Cancer Research and Treatment

Original Articles

Breast Cancer

Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL): Jiyun Lee, Seock-Ah Im, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Yeon Hee Park; Cancer Res Treat. 2021;53(3):695-702. Published online December 17, 2020; DOI: https://doi.org/10.4143/crt.2020.1246

Purpose
YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.
Results
In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

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Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China
Jiao Yang, Bing Zhao, Xiaoling Ling, Donghui Li, Jiuda Zhao, Yonggang Lv, Guangxi Wang, Xinlan Liu, Nanlin Li, Jin Yang
BMC Cancer.2023;[Epub] CrossRef

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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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Prognostic Impact of Elective Supraclavicular Nodal Irradiation for Patients with N1 Breast Cancer after Lumpectomy and Anthracycline Plus Taxane-Based Chemotherapy (KROG 1418): A Multicenter Case-Controlled Study: Haeyoung Kim, Won Park, Jeong Il Yu, Doo Ho Choi, Seung Jae Huh, Yeon-Joo Kim, Eun Sook Lee, Keun Seok Lee, Han-Sung Kang, In Hae Park, Kyung Hwan Shin, Chan Woo Wee, Kyubo Kim, Kyung Ran Park, Yong Bae Kim, Sung Ja Ahn, Jong Hoon Lee, Jin Hee Kim, Mison Chun, Hyung-Sik Lee, Jung Soo Kim, Jihye Cha; Cancer Res Treat. 2017;49(4):970-980. Published online January 4, 2017; DOI: https://doi.org/10.4143/crt.2016.382

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy.
Materials and Methods
We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups.
Results
A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI.
Conclusion
We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.

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Patient-Reported Outcomes Between Whole-Breast Plus Regional Irradiation and Whole-Breast Irradiation Only in pN1 Breast Cancer After Breast-Conserving Surgery and Taxane-Based Chemotherapy: A Randomized Phase 3 Clinical Trial (KROG 17-01)
Nalee Kim, Won Park, Haeyoung Kim, Won Kyung Cho, Sung Ja Ahn, Mi Young Kim, Shin-Hyung Park, Ik Jae Lee, Inbong Ha, Jin Hee Kim, Tae Hyun Kim, Kyu Chan Lee, Hyung-Sik Lee, Tae Gyu Kim, Kyung Hwan Shin, Jong Hoon Lee, Jinhong Jung, Oyeon Cho, Yong Bae Kim
International Journal of Radiation Oncology*Biology*Physics.2025; 121(2): 341. CrossRef
De-escalation of regional nodal irradiation fields in pT1-2N1 breast cancer patients after breast conserving surgery: retrospective real-world clinical experience
Ji Hyun Hong, Jin-Ho Song, Kyu-Hye Choi, Shin Woo Kim, Woo-Chan Park, Jieun Lee, Ahwon Lee, Jun Kang, Byung-Ock Choi
Frontiers in Oncology.2025;[Epub] CrossRef
The optimal regional irradiation volume for breast cancer patients: A comprehensive systematic review and network meta-analysis of published studies
Wei-Xiang Qi, Lu Cao, Cheng Xu, Gang Cai, Jiayi Chen
Frontiers in Oncology.2023;[Epub] CrossRef
Protocol for the postoperative radiotherapy in N1 breast cancer patients (PORT-N1) trial, a prospective multicenter, randomized, controlled, non-inferiority trial of patients receiving breast-conserving surgery or mastectomy
Tae Hoon Lee, Ji Hyun Chang, Bum-Sup Jang, Jae Sik Kim, Tae Hyun Kim, Won Park, Yong Bae Kim, Su Ssan Kim, Wonshik Han, Han-Byoel Lee, Kyung Hwan Shin
BMC Cancer.2022;[Epub] CrossRef
What Is High-risk Breast Cancer With Pathologically Negative Lymph Nodes for Regional Recurrence?
Sang-Won Kim, Won Kyung Cho, Doo Ho Choi, Haeyoung Kim, Oyeon Cho, Won Park, Mison Chun
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Regional nodal irradiation in pT1-2N1 breast cancer patients treated with breast-conserving surgery and whole breast irradiation
Shin-Hyung Park, Jae-Chul Kim
Radiation Oncology Journal.2020; 38(1): 44. CrossRef
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Fabio Corsi, Luca Sorrentino, Sara Albasini, Daniela Bossi, Carlo Morasso, Laura Villani, Marta Truffi
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Locoregional recurrence patterns in women with breast cancer who have not undergone post-mastectomy radiotherapy
Xuran Zhao, Yu Tang, Shulian Wang, Yong Yang, Hui Fang, Jianyang Wang, Hao Jing, Jianghu Zhang, Guangyi Sun, Siye Chen, Jing Jin, Yongwen Song, Yueping Liu, Bo Chen, Shunan Qi, Ning Li, Yuan Tang, Ningning Lu, Hua Ren, Yexiong Li
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Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701)
Haeyoung Kim, Heejung Kim, Won Park, Jong Yun Baek, Sung Ja Ahn, Mi Young Kim, Shin-Hyung Park, Ik Jae Lee, Inbong Ha, Jin Hee Kim, Tae Hyun Kim, Kyu Chan Lee, Hyung-Sik Lee, Tae Gyu Kim, Jin Ho Kim, Jong Hoon Lee, Jinhong Jung, Oyeon Cho, Jee Suk Chang,
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Clinical Significance of Lymph-Node Ratio in Determining Supraclavicular Lymph-Node Radiation Therapy in pN1 Breast Cancer Patients Who Received Breast-Conserving Treatment (KROG 14-18): A Multicenter Study
Jaeho Kim, Won Park, Jin Kim, Doo Choi, Yeon-Joo Kim, Eun Lee, Kyung Shin, Jin Kim, Kyubo Kim, Yong Kim, Sung-Ja Ahn, Jong Lee, Mison Chun, Hyung-Sik Lee, Jung Kim, Jihye Cha
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Breast Conservation Therapy Versus Mastectomy in Patients with T1-2N1 Triple-Negative Breast Cancer: Pooled Analysis of KROG 14-18 and 14-23
Kyubo Kim, Hae Jin Park, Kyung Hwan Shin, Jin Ho Kim, Doo Ho Choi, Won Park, Seung Do Ahn, Su Ssan Kim, Dae Yong Kim, Tae Hyun Kim, Jin Hee Kim, Jiyoung Kim
Cancer Research and Treatment.2018; 50(4): 1316. CrossRef

