000-0003-1072-8954)[ ](https://orcid.org/0000-0003-1072-8954)Seok Won Kim [https://orcid.org/0000-0002-6130-7570](https://orcid.org/0000-0002-6130-7570) A Practical Immunohistochemistry-Based Model for Predicting Pathologic Complete Response in Estrogen Receptor-Strong Positive and HER2-Negative Breast Cancer Su Min Lee 1,*, Jeong Eon Lee 1,*, Seok Jin Nam 1, Seok Won Kim 1, Jonghan Yu 1, Byung Joo Chae 1, Se Kyung Lee 1, Jai Min Ryu 1, Eun Yoon Cho 2, Hyunwoo Lee 2, Woong Ki Park 1 1Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea ABSTRACT Purpose: While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. Methods: Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses. Results: Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9%(low), 10.7%(intermediate), and 36.2%(high) . In the high-score group, pCR was significan

FAQs

What clinical question does the study address?

The study evaluates how to predict pathological complete response (pCR) and select patients in ER-strong positive/HER2-negative breast cancer treated with neoadjuvant chemotherapy.

Which immunohistochemistry markers were used to build the pCR model?

The model used progesterone receptor (PR), Ki-67, EGFR, cytokeratin 5/6 (CK5/6), and p53, with PR, EGFR/CK5/6 basal-like status, and Ki-67 emerging as key predictors.

How does pCR relate to survival outcomes in the scoring model?

In the high-score group, pCR was associated with improved disease-free survival and distant metastasis-free survival, while low and intermediate score groups showed no significant survival differences by pCR status.

Sep 22, 2026

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