Cancer Research and Treatment

Original Articles

Breast cancer

Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions: Bárbara Jaime dos Santos, Débora Balabram, Virginia Mara Reis Gomes, Carolina Costa Café de Castro, Paulo Henrique Costa Diniz, Marcelo Araújo Buzelin, Cristiana Buzelin Nunes; Cancer Res Treat. 2024;56(1):178-190. Published online August 1, 2023; DOI: https://doi.org/10.4143/crt.2023.386

Purpose
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients’ overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS.
Materials and Methods
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Results
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B–like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor–positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
Conclusion
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

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Prognostic Impact of Real-World Immunohistochemical Changes in Breast Cancer Treated with Neoadjuvant Chemotherapy
Marcelo Antonini, André Mattar, Marcelo Madeira, Letícia Xavier Félix, Julio Antonio Pereira de Araújo, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antonio Luis Frasson, Eduardo Camargo Millen, Marina Diógenes Teixeira, Lariss
Clinical Breast Cancer.2026; 26(1): 276. CrossRef
Immunohistochemical Changes After Neoadjuvant Chemotherapy and Their Impact on Breast Cancer Survival: A Systematic Review and Meta-analysis
Marcelo Antonini, André Mattar, Gil Facina, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antônio Luis Frasson, Eduardo Camargo Millen, Rodrigo Caires Campos, Letícia Xavier Félix, Juliana Calado Vieira, Marina Diógenes Teixeira
Clinical Breast Cancer.2026; 26(3): 208. CrossRef
Prognostic value of prognostic nutritional index in breast cancer patients receiving neoadjuvant therapy: a systematic review and meta-analysis
Meihui Shan, Ziqian Zhao, Munawar Anwar, Jiawei Chen, Yuquan Dai, Yeliya Yeerboli, Zuqiang Xu, Zizhang Wang, Le Yang, Chao Dong
Frontiers in Oncology.2026;[Epub] CrossRef
Discordance in Immunohistochemistry Results in Breast Pathologies: Effect of Chemotherapy, Specimen Characteristics, or Pathology Center?
Mustafa Ersoy
Clinical Medicine Insights: Oncology.2025;[Epub] CrossRef
Identifying gene expression signatures of oncolytic virus response in patient-derived pancreatic ductal adenocarcinoma organoids
Marco Huberts, Elham Aida Farshadi, Farzana Mohammad, Jie Ju, Andrew Stubbs, Ron A.M. Fouchier, Bernadette G. van den Hoogen
Molecular Therapy Oncology.2025; 33(4): 201064. CrossRef
Post-Surgical Reassessment of Breast Cancer IHC: Concordance, Δ-Metrics, and Treatment-Relevant Reclassification
Ramona Andreea Cioroianu, Michael Schenker, Tradian Ciprian Berisha, Virginia-Maria Rădulescu, George Ovidiu Cioroianu, Raluca Chirculescu, Ana Maria Petrescu, Mihaela Popescu, Anda Lorena Dijmărescu, Stelian Ștefăniță Mogoantă
Diagnostics.2025; 15(24): 3128. CrossRef

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Effect of Estrogen Receptor Expression Level and Hormonal Therapy on Prognosis of Early Breast Cancer: Kyung-Hwak Yoon, Yeshong Park, Eunyoung Kang, Eun-Kyu Kim, Jee Hyun Kim, Se Hyun Kim, Koung Jin Suh, Sun Mi Kim, Mijung Jang, Bo La Yun, So Yeon Park, Hee-Chul Shin; Cancer Res Treat. 2022;54(4):1081-1090. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.890

Abstract PDF PubReader ePub

Purpose
Estrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1%-10%) of ER expression have been separately defined as ER low positive (ER^low). It is suggested that ER^low tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh).
Materials and Methods
Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ER^low, and ER-negative [ER–]).
Results
A total of 2,162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1,654 (76.5%) were ERhigh, 54 (2.5%) were ER^low, and 454 (21.0%) were ER^- patients. ER^low cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2, negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER– tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ER^low group (p=0.418).
Conclusion
ER^low breast cancer showed distinct clinicopathological features. ER^low tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ER^low breast cancer.

