Cancer Research and Treatment

Original Articles

HER3 Expression and PIK3CA Mutational Status Predict Pathological Response of Neoadjuvant Therapy in HER2-Positive Breast Cancer Patients: Xi Xia, Zhiqiang Zong, Jian Shen, Lingling Zhou, Yang Lei, Jia Li, Lu Zheng, Fanfan Li, Hua Wang; Received March 4, 2025 Accepted July 1, 2025 Published online July 2, 2025; DOI: https://doi.org/10.4143/crt.2025.242 [Epub ahead of print]

Purpose
The main purpose of this study is to explore the predictive value of human epidermal growth factor receptor 3 (HER3) expression level and PIK3CA mutation for the efficacy of neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2)–positive breast cancer patients.
Materials and Methods
The clinicopathological data of HER2-positive non-specific invasive breast cancer patients who received neoadjuvant treatment in the Second Affiliated Hospital of Anhui Medical University from June 2017 to June 2024 were retrospectively analyzed. The correlation between HER3 expression level detected by immunohistochemistry and PIK3CA gene mutation detected by amplification refractory mutation system–polymerase chain reaction and pathological complete response (pCR) was analyzed.
Results
Among 51 patients, 29 (56.9%) had positive HER3 expression, 15 (29.4%) had PIK3CA mutation, and 19 (37.3%) had pCR. The expression level of HER3 was correlated with the pCR rate (χ²=7.905, p=0.019). The PIK3CA mutation status was not correlated with the pCR rate (χ²=0.140, p=0.708). The HER3 expression level combined with PIK3CA mutation status affected the pCR rate (p=0.036). Multivariable regression further identified HER3 positivity as an independent negative predictor of pCR (odds ratio, 0.08; 95% confidence interval, 0.01 to 0.50; p=0.008), underscoring its role in therapeutic resistance.
Conclusion
HER3 expression may serve as a critical biomarker for guiding therapeutic strategies in HER2-positive breast cancer patients. The combinatorial effect of HER3 overexpression and PIK3CA mutations may exacerbate therapeutic resistance, while dual-targeted strategies against the HER3/phosphoinositide 3-kinase pathway could potentially improve clinical outcomes in treatment-resistant populations.

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AGTPBP1 Promotes Breast Cancer Progression via the EVPL/ERK Signaling Axis
Hudeer Song, Hongxia Li, Yanchao Bian, Jingyuan Song, Chenxi Yang, Houke Lu, Yuqi Zhang, Pengfei Li, Rui Xiao
Experimental Cell Research.2026; : 115001. CrossRef

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Breast cancer

Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor–Positive and HER-2–Negative Breast Cancer with Neoadjuvant Chemotherapy: Eun-Gyeong Lee, Dong-Eun Lee, Hyun hee Kim, Jai Hong Han, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Heejung Chae, Sung Hoon Sim, Keun Seok Lee, Youngmee Kwon, So-Youn Jung; Cancer Res Treat. 2023;55(2):542-550. Published online September 8, 2022; DOI: https://doi.org/10.4143/crt.2022.834

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors.
Materials and Methods
We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR.
Results
Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022).
Conclusion
AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.

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Androgen Receptor Positivity in Non-Metastatic Breast Cancer Patients and Its Prognostic Implications—A Retrospective Study
Rexeena Bhargavan, Anitha Mathews, Lakshmi Subhadradevi, Jagathnath K. M. Krishna, Kurian Cherian, Paul Augustine
Indian Journal of Surgical Oncology.2026; 17(3): 499. CrossRef
Development and validation of a pathomics-driven machine learning model for individualized prediction of neoadjuvant chemotherapy response and early recurrence in HR-positive, HER2-negative breast cancer
Jiaxian Yue, Jiaxiang Liu, Xiyu Kang, Pei Yuan, Wei Wang, Zhanyu Wang, Chao Shang, Qingyao Shang, Guangyu Li, Xubin Dong, Tianxiao Wang, Dongmin Yang, Shuhao Wang, Chenxuan Yang, Jianming Ying, Xin Wang
Frontiers in Oncology.2026;[Epub] CrossRef
The prevalence and clinical significance of residual occult breast cancer after neoadjuvant chemotherapy: reassessing surgical pathology in cases initially described as pathological complete response
Di Ai, Eliel N Arrey, Lauren M Postlewait, Yuan Gao, Xiaoxian Li
Histopathology.2025; 86(7): 1112. CrossRef
Neo-adjuvant therapies for ER positive/HER2 negative breast cancers: from chemotherapy to hormonal therapy, CDK inhibitors, and beyond
Athina Stravodimou, Ioannis A. Voutsadakis
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Luminal androgen receptor subtype and tumor-infiltrating lymphocytes groups based on triple-negative breast cancer molecular subclassification
Miseon Lee, Tae-Kyung Yoo, Byung Joo Chae, Ahwon Lee, Yoon Jin Cha, Jieun Lee, Sung Gwe Ahn, Jun Kang
Scientific Reports.2024;[Epub] CrossRef
Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma
Adil Aziz Khan, Sana Ahuja, Kiruthikasri G., Sufian Zaheer
Indian Journal of Surgical Oncology.2024; 15(4): 802. CrossRef
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Angelika M. Starzer, Anna S. Berghoff, Rupert Bartsch
memo - Magazine of European Medical Oncology.2023; 16(1): 42. CrossRef
Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy
Zhendong Shi, Yingxue Liu, Shichao Zhang, Shuanglong Cai, Xu Liu, Jie Meng, Jin Zhang
Discover Oncology.2023;[Epub] CrossRef

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PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane–Based Neoadjuvant Chemotherapy: Sanxing Guo, Sibylle Loibl, Gunter von Minckwitz, Silvia Darb-Esfahani, Bianca Lederer, Carsten Denkert; Cancer Res Treat. 2020;52(3):689-696. Published online February 4, 2020; DOI: https://doi.org/10.4143/crt.2019.497

Abstract PDF PubReader ePub

Purpose
PIK3CA, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. PIK3CAmutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of PIK3CA mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Materials and Methods
A total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of PIK3CA mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues.
Results
Seven of 90 tumors (7.8%) were detectable with a PIK3CA H1047R mutation. Overall, PIK3CA H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056).
Conclusion
TNBC with a PIK3CA H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.

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