Cancer Research and Treatment

Original Articles

Breast cancer

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

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

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Efficacy and Safety of Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Real-World Studies
Hui-Chen Su, Ho-Wei Lin, Ka-Wai Tam
Targeted Oncology.2025; 20(1): 71. CrossRef
Palbociclib Is Safe for Breast Cancer Patients With Mild Hepatic Impairment: A Multicenter Retrospective Study Using Real‐World Data
Alieke K. Bos, Annelieke E.C.A.B. Willemsen, Loes E. Visser, Lennart J. Stoker, Jurjen S. Kingma, Mirjam K. Rommers, Emile M. Kuck, Paul D. van der Linden, Merel van Nuland
Clinical Pharmacology & Therapeutics.2025; 117(4): 1115. CrossRef
Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
Nadia Harbeck, Adam Brufsky, Chloe Grace Rose, Beata Korytowsky, Connie Chen, Krista Tantakoun, Endri Jazexhi, Do Hoang Vien Nguyen, Meaghan Bartlett, Imtiaz A. Samjoo, Timothy Pluard
Frontiers in Oncology.2025;[Epub] CrossRef
Palbociclib

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

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Lobular Carcinoma In Situ during Preoperative Biopsy and the Rate of Upgrade: Jeea Lee, Ga Yoon Ku, Haemin Lee, Hyung Seok Park, Ja Seung Ku, Jee Ye Kim, Seho Park, Byeong-Woo Park; Cancer Res Treat. 2022;54(4):1074-1080. Published online December 21, 2021; DOI: https://doi.org/10.4143/crt.2021.864

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Purpose
There is a potential risk that lobular carcinoma in situ (LCIS) on preoperative biopsy might be diagnosed as ductal carcinoma in situ (DCIS) or invasive carcinoma in the final pathology. This study aimed to evaluate the rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive carcinoma.
Materials and Methods
Data of 55 patients with LCIS on preoperative biopsy were analyzed. All patients underwent surgery between 1991 and 2016 at Severance Hospital in Seoul, Korea. We analyzed the rate of upgrade of preoperative LCIS to DCIS or invasive cancer in the final pathology. The clinicopathologic features related to the upgrade were evaluated.
Results
The rate of upgrade of LCIS to DCIS or invasive carcinoma was 16.4% (9/55). In multivariate analysis, microcalcification and progesterone receptor expression were significantly associated with the upgrade of LCIS (p=0.023 and p=0.044, respectively).
Conclusion
The current study showed a relatively high rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive cancer. The presence of microcalcification and progesterone receptor expression may be potential predictors of upgradation of LCIS on preoperative biopsy. Surgical excision of the LCIS during preoperative biopsy could be a management option to identify the concealed malignancy.

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Impact of Axillary Burden on Survival: A Comparative Study of Invasive Lobular Carcinoma and Invasive Ductal Carcinoma in Early-Stage Breast Cancer
Kwang Hyun Yoon, Jee Hyun Ahn, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Seho Park
Cancers.2025; 17(6): 1002. CrossRef
Upgrade Rate and Long-term Outcomes of Lobular Neoplasia
Sara Ardila, Annabel Chen, Taylor Maramara, Danielle Henry, April Phantana-angkool
Current Breast Cancer Reports.2024; 16(1): 11. CrossRef
Immediate and delayed risk of breast cancer associated with classic lobular carcinoma in situ and its variants
Hannah L. Chung, Lavinia P. Middleton, Jia Sun, Gary J. Whitman
Breast Cancer Research and Treatment.2024; 205(3): 545. CrossRef
De-escalation of Surgical Intervention and Contemporary Management Recommendations for Lobular Neoplasia, Atypical Ductal Hyperplasia, and Ductal Carcinoma In Situ
Amanda L. Amin, Megan E. Miller
Current Breast Cancer Reports.2023; 15(3): 298. CrossRef
In Search of Calcifications : Histologic Analysis and Diagnostic Yield of Stereotactic Core Needle Breast Biopsies
Fazilet Yilmaz, Sean M Hacking, Linda Donegan, Lijuan Wang, Evgeny Yakirevich, Yihong Wang
American Journal of Clinical Pathology.2023; 160(2): 200. CrossRef

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A Phase II Study to Evaluate the Safety and Efficacy of Pegteograstim in Korean Breast Cancer Patients Receiving Dose-Dense Doxorubicin/Cyclophosphamide: Gun Min Kim, Joo Hoon Kim, Ji Heung Kim, Young Up Cho, Seung Il Kim, Seho Park, Hyung Seok Park, Ji Ye Kim, Joohyuk Sohn; Cancer Res Treat. 2019;51(2):812-818. Published online September 19, 2018; DOI: https://doi.org/10.4143/crt.2018.383

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Purpose
Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent metaanalysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT.
Materials and Methods
Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability.
Results
Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%).
Conclusion
Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.

