Cancer Research and Treatment

Radiation-Associated Heart Disease in Korean Women after Radiotherapy for Breast Cancer: Insights from the National Health Insurance Service Database: Jun-Hyuk Lee, Jimin Park, Tae Hyung Kim; Received February 28, 2025 Accepted June 9, 2025 Published online June 11, 2025; DOI: https://doi.org/10.4143/crt.2025.233 [Accepted]

Abstract PDF: Purpose
This study investigated the risk of radiation-associated heart disease (RAHD) in Korean women treated with radiotherapy (RT) for breast cancer (BC) using data from the National Health Insurance Service database.
Materials and Methods
A retrospective cohort analysis was conducted on 65,188 patients with BC treated with RT between 2009 and 2014 and 325,940 controls without BC or prior coronary artery disease (CAD), with 1:5 exact matching by age, type 2 diabetes mellitus, hypertension, and dyslipidemia status. CAD encompassed both incident events and fatal events. Competing risk analysis was conducted to estimate subdistribution hazard ratio (HR) with 95% confidence interval (CI) for CAD, setting mortality from non-CAD causes as a competing risk.
Results
During the mean 9.9 years of follow-up period, 3,852 (1.0%) CAD and 20,999 (5.4%) death from non-CAD causes were reported. Compared to controls, participants with BC who received RT had a significantly lower risk of CAD incidence. HR (95% CI) for CAD in the BC with RT group was 0.66 (0.60–0.73; p<0.001). On the other hand, HR (95% CI) for mortality from non-CAD causes was 3.57 (3.48–3.67; p<0.001).
Conclusion
In this large population-based cohort study, breast cancer patients who received RT did not show an increased incidence of CAD compared with the general population without breast cancer. Individual-level dosimetric data and longer follow-up are needed to clarify the independent risk.

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Secondary Cancer Risk in Breast Cancer with and without Radiotherapy: The Observational Health Data Sciences and Informatics (OHDSI) Cohort Study: Seok Kim, Dachung Boo, Sooyoung Yoo, Borham Kim, Kyubo Kim, Kwangsoo Kim, Eunhye Song, Junmo Kim, Hyun Gee Ryoo, Jin Chul Paeng, In Young Choi, SooJeong Ko, Ie Ryung Yoo, Rae Woong Park, Ho-Young Lee; Received October 8, 2024 Accepted May 25, 2025 Published online June 5, 2025; DOI: https://doi.org/10.4143/crt.2024.968 [Accepted]

Abstract PDF: Purpose
Radiotherapy is used to reduce the risk of breast cancer recurrence after surgery, but it is a potential cause of secondary cancer. We validated the risk of secondary cancer in primary breast cancer who received radiotherapy compared with those who did not from a matched cohort using a large-scale observational study of the Observational Health Data Sciences and Informatics (OHDSI) data network.
Materials and Methods
A retrospective comparative cohort study using propensity score-matched cohorts was performed using two Observational Medical Outcome Partnership common data model databases, from tertiary general hospitals in South Korea. Among female patients who underwent surgery after the diagnosis of breast cancer, the risk of secondary primary malignant occurrence after 1:1 matching was analyzed.
Results
Among 27,078 patients with breast cancer, there was no significant difference in the risk of secondary cancer following radiotherapy in 4,268 patients after 1:1 propensity-score matching. Further, there were no significant differences in the sensitivity analysis according to age, latency period, and number of radiation treatments.
Conclusion
There was no difference in the risk of secondary cancer in the patients diagnosed with breast cancer depending on whether or not radiotherapy was performed after surgery. In the future, it is necessary to analyze including data generated during cancer treatment.

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Gender Disparities in Breast Cancer Survival According to Clinical Treatment Score Post-5 Years (CTS5) Risk Stratification: Ke Liu, Zhen-Zhen Lu, Zhen-Yu He, San-Gang Wu; Received March 31, 2025 Accepted May 21, 2025 Published online May 27, 2025; DOI: https://doi.org/10.4143/crt.2025.361 [Accepted]

Abstract PDF: Purpose
The role of The Clinical Treatment Score post-5 years (CTS5) in male breast cancer (MBC) remains unclear. This study aimed to investigate the characteristics and prognosis of CTS5 between MBC and female breast cancer (FBC).
Materials and Methods
Patients diagnosed with human epidermal growth factor receptor 2 negative /estrogen receptor-positive breast cancer between 2010 and 2015 were identified from the SEER database. The chi-square test, Kaplan-Meier analysis, and multivariate Cox proportional hazard model were used for statistical analysis.
Results
This study included 169869 patients, comprising 168422 (99.1%) FBC and 1447 (0.9%) MBC patients. More MBC patients had intermediate risk (IR)/high risk (HR) disease compared to FBC patients (17.7% vs. 8.7%, p<0.001). MBC patients had an inferior overall survival (OS) but similar breast cancer-specific survival compared to those with FBC. Sensitivity analyses showed that gender was an independent prognostic factor associated with OS but not BCSS in both the low-risk (LR) and IR/HR cohorts. Those with MBC exhibited significantly worse OS (p<0.001) than FBC patients in both cohorts. In MBC patients, those with IR/HR disease had significantly worse OS (P<0.001) and BCSS (p<0.001) compared to those with LR disease. For FBC patients, the IR/HR group had also significantly worse OS (p<0.001) and BCSS (p<0.001) compared to the LR group.
Conclusion
Our findings highlight critical differences in clinical characteristics, treatment patterns, and outcomes between MBC and FBC, suggesting the need for gender-tailored approaches in breast cancer management.