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CanAssist Breast Provides Additional Insightful Prognostic Information in Retrospective, Pooled Secondary Analysis in Clinically Low/ High-Risk Patients With HR+/HER2- EBC
Tejal Deepak Durgekar, Susmita Ghosh, Badada Ananthamurthy Savitha, Payal Shrivastava, Naveen Krishnamoorthy, Manvi Sunder, Deepti KS, Manjiri Bakre
Clinical Breast Cancer.2026; 26(2): 216. CrossRef
The Role of Estrogen Receptor–Targeted PET with 16α-18F-Fluoro-17β-Estradiol in Predicting Response to Endocrine Therapies in Metastatic Breast Cancer: A Metaanalysis
Jennifer M. Specht, Jasper J.L. van Geel, Shaoli Song, Cheng Liu, Daniel S. Hippe, Nicholas A. DiGregorio, Christine J. Brand, Hannah M. Linden
Journal of Nuclear Medicine.2026; 67(1): 36. CrossRef
Phytochemicals in breast cancer therapy: Decoding molecular pathways and pioneering therapeutic strategies
Putri cahaya Situmorang, Denny Satria, Syafruddin Ilyas, Kaniwa Berliani, Nursahara Pasaribu, Nik Mohd Afizan Nik Abd Rahman, Alexander Patera Nugraha
Phytomedicine Plus.2026; 6(1): 100935. CrossRef
Prognosis and endocrine therapy efficacy in early breast cancer with estrogen receptor low expression
Sihua Liu, Beidi Du, Mengmeng Zhang, Duanyang Zhai, Xutu Zhao, Nan Shao, Xiaying Kuang, Yunjian Zhang, Yawei Shi, Liang Yu, Ying Lin
Breast Cancer Research and Treatment.2026;[Epub] CrossRef
Prediction of recurrence-free survival in patients with invasive ductal carcinoma of the breast on the basis of clinicopathological, conventional ultrasound and contrast-enhanced ultrasound imaging characteristics
Y. Kuang, Y. Zheng, G. Li, Y. Du, C. Jia, T. Wu, X. Diao, R. Wu
Clinical Radiology.2026; 96: 107256. CrossRef
Distribution and molecular drivers of the 21-gene recurrence score in early breast cancer with low, intermediate, and high estrogen receptor expression
Shuai Li, Jiahui Huang, Yifei Zhu, Jin Hong, Siji Zhu, Weiqi Gao, Ou Huang, Jianrong He, Weiguo Chen, Yafen Li, Xiaosong Chen, Kunwei Shen, Jiayi Wu
Frontiers in Immunology.2026;[Epub] CrossRef
CYP2D6 Genotyping for Optimization of Tamoxifen Therapy in Indonesian Women with ER+ Breast Cancer
Baitha Palanggatan Maggadani, Kathleen Irena Junusmin, Fatma Aldila, Jessica Audrienna, Bijak Rabbani, Yusuf Maulana, Sabrina Gabriel Tanu, Gabriella Gabriella, Margareta Amelia, Faustina Audrey Agatha, Marco Wijaya, Stevany Tiurma Sormin, Caroline Mahend
Journal of Personalized Medicine.2025; 15(3): 93. CrossRef
Prognosis, clinicopathological characteristics, and treatment patterns of patients with ER-intermediate-positive breast cancer undergoing long-term follow-up
N. Matsumoto, Y. Wanifuchi-Endo, T. Fujita, T. Asano, M. Terada, K. Nozawa, M. Mori, A. Isogai, Y. Niwa, H. Kato, M. Komura, T. Toyama
ESMO Open.2025; 10(4): 104508. CrossRef
Breast tumors with intermediate ER expression differ biologically from ER-low tumors and exhibit a more favorable prognosis
Yuko Ueki, Yoshiya Horimoto, Kazuharu Harada, Yumiko Ushiyama, Yumiko Ishizuka, Hiroko Onagi, Takuo Hayashi, Tsuyoshi Saito, Takahiko Kawate, Takashi Ishikawa, Junichiro Watanabe, Goro Kutomi
Breast Cancer.2025; 32(6): 1255. CrossRef
ER-positive and BRCA2-mutated breast cancer: a literature review
Pu-Chun Li, Yi-Fan Zhu, Wen-Ming Cao, Bei Li
European Journal of Medical Research.2024;[Epub] CrossRef
Affibody PET Imaging of HER2-Expressing Cancers as a Key to Guide HER2-Targeted Therapy
Nina Eissler, Renske Altena, Ali Alhuseinalkhudhur, Olga Bragina, Joachim Feldwisch, Guido Wuerth, Annika Loftenius, Nikolai Brun, Rimma Axelsson, Vladimir Tolmachev, Jens Sörensen, Fredrik Y. Frejd
Biomedicines.2024; 12(5): 1088. CrossRef
Distinct ER and PR expression patterns significantly affect the clinical outcomes of early HER2-positive breast cancer: A real-world analysis of 871 patients treated with neoadjuvant therapy
Haizhu Chen, Xiujuan Gui, Ziwei Zhou, Fengxi Su, Chang Gong, Shunrong Li, Wei Wu, Nanyan Rao, Qiang Liu, Herui Yao
The Breast.2024; 75: 103733. CrossRef
HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis
Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Is the percentage of hormone receptor positivity in HR+ HER2-metastatic breast cancer patients receiving CDK 4/6 inhibitor with endocrine therapy predictive and prognostic?
Merve Keskinkilic, Huseyin Salih Semiz, Tugba Yavuzsen, Ilhan Oztop
Frontiers in Oncology.2024;[Epub] CrossRef
Rat Models of Hormone Receptor-Positive Breast Cancer
Raquel Nicotra, Catrin Lutz, Hendrik A. Messal, Jos Jonkers
Journal of Mammary Gland Biology and Neoplasia.2024;[Epub] CrossRef
Immune and gene-expression profiling in estrogen receptor low and negative early breast cancer
Davide Massa, Claudio Vernieri, Lorenzo Nicolè, Carmen Criscitiello, Florence Boissière-Michot, Séverine Guiu, Angélique Bobrie, Gaia Griguolo, Federica Miglietta, Andrea Vingiani, Riccardo Lobefaro, Beatrice Taurelli Salimbeni, Claudia Pinato, Francesca
JNCI: Journal of the National Cancer Institute.2024; 116(12): 1914. CrossRef
Trends in the incidence and survival of women with hormone receptor-positive breast cancer from 1990 to 2019: a large population-based analysis
Hongbo Huang, Tingting Wei, Aijie Zhang, Heng Zhang, Lingquan Kong, Yunhai Li, Fan Li
Scientific Reports.2024;[Epub] CrossRef
The “lows”: Update on ER-low and HER2-low breast cancer
Nicola Fusco, Giuseppe Viale
The Breast.2024; 78: 103831. CrossRef
Estrogenized HSA induced high-affinity autoantibodies in breast cancer - Novel biomarker for early detection
Subuhi Sherwani, Mohd Wajid Ali Khan, Wahid Ali Khan, Saravanan Rajendrasozhan, Khalid Al-Motair, Hamda Khan, Saheem Ahmad
Frontiers in Oncology.2024;[Epub] CrossRef
Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review)
Juyeon Kim, Hyobin Bang, Cheyun Seong, Eun-Sook Kim, Sun Kim
Oncology Letters.2024;[Epub] CrossRef
Impact of prolactin treatment on enhancing the cellular responses of MCF7 breast cancer cells to tamoxifen treatment
Anwar Shams
Discover Oncology.2024;[Epub] CrossRef
Concomitant Use of Proton Pump Inhibitors and CDK4/6 Inhibitors in Metastatic Hormone-Positive Breast Cancer: A Real-World Cohort Study
Ogur Karhan, Serdar İleri, Zuhat Urakçı, Hayati Arvas, Delyadıl Karakaş Kılıç, Yasin Sezgin, Berrak Merit Erçek, Sezai Tunç
Oncology.2024; 103(6): 498. CrossRef
Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL
Xujuan Zhang, Pengxiang Zhao, Mingshen Ma, Hao Wu, Rui Liu, Ziyi Liu, Zisong Cai, Mengyu Liu, Fei Xie, Xuemei Ma
Frontiers in Medicine.2023;[Epub] CrossRef
Assessment of breast cytoarchitecture and its associated axillary lymph node status under normal and pathological conditions in Egyptian women
Omnia Mansour, Amani Kazem, Abeer El Wakil
Tissue and Cell.2023; 85: 102244. CrossRef
Estrogen-Receptor-Low-Positive Breast Cancer: Pathological and Clinical Perspectives
Christina Panagiotis Malainou, Nikolina Stachika, Aikaterini Konstantina Damianou, Aristotelis Anastopoulos, Ioanna Ploumaki, Efthymios Triantafyllou, Konstantinos Drougkas, Georgia Gomatou, Elias Kotteas
Current Oncology.2023; 30(11): 9734. CrossRef

