Cancer Research and Treatment

Original Articles

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

Abstract PDF: 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 (AUROC) 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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Breast cancer

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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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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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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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;[Epub] 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.2024;[Epub] CrossRef
Palbociclib

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

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2 Crossref

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.

Citations

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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
Biosensing chips for cancer diagnosis and treatment: a new wave towards clinical innovation
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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3 Web of Science
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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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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
The Breast.2023; 72: 103594. CrossRef
Response Rate and Safety of a Neoadjuvant Pertuzumab, Atezolizumab, Docetaxel, and Trastuzumab Regimen for Patients With ERBB2-Positive Stage II/III Breast Cancer
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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9 Web of Science
8 Crossref

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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Diana Todea, Andreea Luca, Ioana R. Podina
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Robert W. Mutter, Cynthia Chauhan, Matthew P. Goetz, Jean L. Wright
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Virtual body and emotions: A pilot study on the use of virtual reality for the management of unpleasant sensations after cancer
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Jie Zhao, Menglian Wang, Runze Huang, Jian Xu, Chen Gan, Sheng Yu, Lingxue Tang, Senbang Yao, Wen Li, Huaidong Cheng
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Factors associated with health-related quality of life in a cohort of cancer survivors in New Jersey
Sharon Manne, Katie Devine, Shawna Hudson, Deborah Kashy, Denalee O’Malley, Lisa E. Paddock, Elisa V. Bandera, Adana A. M. Llanos, Angela Fong, Neetu Singh, Sara Frederick, Andrew M. Evens
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Fear of cancer recurrence in South Korean survivors of breast cancer who have received adjuvant endocrine therapy: a cross-sectional study
Seul Ki Park, Yul Ha Min
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Altered regional homogeneity and homotopic connectivity in Chinese breast cancer survivors with fear of cancer recurrence: A resting-state fMRI study
Li Peng, Xiaofei Hu, Chen Xu, Yuanyuan Xu, Han Lai, Ying Yang, Ju Liu, Yuan Xue, Min Li
Journal of Psychosomatic Research.2023; 173: 111454. CrossRef
Protective Factors against Fear of Cancer Recurrence in Breast Cancer Patients: A Latent Growth Model
Gabriella Bentley, Osnat Zamir, Rawan Dahabre, Shlomit Perry, Evangelos C. Karademas, Paula Poikonen-Saksela, Ketti Mazzocco, Berta Sousa, Ruth Pat-Horenczyk
Cancers.2023; 15(18): 4590. CrossRef
Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea
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, Yoonjung Chang, Hyunsoon Cho
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Cost-effectiveness versus treatment effectiveness: A radiation oncologist's dilemma in low-income and middle-income countries (LMIC)
Priya Iyer
The Lancet Regional Health - Southeast Asia.2022; 4: 100061. CrossRef