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Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices
Noehyun Myung, Hyun-Wook Kang
Asian Journal of Pharmaceutical Sciences.2024; 19(1): 100884. CrossRef
Safety and Efficacy of Pegteograstim on Chemotherapy-induced Neutropenia in Children and Adolescents With Solid Tumors
Hee Won Cho, Ji Won Lee, Hee Young Ju, Ju Kyung Hyun, Keon Hee Yoo, Hong Hoe Koo, Kyunga Kim, Ki Woong Sung
Journal of Pediatric Hematology/Oncology.2022; 44(2): e362. CrossRef
Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity
Michelle Shayne, R. Donald Harvey, Gary H. Lyman
Expert Review of Anticancer Therapy.2021; 21(10): 1145. CrossRef

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Feasibility of Charcoal Tattooing of Cytology-Proven Metastatic Axillary Lymph Node at Diagnosis and Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients: Seho Park, Ja Seung Koo, Gun Min Kim, Joohyuk Sohn, Seung Il Kim, Young Up Cho, Byeong-Woo Park, Vivian Youngjean Park, Jung Hyun Yoon, Hee Jung Moon, Min Jung Kim, Eun-Kyung Kim; Cancer Res Treat. 2018;50(3):801-812. Published online August 17, 2017; DOI: https://doi.org/10.4143/crt.2017.210

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Purpose
Sentinel lymph node biopsy (SLNB) can be performed when node-positive disease is converted to node-negative status after neoadjuvant chemotherapy (NCT). Tattooing nodes might improve accuracy but supportive data are limited. This study aimed to investigate the feasibility of charcoal tattooing metastatic axillary lymph node (ALN) at presentation followed by SLNB after NCT in breast cancers.
Materials and Methods
Twenty patientswith cytology-proven node metastases prospectively underwent charcoal tattooing at diagnosis. SLNB using dual tracers and axillary surgery after NCT were then performed. The detection rate of tattooed node and diagnostic performance of SLNB were analyzed.
Results
All patients underwent charcoal tattooingwithout significant morbidity. Sentinel and tattooed nodes could be detected during surgery after NCT. Nodal pathologic complete response was achieved in 10 patients. Overall sensitivity, false-negative rate (FNR), negative predictive value, and accuracy of hot/blue SLNB were 80.0%, 20.0%, 83.3%, and 90.0%, respectively. Retrieving more nodes and favorable nodal response were associated with improved performance. The best accuracy was observed when excised tattooed node was calculated together (FNR, 0.0%). Cold/non-blue tattooed nodes of five patients were removed during non-sentinel axillary surgery but clinicopathological parameters did not differ compared to patients with hot/blue tattooed node detected during SLNB, suggesting the importance of the tattooing procedure itself to improve performance.
Conclusion
Charcoal tattooing of cytology-confirmed metastatic ALN at presentation is technically feasible and does not limit SLNB after NCT. The tattooing procedure without additional preoperative localization is advantageous for improving the diagnostic performance of SLNB in this setting.

Citations

Citations to this article as recorded by

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Targeted Axillary Dissection for Clinically Node-Positive Breast Cancer Cases that Turn Negative After Neoadjuvant Systemic Therapy Using Charcoal Tattooing
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Andrew Seto, Cynthia Lin, Samantha Norden, Jamie Stratton, Moira O'Riordan, Helen Pass
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Annals of Surgery.2019; 269(3): 432. CrossRef
Axillary Lymph Node Tattooing and Targeted Axillary Dissection in Breast Cancer Patients Who Presented as cN+ Before Neoadjuvant Chemotherapy and Became cN0 After Treatment
Ioannis Natsiopoulos, Stavros Intzes, Triantafyllos Liappis, Konstantinos Zarampoukas, Thomas Zarampoukas, Vasiliki Zacharopoulou, Konstantinos Papazisis
Clinical Breast Cancer.2019; 19(3): 208. CrossRef
Pretreatment Tattoo Marking of Suspicious Axillary Lymph Nodes: Reliability and Correlation with Sentinel Lymph Node
Rupa Patel, Wendy MacKerricher, Jacqueline Tsai, Nicole Choy, Jafi Lipson, Debra Ikeda, Sunita Pal, Wendy De Martini, Kimberly H. Allison, Irene L. Wapnir
Annals of Surgical Oncology.2019; 26(8): 2452. CrossRef
Node positive breast cancer: Concordance between baseline PET/CT and sentinel node assessment after neoadjuvant therapy
Oscar Leopoldo Christin, Jonathan Kuten, Einat Even-Sapir, Joseph Klausner, Tehillah S. Menes
Surgical Oncology.2019; 30: 1. CrossRef
Sentinel Node Lymph Node Surgery After Neoadjuvant Therapy: Principles and Techniques
Jennifer M. Racz, Abigail S. Caudle
Annals of Surgical Oncology.2019; 26(10): 3040. CrossRef
Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer
J M Simons, M L M A van Pelt, A W K S Marinelli, M E Straver, A M Zeillemaker, L M Pereira Arias-Bouda, T J A van Nijnatten, L B Koppert, K K Hunt, M L Smidt, E J T Luiten, C C van der Pol
British Journal of Surgery.2019; 106(12): 1632. CrossRef
Ultrasound-guided dual-localization for axillary nodes before and after neoadjuvant chemotherapy with clip and activated charcoal in breast cancer patients: a feasibility study
Won Hwa Kim, Hye Jung Kim, See Hyung Kim, Jin Hyang Jung, Ho Yong Park, Jeeyeon Lee, Wan Wook Kim, Ji Young Park, Yee Soo Chae, Soo Jung Lee
BMC Cancer.2019;[Epub] CrossRef
Conservative Management of Positive Axilla After Neoadjuvant Systemic Therapy—The Need for, and Review of, Techniques Used for Lymph Node Localization
Matthew Green, Foteini Neamonitou, Raghavan Vidya
Clinical Breast Cancer.2018; 18(5): e739. CrossRef
Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint
Judy C. Boughey, Michael D. Alvarado, Rachael B. Lancaster, W. Fraser Symmans, Rita Mukhtar, Jasmine M. Wong, Cheryl A. Ewing, David A. Potter, Todd M. Tuttle, Tina J. Hieken, Jodi M. Carter, James W. Jakub, Henry G. Kaplan, Claire L. Buchanan, Nora T. Ja
npj Breast Cancer.2018;[Epub] CrossRef

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