Cancer Research and Treatment

Original Articles

Pre-Treatment Ki67 Index for Everolimus Efficacy in Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Multicenter Cohort Study: Yujing Tan, Hanfang Jiang, Fei Ma, Bo Lan, Yang Luo, Jiayu Wang, Pin Zhang, Binghe Xu, Weihong Zhao, Ying Fan; Received May 12, 2025 Accepted January 11, 2026 Published online January 14, 2026; DOI: https://doi.org/10.4143/crt.2025.506 [Accepted]

Abstract PDF: Purpose
The study aims to explore the predictive value of the Ki67 index for everolimus efficacy in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).
Materials and Methods
We collected data on 2,518 cancer patients who received everolimus treatment from three cancer centers in China. Their clinicopathologic characteristics were retrospectively collected. A training cohort and a validation cohort were developed.
Results
A total of 300 patients with HR+/HER2- ABC were included in the study, with 200 patients in the training cohort and 100 patients in the validation cohort. When analyzing the Ki67 index from 14% to 50%, only the Ki67 cut-off of 40% was found to be significantly correlated with progression-free survival (PFS) for patients in the training cohort. Multivariate Cox analyses further showed that Ki67 index of 40% (p=0.03) was significantly associated with PFS in patients treated with everolimus. Patients with Ki67 less than 40% had an improved PFS of 7.0 months, significantly better than 4.6 months for patients with Ki67 more than 40% (p=0.03, HR=0.67, 95CI%=0.46-0.97). In the validation cohort, patients with a Ki67 index of less than 40% had a significantly longer PFS of 4.3 months (2.1 months versus 4.3 months, p<0.001, HR=0.29, 95CI%=0.17-0.51).
Conclusion
The Ki67 cut-off value of 40% was identified as an optimal index for predicting the efficacy of everolimus, which may help with the management of everolimus in Chinese patients with HR+/HER2- ABC.

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Platinum and 5-FU Salvage Therapy for Severe Liver Crisis in Metastatic Breast Cancer: Efficacy and Analysis of Prognostic Factors: I-Wei Ho, Jiun-I Lai, Chun-Yu Liu, Wei-Chi Lin, Muh-Hwa Yang, Ling-Ming Tseng, Ta-Chung Chao; Received November 18, 2025 Accepted December 28, 2025 Published online December 29, 2025; DOI: https://doi.org/10.4143/crt.2025.1262 [Accepted]

Abstract PDF: Purpose
Metastatic breast cancer (MBC) with severe hepatic dysfunction due to liver crisis presents a significant treatment challenge, as conventional chemotherapy often requires dose modifications, leading to reduced efficacy. The combination of platinum, 5-fluorouracil (5FU), and folinate (PFL) offers a rational treatment strategy. This study evaluates the efficacy and safety of PFL in MBC patients with liver crisis and explores predictive markers for treatment response.
Materials and Methods
This retrospective cohort study, conducted at Taipei Veterans General Hospital, Taiwan, included 44 MBC patients with bilirubin ≥3 mg/dL treated between January 2015 and June 2024. Outcomes included bilirubin response rate (≥50% reduction from baseline), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. The AUC analysis was used to determine the optimal cutoff for liver function assessment model, and Cox regression identified independent prognostic factors.
Results
Among the 44 patients, 47.7% achieved a bilirubin response within a median of 19 days. Overall, the median PFS and OS were 1.4 and 1.9 months, respectively, but improved to 4.6 and 7.8 months in those achieving bilirubin response. The ORR was 22.7%, and the DCR was 29.5%. A FIB-4 score <9.1 predicted a 65% bilirubin response rate, while FIB-4 >9.1 was also an independent predictor of OS. Grade 3 adverse events occurred in 36.4% of patients.
Conclusion
The PFL regimen is effective in MBC patients with severe liver crisis with hyperbilirubinemia. A FIB-4 score <9.1 may serve as a potential prognostic factor for bilirubin response and is associated with improved survival outcomes.

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The Application of Contrast-Enhanced Ultrasound Combined with Indocyanine Green Lymphography in the Management of Secondary Upper Limb Lymphedema: Xilong Gong, Lina Wang, Fang Liu, Jiao Zhang, Hui Xiao, Ying Hou, Xuhui Guo, Zhenzhen Liu; Received August 1, 2025 Accepted November 17, 2025 Published online November 18, 2025; DOI: https://doi.org/10.4143/crt.2025.813 [Accepted]

Abstract PDF: To assess the clinical efficacy of contrast-enhanced ultrasound (CEUS) combined with indocyanine green (ICG) lymphography for the treatment of breast cancer–related lymphedema (BCRL).
Materials and Methods
Fifty-two patients with BCRL who underwent lymphaticovenous anastomosis between March 2022 and March 2024 were enrolled, of whom 22 underwent preoperative functional lymphatic vessel localization using ICG lymphography alone and 30 received CEUS combined with ICG lymphography. Treatment efficacy was evaluated using bioimpedance spectroscopy for segmental water content analysis, calculation of the upper extremity lymphedema (UEL) index, and administration of the Lymphedema Quality of Life Questionnaire (LYMQOL). Surgical parameters were also analyzed.
Results
Baseline characteristics were comparable between the groups. However, at both 6 and 12 months postoperatively, patients in the CEUS+ICG group demonstrated significantly improved outcomes compared to those in the ICG-only group, including: Reduced segmental water differences (6 months: 344.3 vs. 474.6 mL, p=0.0221; 12 months: 284.3 vs. 403.6 mL, p=0.0156); Lower UEL index (6 months: 124.2 vs. 134.1, p=0.0010; 12 months: 123.8 vs. 131.9, p=0.0105); Improved LYMQOL scores (6 months: 48.7 vs. 56.6, p=0.0029; 12 months: 47.6 vs. 54.2, p=0.0065). Additionally, the CEUS+ICG group achieved a significantly higher anastomosis success rate (83.2% vs. 63.3%, p<0.001) and reduced procedural time per anastomosis (48.9 vs. 61.6 minutes, p=0.0021).
Conclusion
The combination of CEUS and ICG-L is associated with precise preoperative lymphatic mapping, a reduction in unnecessary incisions, as well as better anastomosis success rates and postoperative decongestion outcomes.

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Response to Neoadjuvant Systemic Therapy May Serve as an Indicator for Omitting Post-BCS Radiation Therapy in Women with Early-Stage Breast Cancer: Chaofan Li, Yusheng Wang, Mengjie Liu, Shiyu Sun, Yiwei Jia, Jingkun Qu, Shuqun Zhang, Chong Du; Received June 1, 2025 Accepted September 7, 2025 Published online September 10, 2025; DOI: https://doi.org/10.4143/crt.2025.584 [Accepted]

Abstract PDF: Abstract Purpose To avoid unnecessary toxicities and optimize the allocation of healthcare resources, it is crucial to adequately select patients with extremely low recurrence risk to downgrade or eliminate radiation therapy.
Materials and Methods
From the SEER database, clinical data of 7,291 female patients with early-stage breast cancer who underwent neoadjuvant systemic therapy (NST) and breast-conserving surgery (BCS) were collected for this study. The patients were stratified by their response to NST, and the long-term survival, and risk of recurrence were assessed using Cox regression analysis and Fine-gray competing risk models for those with and without post-BCS RT, respectively.
Results
Our results showed that female with early-stage breast cancer who achieved complete response (CR) to NST, omitting post-BCS RT achieved the same OS and DFS as those who received the post-BCS RT, and the omission did not increase the risk of recurrence or BCSD. For patients who did not achieve CR to NST, five clinical indicators (including age, N stage, grade, response to NST, and molecular subtype) were employed to construct a nomogram for clinical prediction of the risk of recurrence. The validated results affirmed our model’s ability to accurately discriminate high- and low-risk patients and its promising clinical application value.
Conclusion
Post-BCS RT can be omitted for women with early-stage breast cancer who achieved CR to NST. For those who failed to achieve CR to NST, a nomogram was constructed for clinicians to decide whether to omit post-BCS RT or not based on the individualized assessment.