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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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Cost-effectiveness of talazoparib for patients with germline BRCA1/2 mutated HER2-negative advanced breast cancer in China and the US
Junjie Pan, Ning Ren, Lanqi Ren, YiBei Yang, Qiaoping Xu
Scientific Reports.2024;[Epub] CrossRef
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
Breast Cancer Research and Treatment.2024; 208(1): 155. CrossRef
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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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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ATP6V1D drives hepatocellular carcinoma stemness and progression via both lysosome acidification-dependent and -independent mechanisms
Zhijie Xu, Ruiyang Liu, Haoying Ke, Fuyuan Xu, Pengfei Yang, Weiyu Zhang, Yi Zhan, Zhiju Zhao, Fei Xiao
Autophagy.2024; : 1. CrossRef
Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications
Alejandro Ordaz-Ramos, Olivia Tellez-Jimenez, Karla Vazquez-Santillan
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Beta-1,4-galactosyltransferase-3 deficiency suppresses the growth of immunogenic tumors in mice
Heng Wei, Chie Naruse, Daisuke Takakura, Kazushi Sugihara, Xuchi Pan, Aki Ikeda, Nana Kawasaki, Masahide Asano
Frontiers in Immunology.2023;[Epub] CrossRef
Identification of a Glycosyltransferase Signature for Predicting Prognosis and Immune Microenvironment in Neuroblastoma
Yongliang Sha, Lei Han, Bei Sun, Qiang Zhao
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models
Michela Pucci, Martina Duca, Nadia Malagolini, Fabio Dall’Olio
Cancers.2022; 14(9): 2128. CrossRef
Glycogene Expression Profile of Human Limbal Epithelial Cells with Distinct Clonogenic Potential
Damien Guindolet, Ashley M. Woodward, Eric E. Gabison, Pablo Argüeso
Cells.2022; 11(9): 1575. CrossRef
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
Frontiers in Oncology.2022;[Epub] CrossRef
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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Neurotoxicity-sparing radiotherapy for brain metastases in breast cancer: a narrative review
Dagmara Buczek, Renata Zaucha, Jacek Jassem
Frontiers in Oncology.2024;[Epub] CrossRef
Comparison of the prognostic effect of pyrotinib plus trastuzumab and chemotherapy different lines therapy in HER2-positive advanced breast cancer
Yangqingqing Zhou, Hui Wang, Jiao Yang, Fan Wang, Danfeng Dong, Xiaoai Zhao, Le Wang, Ruiyuan He, Zhiping Ruan, Jin Yang
Journal of Chemotherapy.2024; : 1. CrossRef
HER2-positive metastatic breast cancer with brain metastases responds favorably to pyrotinib and trastuzumab-based treatment: A case report and literature review
Min-long Chen, Wenjie Yu, Binbin Cui, Yijian Yu, Zhaosheng Ma
Frontiers in Oncology.2023;[Epub] CrossRef
Efficacy and safety of inetetamab-containing regimens in patients with HER2-positive metastatic breast cancer: a real-world retrospective study in China
Xiaoyu Liu, Peng Zhang, Chao Li, Xiang Song, Zhaoyun Liu, Wenna Shao, Sumei Li, Xinzhao Wang, Zhiyong Yu
Frontiers in Oncology.2023;[Epub] CrossRef
Evolving management of HER2+ breast cancer brain metastases and leptomeningeal disease
Matthew N. Mills, Whitney King, Aixa Soyano, Yolanda Pina, Brian J. Czerniecki, Peter A. Forsyth, Hatem Soliman, Hyo S. Han, Kamran A. Ahmed
Journal of Neuro-Oncology.2022; 157(2): 249. CrossRef
Temporal Heterogeneity of HER2 Expression and Spatial Heterogeneity of 18F-FDG Uptake Predicts Treatment Outcome of Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer
Chengcheng Gong, Cheng Liu, Zhonghua Tao, Jian Zhang, Leiping Wang, Jun Cao, Yannan Zhao, Yizhao Xie, Xichun Hu, Zhongyi Yang, Biyun Wang
Cancers.2022; 14(16): 3973. CrossRef
Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage
Yuwen Bao, Zhuolin Zhang, Xuan He, Lele Cai, Xiao Wang, Xin Li
Current Oncology.2022; 29(9): 6053. CrossRef
An Insight into Molecular Targets of Breast Cancer Brain Metastasis
Mohammed Kaleem, Mahmood Hassan Dalhat, Lubna Azmi, Turky Omar Asar, Wasim Ahmad, Maimonah Alghanmi, Amal Almostadi, Torki A. Zughaibi, Shams Tabrez
International Journal of Molecular Sciences.2022; 23(19): 11687. CrossRef
Real-World Outcome and Prognostic Factors Among HER2-Positive Metastatic Breast Cancer Patients Receiving Pyrotinib-Based Therapy: A Multicenter Retrospective Analysis
Jing Liu, Xianglu Sun, Qianyu Du, Jinghao Yao, Mengfen Dai, Qianqian Cheng, Han Xu, Yawei Li, Xiuli Liu, Mingliang Zhang, Yongchun Zhou, Yan Yang
Breast Cancer: Targets and Therapy.2022; Volume 14: 491. CrossRef
Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer
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
Pyrotinib Combined With Vinorelbine in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study
Yi Li, Yixuan Qiu, Huihui Li, Ting Luo, Wei Li, Hong Wang, Bin Shao, Biyun Wang, Rui Ge
Frontiers in Oncology.2021;[Epub] CrossRef
Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults
Yueyue Liu, Qian Zhang, Chao Lu, Wei Hu
Drug Design, Development and Therapy.2021; Volume 15: 2485. CrossRef
Brain Metastases in HER2-Positive Breast Cancer: Current and Novel Treatment Strategies
Alejandro Garcia-Alvarez, Andri Papakonstantinou, Mafalda Oliveira
Cancers.2021; 13(12): 2927. CrossRef
Pyrotinib Plus Vinorelbine Versus Lapatinib Plus Capecitabine in Patients With Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Retrospective Study
Yizhao Xie, Yi Li, Luo Ting, Die Sang, Peng Yuan, Wei Li, Huihui Li, Rui Ge, Biyun Wang
Frontiers in Oncology.2021;[Epub] CrossRef
The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study
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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Akanksha Sharma, Lauren Singer, Priya Kumthekar
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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.