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Postmastectomy Radiotherapy in Patients with pT1-2N1 Breast Cancer Treated with Taxane-Based Chemotherapy: A Retrospective Multicenter Analysis (KROG 1418): Yeon-Joo Kim, Won Park, Boram Ha, Boram Park, Jungnam Joo, Tae Hyun Kim, In Hae Park, Keun Seok Lee, Eun Sook Lee, Kyung Hwan Shin, Haeyoung Kim, Jeong Il Yu, Doo Ho Choi, Seung Jae Huh, Chan Woo Wee, Kyubo Kim, Kyung Ran Park, Yong Bae Kim, Sung Ja Ahn, Jong Hoon Lee, Jin Hee Kim, Mison Chun, Hyung-Sik Lee, Jung Soo Kim, Jihye Cha; Cancer Res Treat. 2017;49(4):927-936. Published online December 26, 2016; DOI: https://doi.org/10.4143/crt.2016.508

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy.
Materials and Methods
We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010.
Results
We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [–]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081).
Conclusion
PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.

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Does Post-Mastectomy Radiotherapy Confer Survival Benefits on Patients With 1-3 Clinically Positive Lymph Nodes Rendered Pathologically Negative After Neoadjuvant Systemic Chemotherapy: Consensus from A Pooled Analysis?
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PLOS ONE.2022; 17(6): e0270528. CrossRef
Suggestion for the omission of post-mastectomy chest wall radiation therapy in patients who underwent skin-sparing/nipple-sparing mastectomy
Nalee Kim, Won Park, Won Kyung Cho, Hae Young Kim, Doo Ho Choi, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Jonghan Yu, Byung Joo Chae, Se Kyung Lee, Jai Min Ryu, Goo-Hyun Mun, Jai-Kyong Pyon, Byung-Joon Jeon
The Breast.2022; 66: 54. CrossRef
Post-mastectomy radiation therapy in breast cancer patients with 1–3 positive lymph nodes: No one size fits all
Majd Kayali, Joseph Abi Jaoude, Arafat Tfayli, Nagi El Saghir, Philip Poortmans, Youssef H. Zeidan
Critical Reviews in Oncology/Hematology.2020; 147: 102880. CrossRef
The survival benefit of postmastectomy radiotherapy for breast cancer patients with T1-2N1 disease according to molecular subtype
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Local and regional recurrence following mastectomy in breast cancer patients with 1–3 positive nodes: implications for postmastectomy radiotherapy volume
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Effects of Postoperative Radiotherapy on Leptomeningeal Carcinomatosis or Dural Metastasis after Resection of Brain Metastases in Breast Cancer Patients: Boram Ha, Seung Yeun Chung, Yeon-Joo Kim, Ho-Shin Gwak, Jong Hee Chang, Sang Hyun Lee, In Hae Park, Keun Seok Lee, Seeyoun Lee, Tae Hyun Kim, Dae Yong Kim, Seok-Gu Kang, Chang-Ok Suh; Cancer Res Treat. 2017;49(3):748-758. Published online October 31, 2016; DOI: https://doi.org/10.4143/crt.2016.303