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Impact of High Lymph Node Burden on Brain Metastases in Patients Who Achieved Pathological Complete Response after Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer: Seung Ah Lee, Ki Jo Kim, Do Youn Woen, Su Min Lee, Kawon Oh, Cho Eun Lee, Woong Ki Park, Ji Won Yoo, Dong Seung Shin, Jai Min Ryu, Se Kyung Lee, Byung Joo Chae, Jonghan Yu, Seok Won Kim, Seok Jin Nam, Ji-Yeon Kim, Yeon Hee Park, Eun Young Ko, Eun Sook Ko, Jeong Eon Lee; Received February 24, 2025 Accepted July 6, 2025 Published online July 8, 2025; DOI: https://doi.org/10.4143/crt.2025.219 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
This study aims to investigate the clinical characteristics, outcomes, and predictors of brain metastases in human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer patients who achieved pathological complete response (pCR) following neoadjuvant chemotherapy (NAC). This research seeks to inform surveillance strategies and optimize management for high-risk subgroups.
Materials and Methods
A retrospective analysis of 1,757 patients (2008-2022) classified them into pCR (n=914) and non-pCR (n=843) groups post-NAC. Collected data included demographics, clinical features, and metastasis parameters. Survival outcomes and brain metastasis predictors were assessed using Kaplan-Meier curves, Cox models, and logistic regression.
Results
Among pCR patients, brain metastases accounted for 54.2% of distant metastases, significantly affecting overall survival (p < 0.001). Median distant metastasis-free survival was shorter for brain metastases (13.4 months) compared to extracranial metastases (31.1 months) in the pCR group (p=0.005). Positive supraclavicular node (SCN) fine needle aspiration (FNA) and clinical N3 (cN3) category were the strongest predictors of brain metastases (SCN FNA: odds ratio [OR], 12.9; p < 0.001; cN3: OR, 12.1; p < 0.001). Multivariable Cox regression analysis revealed that positive SCN FNA and cN3 category were strong predictors of reduced distant metastasis-free survival (SCN FNA: hazard ratio, 2.5; 95% confidence interval [CI], 1.3 to 3.6; p < 0.001; cN3: hazard ratio, 11.3; 95% CI, 4.9 to 33.0; p < 0.001).
Conclusion
This study highlights the challenges of brain metastases in HER2-positive pCR patients, emphasizing the need for tailored therapeutic strategies and enhanced surveillance. High lymph node burden prior to NAC is a significant factor in risk assessment. Therefore, it may be advisable to recommend post-surgery surveillance for high-risk patients.

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Breast cancer

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; Cancer Res Treat. 2026;58(1):151-158. Published online March 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1120

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although human epidermal growth factor receptor 2 (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 to 79 years), 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% confidence interval [CI], 114.0 to 127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1 to 93.3), 97.5% (95% CI, 96.4 to 98.7), and 98.8% (95% CI, 98.0 to 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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Microinvasive carcinoma of the breast
Rachel Han, Edi Brogi
Human Pathology.2025; 162: 105856. CrossRef

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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; Cancer Res Treat. 2025;57(3):731-740. Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.937

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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Machine Learning in Clinical Decision Making: Applications, Data Limitations and Multidisciplinary Perspectives
Augusta Raţiu, Emilia-Loredana Pop
Applied Sciences.2026; 16(2): 785. CrossRef

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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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Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study: Ruyan Zhang, Xiaoran Liu, Guohong Song, Yan Zhang, Huiping Li; Cancer Res Treat. 2024;56(3):795-801. Published online December 20, 2023; DOI: https://doi.org/10.4143/crt.2023.1151

Abstract PDF PubReader ePub

Purpose
This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) after progression of trastuzumab.
Materials and Methods
In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495).
Results
A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated.
Conclusion
The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC.

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Efficacy and safety of biosimilar trastuzumab (HLX02) in patients with HER2-positive advanced breast cancer: a retrospective real-world analysis
Xuan Ye, Linlin Wang, Wensheng Liu, Mengmeng Wang, Zihan Guo, Han Shan, Qing Zhai, Qiong Du
Frontiers in Oncology.2025;[Epub] CrossRef

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Assessment of Eligibility and Utilization of Accelerated Partial Breast Irradiation in Korean Breast Cancer Patients (KROG 22-15): Seok-Joo Chun, Ji Hwan Jo, Yong Bae Kim, Sangjoon Park, Sung-Ja Ahn, Su Ssan Kim, Kyubo Kim, Kyung Hwan Shin; Cancer Res Treat. 2024;56(2):549-556. Published online December 8, 2023; DOI: https://doi.org/10.4143/crt.2023.1109

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the proportions of patients eligible for accelerated partial breast irradiation (APBI) among those with pT1-2N0 breast cancer, based on the criteria set by the American Society for Radiation Oncology (ASTRO), the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO), the American Brachytherapy Society (ABS), and the American Society of Breast Surgeons (ASBS). Additionally, we analyzed the rate of APBI utilization among eligible patients.
Materials and Methods
Patients diagnosed with pT1-2N0 breast cancer in 2019 were accrued in four tertiary medical centers in Korea. All patients had undergone breast conserving surgery followed by radiotherapy, either whole breast irradiation or APBI. To determine which guideline best predicts the use of APBI in Korea, the F1 score and Matthews Correlation Coefficient (MCC) were determined for each guideline.
Results
A total of 1,251 patients were analyzed, of whom 196 (15.7%) underwent APBI. The percentages of eligible patients identified by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria were 13.7%, 21.0%, 50.5%, and 63.5%, respectively. APBI was used to treat 54.4%, 37.2%, 27.1%, and 23.7% of patients eligible by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria, respectively. The ASTRO guideline exhibited the highest F1 score (0.76) and MCC (0.67), thus showing the best prediction of APBI utilization in Korea.
Conclusion
The proportion of Korean breast cancer patients who are candidates for APBI is substantial. The actual rate of APBI utilization among eligible patients may suggest there is a room for risk-stratified optimization in offering radiation therapy.

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Impact of the ASTRO 2024 Guideline on Partial Breast Irradiation Eligibility in Breast Cancer Patients (KROG 24-01)
Seok-Joo Chun, Sangjoon Park, Yong Bae Kim, Sung-Ja Ahn, Kyubo Kim, Kyung Hwan Shin
Practical Radiation Oncology.2025; 15(3): e230. CrossRef

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Temporal Trend in Uptake of the National General Health Checkups and Cancer Screening Program among Korean Women with Breast Cancer: Thi Xuan Mai Tran, Soyeoun Kim, Chihwan Cha, Boyoung Park; Cancer Res Treat. 2024;56(2):522-530. Published online October 30, 2023; DOI: https://doi.org/10.4143/crt.2023.729

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study assessed the temporal trends of uptake of national general health and cancer screening among women with breast cancer in Korea between 2009 and 2016.
Materials and Methods
We retrospectively analyzed the claims data from the Korean National Health Insurance Service database. Participants included 101,403 breast cancer patients diagnosed between 2009 and 2016. Information on participation in national screening programs, including breast cancer screening, general health, and gastric, colorectal, and cervical cancers, up to 2020 was collected. Screening participation rates within the first 2 and 5 years postdiagnosis were calculated by diagnosis year and fitted with joinpoint regression models to assess temporal trends.
Results
Overall, the participation rate in breast cancer screening within 2 years postdiagnosis increased from 10.9% to 14.0% from 2009-2016, with an annual percentage change (APC) of 3.7% (p < 0.05). The participation rate in breast cancer screening was lower than that in general health checkup and screening for other cancers within 2 and 5 years postdiagnosis. A steady increase in screening trends was also observed for general health, gastric, colorectal, and cervical cancers, with APC of 5.3%, 5.7%, 6.9%, and 7.6% in the 2-year postdiagnosis rate, and APC of 3.6%, 3.7%, 3.7%, and 4.4% in 5-year postdiagnosis rate, respectively. The screening rate was highest among age groups 50-59 and 60-69 in 2009 and significant upward trends were observed in all age groups for general health checkup and gastric, colorectal, and cervical cancer screening.
Conclusion
Among female breast cancer survivors in Korea, the uptake rate of screenings for general health and various cancers, including breast, gastric, colorectal, and cervical cancers, has shown a gradual increase in recent years.

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Identifying potential medical aid beneficiaries using machine learning: A Korean Nationwide cohort study
Junmo Kim, Su Hyun Park, Hyesu Lee, Su Kyoung Lee, Jihye Kim, Suhyun Kim, Yong Jin Kwon, Kwangsoo Kim
International Journal of Medical Informatics.2025; 195: 105775. CrossRef
Unmet Needs Mediate the Impact of Fear of Cancer Recurrence on Screening Participation Among Cancer Survivors: A Cross-Sectional Study
Mi-Lee Kim, Yeol Kim, Yu-Ri Choe
Healthcare.2025; 13(10): 1184. CrossRef
Screening Adherence for Second Primary Malignancies in Breast Cancer Survivors: Behaviors, Facilitators, and Barriers to Enhance Quality Care
Fernanda Mesa-Chavez, Misael Salazar-Alejo, Cynthia Villarreal-Garza
Seminars in Oncology.2024; 51(5-6): 156. CrossRef

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Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study: Danbee Kang, Seri Park, Hyo Jung Kim, Seok Won Kim, Jeong Eon Lee, Jonghan Yu, Se Kyung Lee, Ji-Yeon Kim, Seok Jin Nam, Juhee Cho, Yeon Hee Park; Cancer Res Treat. 2024;56(1):125-133. Published online September 4, 2023; DOI: https://doi.org/10.4143/crt.2023.673

Abstract PDF PubReader ePub: Purpose
We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study.
Materials and Methods
Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes.
Results
The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis.
Conclusion
In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

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Efficacy of Limited Dose Modifications for Palbociclib-Related Grade 3 Neutropenia in Hormone Receptor–Positive Metastatic Breast Cancer: Seul-Gi Kim, Min Hwan Kim, Sejung Park, Gun Min Kim, Jee Hung Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Byeong Woo Park, Seung Il Kim, Jung Hwan Ji, Joon Jeong, Kabsoo Shin, Jieun Lee, Hyung-Don Kim, Kyung Hae Jung, Joohyuk Sohn; Cancer Res Treat. 2023;55(4):1198-1209. Published online April 11, 2023; DOI: https://doi.org/10.4143/crt.2022.1543