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Comparative Study of Mastectomy Using Conventional Techniques, Multiport and Single-Port Robotic Surgical Systems: Jeea Lee, Jieon Go, Suk Jun Lee, Yonghan Kwon, Nam Hee Kim, Jee Ye Kim, Hyung Seok Park; Received January 31, 2025 Accepted May 6, 2025 Published online May 7, 2025; DOI: https://doi.org/10.4143/crt.2025.115 [Accepted]

Abstract PDF: Purpose
Oncologic and surgical outcomes of robot-assisted nipple-sparing mastectomy (RNSM) compared to conventional NSM (CNSM) is under investigation. This study compared the clinical outcomes of recurrence-free survival and postoperative complication after RNSM and CNSM.
Materials and Methods
We retrospectively reviewed data of 401 patients who underwent da Vinci Si/Xi/SP-assisted RNSM or CNSM with immediate reconstruction between November 2016 and November 2020 at a single institute. Oncological outcomes were collected until March 2022. Primary endpoints were long-term outcomes, such as local recurrence, distant metastasis, disease-free survival, overall survival, and postoperative complications, while secondary endpoints were pathology results, and oncological outcomes.
Results
Patients underwent RNSM (n=162) or CNSM (n=239). Of RNSM cases, 9 (5.6%) were performed using the da Vinci Si System, 96 (59.3%) using the da Vinci Xi System, and 57 (35.2%) using the da Vinci SP System. No significant difference in recurrence-free survival was found between the RNSM and CNSM group, and both groups had a median follow-up of 37 months. The recurrence rate in RNSM patients after a median follow-up of 24.5 months was 3.8%, compared with 5.9% in CNSM patients after a median follow-up of 42 months. No difference in recurrence was seen among RNSM patients with respect to surgical systems (multiport vs. SP, p =0.136). In addition, grade III postoperative complication rate was lower in patients with RNSM than in those with CNSM. Transfusion was only applied in 6.2% of patients.
Conclusion
Robot-assisted surgical systems can be safely used to perform NSM in patients with early breast cancer.

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Safety and Effectiveness of Eribulin in Patients with Advanced or Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes in Real-World Clinical Practice: A 6-Year Post-Marketing Surveillance Study in South Korea: Yee Soo Chae, Kyung A Kwon, Moon Hee Lee, Mi Sun Ahn, Kyung-Hun Lee, Su-Jin Koh, Joohyuk Sohn, Keon Uk Park, Min Young Kim, Youngji Pyo, Bo Young Kim, Kyung Hae Jung; Received November 27, 2024 Accepted April 26, 2025 Published online April 28, 2025; DOI: https://doi.org/10.4143/crt.2024.1142 [Accepted]

Abstract PDF: Purpose
This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes.
Materials and Methods
During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation.
Results
CRFs were collected from 64 investigators at 64 sites for 1079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 TEAEs were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9–11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months.
Conclusion
This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

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Adjuvant Chemotherapy in Breast Cancer After Neoadjuvant Therapy: Essential or Optional?: Di Zhang, Luo Yang, Yuan Zheng, Qi Zhou; Received December 31, 2024 Accepted April 20, 2025 Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1254 [Accepted]

Abstract PDF: Purpose
This study aimed to evaluate the impact of postoperative adjuvant chemotherapy (AC) on survival outcomes in breast cancer (BC) patients who have already undergone neoadjuvant chemotherapy (NAC) followed by surgery.
Materials and Methods
Data from a population-based cohort (2010-2020) were analyzed for BC patients treated with NAC and surgery. Univariate and multivariate Cox regression identified prognostic factors for overall survival (OS), and a nomogram was developed and validated. Personalized scores from the nomogram were used for risk stratification to assess the effect of postoperative AC.
Results
A total of 15,921 BC patients were analyzed, with 11,144 in the training cohort and 4,777 in the validation cohort. The key prognostic indicators for OS included age, race, marital status, histological grade, breast cancer subtype, T stage, N stage, type of surgery, and response to NAC (all p<0.05). The nomogram effectively predicted individualized OS rates and stratified patients into various risk categories. Postoperative AC was found to significantly enhance OS in the high-risk subgroup (p=0.011 in the training cohort, p=0.012 in the overall population). However, for the low-risk subgroup, there was no significant survival benefit from postoperative AC (p=0.130 for the training cohort, p=0.588 for the overall population), suggesting that some patients might safely forgo unnecessary postoperative AC.
Conclusion
This study efficiently differentiates between varying levels of risk, enabling clinicians to identify patients unlikely to benefit from postoperative AC and thus reduce the likelihood of overtreatment.