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Endocrine cancer

Expression of Estrogen and Progesterone Receptors in Papillary Thyroid Carcinoma in Korea: Hwa Young Ahn, Ra-Yeong Song, Hye Shin Ahn, Hee Sung Kim; Cancer Res Treat. 2021;53(4):1204-1212. Published online February 10, 2021; DOI: https://doi.org/10.4143/crt.2020.1201

Abstract PDF PubReader ePub

Purpose
The aim of this study was to examine the rate of expression of estrogen receptor α (ERα) and β1 (ERβ1), progesterone receptor (PR), and rate of overexpression of epidermal growth factor receptor (EGFR) in a relatively large cohort of patients with papillary thyroid carcinoma (PTC). We also aimed to examine whether each receptor influenced clinicopathological characteristics and prognosis of PTC.
Materials and Methods
We made a microarray of paraffin-embedded PTC surgical tissues from 436 patients. We compared the results of the immunohistochemical staining for each hormone receptor with clinicopathological characteristics.
Results
The positive expression rate of hormonal receptors was 40.4% for ERα, 83.7% for ERβ1, and 71.3% for PR in patients with PTC. Overexpression of EGFR was shown in 19.3% of patients with PTC. The age was lower (44.6±12.1 years vs. 47.1±12.5 years, p=0.040) and tumor smaller (0.96±0.69 cm vs. 1.13±0.82 cm, p=0.020) in the ERα positive group, which also showed higher PR positivity (80.7% vs. 65.0%, p < 0.001) and overexpression of EGFR (27.3% vs. 13.8%, p < 0.001). However, neither the positivity of hormone receptors nor overexpression of EGFR affected the recurrence of PTC.
Conclusion
In conclusion, most (94.6%) patients with PTC were found to exhibit positive expression for ERs or PR. We also found that neither the positive expression of hormone receptors nor overexpression of EGFR were associated with the recurrence of PTC.