Abstract PDF Supplementary Material PubReader ePub

Purpose
Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia.
Materials and Methods
Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups.
Results
During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality.
Conclusion
Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

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Efficacy and Safety of Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Real-World Studies
Hui-Chen Su, Ho-Wei Lin, Ka-Wai Tam
Targeted Oncology.2025; 20(1): 71. CrossRef
Palbociclib Is Safe for Breast Cancer Patients With Mild Hepatic Impairment: A Multicenter Retrospective Study Using Real‐World Data
Alieke K. Bos, Annelieke E.C.A.B. Willemsen, Loes E. Visser, Lennart J. Stoker, Jurjen S. Kingma, Mirjam K. Rommers, Emile M. Kuck, Paul D. van der Linden, Merel van Nuland
Clinical Pharmacology & Therapeutics.2025; 117(4): 1115. CrossRef
Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
Nadia Harbeck, Adam Brufsky, Chloe Grace Rose, Beata Korytowsky, Connie Chen, Krista Tantakoun, Endri Jazexhi, Do Hoang Vien Nguyen, Meaghan Bartlett, Imtiaz A. Samjoo, Timothy Pluard
Frontiers in Oncology.2025;[Epub] CrossRef
Adverse Event Costs and Cost-Effectiveness Analyses of Anticancer Drugs
Mingye Zhao, Taihang Shao, Yue Yin, Hongshu Fang, Hanqiao Shao, Wenxi Tang
JAMA Network Open.2025; 8(5): e2512455. CrossRef
Palbociclib treatment in patients with HR+/HER2− advanced or metastatic breast cancer and visceral metastasis: A systematic literature review
Julia C. Radosa, Sara López-Tarruella Cobo, Johanna Dzieran, Esther Glastetter, Connie Chen, Melissa Lingohr-Smith, Vinay Pasupuleti, Adam Brufsky
The Breast.2025; 84: 104569. CrossRef
Palbociclib

Reactions Weekly.2023; 1988(1): 138. CrossRef

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Real-World Evidence of Trastuzumab, Pertuzumab, and Docetaxel Combination as a First-Line Treatment for Korean Patients with HER2-Positive Metastatic Breast Cancer: Yong-Pyo Lee, Min-Sang Lee, HongSik Kim, Ji-Yeon Kim, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park; Cancer Res Treat. 2022;54(4):1130-1137. Published online January 17, 2022; DOI: https://doi.org/10.4143/crt.2021.1103

Abstract PDF Supplementary Material PubReader ePub

Purpose
Trastuzumab has markedly improved the survival outcomes of patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and dual blockade of HER2 using trastuzumab and pertuzumab in combination with taxanes (THP) has become a standard of care for HER2-positive metastatic breast cancer (MBC) worldwide since the CLEOPATRA trial. We assessed the outcomes of THP as a first-line treatment for Korean HER2-positive MBC patients in the real-world setting.
Materials and Methods
Between August 2008 and October 2020, we identified 228 HER2-positive MBC patients who received THP as a first-line palliative chemotherapy. We analyzed survival outcomes, efficacy, and adverse events of THP retrospectively.
Results
After a median follow-up duration of 28.7 months, median overall survival and progression-free survival were 58.3 months (95% confidence interval [CI], 36.6 to 80.0) and 19.1 months (95% CI, 16.2 to 21.9), respectively. Better survival outcomes were observed in patient who received docetaxel for more than six cycles. Patients exposed to anti-HER2 directed therapies in a perioperative setting had poor survival outcomes. The overall response rate was 86.8% with a complete response (CR) rate of 17.7%. Among responders, 16.7% of patients sustained THP over 35 months and showed better survivals and higher CR rates. Adverse events were comparable to those reported in previous studies.
Conclusion
In a real-world context, clinical outcomes of Korean HER2-positive MBC patients treated with THP were similar to those of patients in the CLEOPATRA trial. Much longer follow-up results would be warranted.

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Trastuzumab deruxtecan: Redefining precision oncology across HER2-driven cancers
Pooya Jalali, Azhar Saeed, Sahar Taher, Anwaar Saeed
Critical Reviews in Oncology/Hematology.2026; 217: 105019. CrossRef
From intravenous to subcutaneous pertuzumab/trastuzumab in breast cancer: Clinical and pharmacoeconomic drivers and barriers to switching
Mariangela Gaudio, Anna Floreani, Greta Schivardi, Domiziana Alaimo, Vera Basilico, Isabella Lorenzetti, Cristina Crepaldi, Benedetta Tinterri, Antonella Panzardi, Daniela Strada, Giuseppe Saltalamacchia, Flavia Jacobs, Chiara Benvenuti, Riccardo Gerosa,
Tumori Journal.2026; 112(1): 22. CrossRef
Pertuzumab in Combination with Trastuzumab and Docetaxel as Adjuvant Doublet Therapy for HER2-Positive Breast Cancer: A Systematic Review
Ignacio Ventura, Nerea Pinilla Salcedo, Marcelino Pérez-Bermejo, Javier Pérez-Murillo, Manuel Tejeda-Adell, Francisco Tomás-Aguirre, María Ester Legidos-García, María Teresa Murillo-Llorente
International Journal of Molecular Sciences.2025; 26(5): 1908. CrossRef
Recent advances in immunotherapy for breast cancer
Yi Guo, Gang Zheng, Yu Fan, Liangchang Li, Yang Sun
Discover Oncology.2025;[Epub] CrossRef
Real-world impact of dual anti-HER2 antibodies on cardiac function in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer
Kelvin KH. Bao, Jeffrey CH. Chan, Jocelyn G. Chan, Leone Sutanto, Ka Man Cheung, Harry HY. Yiu
The Breast.2024; 73: 103612. CrossRef
Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review
Rong Qin, Xiangyang Wang, Tingting Fan, Ting Wu, Chao Lu, Xun Shao, Liang Yin
Frontiers in Oncology.2024;[Epub] CrossRef
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Muhammad Javed Iqbal, Zeeshan Javed, Jesús Herrera-Bravo, Haleema Sadia, Faiza Anum, Shahid Raza, Arifa Tahir, Muhammad Naeem Shahwani, Javad Sharifi-Rad, Daniela Calina, William C. Cho
Cancer Cell International.2022;[Epub] CrossRef

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369 Download
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Real World Evidence of Neoadjuvant Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) in Patients with HER2-Positive Early or Locally Advanced Breast Cancer: A Single-Institutional Clinical Experience: Ji-Yeon Kim, Seok Jin Nam, Jeong Eon Lee, Jonghan Yu, Byung Joo Chae, Se Kyung Lee, Jai Min Ryu, Jin Seok Ahn, Young-Hyuck Im, Seok Won Kim, Yeon Hee Park; Cancer Res Treat. 2022;54(4):1091-1098. Published online January 10, 2022; DOI: https://doi.org/10.4143/crt.2021.901

Abstract PDF Supplementary Material PubReader ePub

Purpose
Docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) regimen is frequently used to treat early and locally advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC) in neoadjuvant setting. However, large-scaled real-world evidence did not exist.
Materials and Methods
We retrospectively reviewed medical records of patients with early or locally advanced HER2-positive BC who underwent neoadjuvant TCHP followed by curative surgery at Samsung Medical Center between January 2016 and August 2020.
Results
Of 447 patients, 316 (70.7%) received breast-conserving surgery and 131 (29.3%) received total mastectomy. In terms of neoadjuvant chemotherapy response, pathologic complete response (pCR) and residual cancer burden (RCB) score were analyzed. The rate of pCR was 64% a class of RCB 0 was observed in 65% of cases, RCB class I in 12%, RCB class II in 14%, and RCB class III in 2%. The 3-year event-free survival rate was 90.6%, BC with pCR occurred in 92.8%, and BC with non-pCR in 86.3% (p=0.016). In terms of distant metastasis, the 3-year distant recurrence-free survival rate was 93.5%; BC with pCR occurred in 95.9% and BC with non-pCR in 89.2% (p=0.013). Mucositis (85.2%), pain (83.2%), and diarrhea (70.5%) were the most common non-hematologic adverse events. In terms of hematologic adverse events, anemia (89.9%) was the most commonly observed adverse events followed by thrombocytopenia (29.8%).
Conclusion
Neoadjuvant TCHP therapy had a pCR rate of 64% and a 3-year event-free survival of 90% in real world experience. In terms of toxicity profile, anemia was frequently observed and adequate management including occasional transfusion was required.

