Cancer Research and Treatment

Original Article

Breast cancer

Dural Metastasis in Breast Cancer: MRI-Based Morphological Subtypes and Their Clinical Implications: Sung Jun Ahn, Bio Joo, Mina Park, Hun Ho Park, Sang Hyun Suh, Sung Gwe Ahn, Jihwan Yoo; Cancer Res Treat. 2024;56(4):1105-1112. Published online March 19, 2024; DOI: https://doi.org/10.4143/crt.2024.138

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Purpose
This study aimed to investigate the clinical factors associated with breast cancer (BRCA) dural metastases (DMs), their impact on prognosis compared to brain parenchymal metastases (BPMs) alone, and differences between DM subtypes, aiming to inform clinical decisions.
Materials and Methods
We retrospectively analyzed 119 patients with BRCA with brain metastasis, including 91 patients with BPM alone and 28 patients with DM. Univariate and multivariate analyses were performed to compare the clinical characteristics between the two groups and within subtypes of DM. Overall survival after DM (OSDM) and the interval from DM to leptomeningeal carcinomatosis (LMC) were compared using Kaplan-Meier analysis.
Results
DM was notably linked with extracranial metastasis, luminal-like BRCA subtype (p=0.033), and skull metastases (p < 0.001). Multiple logistic regression revealed a strong association of DM with extracranial and skull metastases, but not with subtype or hormone receptor status. Patients with DM did not show survival differences compared with patients with BPM alone. In the subgroup analysis, nodular-type DM correlated with human epidermal growth factor receptor 2 status (p=0.044), whereas diffuse-type DM was significantly associated with a higher prevalence of the luminal-like subtype (p=0.048) and the presence of skull metastasis (p=0.002). Patients with diffuse DM did not exhibit a significant difference in OSDM but had a notably shorter interval from DM to LMC compared to those with nodular DM (p=0.049).
Conclusion
While the impact of DM on the overall prognosis of patients with BRCA is minimal, our findings underscore distinct characteristics and prognostic outcomes within DM subgroups.

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Small-cell neuroendocrine carcinoma of the cervix with leptomeningeal spread: A rare coincidence report and literature review
Mohammed A. Azab, Oday Atallah, Nour El-Gohary, Ahmed Hazim, Hamed Abdelma’aboud Mostafa
Surgical Neurology International.2024; 15: 310. CrossRef
Left homonymous hemianopia as an atypical manifestation of isolated pachymeningeal metastasis secondary to breast cancer: Case report and review of the literature
Aziz Ahizoune, Moad Belouad, Houda Alloussi, Mohamed Allaoui, Mohamed Hamid, Ahmed Bourazza
Radiology Case Reports.2024; 19(11): 5459. CrossRef

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Review Article

Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer: Eunice Yoojin Lee, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im; Cancer Res Treat. 2023;55(4):1065-1076. Published online October 5, 2023; DOI: https://doi.org/10.4143/crt.2023.846

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Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

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Breast Cancer and Tumor Microenvironment: The Crucial Role of Immune Cells
Tânia Moura, Paula Laranjeira, Olga Caramelo, Ana M. Gil, Artur Paiva
Current Oncology.2025; 32(3): 143. CrossRef
Metastasiertes hormonrezeptorpositives Mammakarzinom – die Qual der Wahl
Marion T. van Mackelenbergh, Michael Friedrich, Nicolai Maass
Die Gynäkologie.2025; 58(5): 306. CrossRef
Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions
Rohan Kalyan Rej, Joyeeta Roy, Srinivasa Rao Allu
Cancers.2024; 16(3): 552. CrossRef

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Original Articles

Breast cancer

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

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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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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
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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Elevated Expression of RIOK1 Is Correlated with Breast Cancer Hormone Receptor Status and Promotes Cancer Progression: Zhiqi Huang, Xingyu Li, Tian Xie, Changjiang Gu, Kan Ni, Qingqing Yin, Xiaolei Cao, Chunhui Zhang; Cancer Res Treat. 2020;52(4):1067-1083. Published online May 8, 2020; DOI: https://doi.org/10.4143/crt.2020.187

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Purpose
RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers—such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context.
Materials and Methods
We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1.
Results
We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)–negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression.
Conclusion
These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

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Establishment of a 5-gene risk model related to regulatory T cells for predicting gastric cancer prognosis
Gang Hu, Ningjie Sun, Jiansong Jiang, Xiansheng Chen
Cancer Cell International.2020;[Epub] CrossRef