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Differences in Responses to Neoadjuvant Anti-HER2 Therapy between HER2 2+ISH+ and HER2 3+ in HER2-Positive Breast Cancer: Lingjun Ma, Ran Zheng, Lingyun Xu, Ying Zhu, Hong Yin, Xiaoqing Zhang, Rong Deng, Jue Wang, Xiaoming Zha; Received December 12, 2024 Accepted April 18, 2025 Published online April 21, 2025; DOI: https://doi.org/10.4143/crt.2024.1200 [Accepted]

Abstract PDF: Purpose
Dual anti-HER2 drugs has become the standard regimen for neoadjuvant systematic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels
Materials and Methods
A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 IHC classes (HER2 2+ISH+ or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro.
Results
Compared to HER2 3+ subgroup, the HER2 2+ISH+ group had a higher proportion of HR+ status (48.7% vs. 76.1%; p < 0.001), more HER2 protein loss after NST, lower pCR rate (46.07% vs. 16.24%; p < 0.001), and tended to have worse DFS. In HER2 2+ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%; p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+ISH+ cell lines, however, T-Dxd drugs had a satisfactory effect.
Conclusion
Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+ISH+ group to be a distinct subtype and defined it as the HER2-moderate-positive (HER2-mod) subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with ADC drugs as potential options.

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The Impact of Obesity on Treatment Outcomes in Patients with Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Receiving CDK 4/6 Inhibitors: Yoo Bin Jung, Hee Kyung Ahn, Hyun-Young Shin, Ji Hyung Hong, Chai Hong Rim; Received January 25, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.110 [Accepted]

Abstract PDF: Purpose
Guidelines from the aromatase inhibitor era for early breast cancer (EBC) treatment recommend maintaining a body mass index (BMI) below 25. In the current era of CDK 4/6 inhibitors, now standard in metastatic breast cancer (MBC), limited data exist on treatment outcomes in obese patients. This study investigates how adiposity affects the treatment outcome of CDK 4/6 inhibitors in patients with hormone receptor (HR)-positive, HER2-negative MBC.
Materials and Methods
We searched PubMed, MEDLINE, and Embase databases, assessing efficacy outcomes such as progression-free survival (PFS) based on obesity markers, including BMI and visceral adipose tissue (VAT) index.
Results
Twelve studies were reviewed, with seven studies and 1,812 patients included in a pooled meta-analysis. Among patients with BMI ≥25, modest improvement in PFS was observed, with a pooled hazard ratio (HR) of 0.944 (95% CI, 0.909-0.980; p = 0.003). Besides, add-on analysis using VAT to define obesity revealed a notable PFS improvement, with a pooled HR of 0.452 (95% CI, 0.256-0.798; p = 0.006).
Conclusion
While BMI-defined obesity showed slight PFS improvement with CDK 4/6 inhibitors and endocrine therapy, using VAT to define obesity revealed significant PFS gains. This highlights the need for further research on biomarker to clarify the role of adiposity in MBC, which may differ from its impact in EBC.

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Spatial Transcriptomic Landscape of Brain Metastases from Triple-Negative Breast Cancer: Comparison of Primary Tumor and Brain Metastases Using Spatial Analysis: Jihwan Yoo, Inho Park, Hyun Jung Kim, Hun Ho Park, Sora Lee, Jee Hung Kim, Yoon Jin Cha; Received January 8, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.033 [Accepted]

Abstract PDF: Purpose
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets.
Materials and Method
Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM.
Results
Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D.
Conclusion
This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

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Comparison of Long-term Oncological Outcome of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope) in Breast Cancer Patients Following Neoadjuvant Chemotherapy: Jinyoung Byeon, Changjin Lim, Eunhye Kang, Ji-Jung Jung, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han; Received December 30, 2024 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2024.1253 [Accepted]

Abstract PDF: Purpose
Sentinel lymph node biopsy (SLNB) using dye and isotope (DUAL) is recommended over the dye-only (DYE) method after neoadjuvant chemotherapy (NCT) due to potentially lower false-negative rates. However, the long-term outcome of either method is unclear. We aimed to compare the long-term oncological outcomes of DYE versus DUAL SLNB methods in patients who received NCT.
Materials and Methods
In this retrospective cohort study, 893 patients who underwent SLNB following NCT and had pathologically negative lymph nodes were included. After propensity score matching for cT, cN, and pT stages, 280 patients were in the DYE group and 560 in the DUAL group. Indigo carmine was used for dye and Tc-99m antimony trisulfate for isotope mapping.
Results
Median follow-up was 75.6 months in the DYE group and 83.0 months in the DUAL group. Mean (±SD) number of harvested sentinel nodes was 6.7 (±3.4) and 6.7 (±3.8) in the DYE and DUAL groups (p=0.51). Five-year distant metastasis-free survival was 95.2% in DYE group and 93.3% in DUAL group (HR=1.45; 95% CI, 0.82–2.57; p=0.19). Disease-free survival (HR=0.97; 95% CI, 0.69–1.50; p=0.91) and overall survival (HR=0.98; 95% CI, 0.56–1.69; p=0.95) were not significantly different. Axillary recurrence rate was 1.8% and 2.5% in DYE and DUAL groups(p=0.64).
Conclusion
Long-term oncological outcomes did not significantly differ between DYE and DUAL SLNB methods. The dye-only method can be safely recommended for breast cancer patients who received NCT.