Citations

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The epidemiology of female thyroid cancer and its life-stage trends: A global study of regional disparities
Pei-Pei Li, Fen-Fen Li, Bing-Yu Liang, Yan-Xun Han, Yu-Chen Liu, Ye-Hai Liu, Mao-Yu Jiang
Journal of the National Medical Association.2026; 118(2): 239. CrossRef
Research progress on estrogen and estrogen receptors in the occurrence and progression of autoimmune thyroid diseases
Jiewen Xie, Jie Wang, Xuejiao Cui
Autoimmunity Reviews.2025; 24(6): 103803. CrossRef
Multi-disease transcriptomic analysis of sex hormone genes reveals a novel prognostic model for thyroid cancer with breast cancer correlations
Lixue Qiao, Hao Li, Keyu Yin, Runsheng Ma, Yifei Zhang, Yue Guo, Detao Yin
Frontiers in Oncology.2025;[Epub] CrossRef
Estrogen Receptors as Key Factors in Carcinogenesis
Oliwia Gruszka, Magdalena Jurzak, Ilona Anna Bednarek
Biomedicines.2025; 13(11): 2620. CrossRef
Expression Pattern of Oestrogen Receptor in Follicular Thyroid Cancers: A 23 Years Retrospective Multicentre Study in Jos Metropolis, North-Central, Nigeria
Samuel Kelechi Richard, Barka Vandi Kwaghe, Nwadiokwu John Ifeanyi, Abdulrazaq Ajanaku Jimoh
Nigerian Postgraduate Medical Journal.2025; 32(4): 315. CrossRef
Struma Ovarii during Pregnancy
Gabriela Dumachița-Șargu, Răzvan Socolov, Teodora Ana Balan, Dumitru Gafițanu, Mona Akad, Raluca Anca Balan
Diagnostics.2024; 14(11): 1172. CrossRef
Serum sex hormones correlate with pathological features of papillary thyroid cancer
Fa-Zhan Xu, Lu-Lu Zheng, Ke-Hao Chen, Ru Wang, Dan-Dan Yi, Chao-Yu Jiang, Zhi-Jian Liu, Xian-Biao SHI, Jian-Feng Sang
Endocrine.2023; 84(1): 148. CrossRef
Diagnostic and Prognostic Impact of Progesterone Receptor Immunohistochemistry: A Study Evaluating More Than 16,000 Tumors
Florian Viehweger, Lisa-Marie Tinger, David Dum, Natalia Gorbokon, Anne Menz, Ria Uhlig, Franziska Büscheck, Andreas M. Luebke, Claudia Hube-Magg, Andrea Hinsch, Doris Höflmayer, Christoph Fraune, Patrick Lebok, Sören Weidemann, Maximilian Lennartz, Frank
Analytical Cellular Pathology.2022; 2022: 1. CrossRef
Case report: Lymph node metastases of breast cancer and thyroid cancer encountered in axilla
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Frontiers in Oncology.2022;[Epub] CrossRef

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Omitting Adjuvant Radiotherapy for Hormone Receptor‒Positive Early-Stage Breast Cancer in Old Age: A Propensity Score Matched SEER Analysis: Yi-Jun Kim, Kyung Hwan Shin, Kyubo Kim; Cancer Res Treat. 2019;51(1):326-336. Published online May 10, 2018; DOI: https://doi.org/10.4143/crt.2018.163

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the non-inferiority of omitting radiotherapy (RT) after breast-conserving surgery (BCS) for hormone receptor (HR)‒positive T1N0 breast cancer in elderly women.
Materials and Methods
From 2004 to 2014, HR-positive T1N0 breast cancer patients aged 50 years or older and receiving BCS were retrieved from the Surveillance, Epidemiology, and End Results 18 database. After propensity score matching between the no-RT and RT groups, univariate and multivariate analyses were performed. Identified prognostic factors were used to stratify the risk groups. In each risk group, 10-year cancer-specific survival (CSS) rates were compared between the no-RT and RT groups.
Results
After propensity score matching, the numbers of patients in the no-RT and RT groups were both 18,586. For patients who satisfied both a tumor size of 1-10 mm and a tumor grade of 1-2, omitting RT did not decrease the CSS rate at any age group, ranging from ≥ 50 to ≥ 85 years; for patients aged ≥ 50 years, the 10-year CSS rates in the no-RT and RT groups were 97.2% and 96.8%, respectively (adjusted hazard ratio, 0.862; p=0.312). However, for patients with a tumor size of 11-20 mm or tumor grade of 3-4, RT significantly increased the CSS rate irrespective of age.
Conclusion
RT after BCS for HR-positive T1N0 breast cancer in elderly women might be omitted without causing a decrease in the CSS rate, but only in patients who satisfy both a small tumor size (≤ 10 mm) and low tumor grade (1-2).

Citations

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Meta-Analysis of Different Surgical Methods for Breast Cancer Patients
Xiaoshu Zhao, Xunan Wei, Qing Shen, Xuanhong Zhou
International Journal of Pharmacology.2024; 20(5): 892. CrossRef
Radiotherapy is recommended for hormone receptor-negative older breast cancer patients after breast conserving surgery
Yaxiong Liu, Jinsong Li, Honghui Li, Gongyin Zhang, Changwang Li, Changlong Wei, Jinsheng Zeng
Scientific Reports.2024;[Epub] CrossRef
Comparison of breast‐conserving surgery without radiotherapy and mastectomy in the treatment of elderly patients with early breast cancer: A PSM and SEER database study
Baiyang Fu, Xi Chen, Wenlong Liang, Yao Wang, Yuan Yao, Jianguo Zhang
Cancer Medicine.2023; 12(14): 15229. CrossRef
Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting
Cynthia Aristei, Yasemin Bölükbaşı, Orit Kaidar-Person, Raphael Pfeffer, Meritxell Arenas, Liesbeth J. Boersma, Antonella Ciabattoni, Charlotte E. Coles, Pierfrancesco Franco, Marco Krengli, Maria Cristina Leonardi, Fabio Marazzi, Valeria Masiello, Icro M
Critical Reviews in Oncology/Hematology.2022; 177: 103774. CrossRef
Research on the cutoff tumor size of omitting radiotherapy for BCSS after breast conserving surgery in women aged 65 years or oder with low-risk invasive breast carcinoma: Results based on the SEER database
Zejian Yang, Kunlong Li, Pei Qiu, Yifei Ma, Bin Wang, Yu Yan, Du Meng, Chen Feng, Yu Ren, Yijun Li, Pingping Li, Can Zhou
The Breast.2021; 60: 287. CrossRef
Effectiveness of radiotherapy after breast-conserving surgery in older patients with T1-2N0 breast cancer
Anna Z. de Boer, Esther Bastiaannet, Nienke A. de Glas, Perla J. Marang-van de Mheen, Olaf M. Dekkers, Sabine Siesling, Linda de Munck, Kelly M. de Ligt, Johanneke E. A. Portielje, Gerrit Jan Liefers
Breast Cancer Research and Treatment.2019; 178(3): 637. CrossRef