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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
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; 2021: 1. 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
Cancers.2021; 13(24): 6278. CrossRef
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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Germline mutations of 4567 patients with hereditary breast-ovarian cancer spectrum in Thailand
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Mugip Rahaman Abdul Wahab, Thirunavukkarasu Palaniyandi, Swarnakala Thamada, Sandhiya Viswanathan, Gomathy Baskar, Hemapreethi Surendran, P Baraneedharan, J Kannan, Maddaly Ravi, Suba Rajinikanth, Mohamed A. El-Tayeb, Shaban Syed
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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.

Citations

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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
Cancer Biomarkers.2023; 36(3): 207. CrossRef
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
F1000Research.2023; 12: 1537. CrossRef
Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations
Sadia Ajaz, Sani-e-Zehra Zaidi, Saleema Ali, Aisha Siddiqa, Muhammad Ali Memon
Frontiers in Genetics.2022;[Epub] CrossRef
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
HPB.2022; 24(12): 2134. CrossRef
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

10,723 View
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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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Risk-reducing decisions regarding germlineBRCApathogenic 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
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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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Signifikanter Überlebensvorteil durch Sacituzumab-Govitecan beim TNBC
Sebastian Weiße, Svenja Quaester, Jürgen Dunst
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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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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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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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Reconceptualizing the clinicopathological features, locoregional therapy and prognostic factors of occult breast cancer in the era of molecular subtyping
Xin Ye, Li Yang, Qi He, Xiaoyan Lin, Jie Wang, Rongrong Cui, Cheng Xu
Women & Health.2023; 63(2): 105. CrossRef
Prognostic Models Using Machine Learning Algorithms and Treatment Outcomes of Occult Breast Cancer Patients
Jingkun Qu, Chaofan Li, Mengjie Liu, Yusheng Wang, Zeyao Feng, Jia Li, Weiwei Wang, Fei Wu, Shuqun Zhang, Xixi Zhao
Journal of Clinical Medicine.2023; 12(9): 3097. CrossRef
Best treatment options for occult breast cancer: A meta-analysis
Rong Wang, Hong-xin Yang, Jie Chen, Jian-jun Huang, Qing Lv
Frontiers in Oncology.2023;[Epub] CrossRef
Occult Breast Cancer Patients with Mastectomy have Better Prognosis than those with Breast-Conserving Therapy
Jiayi Li, Gang Liu, Ziqi Jia, Fei Ren, Dawei Dong, Menglu Zhang, Xiang Wang, Yipeng Wang
Future Oncology.2023; 19(36): 2405. CrossRef
Surgical treatment trends and identification of primary breast tumors after surgery in occult breast cancer: a study based on the Japanese National Clinical Database—Breast Cancer Registry
Mitsuo Terada, Minoru Miyashita, Hiraku Kumamaru, Hiroaki Miyata, Kenji Tamura, Masayuki Yoshida, Etsuyo Ogo, Masayuki Nagahashi, Sota Asaga, Yasuyuki Kojima, Takayuki Kadoya, Kenjiro Aogi, Naoki Niikura, Kotaro Iijima, Naoki Hayashi, Makoto Kubo, Yutaka
Breast Cancer.2022; 29(4): 698. CrossRef
Occult Breast Cancer Presented with Axillary Lymph Node Metastases: A Small Case Series to a Frustrating Medical Issue
D. Mantas, Z. Garoufalia, C. Kontzoglou
Indian Journal of Surgery.2021; 83(S2): 364. CrossRef
Treatment for occult breast cancer: A propensity score analysis of the National Cancer Database
Catherine Tsai, Beiqun Zhao, Theresa Chan, Sarah L. Blair
The American Journal of Surgery.2020; 220(1): 153. CrossRef
Outcome of breast-conserving treatment for axillary lymph node metastasis from occult breast cancer with negative breast MRI
Haeyoung Kim, Won Park, Su Ssan Kim, Sung Ja Ahn, Yong Bae Kim, Tae Hyun Kim, Jin Hee Kim, Jin-Hwa Choi, Hae Jin Park, Jee Suk Chang, Doo Ho Choi
The Breast.2020; 49: 63. CrossRef
Breast-Conserving Surgery in Patients With Mammary Paget's Disease
Yufeng Yao, Li Sun, Yan Meng, Yan Zhuang, Lin Zhao, Qiao Yu, Chengshuai Si
Journal of Surgical Research.2019; 241: 178. CrossRef
Evaluation of the benefit of post‑mastectomy radiotherapy in patients with early‑stage breast cancer: A propensity score matching study
Wenjie Shi, Youhong Luo, Dongkang Zhao, Hao Huang, Weiyi Pang
Oncology Letters.2019;[Epub] CrossRef