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Ten-Year Follow-Up Clinical Outcomes and the Role of Adjuvant Chemotherapy in HER2-Positive Patients with Microinvasive Breast Cancer: Yeokyeong Shin, Soo-Young Lee, Hyehyun Jeong, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, BeomSeok Ko, Ji Sun Kim, Il Yong Chung, Hee Jin Lee, Gyungyub Gong, Sae Byul Lee, Jae Ho Jeong; Received November 22, 2024 Accepted March 3, 2025 Published online March 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1120 [Accepted]

Abstract PDF: Purpose
Although HER2 positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy.
Materials and Methods
The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed.
Results
The analysis included 799 female patients. The median age was 51 years (range, 23–79), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n = 238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% CI, 114.0–127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1–93.3), 97.5% (95% CI, 96.4–98.7), and 98.8% (95% CI, 98.0–99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease.
Conclusion
A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

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Association Between Benign Thyroid Disorders and Breast Cancer Risk in Korean Women: Boyoung Park, Thi Xuan Mai Tran; Received August 16, 2024 Accepted February 25, 2025 Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.787 [Accepted]

Abstract PDF: Purpose
This study aimed to investigate the potential association between thyroid disorders and breast cancer (BC) risk in a cohort of Korean women.
Materials and Methods
Data for this retrospective cohort study were obtained from the Korean National Health Insurance database, including all women aged ≥ 40 who underwent BC screening from 2009 to 2010 in Korea. Thyroid disorders were identified using medical records from 2009 to 2010 and extracted using the ICD-10 codes for thyroid nodules, hypothyroidism, and hyperthyroidism. BC cases were defined using the ICD-10 codes and tracked until December 2021. A Cox regression model was used to evaluate the association between thyroid disorders and the risk of BC. Additionally, we evaluated the association between well-known risk factors of BC and thyroid disorders using logistic regression analysis.
Results
Among 5,051,633 women, the mean (standard deviation) age was 55.2 (10.7) years, and the median follow-up was 11.6 years, with 87,784 BC cases recorded. The proportions of patients with thyroid nodules, hypothyroidism, and hyperthyroidism were 2.5, 1.8, and 0.9%, respectively. The hazard ratio (HR) for BC risk associated with thyroid nodules was 1.16 (95% CI 1.11–1.20), for hypothyroidism was 0.98 (95% CI 0.93–1.03), and for hyperthyroidism was 1.13 (95% CI 1.06–1.21). In both premenopausal and postmenopausal women, an increased risk of BC was significantly associated with thyroid nodules (aHR 1.16 and 1.13) and hyperthyroidism (aHR 1.11 and 1.16). History of benign breast disease, oral contraceptive use, breastfeeding, menopausal status, and hormone replacement therapy were associated with thyroid nodules and hyperthyroidism.
Conclusion
Our findings suggest an increased risk of BC in women with a history of thyroid nodules and hyperthyroidism, whereas no such association was found in women with hypothyroidism.

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Novel Breast Cancer Risk Assessment Tools for Pre- and Post-Menopausal Asian Women: Development and Validation in a Nationwide Mammographic Screening Cohort: Wonyoung Jung, Yong-Moon Mark Park, Sang Hyun Park, Kyungdo Han, Junhee Park, Yohwan Yeo, Jung Kwon Lee, Dale P. Sandler, Dong Wook Shin; Received September 4, 2024 Accepted January 30, 2025 Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.861 [Accepted]

Abstract PDF: Purpose
Widely used breast cancer risk-prediction tools are based on data from Western countries, but risk factors may differ for Asian women. Hence, we aimed to develop a risk assessment tool for breast cancer in Asian women using a nationwide, population-based mammographic screening cohort.
Materials and Methods
Women aged ≥40 years who underwent breast cancer screening and general health examination in 2009 were included. Age, body mass index (BMI), breast density, lifestyle and reproductive factors, and comorbidities were used to develop 5-year breast cancer risk-prediction models for premenopausal (n=771,856) and postmenopausal (n=1,108,047) women at baseline. The best-fit risk prediction model was constructed using backward stepwise selection in a Cox proportional hazards model and was transformed into a risk score nomogram. The performance was assessed by discrimination and calibration.
Results
In premenopausal women, high BMI, low parity, short breastfeeding period, early age at menarche, high breast density, a history of benign breast masses, and family history of breast cancer contributed to the risk prediction of breast cancer. In postmenopausal women, age, diabetes mellitus, dyslipidemia, late-onset menopause, and hormone replacement therapy use were additional risk predictors of breast cancer. Our risk-prediction model showed a concordant statistic of 0.58 (0.57–0.59) for premenopausal women and 0.64 (0.63–0.65) for postmenopausal women. The calibration plot demonstrated good correlations for both models.
Conclusion
Our breast cancer risk-prediction model demonstrated performance comparable to that of Western countries, especially among postmenopausal women. This provides a foundation for implementing risk-based screening recommendations in Asian women.