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Efficacy, safety, and biomarkers of neoadjuvant trastuzumab and pertuzumab combined with chemotherapy in Chinese patients with HER2-positive breast cancer: a multicenter retrospective cohort study
Xiaowei Qi, Hong Hu, Pengfei Qiu, Wenlin Chen, Xiaochun Wang, Qiyun Shi, Yan Xu, Shu Liu, Yanman Fang, Taolang Li, Jia Ming, Sihai Zhou, Fan Chai, Yueyang Liang, Yuanming Fan, Peng Tang, Li Chen, Shushu Wang, Jun Jiang, Mengyuan Wang, Yi Zhang, Jianyun Ni
International Journal of Surgery.2026; 112(1): 1318. CrossRef
Decrease in Calcifications After Neoadjuvant Treatment Predicts Invasive Tumor Response but Not Complete DCIS Eradication: Systematic Review and Meta-Analysis
Noam Weiner, Yaron Niv, Eran Sharon
Clinical Breast Cancer.2025; 25(7): e990. CrossRef
Comparison of T-DM1 and trastuzumab-pertuzumab in HER2-positive breast cancer patients with residual disease after neoadjuvant therapy: a retrospective study
Junxiao Wang, Yushuai Yu, Qisheng Lin, Xin Wang
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Pertuzumab/Docetaxel/Carboplatin/Trastuzumab Regimen in Human Epidermal Growth Factor Receptor 2–Positive Early, Locally Advanced, and Oligometastatic Breast Cancer: Real-World Outcomes From India
Ajay Gogia, Atul Batra, Ashutosh Mishra, Kamal Kataria, Surendra K. Saini, Sandeep Mathur, Chandra P. Prasad, Hari Krishna Raju Sagiraju
JCO Global Oncology.2025;[Epub] CrossRef
De-escalation of neoadjuvant taxane and carboplatin therapy in HER2-positive breast cancer with dual HER2 blockade: a multicenter real-world experience in China
Song Wu, Li Bian, Haibo Wang, Shaohua Zhang, Tao Wang, Zhigang Yu, Jianbin Li, Feng Li, Kun Wang, Zefei Jiang
World Journal of Surgical Oncology.2024;[Epub] 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
Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study
Ahmet Bilici, Omer Fatih Olmez, Muhammed Ali Kaplan, Berna Oksuzoglu, Ahmet Sezer, Nuri Karadurmus, Erdem Cubukcu, Mehmet Ali Nahit Sendur, Sercan Aksoy, Dilek Erdem, Gul Basaran, Burcu Cakar, Abdallah T. M. Shbair, Cagatay Arslan, Ahmet Taner Sumbul, Sem
Acta Oncologica.2023; 62(4): 381. CrossRef
Pathologic Complete Response Achieved in Early-Stage HER2-Positive Breast Cancer After Neoadjuvant Therapy With Trastuzumab and Chemotherapy vs. Trastuzumab, Chemotherapy, and Pertuzumab: A Systematic Review and Meta-Analysis of Clinical Trials
Faizan Fazal, Muhammad Nauman Bashir, Maham Leeza Adil, Usama Tanveer, Mansoor Ahmed, Taha Zahid Chaudhry, Ali Ahmad Ijaz, Muhammad Haider
Cureus.2023;[Epub] CrossRef
Trends of axillary surgery in breast cancer patients with axillary lymph node metastasis: a comprehensive single-center retrospective study
Yeon Jin Kim, Hye Jin Kim, Soo Yeon Chung, Se Kyung Lee, Byung Joo Chae, Jonghan Yu, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jai Min Ryu
Annals of Surgical Treatment and Research.2023; 105(1): 10. CrossRef
Anthracyclines versus No Anthracyclines in the Neoadjuvant Strategy for HER2+ Breast Cancer: Real-World Evidence
Inês Soares de Pinho, Paulo Luz, Lucy Alves, Raquel Lopes-Brás, Vanessa Patel, Miguel Esperança-Martins, Lisa Gonçalves, Ritas Freitas, Diana Simão, Maria Roldán Galnares, Isabel Fernandes, Silvia Artacho Criado, Salvador Gamez Casado, Jose Baena Cañada,
Clinical Drug Investigation.2023; 43(9): 691. CrossRef
Benefit of postoperative regional nodal irradiation in patients receiving preoperative systemic therapy with docetaxel/carboplatin/trastuzumab/pertuzumab for HER2-positive breast cancer
Nalee Kim, Ji-Yeon Kim, Won Park, Won Kyung Cho, Tae Gyu Kim, Young-Hyuck Im, Jin Seok Ahn, Jeong Eon Lee, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Sei Kyung Lee, Jai-Min Ryu, Yeon Hee Park, Haeyoung Kim
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Hee Kyung Ahn, Sung Hoon Sim, Koung Jin Suh, Min Hwan Kim, Jae Ho Jeong, Ji-Yeon Kim, Dae-Won Lee, Jin-Hee Ahn, Heejung Chae, Kyung-Hun Lee, Jee Hyun Kim, Keun Seok Lee, Joo Hyuk Sohn, Yoon-La Choi, Seock-Ah Im, Kyung Hae Jung, Yeon Hee Park
JAMA Oncology.2022; 8(9): 1271. CrossRef

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Fear of Cancer Recurrence and Its Negative Impact on Health-Related Quality of Life in Long-term Breast Cancer Survivors: Thi Xuan Mai Tran, So-Youn Jung, Eun-Gyeong Lee, Heeyoun Cho, Na Yeon Kim, Sungkeun Shim, Ho Young Kim, Danbee Kang, Juhee Cho, Eunsook Lee, Yoon Jung Chang, Hyunsoon Cho; Cancer Res Treat. 2022;54(4):1065-1073. Published online December 8, 2021; DOI: https://doi.org/10.4143/crt.2021.835

Abstract PDF Supplementary Material PubReader ePub

Purpose
Fear of cancer recurrence (FCR) is a common psychological issue in breast cancer (BC) survivors during early survivorship but whether the same is true among long-term survivors has yet to be empirically evaluated. This study investigated FCR level, its associated factors, and impact on quality of life (QoL) in long-term BC survivors.
Materials and Methods
Participants included women diagnosed with BC between 2004 and 2010 at two tertiary hospitals. Survey was conducted in 2020. The study measured FCR with the Fear of Cancer Recurrence Inventory and other patient-reported outcomes, including depression and cancer-related QoL. Logistic regression was used to identify factors associated with FCR, and structural equation modeling was conducted to explore the impact of FCR on other outcomes.
Results
Of 333 participants, the mean age at diagnosis was 45.5, and 46% experienced FCR. Age at diagnosis ≤ 45 (adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.51 to 4.60), shorter time since diagnosis (aOR, 1.75, 95% CI, 1.08 to 2.89), and having a history of recurrence (aOR, 2.56; 95% CI, 1.16 to 5.65) was associated with more FCR. FCR was significantly associated with an increased risk of depression (β=0.471, p < 0.001) and negatively impacted emotional functioning (β=–0.531, p < 0.001). In addition, a higher FCR level may impair overall health-related QoL in long-term BC survivors (β=–0.108, p=0.021).
Conclusion
Ten years after diagnosis, long-term BC survivors still experienced a high level of FCR. Further, the negative impact of FCR on QoL and increased depression risk require an FCR screening and appropriate interventions to enhance long-term BC survivors' QoL.

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D. Azria, C. Bourgier, C. Lemanski
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Clinicopathological Characterization of Double Heterozygosity for BRCA1 and BRCA2 Variants in Korean Breast Cancer Patients: Yoon Ju Bang, Won Kyung Kwon, Seok Jin Nam, Seok Won Kim, Byung-Joo Chae, Se Kyung Lee, Jai Min Ryu, Jong-Won Kim, Jonghan Yu, Jeong Eon Lee; Cancer Res Treat. 2022;54(3):827-833. Published online October 13, 2021; DOI: https://doi.org/10.4143/crt.2021.791

Abstract PDF Supplementary Material PubReader ePub

Purpose
Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant.
Materials and Methods
This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants (PVs/LPVs) were reviewed.
Results
A younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer (TNBC) and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All 7 cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected.
Conclusion
We suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1.