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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.

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Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer
Jeong Dong Lee, Won-Ji Ryu, Hyun Ju Han, Tae Yeong Kim, Min Hwan Kim, Joohyuk Sohn
Cancers.2022; 14(10): 2405. CrossRef
Analysis of BRCA1/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study
Joo Heung Kim, Sunggyun Park, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Sung-Won Kim, Jong Won Lee, Min Hyuk Lee, Sue K. Park, Woo-Chul Noh, Doo Ho Choi, Wonshik Han, Sung Hoo Jung
Scientific Reports.2021;[Epub] CrossRef
Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant
Hyung Seok Park, Jai Min Ryu, Ji Soo Park, Seock-Ah Im, So-Youn Jung, Eun-Kyu Kim, Woo-Chan Park, Jun Won Min, Jeeyeon Lee, Ji Young You, Jeong Eon Lee, Sung-Won Kim
Cancer Research and Treatment.2020; 52(3): 680. CrossRef
Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population
Yue Jiang, Ting Tian, Chengxiao Yu, Wen Zhou, Junzhe Yang, Yifeng Wang, Yang Wen, Jiaping Chen, Juncheng Dai, Guangfu Jin, Hongxia Ma, Hongbing Shen, Zhibin Hu
BioMed Research International.2020; 2020: 1. CrossRef
Reinterpretation of BRCA1 and BRCA2 variants of uncertain significance in patients with hereditary breast/ovarian cancer using the ACMG/AMP 2015 guidelines
Min-Kyung So, Tae-Dong Jeong, Woosung Lim, Byung-In Moon, Nam Sun Paik, Seung Cheol Kim, Jungwon Huh
Breast Cancer.2019; 26(4): 510. CrossRef
BRCA gene mutations: A population based review
Ratika Samtani, Deepti Saksena
Gene Reports.2019; 15: 100380. CrossRef
Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer
Min Chul Choi, Ja-Hyun Jang, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Je Ho Lee
International Journal of Gynecological Cancer.2018; 28(2): 308. CrossRef
Differences in attitudes toward genetic testing among the public, patients, and health-care professionals in Korea
Heesang Eum, Mangyeong Lee, Junghee Yoon, Juhee Cho, Eun Sook Lee, Kui Son Choi, Sangwon Lee, So-Youn Jung, Myong Cheol Lim, Sun-Young Kong, Yoon Jung Chang
European Journal of Human Genetics.2018; 26(10): 1432. CrossRef
Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort
Jee-Soo Lee, Sohee Oh, Sue Kyung Park, Min-Hyuk Lee, Jong Won Lee, Sung-Won Kim, Byung Ho Son, Dong-Young Noh, Jeong Eon Lee, Hai-Lin Park, Man Jin Kim, Sung Im Cho, Young Kyung Lee, Sung Sup Park, Moon-Woo Seong
Journal of Medical Genetics.2018; 55(12): 794. CrossRef
Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from ‘unknown significance’ to ‘Likely pathogenic’ based on clinical evidence in Korea
Jai Min Ryu, Goeun Kang, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Se Kyung Lee, Soo Youn Bae, Sungmin Park, Hyun-June Paik, Jong-Won Kim, Sung-Shin Park, Jeong Eon Lee, Sung-Won Kim
The Breast.2017; 33: 109. CrossRef