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Prognostic Performance of the Next-Generation Sequencing-Based Multigene Assay in Early Breast Cancer Patients Treated According to the 21-Gene Assay Results: Eunhye Kang, Jong-Ho Cheun, Jeeyeon Lee, Jiwon Koh, Hyunwoo Lee, Ji-Young Park, Hee Jin Lee, Byeongju Kang, Woong Ki Park, Jeongeun Son, Bumjoon Kim, Woosung Chung, Wonshik Han, Han-Byoel Lee, Sae Byul Lee, Jai Min Ryu; Received October 28, 2024 Accepted December 22, 2024 Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.1035 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Multigene assays guide treatment decisions in early-stage hormone receptor-positive breast cancer. OncoFREE, a next-generation sequencing assay using 179 genes, was developed for this purpose. This study aimed to evaluate the concordance between the Oncotype DX (ODX) recurrence score (RS) and the OncoFREE Decision Index (DI) and to compare their performance.
Materials and Methods
We retrospectively collected tumor blocks from patients who underwent ODX and treatment between 2012 and 2022 at four tertiary hospitals and performed OncoFREE on these samples. Distant metastasis-free survival (DMFS) was compared using RS and DI, with score cut-offs of 25 and 20, respectively.
Results
Among 838 patients, a strong correlation was observed between RS and DI (Pearson correlation coefficient 0.83). At a median follow-up of 54 months, patients with high DI had significantly worse DMFS compared to those with low-DI (log-rank p < 0.001; hazard ratio [HR], 5.73; 95% confidence interval [CI], 1.87 to 17.57; multivariable p=0.048; HR, 3.45; 95% CI, 1.01 to 11.76). In 513 patients aged ≤ 50 years, DMFS was significantly different as a function of DI (p=0.035; HR, 3.98; 95% CI, 1.00 to 15.89) but not RS (p=0.792). Among 376 patients aged ≤ 50 years who avoided chemotherapy based on low-RS, 64 with high DI had worse DMFS (p=0.015; HR, 5.91; 95% CI, 1.17 to 29.78).
Conclusion
OncoFREE showed strong concordance with ODX and effectively identified high-risk patients, particularly in younger individuals. It could be an affordable alternative to ODX for guiding treatment in hormone receptor-positive early breast cancer.

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Evaluating the Effects of Mindfulness-Based Self-Help via an OTT Platform on Breast Cancer Patients Undergoing Radiotherapy: A Prospective Nonrandomized Controlled Trial: Hyejo Ryu, Si Nae You, Sohee Oh, Bora Kim, Jeong-Hyun Kim, In Ah Kim; Received October 1, 2024 Accepted November 20, 2024 Published online November 25, 2024; DOI: https://doi.org/10.4143/crt.2024.955 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Previous research showed the benefits of mindfulness meditation on the mental health and quality of life of breast cancer patients. Traditionally, these programs relied on in-person interactions, but the coronavirus disease 2019 pandemic necessitated alternative delivery methods. This study evaluated the effectiveness and feasibility of a mindfulness-based self-help (MBSH) program via Netflix for breast cancer patients undergoing radiotherapy.
Materials and Methods
This prospective nonrandomized controlled study assigned patients to a control or MBSH group based on age and preference. The MBSH group watched episodes of “Headspace Guide to Meditation” on Netflix and practiced guided meditation at least twice per week for four weeks. Participants completed questionnaires assessing depression, anxiety, stress, insomnia, mindfulness, mental adjustment to cancer, and quality of life at weeks 0 and 8. Data were analyzed using a two-way repeated measures ANOVA.
Results
Ninety-six patients participated, with 84 eligible for final analysis (44 control, 40 MBSH). Intention-to-treat analysis revealed a significant improvement in depression (f=4.306, p=0.041). Half of the experimental group (n=20) adhered to the study protocol. At week 8, the experimental group showed significant improvement compared to the control group in cognitive avoidance (f=8.530, p=0.005) and positive attitude (f=5.585, p=0.021), both indicative of adaptive coping strategies.
Conclusion
This study firstly investigated the effect and feasibility of a Netflix-based MBSH program for breast cancer patients undergoing radiotherapy. Findings suggest MBSH on Netflix can improve mental health and adaptive mental adjustment, highlighting the potential of self-help mindfulness interventions to enhance the well-being of cancer patients and need for further research.

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Machine Learning–Based Prognostic Gene Signature for Early Triple-Negative Breast Cancer: Ju Won Kim, Jonghyun Lee, Sung Hak Lee, Sangjeong Ahn, Kyong Hwa Park; Received September 26, 2024 Accepted November 18, 2024 Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.937 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to develop a machine learning–based approach to identify prognostic gene signatures for early-stage triple-negative breast cancer (TNBC) using next-generation sequencing data from Asian populations.
Materials and Methods
We utilized next-generation sequencing data to analyze gene expression profiles and identify potential biomarkers. Our methodology involved integrating various machine learning techniques, including feature selection and model optimization. We employed logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curves to validate the identified gene signatures.
Results
We identified a gene signature significantly associated with relapse in TNBC patients. The predictive model demonstrated robustness and accuracy, with an area under the ROC curve of 0.9087, sensitivity of 0.8750, and specificity of 0.9231. The Kaplan-Meier survival analysis revealed a strong association between the gene signature and patient relapse, further validated by logistic regression analysis.
Conclusion
This study presents a novel machine learning-based prognostic tool for TNBC, offering significant implications for early detection and personalized treatment. The identified gene signature provides a promising approach for improving the management of TNBC, contributing to the advancement of precision oncology.