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Laminin Modulates the Stem Cell Population in LM05-E Murine Breast Cancer Cells through the Activation of the MAPK/ERK Pathway: Damián E. Berardi, Diego Raffo, Laura B. Todaro, Marina Simian; Cancer Res Treat. 2017;49(4):869-879. Published online December 6, 2016; DOI: https://doi.org/10.4143/crt.2016.378

Abstract PDF PubReader ePub

Purpose
We investigated the effects of laminin on the fraction of cells with self-renewing capacity in the estrogen-dependent, tamoxifen-sensitive LM05-E breast cancer cell line. We also determined whether laminin affected the response to tamoxifen.
Materials and Methods
The LM05-E breast cancer cell line was used as a model for all experiments. Aldehyde dehydrogenase (ALDH) activity, clonogenic and mammosphere assays were performed to measure the effects of laminin on modulation of the stem cell subpopulation. Pluripotent gene expression was analyzed by reverse transcriptase–polymerase chain reaction. The involvement of the mitogen-activated protein kinase (MAPK)/ERK pathway was determined using specific inhibitors. The effects of laminin on the response to tamoxifenwere determined and the involvement of α6 integrin was investigated.
Results
We found that pretreatment with laminin leads to a decrease in cells with the ability to form mammospheres that was accompanied by a decrease in ALDH activity. Moreover, exposure of mammospheres to laminin reduced the capacity to form secondary mammospheres and decreased the expression of Sox-2, Nanog, and Oct-4. We previously reported that 4-OH-tamoxifen leads to an increase in the expression of these genes in LM05-E cells. Treatment with signaling pathway inhibitors revealed that the MAPK/ERK pathway mediates the effects of laminin. Finally, laminin induced tamoxifen resistance in LM05-E cells through α6 integrin.
Conclusion
Our results suggest that the final number of cells with self-renewing capacity in estrogen-dependent breast tumors may result from the combined effects of endocrine treatment and microenvironmental cues.

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Prognostic Role of Interleukin-6, Interleukin-8, and Leptin Levels According to Breast Cancer Subtype: Young Ae Cho, Mi-Kyung Sung, Jee-Young Yeon, Jungsil Ro, Jeongseon Kim; Cancer Res Treat. 2013;45(3):210-219. Published online September 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.3.210

Abstract PDF PubReader ePub

PURPOSE
Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes.
MATERIALS AND METHODS
This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method.
RESULTS
Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2- tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)+/progesterone receptor (PR)+ tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2- tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER+/PR+ tumors (p=0.022).
CONCLUSION
We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.

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Implications of Bone-Only Metastases in Breast Cancer: Favorable Preference with Excellent Outcomes of Hormone Receptor Positive Breast Cancer: Su Jin Lee, Silvia Park, Hee Kyung Ahn, Jun Ho Yi, Eun Yoon Cho, Jong Mu Sun, Jeong Eon Lee, Seok Jin Nam, Jung-Hyun Yang, Yeon Hee Park, Jin Seok Ahn, Young-Hyuck Im; Cancer Res Treat. 2011;43(2):89-95. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.89

Abstract PDF PubReader ePub

PURPOSE
The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis.
MATERIALS AND METHODS
Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases.
RESULTS
The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077).
CONCLUSION
Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'

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Mohamed K. Abdelhakiem, Candice Johnstone, Carmen Bergom, Adam Currey, Jared R. Robbins
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Iain R. Macpherson, Caroline Bray, Carol Hopkins, Rosemary A. Hannon, Liz-Anne Lewsley, Diana M. Ritchie, Peter Canney
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D.K. Woolf, A.R. Padhani, A. Makris
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The Relationship between Expression of the Sodium/iodide Symporter Gene and the Status of Hormonal Receptors in Human Breast Cancer Tissue: Hyun Jung Oh, June-Key Chung, Joo Hyun Kang, Won Jun Kang, Dong Young Noh, In Ae Park, Jae Min Jeong, Dong Soo Lee, Myung Chul Lee; Cancer Res Treat. 2005;37(4):247-250. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.247

Abstract PDF PubReader ePub

Purpose

It has been reported that the sodium/iodide symporter (NIS) gene is expressed in several breast cancer tissues, suggesting the possibility of radionuclide imaging and therapy. However, the regulatory mechanism of NIS gene expression in breast cancer is not yet understood. To assess the relationship between the hormonal status and the NIS expression in breast cancer tissue, we investigated the NIS expression and correlated it to the expression of the thyrotropin receptor (thyroid stimulating hormone receptor, TSH-R), the estrogen receptor (ER) and the progesterone receptor (PR) in human breast cancer tissues.

Materials and Methods

Breast cancer tissues were obtained from 44 patients. Pathological examination showed 2 cases of Grade I, 17 of Grade II, 22 of Grade III, and 3 of unknown grade. We measured the expression of NIS and TSH-R genes by using RT-PCR and we measured the status of ER and PR by using immunohistochemistry.