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An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer: In Hae Park, Joo Hyuk Sohn, Sung Bae Kim, Keun Seok Lee, Joo Seop Chung, Soo Hyeon Lee, Tae You Kim, Kyung Hae Jung, Eun Kyung Cho, Yang Soo Kim, Hong Suk Song, Jae Hong Seo, Hun Mo Ryoo, Sun Ah Lee, So Young Yoon, Chul Soo Kim, Yong Tai Kim, Si Young Kim, Mi Ryung Jin, Jungsil Ro; Cancer Res Treat. 2017;49(3):569-577. Published online September 12, 2016; DOI: https://doi.org/10.4143/crt.2016.289

Abstract PDF PubReader ePub

Purpose
Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol).
Materials and Methods
Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR).
Results
The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p_{non-inferiority}=0.021, p_superiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments.
Conclusion
Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

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

Abstract PDF PubReader ePub

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

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

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Review Article

Improving Conventional or Low Dose Metronomic Chemotherapy with Targeted Antiangiogenic Drugs: Robert S. Kerbel; Cancer Res Treat. 2007;39(4):150-159. Published online December 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.4.150

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One of the most significant developments in medical oncology practice has been the approval of various antiangiogenic drugs for the treatment of a number of different malignancies. These drugs include bevacizumab (Avastin®), the anti-VEGF monoclonal antibody. Thus far, bevacizumab appears to induce clinical benefit in patients who have advanced metastatic disease only or primarily when it is combined with conventional chemotherapy. The reasons for the chemo-enhancing effects of bevacizumab are unknown, and this is a subject that we have been actively studying along with additional ways that antiangiogenic drugs may be combined with chemotherapy. In this respect, we have focused much of our effort on metronomic low dose chemotherapy. We have been studying the hypothesis that some chemotherapy drugs at maximum tolerated doses or other cytotoxic- like drugs such as acute "vascular disrupting agents" (VDAs) can cause an acute mobilization of proangiogenic cells from the bone marrow which home to and colonize the treated tumors, thus accelerating their recovery. These cells include endothelial progenitor cells. This systemic process can be largely blocked by a targeted antiangiogenic drug, e.g. anti-VEGFR-2 antibodies. In addition, metronomic chemotherapy, i.e., close regular administration of chemotherapy drugs at low non-toxic doses with no breaks, over prolonged periods of time not only prevents the acute CEP bone marrow response, but can even target the cells. This potential antiangiogenic effect of metronomic chemotherapy can also be boosted by combination with a targeted antiangiogenic agent. Treatment combinations of metronomic chemotherapy and an antiangiogenic drug have moved into phase II clinical trial testing with particularly encouraging results thus far reported in metastatic breast and recurrent ovarian cancer. Oral chemotherapy drugs such as cyclophosphamide (CTX), methotrexate are the main chemotherapeutics used for such trials. Oral 5-FU prodrugs such as UFT would also appear to be highly suitable based on long term adjuvant therapy studies in patients. Recent preclinical results using metronomic cyclophosphamide and metronomic UFT in models of advanced metastatic breast cancer suggest that this type of combination might be particularly promising for metronomic chemotherapy in this indication, particularly when combined with a targeted antiangiogenic drug.

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Case Report

A Locally Advanced Breast Cancer with Difficult Differential Diagnosis of Carcinosarcoma and Atypical Medullary Carcinoma, which had Poor Response to Adriamycin- and Taxane-based Neoadjuvant Chemotherapy: A Case Report: Se Hyun Kim, Hyun Cheol Chung, Jaeheon Jeong, Ji Hoon Kim, Sun Young Rha, Joong Bae Ahn, Nam Hoon Cho, Hei-Cheul Jeung; Cancer Res Treat. 2007;39(3):134-137. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.134