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Estimation of Population Attributable Fraction by Hormone and Reproductive Factors on Female Cancer in the Republic of Korea, 2015 to 2030: Youjin Hong, Soseul Sung, Woojin Lim, Sungji Moon, Kwang-Pil Ko, Jung Eun Lee, Inah Kim, Sun Ha Jee, Sun-Seog Kweon, Min-Ho Shin, Sangmin Park, Seung-Ho Ryu, Sun Young Yang, Jeongseon Kim, Sang-Wook Yi, Yoon-Jung Choi, Jeong-Soo Im, Hong Gwan Seo, Sue K. Park; Received July 26, 2024 Accepted November 18, 2024 Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.707 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Population attributable fractions (PAFs) for hormone and reproductive factors have been estimated in several countries. International Agency for Research on Cancer (IARC) designated as group 1 and group 2A carcinogen for hormone factors in breast, ovarian, endometrial and uterine cervix cancer. This study aimed to estimate the PAFs of hormone/reproductive factor attributed to cancer incidence and deaths in Korean women and projected trends from 2015 to 2030.
Materials and Methods
The PAF was estimated with using the 2005 standardized prevalence rates and 2020 incidence and deaths with a 15-year latency. Based on the Levin’s formula, prevalence rates were calculated using the Korea National Health and Nutrition Examination Survey (KNHANES) and the relative risks, which were the risk of selected female cancer associated with oral contraceptive, hormone replacement therapy and duration of breastfeeding, were estimated from the meta-analysis of studies performed in Korean women population. Studies based on the Asian and Global populations were calculated as a sensitivity analysis.
Results
The estimation PAFs for hormone was 1.02% with 1,192 cases and reproductive was 2.67% with 3,112 cases. Moreover, 0.40% (125 deaths) and 1.09% (342 deaths) in female-related cancer deaths in order. Estrogen-progesterone combined hormone replacement therapy (HRT) accounted the most proportion in hormone factors and breastfeeding in reproductive factors. Also, the breast cancer had the highest percent in both hormone and reproductive factors.
Conclusion
Through this study, 1.02% and 2.67% of female-related cancer incidence will be reduced by encouraging avoiding the use of oral contraceptives and HRT and breastfeeding for more than 6 months in reproductive factors. Additionally, among four selected female cancers in this study, breast cancer was observed to be a significant level of prevention.

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Breast cancer

Kinect-Based Mixed Reality Exercise Program Improves Physical Function and Quality of Life in Breast Cancer Survivors: A Randomized Clinical Trial: Byunggul Lim, Xinxing Li, Yunho Sung, Parivash Jamrasi, SoYoung Ahn, Hyejung Shin, Wook Song; Cancer Res Treat. 2025;57(2):478-491. Published online October 30, 2024; DOI: https://doi.org/10.4143/crt.2024.758

Abstract PDF PubReader ePub: Purpose
Exercise is an effective non-pharmacological approach for alleviating treatment-related adverse effects and enhancing physical fitness in breast cancer survivors. A Kinect-based mixed reality device (KMR), with real-time feedback and user data collection, is an innovative exercise intervention for breast cancer survivors. This study aimed to investigate the effect of KMR exercise program on quality of life (QOL) and physical function in breast cancer survivors.
Materials and Methods
Seventy-seven participants were randomly assigned to either the KMR exercise group or home stretching group with an 8-week intervention. Physical function (shoulder range of motion, body composition, aerobic capacity, and hand grip strength) was evaluated before and after the intervention period. Participants completed questionnaires such as the Disabilities of the Arm, Shoulder, and Hand (DASH), Functional Assessment of Cancer Therapy-Breast, and International Physical Activity Questionnaire (IPAQ) to assess upper extremity disabilities, QOL, and physical activity levels.
Results
Significant group-by-time interaction was found for flexion of the operated arm (154.3±12.5 to 165.8±11.2), and the non-operated arm (158.2±13.8 to 166.5±12.2), abduction of the non-operated arm (154.8±31.6 to 161.1±28.1), and adduction of the operated arm (46.5±9.1 to 52.6±7.2). Significant improvements were also observed in DASH (46.8±9.1 to 40.8±9.3) and IPAQ (1,136.3±612.8 to 1,287±664.1).
Conclusion
The KMR exercise program effectively improved the physical function, alleviated edema, reduced upper extremity disability, and enhanced the QOL in breast cancer survivors. Coupled with significant group-by-time interactions for various outcomes, the results emphasize the potential benefits of incorporating the KMR exercise program to improve the QOL in breast cancer survivors.