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Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer in Korea: Seung Hoon Beom, Jisu Oh, Tae-Yong Kim, Kyung-Hun Lee, Yaewon Yang, Koung Jin Suh, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, Tae-You Kim, Dong-Young Noh, Seock-Ah Im; Cancer Res Treat. 2017;49(2):454-463. Published online August 23, 2016; DOI: https://doi.org/10.4143/crt.2016.259

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Purpose
Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients.
Materials and Methods
This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment historywere extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity.
Results
The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated.
Conclusion
Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

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Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis
Josee-Lyne Ethier, Danielle N. Desautels, Eitan Amir, Helen MacKay
Gynecologic Oncology.2017; 147(1): 158. CrossRef

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Expression of Gonadotropin-Releasing Hormone Receptor in Human Uterine Endometrial and Ovarian Tissues: Jin Woo Kim, Sung Eun Namkoong; J Korean Cancer Assoc. 1997;29(1):117-127.

Abstract PDF: PURPOSE
Gonadotropin-releasing hormone (Gn-RH) can cause regression of hormonedependent human tumors, including uterine endometrial and ovarian carcinomas. These effects were thought to be mediated through the inhibition of gonadotropic and steroid hormone from the hypothalamus. But, in addition to its classic hypophysiotropic action, Gn-RH might play a role as a modulator of activity in the brain and many peripheral organs. It has been reported that this analog has a direct inhibitory effect on the tumor and that the specific binding sites for Gn-RH were demonstrated in certain tumors responsive to Gn-RH. In support of a possible clinical use of Gn-RH analogs in the treatment of the endometrial and ovarian carcinomas, we tried to find out whether Gn-RH receptors are present on hormone dependent tumors.
MATERIALS AND METHODS
We have studied endometrial and ovarian tumor specimens and established uterine endometrial and ovarian carcinoma cell lines for the presence of Gn-RH receptor by the detection of its messenger ribonucleic acid (mRNA). We also compared the results obtained from tumor tissue specimens with the results from their corresponding normal tissues. Gn-RH receptor mRNA was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence.
RESULTS
Gn-RH receptor mRNA was detected in all normal endometrium and abnormally proliferative endometrium presenting dysfunctional bleeding, but not all in endometrial carcinomas (83%). Tumor stage and histologic grading had no relationship with receptor positivity. And, Gn-RH receptor mRNA was detected in less than 40% in normal myometrium and myomas. Gn-RH receptor expression was detected in same frequencies (86%) in normal ovarian tissues and ovarian carcinomas. Receptors were detected in a high proportion of the specimens from epithelial carcinomas (92%) and stromal tumors (100%) of the ovary. But, Gn-RH receptor was not detected in germ-cell derived tumors of the ovary. Established endometrial carcinoma (CUME-1) and epithelial ovarian carcinoma (CUMO-2) cell lines also demonstrated Gn-RH receptor mRNA, respectively.
CONCLUSIONS
The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of hormone-dependent normal tissues and their respective tumors, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in endometrial and ovarian malignancies.

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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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Significance of Hormaone Receptors and nm23 Protein Expression in Human Breast Cancer: Ki Hoon Jung, Eun Sook Lee, Won Jun Choi, Jeoung Won Bae, Young Chul Kim, Bum Hwan Koo, Chul Hwan Kim, In Sun Kim; J Korean Cancer Assoc. 1996;28(6):1010-1021.

Abstract PDF: The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines which have low and high metastatic potential, and located in the chromosome 17q22. This gene has known to be involved in metastasis of several cancers and its down-regulation usually associated with metastasis or disease progression in breast cancer. This study was designed to determine the significance of overexpression of the entimetastatic gene nm23 protein in human breast cancer and to compare it with established clinicopatholoaical prognostic factors such as the tumor size, number of involved lymph nodes, grade of differentiation, and hormone receptor status. 118 surgical specimens, which were obtained from breast cancer between July of 1989 and June of 1993 were used to evaluate nm23 protein expression using immunohistochemical staining. All patients were female. The nm23 protein expression was positive in 74 cases(63%) and was negative in 44 cases(37%). There was a significant inverse relationship between nm23 pratein overexpression and Bloom and Richardson histologic grade(p=0.023). Also overexpression of nm23 was significantly correlated with estrogen and progesterone receptor(p=0.031, 0.001) and with longer disease free survival and overall survival(p=0.0048, 0.0026). In conclusion, nm23 protein overexpression is one of good prognostic indicators independently in human breast cancer.

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