Abstract PDF PubReader ePub

Atypical medullary carcinomas and carcinosarcoma have unique histopathological features. Here we present a case with a breast malignancy that had pathological characteristics of both. A 54-year old patient with a malignant breast mass received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of paclitaxel monotherapy, and had a poor clinical response to treatment. A modified radical mastectomy was performed. The pathological diagnosis was complicated by an inability to distinguish between atypical medullary carcinoma and carcinosarcoma. The findings included a tumor that was well-circumscribed, high grade and a syncytial growth pattern as well as biphasic sarcomatous and carcinomatous characteristics. In conclusion, atypical medullary carcinoma and carcinosarcoma of the breast have entirely different prognoses and should be managed differently. Both should be treated by surgical resection, and additional therapy should be considered based on the cancer with the poorer prognosis.

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Gunjesh Kumar Singh, Pragya Singh, KT Bhowmik
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Original Articles

Effects of the Expression of Leptin and Leptin Receptor (OBR) on the Prognosis of Early-stage Breast Cancers: Yongnam Kim, Si-Young Kim, Jae Jin Lee, Jeongho Seo, Youn-Wha Kim, Suck Hwan Koh, Hwi-Joong Yoon, Kyung Sam Cho; Cancer Res Treat. 2006;38(3):126-132. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.126

Abstract PDF PubReader ePub

Purpose

Obesity-related leptin and leptin receptor (OBR) have a relation to the development of cancer and metastasis and also the low survival rate for breast cancer patients. Leptin has been associated with increased aromatase activity and it displays functional cross-talk with estrogen. This study was designed to determine the relationship between the expression of leptin and OBR in breast cancer tissue and the prognosis of early-stage breast cancer patients, and especially for the tamoxifen-treated patients.

Materials and Methods

Ninety-five patients with early-stage breast cancer and who had undergone surgical treatment at Kyung Hee University Hospital between January 1994 and June 2004 were analyzed. The surgical specimens underwent immunohistochemical analysis for leptin and OBR. The patients' survival and clinical characteristics were obtained from the medical records.

Results

Of the 95 patients, 79 (83%) and 32 (33.7%) showed the expression of leptin and OBR in breast cancer tissue, respectively. The expression of leptin and OBR in breast cancer tissue was not significantly related to the clinicopathological characteristics, including obesity, the expression of hormonal receptor, the HER-2/neu expression, menopause, stage and the nuclear grade. The expression of leptin and OBR was not significantly related to the overall disease-free survival (DFS). For the tamoxifen-treated postmenopausal obese patients, the DFS of the leptin-positive group was higher than that of the leptin-negative group (p=0.017).

Conclusion

The expression of leptin and OBR in breast cancer tissue may be not a prognostic factor for disease-free survival of breast cancer patients. In the future, further studies are needed to determine whether leptin expression could be a predictive factor for tamoxifen therapy in the postmenopausal obese subgroup among the early breast cancer patients.