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Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells: Chang Liu, Jing Yu, Yongjun Du, Yu Xie, Xiaofei Song, Chang Liu, Yan Yan, Yue Wang, Junfang Qin; Cancer Res Treat. 2025;57(2):457-477. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.368

Abstract PDF Supplementary Material PubReader ePub

Purpose
Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear.
Materials and Methods
The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2.
Results
LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects.
Conclusion
This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

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Dilated Cardiomyopathy May Be Associated With a Novel Mitochondrial tRNASer(AGY) Mutation
Yu Ding, Xuejiao Yu, Jian Xu, Shunrong Zhang, Jianhang Leng, Lars Bertram
Human Mutation.2025;[Epub] CrossRef

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Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study: Chunfang Hao, Xu Wang, Yehui Shi, Zhongsheng Tong, Shufen Li, Xiaodong Liu, Lan Zhang, Jie Zhang, Wenjing Meng, Li Zhang; Cancer Res Treat. 2025;57(2):434-442. Published online August 9, 2024; DOI: https://doi.org/10.4143/crt.2024.340

Abstract PDF PubReader ePub

Purpose
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

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Adjuvant Metronomic Chemotherapy After Surgery in pT1-T2 N0 M0 HER2-Positive and ER/PR-Positive Breast Cancer Plus Targeted Therapy, Anti-Hormonal Therapy, and Radiotherapy, with or Without Immunotherapy: A New Operational Proposal
Luca Roncati
Cancers.2025; 17(8): 1323. CrossRef

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Trends in Cancer-Screening Rates in Korea: Findings from the National Cancer Screening Survey, 2004-2023: EunKyo Kang, Kui Son Choi, Jae Kwan Jun, Yeol Kim, Hyeon Ji Lee, Chang Kyun Choi, Tae Hee Kim, Sun Hwa Lee, Mina Suh; Cancer Res Treat. 2025;57(1):28-38. Published online August 2, 2024; DOI: https://doi.org/10.4143/crt.2024.325

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to report the overall national trends in the rates of cancer screening based on recommendations and provide insights into the changing trends of these rates across different demographics.
Materials and Methods
This study used data from the Korean National Cancer Screening Survey (KNCSS), which surveys nationwide cancer-screening rates and includes 4,500 individuals meeting the Korean National Cancer Screening Program (NCSP) protocol age criteria. Cancer-screening rates were assessed using structured questionnaires; yearly trends were analyzed for both lifetime cancer-screening rates and rates of screening based on recommendations, and subgroup analyses were performed based on age and sex.
Results
The rates of cancer screening based on recommendations showed significant increments: the stomach cancer-screening rate increased from 39.2% in 2004 to 77.5% in 2023 (3.50% per year), the liver cancer-screening rate increased from 20.0% to 48.8% (4.30% per year), and the colorectal cancer, increased from 19.9% to 70.7% (5.15% per year). The breast cancer-screening rate increased from 33.2% to 72.7% (2.88% per year), and the cervical cancer, increased from 58.3% to 70.2% (1.08% per year). Despite some differences, particularly in relation to sociodemographic factors, screening rates increased significantly for all cancer types.
Conclusion
Cancer-screening rates in Korea increased consistently from 2004 to 2023, demonstrating the effectiveness of the national cancer-screening program. However, the increments in breast, cervical and lung cancer-screening rates were relatively lower, indicating the need for additional efforts and strategies.

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Association Between Suicidal Ideation and Cancer Screening Uptake: Results from Middle-Aged and Older Adults in Korea
Seong-Uk Baek, Jin-Ha Yoon
Cancers.2025; 17(6): 956. CrossRef

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Breast cancer

Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14): Sang Min Lee, Bum-Sup Jang, Won Park, Yong Bae Kim, Jin Ho Song, Jin Hee Kim, Tae Hyun Kim, In Ah Kim, Jong Hoon Lee, Sung-Ja Ahn, Kyubo Kim, Ah Ram Chang, Jeanny Kwon, Hae Jin Park, Kyung Hwan Shin; Cancer Res Treat. 2025;57(1):150-158. Published online July 12, 2024; DOI: https://doi.org/10.4143/crt.2024.201

Abstract PDF PubReader ePub

Purpose
This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data.
Materials and Methods
A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed.
Results
Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS.
Conclusion
BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

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Adenoid Cystic Carcinoma of the Breast: A Narrative Review and Update on Management
Taylor Neilson, Zaibo Li, Christina Minami, Sara P. Myers
Cancers.2025; 17(7): 1079. CrossRef

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A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of ¹⁸F-FES PET-CT and Metabolites with Treatment Response: Qing Shao, Ningning Zhang, Xianjun Pan, Wenqi Zhou, Yali Wang, Xiaoliang Chen, Jing Wu, Xiaohua Zeng; Cancer Res Treat. 2025;57(1):126-139. Published online July 9, 2024; DOI: https://doi.org/10.4143/crt.2023.1251

Abstract PDF Supplementary Material PubReader ePub: Purpose
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (¹⁸F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received ¹⁸F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of ¹⁸F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. ¹⁸F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