Abstract PDF Supplementary Material PubReader ePub

Purpose
In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer.
Materials and Methods
Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not.
Results
With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM.
Conclusion
WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

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Jerome J. Graber, Santosh Kesari
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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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Xin-shuai Wang, De-jiu Kong, Tzu-yin Lin, Xiao-cen Li, Yoshihiro Izumiya, Xue-zhen Ding, Li Zhang, Xiao-chen Hu, Jun-qiang Yang, She-gan Gao, Kit S Lam, Yuan-pei Li
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Case Report

A Rare Case of Phyllodes Tumor Metastasis to the Stomach Presenting as Anemia: Do Il Choi, Ho Seok Chi, Sang Ho Lee, Youngmee Kwon, Seog Yun Park, Sung Hoon Sim, In Hae Park, Keun Seok Lee; Cancer Res Treat. 2017;49(3):846-849. Published online September 1, 2016; DOI: https://doi.org/10.4143/crt.2016.188

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Metastasis of a phyllodes tumor to the stomach is an extremely rare condition with important clinical implications. A 44-year-old woman was initially diagnosed with a phyllodes tumor in her right breast in 2008, and subsequently presented to an outpatient clinic with dizziness on December 16, 2013. We found that she had severe anemia (hemoglobin levels, 6.7 g/dL), and we quickly performed esophagogastroduodenoscopy to identify the cause. This procedure revealed large ulcerofungating masses with active bleeding in the stomach. Histopathological examination revealed that the masses were consistent with phyllodes tumor metastases. In patients with a metastatic phyllodes tumor presenting as anemia, gastric metastasis should be considered as one of the differential diagnoses because overlooking the possibility might have dire consequences if cytotoxic chemotherapy were administered.

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Unusual Metastatic Sites in Malignant Phyllodes Tumor Detected on FDG PET/CT
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NKILA is a novel suppressor of local recurrence in women breast malignant phyllodes tumor patients via inhibition of the NF-κB pathway
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A rare case of metastatic malignant phyllodes tumor with osteosarcomatous differentiation presenting with intestinal obstruction
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Indian Journal of Pathology and Microbiology.2023; 66(1): 184. CrossRef
Clinical perspectives and outcomes of the giant breast phyllodes tumor and sarcoma: a real-world retrospective study
Naiquan Liu, Ye Kang, Ningxin Qu, Chenhui Kong, Ye Han
BMC Cancer.2023;[Epub] CrossRef
Metastasis to the stomach: a systematic review
Arturan Ibrahimli, Altay Aliyev, Aykhan Majidli, Aysegul Kahraman, Aysuna Galandarova, Emil Khalilzade, Heydar Mammadli, Kamran Huseynli, Karam Assaf, Cagatay Kilinc, Nijat Muradov, Omer F. Alisan, Sabir Abdullayev, Yeliz I. Sahin, Elgun Samadov
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Significant Antitumor Activity of Pazopanib in a Patient with PDGFRB-Mutated Metastatic Phyllodes Tumor: a Case Report
Mieko Ochi, Shingo Miyamoto, Keita Nakao, Yoshiaki Furuhata, Yusuke Tabei, Shunsuke Ichi, Yuan Bae, Toshio Kumasaka, Shingo Kato, Hideo Kunitoh
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Malignant phyllodes tumor of the breast: case report, tumor characteristics, treatment approach
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A giant malignant phyllodes tumor of breast post mastectomy with metastasis to stomach manifesting as anemia: a case report and review of literature
Hui-Pu Liu, Wen-Yen Chang, Chin-Wen Hsu, Shan-Tao Chien, Zheng-Yi Huang, Wen-Ching Kung, Ping-Hung Liu
BMC Surgery.2020;[Epub] CrossRef
Distant metastases in phyllodes tumours of the breast: an overview
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Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review
Tiphaine de Foucher, Hélène Roussel, Mikael Hivelin, Léa Rossi, Caroline Cornou, Anne-Sophie Bats, Myriam Deloménie, Fabrice Lécuru, Charlotte Ngô
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Original Articles