Results

The NIS gene was expressed in 15 (34%) of the 44 breast cancer tissues. The NIS gene was expressed in 32% of the cases with TSH-R gene expression. The NIS gene was expressed in 40% of the breast cancer tissues with a positive PR and in 31% with a negative PR (p>0.05). It was positive for PR in 18% of the cases and negative for PR in 39% of the cases (p>0.05).

Conclusion

The NIS gene is expressed in approximately one-third of the human breast cancer tissues. Its expression was not related to the presence of the TSH-R gene or hormonal receptors, ER and PR.

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Benign thyroid disease and the risk of breast cancer: An updated systematic review and meta-analysis
Mingyue Han, Yao Wang, Yuanhui Jin, Xue Zhao, Haiying Cui, Guixia Wang, Xiaokun Gang
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Links between Breast and Thyroid Cancer: Hormones, Genetic Susceptibility and Medical Interventions
Man Lu, Hanqing Liu, Bilian Zheng, Shengrong Sun, Chuang Chen
Cancers.2022; 14(20): 5117. CrossRef
Competitive Endogenous Role of the LINC00511/miR-185-3p Axis and miR-301a-3p From Liquid Biopsy as Molecular Markers for Breast Cancer Diagnosis
Marwa M. Mahmoud, Eman F. Sanad, Reham A.A. Elshimy, Nadia M. Hamdy
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The correlation between breast cancer and urinary iodine excretion levels
Fatma Umit Malya, Huseyin Kadioglu, Mustafa Hasbahceci, Kemal Dolay, Mehmet Guzel, Yeliz Emine Ersoy
Journal of International Medical Research.2018; 46(2): 687. CrossRef
Different expression of sodium–iodide importer (NIS) between lactating breast and thyroid tissues may be due to structural difference of thyroid-stimulating hormone receptor (TSHR)
X.-Z. Shi, L. Xue, X. Jin, P. Xu, S. Jia, H.-M. Shen
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Is there an association between thyroid function abnormalities and breast cancer?
Anna Angelousi, Evanthia Diamanti-Kandarakis, Evangelia Zapanti, Afroditi Nonni, Eftuxios Ktenas, Aimilia Mantzou, Konstantinos Kontzoglou, Grigorios Kouraklis
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Iodide transport and breast cancer
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The prognosis and treatment of primary thyroid cancer occurred in breast cancer patients: comparison with ordinary thyroid cancer
Chang Min Park, Young Don Lee, Eun Mee Oh, Kwan-Il Kim, Heung Kyu Park, Kwang-Pil Ko, Yoo Seung Chung
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Sodium iodide symporter (NIS) in extrathyroidal malignancies: focus on breast and urological cancer
Salvatore Micali, Stefania Bulotta, Cinzia Puppin, Angelo Territo, Michele Navarra, Giampaolo Bianchi, Giuseppe Damante, Sebastiano Filetti, Diego Russo
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TSH receptor antibodies have predictive value for breast cancer – retrospective analysis
Paweł Szychta, Wojciech Szychta, Adam Gesing, Andrzej Lewiński, Małgorzata Karbownik-Lewińska
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Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer
Sushmita Chatterjee, Renu Malhotra, Frency Varghese, Amirali B. Bukhari, Asawari Patil, Ashwini Budrukkar, Vani Parmar, Sudeep Gupta, Abhijit De, Pranela Rameshwar
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Sasha J Beyer, Xiaoli Zhang, Rafael E Jimenez, Mei-Ling T Lee, Andrea L Richardson, Kun Huang, Sissy M Jhiang
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Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?
S. J. Beyer, R. E. Jimenez, C. L. Shapiro, J. Y. Cho, S. M. Jhiang
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Expression of Cyclooxygenase-2 in Human Breast Carcinoma: Relevance to Tumor Angiogenesis and Expression of Estrogen Receptor: Haeng Ji Kang, Gu Gong, Se Jin Jang, Pa Jong Jung, Chan Kum Park; Cancer Res Treat. 2001;33(4):286-295. Published online August 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.4.286

Abstract PDF

PURPOSE
This study investigates the COX-2 expression in human primary breast carcinomas and its relationship with both angiogenesis and the expression of estrogen receptor.
MATERIALS AND METHODS
COX-2 expression, angiogenesis, and estrogen receptor expression were examined by immunohistochemical methods in 167 human breast carcinomas by using monoclonal antibodies against COX-2, CD34, and estrogen receptor protein.
RESULTS
Although COX-2 was expressed in 77.8% of the breast carcinomas (130/167) regardless of histological types, it was not detected at all in benign epithelial cells. Interestingly, COX-2 expression was found to be significantly correlated with tumor angiogenesis (p=0.004), but not with estrogen receptor and other histopathologic parameters.
CONCLUSION
The results suggest that COX-2 expression occurs frequently in breast tissue during transformation of benign epithelial cells to malignant cells regardless of the estrogen receptor status. COX-2 expression may play a role in tumor angiogenesis that is responsible for tumor growth and metastasis.