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Molecular Classification of Breast Cancer Using Weakly Supervised Learning: Wooyoung Jang, Jonghyun Lee, Kyong Hwa Park, Aeree Kim, Sung Hak Lee, Sangjeong Ahn; Cancer Res Treat. 2025;57(1):116-125. Published online June 25, 2024; DOI: https://doi.org/10.4143/crt.2024.113

Abstract PDF Supplementary Material PubReader ePub: Purpose
The molecular classification of breast cancer is crucial for effective treatment. The emergence of digital pathology has ushered in a new era in which weakly supervised learning leveraging whole-slide images has gained prominence in developing deep learning models because this approach alleviates the need for extensive manual annotation. Weakly supervised learning was employed to classify the molecular subtypes of breast cancer.
Materials and Methods
Our approach capitalizes on two whole-slide image datasets: one consisting of breast cancer cases from the Korea University Guro Hospital (KG) and the other originating from The Cancer Genomic Atlas dataset (TCGA). Furthermore, we visualized the inferred results using an attention-based heat map and reviewed the histomorphological features of the most attentive patches.
Results
The KG+TCGA-trained model achieved an area under the receiver operating characteristics value of 0.749. An inherent challenge lies in the imbalance among subtypes. Additionally, discrepancies between the two datasets resulted in different molecular subtype proportions. To mitigate this imbalance, we merged the two datasets, and the resulting model exhibited improved performance. The attentive patches correlated well with widely recognized histomorphologic features. The triple-negative subtype has a high incidence of high-grade nuclei, tumor necrosis, and intratumoral tumor-infiltrating lymphocytes. The luminal A subtype showed a high incidence of collagen fibers.
Conclusion
The artificial intelligence (AI) model based on weakly supervised learning showed promising performance. A review of the most attentive patches provided insights into the predictions of the AI model. AI models can become invaluable screening tools that reduce costs and workloads in practice.

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Endoxifen Concentration Is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients: Beomki Lee, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung-Joo Chae, Se Kyung Lee, Jai Min Ryu, Jeong Eon Lee, Soo-Youn Lee; Cancer Res Treat. 2025;57(1):140-149. Published online June 18, 2024; DOI: https://doi.org/10.4143/crt.2023.1285

Abstract PDF PubReader ePub: Purpose
The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dose. However, the clinical significance of endoxifen for the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication.
Materials and Methods
The study included 478 breast cancer patients. Tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry. An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff.
Results
An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and the high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% confidence interval [CI], 77.0 to 89.9) and 88.3% (95% CI, 83.3 to 93.5) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor associated with prognosis.
Conclusion
Endoxifen could serve as a marker for appropriate tamoxifen treatment with a cutoff of 21.00 ng/mL. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying suboptimal endoxifen concentrations.

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A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Kyunghee Park, Jong-Han Yu, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong; Cancer Res Treat. 2024;56(4):1113-1125. Published online May 10, 2024; DOI: https://doi.org/10.4143/crt.2024.100

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

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Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan’s National Database
Kyoka Kawabata, Hinano Nishikubo, Saki Kanei, Rika Aoyama, Yuki Tsukada, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Qiang Wang, Zhonglin Zhu, Canfeng Fan, Masakazu Yashiro
Genes.2024; 15(6): 792. CrossRef

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156 Download
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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

Abstract PDF Supplementary Material PubReader ePub

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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A Nationwide Study on HER2-Low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols: Min Chong Kim, Eun Yoon Cho, So Yeon Park, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Ho-chang Lee, Jin Ye Yoo, Hee Sung Kim, Bomi Kim, Wan Seop Kim, Nari Shin, Young Hee Maeng, Hun Soo Kim, Sun Young Kwon, Chungyeul Kim, Sun-Young Jun, Gui Young Kwon, Hye Jeong Choi, So Mang Lee, Ji Eun Choi, Ae Ri An, Hyun Joo Choi, EunKyung Kim, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; Cancer Res Treat. 2024;56(4):1096-1104. Published online March 6, 2024; DOI: https://doi.org/10.4143/crt.2024.092

Abstract PDF Supplementary Material PubReader ePub

Purpose
Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results.
Materials and Methods
The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected.
Results
Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients.
Conclusion
The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

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Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer
Min Chong Kim, Sun Young Kwon, Hye Ra Jung, Young Kyung Bae
Virchows Archiv.2024; 485(6): 1117. CrossRef
Breast Cancer: Extracellular Matrix and Microbiome Interactions
Lourdes Herrera-Quintana, Héctor Vázquez-Lorente, Julio Plaza-Diaz
International Journal of Molecular Sciences.2024; 25(13): 7226. CrossRef

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Implementation of BRCA Test among Young Breast Cancer Patients in South Korea: A Nationwide Cohort Study: Yung-Huyn Hwang, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Beom Seok Ko, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, Il Yong Chung; Cancer Res Treat. 2024;56(3):802-808. Published online February 19, 2024; DOI: https://doi.org/10.4143/crt.2023.1186

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea.
Materials and Methods
We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing.
Results
From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively.
Conclusion
The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.

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