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Multi-locus inherited neoplasia alleles syndromes in cancer: implications for clinical practice
Jeanette Yuen, Siqin Zhou, Rebecca Caeser, Mallika Venkatramani, Diana Nur Bte Ishak, Shao-Tzu Li, Zewen Zhang, Jianbang Chiang, Sock Hoai Chan, Joanne Ngeow
European Journal of Human Genetics.2025; 33(3): 289. CrossRef
Carcinoma erysipeloides secondary to male breast cancer in a patient with BRCA1 and BRCA2 mutations: a clinical presentation and management
Ayushya Ajmani, Daniel W Witheiler, Dario Kivelevitch
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Double heterozygosity for BRCA1 and BRCA2 in breast cancer: considerations in surveillance and cancer risk management
Nonoko Wakaki, Tatsunori Shimoi, Shogo Nakamoto, Yuichiro Kikawa, Aki Ito, Takayuki Iwamoto
BMJ Case Reports.2025; 18(4): e263687. CrossRef
Two-hit events occurred independently in bilateral breast cancers in a germline double heterozygous carrier for BRCA1 and BRCA2
Ryoko Semba, Hidetaka Eguchi, Mizuki Takatsu, Toko Hashizume, Hideaki Moteki, Kazuma Maeno, Fumi Murakami, Junichiro Watanabe, Goro Kutomi, Masami Arai
Breast Cancer.2025; 32(6): 1472. CrossRef
Prevalence of MUTYH Monoallelic Variants in Patients With Hereditary Cancer Using Multigene Panel Testing
Gemma Caliendo, Chiara Della Pepa, Alessia Mignano, Luisa Albanese, Luana Passariello, Anna Cozzolino, Francesca Iengo, Anna Maria Molinari, Laura Pesce, Maria Teresa Vietri
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Clinicopathological features of Chinese ovarian cancer patients with double heterozygosity for cancer-predisposed genes
Yikun Jin, Wenyan Wang, Manqi Wu, Yiming Fan, Tongxia Wang, Cuiyu Huang, Tong Gao, Yan Liu, Yuan Li, Qiyu Liu, Hongyan Guo
BMC Cancer.2025;[Epub] CrossRef
Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study
Limei Zheng, Qianyuan Zhu, Fenglan Zhang, Hao Qiu, Lan Qin, Jianhua Yang, Ming Qi
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Double Pathogenic or Likely Pathogenic Variants in Cancer Predisposition Genes in Hungarian Cancer Patients
Tímea Pócza, János Papp, Anikó Bozsik, Vince Kornél Grolmusz, Petra Nagy, Attila Patócs, Henriett Butz
International Journal of Molecular Sciences.2025; 26(17): 8390. CrossRef
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Junjie Pan, Ning Ren, Lanqi Ren, YiBei Yang, Qiaoping Xu
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Characteristics of Chinese breast cancer patients with double heterozygosity for BRCA1 and BRCA2 germline pathogenic variants
Song Wen, Meng Zhang, Jiuan Chen, Li Hu, Jie Sun, Lu Yao, Ye Xu, Juan Zhang, Yuntao Xie
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Discovery of BRCA1/BRCA2 founder variants by haplotype analysis
Won Kyung Kwon, Hyeok-Jae Jang, Jeong Eon Lee, Yeon Hee Park, Jai Min Ryu, Jonghan Yu, Ja-Hyun Jang, Jong-Won Kim
Cancer Genetics.2022; 266-267: 19. CrossRef

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Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02): Yeon Joo Kim, Yeon-Joo Kim, Yong Bae Kim, Ik Jae Lee, Jeanny Kwon, Kyubo Kim, Jihye Cha, Myungsoo Kim, In Young Jo, Jung Hoon Kim, Jaehyeon Park, Jin Hee Kim, Juree Kim, Kyung Hwan Shin, Su Ssan Kim; Cancer Res Treat. 2022;54(2):478-487. Published online July 12, 2021; DOI: https://doi.org/10.4143/crt.2021.632

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT.
Materials and Methods
This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively.
Results
The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3.
Conclusion
PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

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Pingchuan Li, Lineng Wei, Yinan Ji, Huawei Yang
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Yi-Yan Hong, Hong-Liang Zhan, Guan-Qiao Li, Qiu-Yan Chen, San-Gang Wu, Fu-Xing Zhang
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Anna Maria Merlotti, Stefania Martini, Anna Maria Vandone, Riccardo Bonomi, Salvatore Dario Solla, Francesco Olivero, Lavinia Spinelli, Paola Critelli, Luca Gianello, Riccardo Vigna Taglianti, Grazia Sciancalepore, Alessio Garetto, Gianmauro Numico, Richa
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E. V. Timoshkina, S. I. Tkachev, O. P. Trofimova, M. V. Chernykh, Yu. I. Pryamikova
Tumors of female reproductive system.2025; 21(3): 16. CrossRef
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Yaping Miao, Lexin Wang, Ping Chen, Jiaan Lu, Guanhu Yang, Hao Chi
World Journal of Urology.2024;[Epub] CrossRef
The prognostic differences and the effect of postmastectomy radiotherapy between post‐chemotherapy ypT1‐2ypN1 and de novo pT1‐2N1 breast cancer
Tian Yang, Xiaorong Zhong, Jun Wang, Zhongzheng Xiang, Yuanyuan Zeng, Siting Yu, Zelei Dai, Ningyue Xu, Ting Luo, Lei Liu
Cancer Medicine.2023; 12(7): 8112. CrossRef
Impact of high dose radiotherapy for breast tumor in locoregionally uncontrolled stage IV breast cancer: a need for a risk-stratified approach
Nalee Kim, Haeyoung Kim, Won Park, Won Kyung Cho, Tae Gyu Kim, Young-Hyuck Im, Jin Seok Ahn, Yeon Hee Park, Ji-Yeon Kim
Radiation Oncology.2023;[Epub] CrossRef
Machine learning predicts the prognosis of breast cancer patients with initial bone metastases
Chaofan Li, Mengjie Liu, Jia Li, Weiwei Wang, Cong Feng, Yifan Cai, Fei Wu, Xixi Zhao, Chong Du, Yinbin Zhang, Yusheng Wang, Shuqun Zhang, Jingkun Qu
Frontiers in Public Health.2022;[Epub] CrossRef
Factors Influencing Prognosis in Patients with De Novo Stage IV Breast Cancer: A Systematic Review and Meta-Analysis
Meilin Zhang, Zining Jin, Yingying Xu, Bo Chen, Jian Song, Muyao Li, Feng Jin, Ang Zheng
SSRN Electronic Journal .2022;[Epub] CrossRef

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β1,4-Galactosyltransferase V Modulates Breast Cancer Stem Cells through Wnt/β-catenin Signaling Pathway: Wei Tang, Meng Li, Xin Qi, Jing Li; Cancer Res Treat. 2020;52(4):1084-1102. Published online May 27, 2020; DOI: https://doi.org/10.4143/crt.2020.093

Abstract PDF Supplementary Material PubReader ePub

Purpose
Breast cancer stem cells (BCSCs) contribute to the initiation, development, and recurrence of breast carcinomas. β1,4-Galactosyltransferase V (B4GalT5), which catalyzes the addition of galactose to GlcNAcβ1-4Man of N-glycans, is involved in embryogenesis. However, its role in the modulation of BCSCs remains unknown.
Materials and Methods
The relationship between B4GalT5 and breast cancer stemness was investigated by online clinical databases and immunohistochemistry analysis. Mammosphere formation, fluorescence-activated cell sorting (FACS), and in-vivo assays were used to evaluate B4GalT5 expression in BCSCs and its effect on BCSCs. B4GalT5 regulation of Wnt/β-catenin signaling was examined by immunofluorescence and Ricinus communis agglutinin I pull-down assays. Cell surface biotinylation and FACS assays were performed to assess the association of cell surface B4GalT5 and BCSCs.
Results
B4GalT5, but not other B4GalTs, was highly correlated with BCSC markers and poor prognosis. B4GalT5 significantly increased the stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) and promoted the production of CD44⁺CD24^–/low cells and the formation of mammospheres. Furthermore, B4GalT5 overexpression resulted in dramatic tumor growth in vivo. Mechanistically, B4GalT5 modified and protected Frizzled-1 from degradation via the lysosomal pathway, promoting Wnt/β-catenin signaling which was hyperactivated in BCSCs. B4GalT5, located on the surface of a small subset of breast carcinoma cells, was not responsible for the stemness of BCSCs.
Conclusion
B4GalT5 modulates the stemness of breast cancer through glycosylation modification to stabilize Frizzled-1 and activate Wnt/β-catenin signaling independent of its cell surface location. Our studies highlight a previously unknown role of B4GalT5 in regulating the stemness of breast cancer and provide a potential drug target for anticancer drug development.

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Shaoqin Jiang, Mengqiang Li, Qingfu Su, Ruiling Dou, Shaoshan Lin, Jili Zhang, Xiaochen Sun, Haolan Yu, Wei Bao, Min Qu, Yan Wang, Chenghua Yang, Xu Gao
Advanced Science.2026;[Epub] CrossRef
ATP6V1D drives hepatocellular carcinoma stemness and progression via both lysosome acidification-dependent and -independent mechanisms
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Autophagy.2025; 21(3): 513. CrossRef
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Mou Yan
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Heng Wei, Chie Naruse, Daisuke Takakura, Kazushi Sugihara, Xuchi Pan, Aki Ikeda, Nana Kawasaki, Masahide Asano
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Yongliang Sha, Lei Han, Bei Sun, Qiang Zhao
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Michela Pucci, Martina Duca, Nadia Malagolini, Fabio Dall’Olio
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Glycogene Expression Profile of Human Limbal Epithelial Cells with Distinct Clonogenic Potential
Damien Guindolet, Ashley M. Woodward, Eric E. Gabison, Pablo Argüeso
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ALDH1: A potential therapeutic target for cancer stem cells in solid tumors
Yaolu Wei, Yan Li, Yenan Chen, Pei Liu, Sheng Huang, Yuping Zhang, Yanling Sun, Zhe Wu, Meichun Hu, Qian Wu, Hongnian Wu, Fuxing Liu, Tonghui She, Zhifeng Ning
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The Wnt/β-catenin pathway in breast cancer therapy: a pre-clinical perspective of its targeting for clinical translation
Dezaree Raut, Amisha Vora, Lokesh Kumar Bhatt
Expert Review of Anticancer Therapy.2021;[Epub] CrossRef
Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
Valeria De Pasquale, Luigi Michele Pavone
International Journal of Molecular Sciences.2020; 21(18): 6588. CrossRef