Citations

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Alexandra Moisand, Mathilde Madéry, Thomas Boyer, Charlotte Domblides, Céline Blaye, Nicolas Larmonier
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Antonio Carlos de Freitas, Eliane Campos Coimbra, Maria da Conceição Gomes Leitão
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Clinicopathologic Implications of the Epidermal Growth Factor Receptor, Cyclooxygenase 2 Expression, and Human Papillomavirus Status in Squamous Cell Carcinoma of the Uterine Cervix in the Elderly
Giovanna Giordano, Tiziana D’Adda, Barbara Dal Bello, Francesca Brigati, Alessandra Bersiga, Nicoletta Campanini, Roberto Berretta, Alba Rocco, Carla Merisio
International Journal of Gynecological Cancer.2011; 21(2): 337. CrossRef
Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors
Eunmi Nam, Soon Nam Lee, Seock-Ah Im, Do-Yeun Kim, Kyoung Eun Lee, Sun Hee Sung
Cancer Research and Treatment.2005; 37(3): 165. CrossRef
Coexpression of cyclooxygenase-2 and thymidine phosphorylase as a prognostic indicator in patients with FIGO stage IIB squamous cell carcinoma of uterine cervix treated with radiotherapy and concurrent chemotherapy
Hongryull Pyo, Yong Bae Kim, Nam Hoon Cho, Chang Ok Suh, Tchan Kyu Park, Yeon Sook Yun, Gwi Eon Kim
International Journal of Radiation Oncology*Biology*Physics.2005; 62(3): 725. CrossRef
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Clinical Value of Cyclooxygenase-2 Expression in Human Breast Carcinoma
Jin-Hee Ahn, Sung-Bae Kim, Sei-Hyun Ahn, Gyung-Yub Gong, Myung-Ju Ahn, Yoon-Koo Kang, Jung-Shin Lee, Woo Kun Kim
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Jong-Ho Won
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Kyubo Kim, Hong-Gyun Wu, Suk Won Park, Chong Jai Kim, Charn Il Park
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Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix
Gwi Eon Kim, Yong Bae Kim, Nam Hoon Cho, Hyun-Cheol Chung, Hong Ryull Pyo, Jong Doo Lee, Tchan Kyu Park, Woong Sub Koom, Mison Chun, Chang Ok Suh
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Yong Bae Kim, Gwi Eon Kim, Nam Hoon Cho, Hong Ryull Pyo, Su Jung Shim, Sei Kyung Chang, Hee Chul Park, Chang Ok Suh, Tchan Kyu Park, Byung Soo Kim
Cancer.2002; 95(3): 531. CrossRef

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The Prognostic Value of Epidermal Growth Factor Receptor in Primary Breast Cancer: Bong Geun Park, Sung Jae Cha, Sung Joon Park; J Korean Cancer Assoc. 1998;30(4):711-718.

Abstract PDF: PURPOSE
The objective of this study was to ascertain the relationship between epidermal growth factor receptor(EGFR) status and estrogen receptor(ER) and other prognostic factors in primary human breast cancer patients. We tried to evaluate the value of EGFR as a prognostic factor.
MATERIALS AND METHODS
EGFR and ER were measured by immunohistochemical staining. It was performed on section from paraffin blocks of 60 primary breast cancer patients who underwent mastectomy at Chung-Ang University Hospital. And we evaluate the relationship between EGFR and ER and other prognostic factors.
RESULTS
In 20 of 60 patients(33.3%), the staining was positive for the expression of EGFR. Of the 60 patients, 6 were both positive for EGFR and ER, 25 were both negative, 14 were EGFR positive and ER negative, 15 were EGFR negative and ER positive. Between EGFR and estrogen receptor(ER) status, previously known clear inverse relationship was not observed in our study. The EGFR status was not correlated with axillary lymph node involvement, histologic type, and histologic grading. But it was correlated with tumor size(p=0.049), and there was a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors(p=0.078).
CONCLUSION
EGFR status may be valuable as a prognostic factor in determining the prognosis of breast cancer. However, the study of more cases will be needed for the significance of the information about the EGFR as an independent prognostic factor.

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Restoration of Hormone Dependency in Estrogen Receptor - Lipofected MDA-MB-231 Human Breast Cancer Cells: Young Jin Suh, Jae Hee Chang, Chung Soo Chun; J Korean Cancer Assoc. 1999;31(3):473-482.

Abstract PDF: PURPOSE
The loss of estrogen and progesterone receptors appeats to be associated with a progression to less differentiated and hormone-independent tumors. The gain of hormone independency over time even in estrogen receptor-positive tumors has become another obstacle to endocrine therapy for breast cancer. We tried to regain the hormone dependency in estrogen receptor-negative breast cancer cells by lipofecting estmgen receptor cDNA.
MATERIALS AND METHODS
The mutant human estrogen receptor cDNA (pSGS-HEO) was lipofected into estrogen receptor-negative human breast cancer cell line MDA-MB-231, in an attempt to restore their sensitivity to antiestrogen. Then the effects of 17p-estradiol and tamoxifen were studied by counting viable cell numbers after treating the lipofected cell line with either one or together.
RESULTS
Culture medium cantaining phenol red, a weak estrogen, has growth advantages compared with culture medium without it. In both culture conditions, cell growth was most profoundly inhibited in 4 days after lipofection with mutant human estrogen receptor cDNA, which was overcome after that day. Tamoxifen, as an antiestrogen, showed a growth inhibitory effect slightly stronger tban combined conditions of tamoxifen and 17- estradiol compared to estrogen-treated group and to control, and the inhibitory effect was lasted 4 days.
CONCLUSION
The temporary induction of estrogen receptor by lipofection with pSGS-HEO on estrogen receptor-negative human breast cancer cell line MDA-MB-231 showed negative growth control on these cells by tamoxifen, indicating that liposome-mediated estrogen receptor transfection may be used as a novel therapeutic strategy for hormane independent human breast cancers in the near future.