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Exploring the multifaceted role of obesity in breast cancer progression
Sooraj Kakkat, Prabhat Suman, Elba A. Turbat- Herrera, Seema Singh, Debanjan Chakroborty, Chandrani Sarkar
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Greater Body Fatness Is Associated With Higher Protein Expression of LEPR in Breast Tumor Tissues: A Cross-Sectional Analysis in the Women’s Circle of Health Study
Adana A.M. Llanos, John B. Aremu, Ting-Yuan David Cheng, Wenjin Chen, Marina A. Chekmareva, Elizabeth M. Cespedes Feliciano, Bo Qin, Yong Lin, Coral Omene, Thaer Khoury, Chi-Chen Hong, Song Yao, Christine B. Ambrosone, Elisa V. Bandera, Kitaw Demissie
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Yan Li, Chunyan Yu, Weimin Deng
European Journal of Pharmacology.2021; 899: 174019. CrossRef
Immunohistochemical analysis of adipokine and adipokine receptor expression in the breast tumor microenvironment: associations of lower leptin receptor expression with estrogen receptor-negative status and triple-negative subtype
Adana A. M. Llanos, Yong Lin, Wenjin Chen, Song Yao, Jorden Norin, Marina A. Chekmareva, Coral Omene, Lei Cong, Angela R. Omilian, Thaer Khoury, Chi-Chen Hong, Shridar Ganesan, David J. Foran, Michael Higgins, Christine B. Ambrosone, Elisa V. Bandera, Kit
Breast Cancer Research.2020;[Epub] CrossRef
Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression
Tsung-Chieh Lin, Kuan-Wei Huang, Chia-Wei Liu, Yu-Chan Chang, Wei-Ming Lin, Tse-Yen Yang, Michael Hsiao
Oncotarget.2018; 9(24): 17210. CrossRef
Immunohistochemical staining of leptin is associated with grade, stage, lymph node involvement, recurrence, and hormone receptor phenotypes in breast cancer
Mohamad Nidal Khabaz, Amer Abdelrahman, Nadeem Butt, Lila Damnhory, Mohamed Elshal, Alia M. Aldahlawi, Swsan Ashoor, Basim Al-Maghrabi, Pauline Dobson, Barry Brown, Kaltoom Al-Sakkaf, Mohmmad Al-Qahtani, Jaudah Al-Maghrabi
BMC Women's Health.2017;[Epub] CrossRef
Leptin, adipocytes and breast cancer: Focus on inflammation and anti-tumor immunity
Laetitia Delort, Adrien Rossary, Marie-Chantal Farges, Marie-Paule Vasson, Florence Caldefie-Chézet
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Leptine : implication dans la physiopathologie du cancer du sein
Florence Caldefie-Chézet, Virginie Dubois, Laetitia Delort, Adrien Rossary, Marie-Paule Vasson
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Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs)
Mehmet Artac, Hakan Bozcuk, Aysel Kıyıcı, Orhan Onder Eren, Melih Cem Boruban, Mustafa Ozdogan
Breast Cancer.2013; 20(2): 174. CrossRef
Leptin attenuates the anti-estrogen effect of tamoxifen in breast cancer
Xiaofeng Chen, Xiaoming Zha, Wei Chen, Tingting Zhu, Jinrong Qiu, Oluf Dimitri Røe, Jun Li, Zhaoxia Wang, Yongmei Yin
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Serum HER2 as a Response Indicator to Various Chemotherapeutic Agents in Tissue HER2 Positive Metastatic Breast Cancer: Sun-Young Kong, Do Hoon Lee, Eun Sook Lee, Susan Park, Keun Seok Lee, Jungsil Ro; Cancer Res Treat. 2006;38(1):35-39. Published online February 28, 2006; DOI: https://doi.org/10.4143/crt.2006.38.1.35

Abstract PDF PubReader ePub

Purpose

The aim of study was to evaluate the usefulness of serum HER2 as a therapeutic response indicator in patients with HER2 positive metastatic breast cancer (MBC).

Materials and Methods

The levels of serum HER2 and CA15.3 were assayed in 148 serial serum samples from 50 HER2 positive MBC patients at both the baseline and follow-ups. The changes in the levels of serum HER2 and CA15.3 in relation to the tumor responses to the various chemotherapy regimens were monitored.

Results

The levels of serum HER2 and CA15.3 were elevated in 82% and 62% of tissue HER2 positive patients, respectively, prior to therapies, with the changes in both tumor markers showing statistical significance in relation to the tumor responses (p<0.01) in patients with elevated baseline serum markers.

Conclusion

The level of serum HER2 could be a valuable response indicator, not only for trastuzumab containing therapy, but also for other common MBC chemotherapeutic agents. Also, as it is more frequently elevated, the serum level of HER2 may also be a more useful tumor marker than CA15.3 in HER2 positive MBC.

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Shivanshu Mishra, Pharyanshu Kachhawa, Prasenjit Mondal, Surajit Ghosh, Chaturvedula Tripura, Nidhi Chaturvedi
IEEE Transactions on Electron Devices.2022; 69(8): 4527. CrossRef
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Journal of Cancer Research and Clinical Oncology.2016; 142(1): 157. CrossRef
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Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors: Eunmi Nam, Soon Nam Lee, Seock-Ah Im, Do-Yeun Kim, Kyoung Eun Lee, Sun Hee Sung; Cancer Res Treat. 2005;37(3):165-170. Published online June 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.3.165

Abstract PDF PubReader ePub

Purpose

Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features.

Materials and Methods

We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression.

Results

The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression.

Conclusion

This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.

Citations

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