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Real-World Data of Pyrotinib-Based Therapy in Metastatic HER2-Positive Breast Cancer: Promising Efficacy in Lapatinib-Treated Patients and in Brain Metastasis: Ying Lin, Mingxi Lin, Jian Zhang, Biyun Wang, Zhonghua Tao, Yiqun Du, Sheng Zhang, Jun Cao, Leiping Wang, Xichun Hu; Cancer Res Treat. 2020;52(4):1059-1066. Published online April 24, 2020; DOI: https://doi.org/10.4143/crt.2019.633

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis.
Materials and Methods
One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included.
Results
Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea.
Conclusion
Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

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Dagmara Buczek, Renata Zaucha, Jacek Jassem
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Matthew N. Mills, Whitney King, Aixa Soyano, Yolanda Pina, Brian J. Czerniecki, Peter A. Forsyth, Hatem Soliman, Hyo S. Han, Kamran A. Ahmed
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Jing Liu, Xianglu Sun, Qianyu Du, Jinghao Yao, Mengfen Dai, Qianqian Cheng, Han Xu, Yawei Li, Xiuli Liu, Mingliang Zhang, Yongchun Zhou, Yan Yang
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D. J Ouyang, Q. T Chen, M. Anwar, N. Xie, Q. C. Ouyang, P. Z. Fan, L. Y. Qian, G. N. Chen, E. X. Zhou, L. Guo, X. W. Gu, B. N. Ding, X. H. Yang, L. P. Liu, C. Deng, Z. Xiao, J. Li, Y. Q. Wang, S. Zeng, Shouman Wang, Wenjun Yi
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425 Download
41 Web of Science
18 Crossref

RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer: Tian-Hao Weng, Min-Ya Yao, Xiang-Ming Xu, Chen-Yu Hu, Shu-Hao Yao, Yi-Zhi Liu, Zhi-Gang Wu, Tao-Ming Tang, Pei-Fen Fu, Ming-Hai Wang, Hang-Ping Yao; Cancer Res Treat. 2020;52(3):973-986. Published online April 22, 2020; DOI: https://doi.org/10.4143/crt.2019.726

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment.
Materials and Methods
We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model.
Results
Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060.
Conclusion
RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.

Citations

Citations to this article as recorded by

Humanized dual-targeting antibody–drug conjugates specific to MET and RON receptors as a pharmaceutical strategy for the treatment of cancers exhibiting phenotypic heterogeneity
Minghai Wang, Qi Ma, Sreedhar Reddy Suthe, Rachel E. Hudson, Jing-ying Pan, Constantinos Mikelis, Miao-jin Zhu, Zhi-gang Wu, Dan-rong Shi, Hang-ping Yao
Acta Pharmacologica Sinica.2025; 46(5): 1375. CrossRef
Nuclear translocation of RON receptor tyrosine kinase. New mechanistic and functional insights
Yi-Lin Chen, Chien-An Chu, Jiu-Yao Wang, Wan-Li Chen, Yi-Wen Wang, Chung-Liang Ho, Chung-Ta Lee, Nan-Haw Chow
Cytokine & Growth Factor Reviews.2025; 81: 9. CrossRef
The Development of meso-Methyl-BODIPY Conjugates with Boc-seco-CBI and Cabozantinib: The Practical Challenges of Red-Light-Activated Prodrugs for Anticancer PDT
Natalia S. Kuzmina, Galina P. Gribova, Elizaveta M. Pnachina, Lubov V. Krylova, Ekaterina A. Fedotova, Irina V. Balalaeva, Alexey Yu. Fedorov, Vasilii F. Otvagin
Bioconjugate Chemistry.2025; 36(9): 2061. CrossRef
MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence
Kai Wu, Jia Ji, Jingying Pan, Miaojin Zhu, Jiale Zhang, Ting Sun, Dan Lv, Mudan Wei, Minghai Wang, Hangping Yao
Cell Communication and Signaling.2025;[Epub] CrossRef
c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer
Jieun Park, Eun Sol Chang, Ji-Yeon Kim, Chaithanya Chelakkot, Minjung Sung, Ji-Young Song, Kyungsoo Jung, Ji Hye Lee, Jun Young Choi, Na Young Kim, Hyegyeong Lee, Mi-Ran Kang, Mi Jeong Kwon, Young Kee Shin, Yeon Hee Park, Yoon-La Choi
Breast Cancer Research.2024;[Epub] CrossRef
MET alterations detection platforms and clinical implications in solid tumors: a comprehensive review of literature
Pei Yuan, Xuemin Xue, Tian Qiu, Jianming Ying
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer
Sara K. Jaradat, Nehad M. Ayoub, Ahmed H. Al Sharie, Julia M. Aldaod
Technology in Cancer Research & Treatment.2024;[Epub] CrossRef
Recent advancement in developing small molecular inhibitors targeting key kinase pathways against triple-negative breast cancer
Rajibul Islam, Khor Poh Yen, Nur Najihah ’Izzati Mat Rani, Md. Selim Hossain
Bioorganic & Medicinal Chemistry.2024; 112: 117877. CrossRef
TYRO3 and EPHA2 Expression Are Dysregulated in Breast Cancer
Ananda Cristina Fernandes de Aguiar, Nancy Cristina Ferraz de Lucena Ferreira, Maria Amelia Carlos Souto Maior Borba, Darley de Lima Ferreira Filho, Glauber Moreira Leitão, Luiz Alberto Mattos, José Luiz de Lima Filho, Danyelly Bruneska Gondim Martins
Cell Biochemistry and Function.2024;[Epub] CrossRef
The MET Oncogene Network of Interacting Cell Surface Proteins
Simona Gallo, Consolata Beatrice Folco, Tiziana Crepaldi
International Journal of Molecular Sciences.2024; 25(24): 13692. CrossRef
Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials
Kasshish Mehta, Mangala Hegde, Sosmitha Girisa, Ravichandran Vishwa, Mohammed S. Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Ajaikumar B. Kunnumakkara
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Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells
María Luisa Sánchez-León, Carlos Jiménez-Cortegana, Silvia Silva Romeiro, Carmen Garnacho, Luis de la Cruz-Merino, Daniel J. García-Domínguez, Lourdes Hontecillas-Prieto, Víctor Sánchez-Margalet
International Journal of Molecular Sciences.2023; 24(6): 5208. CrossRef
2D Nanosilicate for additive manufacturing: Rheological modifier, sacrificial ink and support bath
Satyam Rajput, Kaivalya A. Deo, Tanmay Mathur, Giriraj Lokhande, Kanwar Abhay Singh, Yuxiang Sun, Daniel L. Alge, Abhishek Jain, Tapasree Roy Sarkar, Akhilesh K. Gaharwar
Bioprinting.2022; 25: e00187. CrossRef
The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies
Alex Cazes, Betzaira G. Childers, Edgar Esparza, Andrew M. Lowy
Cancers.2022; 14(8): 2037. CrossRef
Antibody-drug Conjugate PCMC1D3-Duocarmycin SA as a Novel Therapeutic Entity for Targeted Treatment of Cancers Aberrantly Expressing MET Receptor Tyrosine Kinase
Rachel Hudson, Hang-Ping Yao, Sreedhar Reddy Suthe, Dhavalkumar Patel, Ming-Hai Wang
Current Cancer Drug Targets.2022; 22(4): 312. CrossRef
Pharmaceutical strategies in the emerging era of antibody-based biotherapeutics for the treatment of cancers overexpressing MET receptor tyrosine kinase
Hang-Ping Yao, Xiang-Min Tong, Ming-Hai Wang
Drug Discovery Today.2021; 26(1): 106. CrossRef
Small-Molecule Drug Discovery in Triple Negative Breast Cancer: Current Situation and Future Directions
Minru Liao, Jin Zhang, Guan Wang, Leiming Wang, Jie Liu, Liang Ouyang, Bo Liu
Journal of Medicinal Chemistry.2021; 64(5): 2382. CrossRef
The MSP‐RON pathway regulates liver fibrosis through transforming growth factor beta‐dependent epithelial–mesenchymal transition
Tianhao Weng, Dong Yan, Danrong Shi, Miaojin Zhu, Yizhi Liu, Zhigang Wu, Taoming Tang, Linwei Zhu, Hong Zhang, Hangping Yao, Lanjuan Li
Liver International.2021; 41(8): 1956. CrossRef
MicroRNA Expression Profiling of Lung Cancer with Differential Expression of the RON Receptor Tyrosine Kinase
Huilin Ou, Keda Chen, Hongcheng Wu, Yuan Seng Wu
Journal of Oncology.2021; 2021: 1. CrossRef
RON Mediates Tumor‐Promoting Effects in Endometrial Adenocarcinoma
Qin Yu, Jianzhang Wang, Tiantian Li, Xinxin Xu, Xinyue Guo, Shaojie Ding, Libo Zhu, Gen Zou, Yichen Chen, Xinmei Zhang, Bing Wang
BioMed Research International.2021;[Epub] CrossRef
Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer
Zainab Al-Taie, Mark Hannink, Jonathan Mitchem, Christos Papageorgiou, Chi-Ren Shyu
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Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
Wei Peng, Jian-Di Li, Jing-Jing Zeng, Xiao-Ping Zou, Deng Tang, Wei Tang, Min-Hua Rong, Ying Li, Wen-Bin Dai, Zhong-Qing Tang, Zhen-Bo Feng, Gang Chen
Cancer Cell International.2020;[Epub] CrossRef

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Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test: Hee-Chul Shin, Han-Byoel Lee, Tae-Kyung Yoo, Eun-Shin Lee, Ryong Nam Kim, Boyoung Park, Kyong-Ah Yoon, Charny Park, Eun Sook Lee, Hyeong-Gon Moon, Dong-Young Noh, Sun-Young Kong, Wonshik Han; Cancer Res Treat. 2020;52(3):697-713. Published online February 4, 2020; DOI: https://doi.org/10.4143/crt.2019.559

Abstract PDF Supplementary Material PubReader ePub

Purpose
Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).
Materials and Methods
A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.
Results
Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1.
Conclusion
NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

Citations

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

Abstract PDF PubReader ePub

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

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Prevalence of PALB2 Germline Mutations in Early-onset and Familial Breast/Ovarian Cancer Patients from Pakistan: Muhammad Usman Rashid, Faiz Ali Khan, Noor Muhammad, Asif Loya, Ute Hamann; Cancer Res Treat. 2019;51(3):992-1000. Published online October 11, 2018; DOI: https://doi.org/10.4143/crt.2018.356

Abstract PDF PubReader ePub

Purpose
Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan.
Materials and Methods
PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations.
Results
A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated.
Conclusion
Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.