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A Study of Estrogen Receptors in Gastric Cancer: Young Jin Kim, Moon Oh Bae, Shin Kon Kim; J Korean Cancer Assoc. 1994;26(5):722-728.

Abstract PDF: Recently the presence of estrogen receptor(ER) has been demonstrated in some cases of cancer of the digestive tract such as stomach, large intestine, pancreas and the liver which are non-target organs of sex hormones. The authors studied ER in tumors from 95 gastric adenocarcinomas using immunohisto- chemical staining with monoclonal antibody. DNA ploidy using flow cytometry was also as- sessed in 75 cases of gastric carcinomas. ER positivity was 40 of 95(42.1%) gastric carcinomas. The tendency of receptor positivity increased with progression of tumor and lower differentiation. There was no positive relationship between ER positivity and sex, age, gross type, DNA ploidy and the level of carcinoem- bryonic antigen. The results of this study show that hormonal factors are involved in gastric carcinomas and that the cancers have endocrinic characteristics. The sturdies clarifying the rofe of hormones to cancer cells will be valuable in the design of hormonal therapy.

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Identification of Estrogen Receptor Gene in Breast Cancer: Young Jin Suh, In Chul Kim, Sang Seol Jung; J Korean Cancer Assoc. 1996;28(5):796-806.

Abstract PDF: Background
The initiation and progression of breast carcinoma are profoundly influenced by hormonal factors. Breast tumors that express the estrogen receptor (ER) are slower growing, associated with better long-term disease-free survival, and amenable to endocrine therapy with agents such as the antiestrogen. But only 60% of the ER-positive breast cancer patients respond to endocrine manipulation. In addition, many ER-positive cancers that initially respond to endocrine therapy ultimately progress to a more aggressive hormone-independent phenotype. Loss of estrogen receptor expression is an important means of hormone resistance, but the mechanisms involved are poorly understood. Materials & Method: We examined the ER by dextran-coated charcoal assay and the ER cDNA by reverse transcription-palymerase chain reaction in 19 primary breast cancers to determine if alterations of the gene are associated with the ER-negative status. Results: From this study, we could see the expression of the ER gene in all of the ER- positive specimens, but ER-negative group showed inconsistent results. Four out of 9 ER- negative specimens expressed ER gene. Three of these four were progesterone receptor-positive. Conclusion: This results suggest that ER expression may be determined at the transcription level and that genomic analysis of the ER may be more accurate than conventional ER assays in clinical setting.

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Obesity Related to Breast Cancer Risk by Hormonal Receptor Status: Keun Young Yoo, Sue Kyung Park, Daehee Kang; J Korean Cancer Assoc. 2000;32(5):962-971.

Abstract PDF: PURPOSE
A hospital-based case-control study was designed to assess whether obesity may differ in breast cancer risk according to the estrogen receptor (ER) or progesterone receptor (PR) status.
MATERIALS AND METHODS
Information on life-styles was obtained in a hospital-based cancer registry at the Aichi Cancer Center Hospital, Japan, 1988~1992. Newly diagnosed cases with breast cancer (n=1,154) and controls with no history of cancer (n=21,714) were selected. Body mass index with known and suspected risk factors for breast cancer was included simultaneously in the logistic regression model. Hypothesis tests for differences in odds ratios were done by Wald test based on the polytomous logistic regression models.
RESULTS
Both current weight and body mass index were significantly related to the risk of breast cancer; OR for body weight per 5 kg=1.11 (1.05~1.73), OR for body mass index per 10 kg/m2=1.54 (1.25~1.90). The risks of both body weight and body mass index, however, was not modified by ER, nor by PR.
CONCLUSION
This study strongly suggests that obesity may be associated with breast cancer risk. The possibility that obesity differs according to hormonal receptor status should be pursued in further studies.

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Relation Between Hormone Receptor (Enzyme-Immunoassay and Immunohistochemistry), Histologic Grade and Mammographic Findings in Patients with Primary Breast Cancer: Byung Chul Kang, Ki Keun Oh, Jae Keun Kim, Woo Hee Jung, Hy De Lee, Kyung Soon Song; J Korean Cancer Assoc. 1997;29(1):53-61.

Abstract PDF: PURPOSE
To evaluate the relationship between the hormone receptor status, histologic grade and, the film-mammographic findings in primary breast cancer.
MATERIALS AND METHODS
198 breast cancer patients with hormonal receptor assay were included in this study. Estrogen receptor (ER) and progesterone receptor (PR) were determined by immunohistochemical method and enzyme-immunoassay. And film-mammographic findings were evaluated to disclose the relationship among the three variables (film-mmamographic findings, histologic grade and hormonal receptor status). Film- mammographic findings of the breast cancer are classified as spiculation, increased parenchymal density, calcification and mass.
RESULTS
There is no correlation between estrogen receptor and histologic grade in 154 patients. Some correlation between estrogen receptor by enzyme-immunoassay and by immunohistochemistrical methods with 28 available data were observed (R=0.428). Among high estrogen receptor (ER) patients, there is a high possibility of spiculation or mass in mammography with 79 available data (Modified t-test, P<0.01).
CONCLUSION
Spiculation or/and mass of the mammography can be related to the high possibile factor of the positive estrogen receptor or high level of estrogen receptor in primary breast cancer.

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