Feasibility and Efficacy of Eribulin Mesilate in Korean Patients with Metastatic Breast Cancer: Korean Multi-center Phase IV Clinical Study Results: Yeon Hee Park, Tae Yong Kim, Young-Hyuck Im, Keun-Seok Lee, In Hae Park, Joohyuk Sohn, Soo-Hyeon Lee, Seock-Ah Im, Jee Hyun Kim, Se Hyun Kim, Soo Jung Lee, Su-Jin Koh, Ki Hyeong Lee, Yoon Ji Choi, Eun Kyung Cho, Suee Lee, Seok Yun Kang, Jae Hong Seo, Sung-Bae Kim, Kyung Hae Jung; Cancer Res Treat. 2017;49(2):423-429. Published online August 3, 2016; DOI: https://doi.org/10.4143/crt.2016.191

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Purpose
Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC),who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials.
Materials and Methods
In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2 dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease.
Results
A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively.
Conclusion
This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

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Kun-Ming Rau, Fu Ou-Yang, Ta-Chung Chao, Yao-Lung Kuo, Tsui-Fen Cheng, Tsu-Yi Chao, Dar-Ren Chen, Yen-Dun Tzeng, Being-Whey Wang, Chun-Yu Liu, Ming-Hung Hu, Yin-Che Lu, Wei-Jen Ou, Chin-Ho Kuo, Chieh-Han Chuang, Jung-Yu Kan, Fang-Ming Chen, Ming-Feng Hou
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Lenka Varinska, Peter Kubatka, Jan Mojzis, Anthony Zulli, Katarina Gazdikova, Pavol Zubor, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Iveta Gasparova, Martin Klabusay, Martin Pec, Eitan Fibach, Mariusz Adamek, Peter Kruzliak
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Oncotarget.2017; 8(67): 112076. CrossRef

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Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A Multicenter Retrospective Cohort Study: Se Hyun Kim, Kyung Hae Jung, Tae-Yong Kim, Seock-Ah Im, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, Sarah Park, In Hae Park, Keun Seok Lee, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Jee Hyun Kim; Cancer Res Treat. 2016;48(4):1373-1381. Published online March 23, 2016; DOI: https://doi.org/10.4143/crt.2015.475

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy.
Materials and Methods
This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model.
Results
A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2– subtype.
Conclusion
LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2– patients is notable and worthy of further investigation.

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Journal of Breast Cancer.2016; 19(4): 394. CrossRef

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Locoregional Recurrence by Tumor Biology in Breast Cancer Patients after Preoperative Chemotherapy and Breast Conservation Treatment: Eunjin Jwa, Kyung Hwan Shin, Ja Young Kim, Young Hee Park, So-Youn Jung, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, Yeon-Joo Kim, Tae Hyun Kim; Cancer Res Treat. 2016;48(4):1363-1372. Published online February 18, 2016; DOI: https://doi.org/10.4143/crt.2015.456

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Purpose
The purpose of this study is to determine whether breast cancer subtype can affect locoregional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) after neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). Materials and Methods We evaluated 335 consecutive patients with clinical stage II-III breast cancer who received NAC plus BCT from 2002 to 2009. Patients were classified according to six molecular subtypes: luminal A (hormone receptor [HR]+/HER2–/Ki-67 < 15%, n=113), luminal B1 (HR+/HER2–/Ki-67 ≥ 15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab (HER2[T+]) (HR–/HER2+/use of trastuzumab, n=14), HER2 without trastuzumab (HER2[T–]) (HR–/HER2+, n=31), and triple negative (TN) (HR–/HER2–, n=61).
Results
After a median follow-up period of 7.2 years, 26 IBTRs and 37 LRRs occurred. The 5-year LRR-free survival rates were luminal A, 96.4%; B1, 93.9%; B2, 90.3%; HER2(T+), 92.9%; HER2(T–), 78.3%; and TN, 79.6%. The 5-year IBTR-free survival rates were luminal A, 97.2%; B1, 93.9%; B2, 92.8%; HER2(T+), 92.9%; HER2(T–), 89.1%; and TN, 84.6%. In multivariate analysis, HER2(T–) (IBTR: hazard ratio, 4.2; p=0.04 and LRR: hazard ratio, 7.6; p < 0.01) and TN subtypes (IBTR: hazard ratio, 6.9; p=0.01 and LRR: hazard ratio, 8.1; p < 0.01) were associated with higher IBTR and LRR rates. A pathologic complete response (pCR) was found to show correlation with better LRR and a tendency toward improved IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03). Conclusion The TN and HER2(T–) subtypes predict higher rates of IBTR and LRR after NAC and BCT. A pCR is predictive of improved IBTR or LRR in TN subtype.