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FN1 as a key gene in modulating the integrin cell surface pathway in breast cancer
Mahboubeh Sadeghi, Abbas Ghaderi, Pegah Mousavi, Soudabeh Sabetian, Amin Ramezani, Mohammad Reza Haghshenas
Medical Oncology.2026;[Epub] CrossRef
Anticipation effect in Pakistani breast cancer families with or without BRCA1/2 pathogenic variants
Noor Muhammad, Humaira Naeemi, Shumaila Arif, Ute Hamann, Muhammad Usman Rashid
Cancer Epidemiology.2025; 96: 102782. CrossRef
Genetic landscape of Pakistani familial breast cancer patients using multigene panel testing
Muhammad Usman Rashid, Noor Muhammad, Shumaila Arif, Humaira Naeemi, Ute Hamann
International Journal of Cancer.2025; 157(10): 2081. CrossRef
Molecular Symphony in Breast Cancer: Insights on Genomic Discoveries and Epigenetic Regulation
Kalyani R. Thombre, Krishna Radheshyam Gupta, Milind Janrao Umekar
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Prevalence of FANCM germline variants in BRCA1/2 negative breast and/or ovarian cancer patients from Pakistan
Muhammad Usman Rashid, Noor Muhammad, Umara Shehzad, Faiz Ali Khan, Asif Loya, Ute Hamann
Familial Cancer.2023; 22(1): 31. CrossRef
Potential prognostic role of somatic mutations in a set of cancer susceptibility genes in ovarian carcinoma: A follow-up multicentric study from Pakistan
Atika Masood, Rahat Sarfaraz, Saima Zaki, Amira Shami, Saba Khaliq, Nadia Naseem
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Contribution of constitutional BRCA1 promoter methylation to early-onset and familial breast cancer patients from Pakistan
Noor Muhammad, Ayesha Azeem, Muhammad Abu Bakar, Karolina Prajzendanc, Asif Loya, Anna Jakubowska, Ute Hamann, Muhammad Usman Rashid
Breast Cancer Research and Treatment.2023; 202(2): 377. CrossRef
Low prevalence of germline TP53 and PALB2 mutations in unselected cohort of breast cancer patients from Brunei Darussalam
Siti Nur Idayu Matusin, Zen Huat Lu, Mas Rina Wati Haji Abdul Hamid
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Sadia Ajaz, Sani-e-Zehra Zaidi, Saleema Ali, Aisha Siddiqa, Muhammad Ali Memon
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Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan
Fizza Akbar, Zahraa Siddiqui, Muhammad Talha Waheed, Lubaina Ehsan, Syed Ibaad Ali, Hajra Wiquar, Azmina Tajuddin Valimohammed, Shaista Khan, Lubna Vohra, Sana Zeeshan, Yasmin Rashid, Munira Moosajee, Adnan Abdul Jabbar, Muhammad Nauman Zahir, Naila Zahid
Hereditary Cancer in Clinical Practice.2022;[Epub] CrossRef
Contribution of germline PALB2 variants to an unselected and prospectively registered pancreatic cancer patient cohort in Pakistan
Noor Muhammad, Rida Sadaqat, Humaira Naeemi, Iqra Masood, Usman Hassan, Bushra Ijaz, Faisal Hanif, Aamir A. Syed, Muhammed A. Yusuf, Muhammad U. Rashid
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Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients
Muhammad Usman Rashid, Noor Muhammad, Faiz Ali Khan, Umara Shehzad, Humaira Naeemi, Naila Malkani, Ute Hamann
Hereditary Cancer in Clinical Practice.2020;[Epub] CrossRef

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Different Patterns of Risk Reducing Decisions in Affected or Unaffected BRCA Pathogenic Variant Carriers: Eun-Gyeong Lee, Hyok Jo Kang, Myong Cheol Lim, Boyoung Park, Soo Jin Park, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Sang-Yoon Park, Boram Park, Jungnam Joo, Jai Hong Han, Sun-Young Kong, Eun Sook Lee; Cancer Res Treat. 2019;51(1):280-288. Published online May 4, 2018; DOI: https://doi.org/10.4143/crt.2018.079

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers.
Materials and Methods
The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management.
Results
Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001).
Conclusion
RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.

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Family Caring, Culture, and Communication: Barriers to BRCA-Related Risk Disclosure in Korea—A Qualitative Study
Juhye Jin, Jeehee Han, Soo Yeon Kim, Maria C. Katapodi, Sue Kim
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Motaz Daraghma, Aiah Alatoum, Bruna M Thompson Jacinto, Fabiola P Kestelman, Reine I Fahed, Fabiana C Policeni, Su J Kim Hsieh
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Risk-reducing decisions regarding germline BRCA pathogenic variant: focusing on the timing of genetic testing and RRSO
Akiko Abe, Hidetaka Nomura, Atsushi Fusegi, Mayu Yunokawa, Arisa Ueki, Eri Habano, Hiromi Arakawa, Keika Kaneko, Yuko Minoura, Hitoshi Inari, Takayuki Ueno, Hiroyuki Kanao
Journal of Medical Genetics.2024; 61(4): 392. CrossRef
BRCA Mutation Patients: Are There Other Predisposing Factors for Ovarian Cancer Occurrence? A Multicenter Retrospective Study
Vera Loizzi, Michele Mongelli, Francesca Arezzo, Isabella Romagno, Gerardo Cazzato, Ondina Popescu, Francesco Legge, Paolo Trerotoli, Erica Silvestris, Anila Kardhashi, Gennaro Cormio
Gynecologic and Obstetric Investigation.2024; 89(2): 87. CrossRef
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 Research and Treatment.2024; 56(3): 802. CrossRef
Pattern Anlysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers
Dabin Kim, Jai Min Ryu, Sang-Ah Han, Zisun Kim, Sung-Won Kim
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Impact of graphical display on the intention to undergo risk-reducing salpingo-oophorectomy and mastectomy in individuals positive for BRCA pathogenic variant
Yoon-Jung Choi, Younju Park, Boyoung Park, Heejung Chae, So-Youn Jung, Kum Hei Ryu, Myong Cheol Lim, Soo Jin Park, Yoon Jung Chang, Sun-Young Kong
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Impact of the coverage of risk-reducing salpingo-oophorectomy by the national insurance system for women with BRCA pathogenic variants in Japan
Hidetaka Nomura, Akiko Abe, Atsushi Fusegi, Teruyuki Yoshimitsu, Satoki Misaka, Atsushi Murakami, Tsuyoshi Matsumoto, Shiho Tsumura, Motoko Kanno, Yoichi Aoki, Sachiho Netsu, Makiko Omi, Terumi Tanigawa, Sanshiro Okamoto, Kohei Omatsu, Mayu Yunokawa, Hiro
Scientific Reports.2023;[Epub] CrossRef
Characteristics of second primary breast cancer after ovarian cancer: a Korea central cancer registry retrospective study
Eun-Gyeong Lee, Jiwon Lim, Hyeong In Ha, Myong Cheol Lim, Yoon Jung Chang, Young-Joo Won, So-Youn Jung
Frontiers in Oncology.2023;[Epub] CrossRef
Differences in Willingness to Undergo BRCA1/2 Testing and Risk Reducing Surgery among the General Public, Cancer Patients, and Healthcare Professionals: A Large Population-Based Survey
Yoon Jung Chang, Seungyeon Cho, Jungnam Joo, Kum Hei Ryu, Sangwon Lee, Juhee Cho, Myong Cheol Lim, So-Youn Jung, Jai Hong Han, Eun Sook Lee, Sun-Young Kong
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Management of patients with BRCA mutation from the point of view of a breast surgeon
M.L. Riis
Annals of Medicine and Surgery.2021; 65: 102311. CrossRef
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Young Min Hur, Jaehee Mun, Mi-Kyung Kim, Maria Lee, Yun Hwan Kim, Seung-Cheol Kim
Journal of Korean Medical Science.2021;[Epub] CrossRef
Clinical significance of gene polymorphisms for hereditary predisposition to breast and ovarian cancer (review of literature)
D. I. Vodolazhsky, A. V. Mayakovskaya, A. V. Kubyshkin, K. A. Aliev, I. I. Fomochkina
Russian Clinical Laboratory Diagnostics.2021; 66(12): 760. CrossRef
Trends in Risk-Reducing Mastectomy and Risk-Reducing Salpingo-Oophorectomy in Korean Carriers of the BRCA1/2 Mutation
Sung Mi Jung, Jai Min Ryu, Hyung Seok Park, Ji Soo Park, Eunyoung Kang, Seeyoun Lee, Han-Byoel Lee, Hyun Jo Youn, Tae-Kyung Yoo, Jisun Kim, Jeong Eon Lee, Sang Ah Han, Dongwon Kim, Sung-Won Kim
Journal of Breast Cancer.2020; 23(6): 647. CrossRef

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Psychosocial Health of Disease-Free Breast Cancer Survivors Compared with Matched Non-cancer Controls: Boyoung Park, Moo Hyun Lee, Sun-Young Kong, Eun Sook Lee; Cancer Res Treat. 2019;51(1):178-186. Published online April 5, 2018; DOI: https://doi.org/10.4143/crt.2017.585

Abstract PDF PubReader ePub

Purpose
The present study investigated the psychosocial health of disease-free breast cancer survivors who receive health examinations compared to matched non-cancer controls in a community setting.
Materials and Methods
We used baseline data from the Health Examinee cohort, which is composed of subjects participating in health. The disease-free breast cancer survivors were defined as those who were ≥ 2 years from initial diagnosis of breast cancer who had completed treatment. Females without a history of cancer were randomly selected at 1:4 ratio by 5-year age groups, education, and household income as a comparison group. We analyzed results from the Psychosocial Well-being Index-Short Form (PWI-SF) as a psychosocial health measurement.
Results
A total of 347 survivors of breast cancer and 1,388 matched controls were included. Total scores on the PWI-SF were lower in breast cancer survivors than matched non-cancer controls (p=0.006), suggesting a lower level of psychosocial stress in breast cancer survivors. In comparison to the control group, prevalence of drinking, smoking and obesity were lower, while exercising for ≥ 150 min/wk was higher in breast cancer survivors (p < 0.05). These findings suggest that breast cancer survivors have better health behaviors than their noncancer controls. After adjusting for other sociodemographic variables, breast cancer survivors were 36% less likely to be included in the stress group (odds ratio, 0.64; 95% confidence interval, 0.42 to 0.98).
Conclusion
The disease-free breast cancer survivors resuming daily life demonstrated better psychosocial health status compared to matched non-cancer controls.

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Kyunghwa Lee, Doo Ree Kim
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Minji Kim, Yangha Kim
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Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01): In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro; Cancer Res Treat. 2019;51(1):43-52. Published online February 14, 2018; DOI: https://doi.org/10.4143/crt.2017.562

Abstract PDF PubReader ePub

Purpose
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
Materials and Methods
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
Results
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
Conclusion
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

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Safety Results and Analysis of Eribulin Efficacy according to Previous Microtubules-Inhibitors Sensitivity in the French Prospective Expanded Access Program for Heavily Pre-treated Metastatic Breast Cancer: Renaud Sabatier, Véronique Diéras, Xavier Pivot, Etienne Brain, Henri Roché, Jean-Marc Extra, Audrey Monneur, Magali Provansal, Carole Tarpin, François Bertucci, Patrice Viens, Christophe Zemmour, Anthony Gonçalves; Cancer Res Treat. 2018;50(4):1226-1237. Published online December 28, 2017; DOI: https://doi.org/10.4143/crt.2017.446

Abstract PDF Supplementary Material PubReader ePub

Purpose
Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored.
Materials and Methods
Safety data were collected prospectively and we retrospectively collected efficacy data from the five French centres that participated in the Eribulin E7389-G000-398 expanded access program. Our main objectiveswere exploration of safety and analysis of eribulin efficacy (progression-free survival [PFS] and overall survival [OS]) according to sensitivity to the last microtubule-inhibiting agent administered.
Results
Median eribulin treatment duration was 3.3 months for the 250 patients included in this prospective single-arm study. Two hundreds and thirty-nine patients (95.6%) experienced an adverse event (AE) related to treatment including 129 (51.6%) with grade ≥ 3 AEs. The most frequently observed toxicities were cytopenias (59.6% of included patients), gastrointestinal disorders (59.2%), and asthenia (56.4%). The most frequent grade 3-4 AE was neutropenia (37.2% with 4.8% febrile neutropenia). Median PFS and OS were 4.6 and 11.8 months, respectively. Patients classified as responders to the last microtubule-inhibiting therapy had a longer OS (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51 to 0.94; p=0.017), and tended to display a better PFS (HR, 0.78; 95% CI, 0.58 to 1.04; p=0.086). OS improvement was still significant in multivariate analysis (adjusted HR, 0.53; 95% CI, 0.35 to 0.79; p=0.002).
Conclusion
This work based on a prospective study suggests that identification of patients likely to be more sensitive to eribulin could be based on their previous response to microtubules inhibitors.

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Cancer Chemotherapy and Pharmacology.2022; 89(2): 197. CrossRef
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Renaud Sabatier, Johan Martin, Cécile Vicier, Mathilde Guérin, Audrey Monneur, Magali Provansal, Louis Tassy, Carole Tarpin, Jean-Marc Extra, Frédéric Viret, Anthony Goncalves
Journal of Clinical Medicine.2021; 10(6): 1272. CrossRef
The relative effectiveness of eribulin for advanced breast cancer treatment: a study of the southeast Netherlands advanced breast cancer registry
X. G. L. V. Pouwels, S. M. E. Geurts, B. L. T. Ramaekers, F. Erdkamp, B. E. P. J. Vriens, K. N. A. Aaldering, A. J. van de Wouw, M. W. Dercksen, T. J. Smilde, N. A. J. B. Peters, J. M. van Riel, M. J. Pepels, J. Heijnen-Mommers, M. A. Joore, V. C. G. Tjan
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Systematic review of Real-World effectiveness of eribulin for locally advanced or metastatic breast cancer
Isabelle Chabot, Qi Zhao, Yun Su
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Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program
William Jacot, Pierre‐Etienne Heudel, Julien Fraisse, Sophie Gourgou, Séverine Guiu, Florence Dalenc, Barbara Pistilli, Mario Campone, Christelle Levy, Marc Debled, Marianne Leheurteur, Marie Chaix, Claudia Lefeuvre, Anthony Goncalves, Lionel Uwer, Jean‐M
International Journal of Cancer.2019; 145(12): 3359. CrossRef

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Evaluation of the Benefit of Radiotherapy in Patients with Occult Breast Cancer: A Population-Based Analysis of the SEER Database: Byoung Hyuck Kim, Jeanny Kwon, Kyubo Kim; Cancer Res Treat. 2018;50(2):551-561. Published online June 1, 2017; DOI: https://doi.org/10.4143/crt.2017.189

Abstract PDF Supplementary Material PubReader ePub

Purpose
Few studies for occult breast cancer (OBC) have evaluated the effect of radiotherapy (RT) after mastectomy or axillary lymph node dissection (ALND) with/without breast surgery. Therefore, we investigated clinicopathologic factors of OBC with the impact of postoperative RT to determine its prognostic significance using large population-based data.
Materials and Methods
We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from 1983 to 2013. A total of 1,045 eligible patients with OBC were identified. We compared overall survival (OS) using Cox proportional hazards regression with propensity score matching after verifying an imbalance of prognosticators between RT group (n=518) and non-RT group (n=479).
Results
Patients with age < 70 (p=0.033), married marital status (p < 0.001), undergoing ALND (p < 0.001), more examined lymph nodes (LNs) (p < 0.001), and more metastatic LNs (p < 0.001) were more likely to receive RT. Multivariate analysis after propensity score matching (n=798) showed that patients treated with RT survived significantly longer than those without RT (5-year OS, 81.5% vs. 78.3%; p=0.014). A significantly prolonged OS was observed when RT was given to patients treated with mastectomy (p=0.033), those treated with ALND (p=0.036), or those with more than seven metastatic LNs (p=0.016).
Conclusion
RT may offer survival benefit in OBC even after mastectomy or ALND, especially in patients with more than seven metastatic LNs. Further prospective studies are needed to validate these findings.

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Clinically Significant Unclassified Variants in BRCA1 and BRCA2 Genes among Korean Breast Cancer Patients: Kyong-Ah Yoon, Boyoung Park, Byung Il Lee, Moon Jung Yang, Sun-Young Kong, Eun Sook Lee; Cancer Res Treat. 2017;49(3):627-634. Published online September 13, 2016; DOI: https://doi.org/10.4143/crt.2016.292

Abstract PDF PubReader ePub

Purpose
Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls.
Materials and Methods
A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast CancerInformation Core databasewere selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico.
Results
Genetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function.
Conclusion
This study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families.

Citations

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