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Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane: Hyeon Kang Koh, Kyung Hwan Shin, Kyubo Kim, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, So-Youn Jung, Seeyoun Lee, Seok Won Kim, Han-Sung Kang, Eui Kyu Chie, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee, Seock-Ah Im, Sung Whan Ha; Cancer Res Treat. 2016;48(2):483-490. Published online June 5, 2015; DOI: https://doi.org/10.4143/crt.2015.111

Abstract PDF PubReader ePub

Purpose
This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. Materials and Methods From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome.
Results
The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. Conclusion RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.

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Timing of Postmastectomy Radiotherapy Following Adjuvant Chemotherapy for High-Risk Breast Cancer: A Post-Hoc Analysis of a Randomised Controlled Clinical Trial
Si-Ye Chen, Guang-Yi Sun, Yu Tang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Xu-Ran Zhao, Yu-Chun Song, Bo Chen, Shu-Nan Qi, Yuan Tang, Ning-Ning Lu, Ning Li, Hui Fang, Ye-Xiong Li, Shu-Lian Wang
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Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome: Siew Kuan Lim, Moo Hyun Lee, In Hae Park, Ji Young You, Byung-Ho Nam, Byeong Nam Kim, Jungsil Ro, Keun Seok Lee, So-Youn Jung, Young Mee Kwon, Eun Sook Lee; Cancer Res Treat. 2016;48(1):133-141. Published online April 7, 2015; DOI: https://doi.org/10.4143/crt.2014.262

Abstract PDF PubReader ePub

Purpose
The aim of this study was to examine molecular subtype conversions in patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical implications.
Materials and Methods
We included consecutive breast cancer patients who received NAC at the National Cancer Center, Korea, between August 2002 and June 2011, and had available data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and PR Allred scores before and after NAC were compared, and the long-term outcomes were analyzed.
Results
Of 322 patients, 32 (9.9%) achieved a pathologic complete response after NAC. HR+/HER2– tumors tended to convert into triple negative (TN) tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become HR+/HER2– tumors. Clinical outcomes of molecular subtype conversion groups were compared against patients who remained as HR+/HER2– throughout. The HR+/HER2– to TN group had significantly poorer recurrencefree survival (RFS) (hazard ratio, 3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS) (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN to HR+/HER2– showed improved comparable survival outcomes.
Conclusion
Molecular subtypes of breast cancers changed frequently after NAC, resulting in different tumor prognostication. Tumor subtyping should be repeated after NAC in patients with breast cancer.

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Breast Cancer–Related Lymphedema after Neoadjuvant Chemotherapy: Myungsoo Kim, In Hae Park, Keun Seok Lee, Jungsil Ro, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Tae Hyun Kim, Kwan Ho Cho, Kyung Hwan Shin; Cancer Res Treat. 2015;47(3):416-423. Published online November 17, 2014; DOI: https://doi.org/10.4143/crt.2014.079

Abstract PDF PubReader ePub

Purpose
The risk for lymphedema (LE) after neoadjuvant chemotherapy (NCT) in breast cancer patients has not been fully understood thus far. This study is conducted to investigate the incidence and time course of LE after NCT. Materials and Methods A total of 313 patients with clinically node-positive breast cancer who underwent NCT followed by surgery with axillary lymph node (ALN) dissection from 2004 to 2009 were retrospectively analyzed. All patients received breast and supraclavicular radiation therapy (SCRT). The determination of LE was based on both objective and subjective methods, as part of a prospective database. Results At a median follow-up of 5.6 years, 132 patients had developed LE: 88 (28%) were grade 1; 42 (13%) were grade 2; and two (1%) were grade 3. The overall 5-year cumulative incidence of LE was 42%. LE first occurred within 6 months after surgery in 62%; 1 year in 77%; 2 years in 91%; and 3 years in 96%. In a multivariate analysis, age (hazard ratio [HR], 1.66; p < 0.01) and the number of dissected ALNs (HR, 1.68; p < 0.01) were independent risk factors for LE. Patients with both of these risk factors showed a significantly higher 5-year cumulative incidence of LE compared with patients with no or one risk factor (61% and 37%, respectively; p < 0.001). The addition of adjuvant chemotherapy did not significantly correlate with LE. Conclusion LE after NCT, surgery, and SCRT developed early after treatment, and with a high incidence rate. More frequent surveillance of arm swelling may be necessary in patients after NCT, especially during the first few years of follow-up.

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