Cancer Research and Treatment

Review Articles

Toward Sustainable Care in HER2-Positive Metastatic Breast Cancer: Emerging Evidence for Treatment De-escalation: Matilda Xinwei Lee, Soo Chin Lee; Received October 16, 2025 Accepted April 23, 2026 Published online April 23, 2026; DOI: https://doi.org/10.4143/crt.2025.1131 [Accepted]

Abstract PDF: Major advances in the management of HER2-positive (HER2+) metastatic breast cancer (MBC) have been achieved through treatment intensification with novel HER2-targeted agents and combination strategies, resulting in substantial survival gains. However, indefinite exposure to systemic therapy imposes cumulative toxicity, financial strain, and quality-of-life burdens. In contrast, the concept of treatment de-escalation, aimed at maintaining disease control with less intensive therapy, has only recently emerged as a complementary paradigm. This review highlights two evolving avenues of treatment de-escalation. First, in hormone receptor-positive (HR+)/ HER2+ disease, randomized trials have demonstrated that combining HER2 blockade with endocrine therapy and CDK4/6 inhibitors can overcome endocrine resistance, offering a chemotherapy-sparing approach with outcomes comparable to chemotherapy or antibody-drug conjugates. Second, in long-term responders, retrospective analyses and ongoing prospective trials are evaluating whether discontinuation of prolonged maintenance HER2 therapy can safely reduce treatment burden while preserving disease control, with the added potential for effective rechallenge upon relapse. Together, these developments suggest that treatment de-escalation represents a rational and necessary treatment strategy. Future progress will depend on biomarker-driven patient selection and prospective validation. Redefining success in HER2+ MBC to include not only survival but also quality of life and sustainability represents an important step toward patient-centered cancer care.

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Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer: Eunice Yoojin Lee, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im; Cancer Res Treat. 2023;55(4):1065-1076. Published online October 5, 2023; DOI: https://doi.org/10.4143/crt.2023.846

Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

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Breast cancer: taxonomy, distribution analysis, risk factors, predictive biomarkers, and modern treatment method
Abhiroop Sengupta, Parasmita Saha, Ritama Chakraborty, Arnab K. Maiti, Soumya Chakraborty, Aparna Datta, Ananda S. Datta
Apoptosis.2026;[Epub] CrossRef
Association study of aromatase inhibitors and adverse events related to osteoporosis: based on pharmacovigilance data
Nan Yang, Wei Zhang, Xinliang Cui, Leimin Xi, Yue Zhou, Haoyu Feng
Naunyn-Schmiedeberg's Archives of Pharmacology.2026;[Epub] CrossRef
MicroRNA-Directed Biomarkers and Breast Cancer Therapeutics—Potential to Advance Personalised Approaches in Clinical Trials
Luis Bouz Mkabaah, Eoin P. Kerin, Matthew G. Davey, Eleftheria Filandrianou, Vinitha Richard, Michael J. Kerin
International Journal of Molecular Sciences.2026; 27(9): 3996. CrossRef
Molecular Profiling and Targeted Therapeutic Strategies in Breast Cancer: Clinical Integration of HER2, CDK4/6, and PI3K Inhibition with Trastuzumab, Abemaciclib and Alpelisib
Piotr Kawczak, Tomasz Bączek
Journal of Clinical Medicine.2026; 15(10): 3715. CrossRef
Breast Cancer and Tumor Microenvironment: The Crucial Role of Immune Cells
Tânia Moura, Paula Laranjeira, Olga Caramelo, Ana M. Gil, Artur Paiva
Current Oncology.2025; 32(3): 143. CrossRef
Metastasiertes hormonrezeptorpositives Mammakarzinom – die Qual der Wahl
Marion T. van Mackelenbergh, Michael Friedrich, Nicolai Maass
Die Gynäkologie.2025; 58(5): 306. CrossRef
Risk factors for adverse reactions caused by abemaciclib in breast cancer therapy
Xianghua Quan, CaiHong Sun, Bing Han, ChuanZhou Zhang, HuaiQin Cang, Xiaomin Xing, Qie Guo
Frontiers in Oncology.2025;[Epub] CrossRef
Phase 1/2 study of H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive, HER2-negative breast cancer
Erika Hamilton, Timothy Pluard, Judy S. Wang, Aki Morikawa, Stephen Johnston, E. Claire Dees, Christos Vaklavas, Anne Armstrong, Pamela Munster, Nisha Unni, Gail S. Wright, Fadi Kayali, Tingting Song, Yuanxin Rong, Kohei Yamaguchi, Dejan Juric
Breast Cancer Research.2025;[Epub] CrossRef
The experience of musculoskeletal symptoms among patients with breast cancer during aromatase inhibitor therapy: A qualitative study
Yuling Cao, Feng Jing, Lingyun Jiang, Maoting Tian, Jiajia Qiu, Lichen Tang, Yan Hu
Asia-Pacific Journal of Oncology Nursing.2025; 12: 100784. CrossRef
Recurrent Hormone Receptor–Positive Breast Cancer With Multiple Sites of Distant Metastasis: A Case Report and Review of the Literature
Lu Li, Hui Liu, Xiangxin Huang, Haojun Luo, Sreeja Dattachoudhury
International Journal of Breast Cancer.2025;[Epub] CrossRef
Human Epidermal Growth Factor Receptor 2 (HER2)-Ultralow Breast Cancer: Incidence, Clinicopathologic Features, and Need for Refined Scoring System
Doaa Morrar, Edi Brogi, Christopher J. Schwartz, Fresia Pareja, Hannah Y. Wen, Dara S. Ross
Modern Pathology.2025; 38(12): 100901. CrossRef
A LITERATURE REVIEW ON THE ROLE OF ADIPOCYTOKINES IN BREAST CANCER AND METABOLIC SYNDROME
DEEPTHI ENUMULA, YASHASWI GUNTUPALLI, VANITHA RANI NAGASUBRAMANIAN, PRATHAP REDDY BASANI, BHAWNA DEV, SHYAM SUNDER ANCHURI, SHABNA ROUPAL
Asian Journal of Pharmaceutical and Clinical Research.2025; : 4. CrossRef
Imlunestrant (Inluriyo®) en cáncer de mama avanzado: una revisión narrativa
Laura Jimena Sierra Dueñas, Camilo Vega-Useche, María José Erazo Muñoz, Lina Aracely Ávila Álvarez, Valentina Arteaga Umeje, Miguel Santiago Paiba Montaña, Beatriz Arssinoe Martínez Obregón, Leonel Vega-Useche
Revista Investigación en Salud Universidad de Boyacá.2025;[Epub] CrossRef
Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions
Rohan Kalyan Rej, Joyeeta Roy, Srinivasa Rao Allu
Cancers.2024; 16(3): 552. CrossRef

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Original Articles

Breast cancer

Clinical Evidence of Chemotherapy or Endocrine Therapy Maintenance in Patients with Metastatic Breast Cancer: Meta-Analysis of Randomized Clinical Trials and Propensity Score Matching of Multicenter Cohort Study: Wei Ren, Yunfang Yu, Huangming Hong, Ying Wang, Quanlong Gao, Yongjian Chen, Peixian Chen, Jianli Zhao, Qiyun Ou, Dagui Lin, Tuping Fu, Yujie Tan, Chenchen Li, Xinxin Xie, Guolin Ye, Jun Tang, Herui Yao; Cancer Res Treat. 2022;54(4):1038-1052. Published online February 4, 2022; DOI: https://doi.org/10.4143/crt.2021.698

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients.
Materials and Methods
The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163.
Results
A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment.
Conclusion
This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

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Psychosocial interventions indicate prolonged survival in cancer patients in a systematic review, meta-analysis, and multiverse meta-analysis of randomized controlled trials
Kenji D. Asakawa-Haas, David Spiegel, Lukas Bossert, Aleksandra Garic, Katrin Schwartz, Martin Voracek, Ulrich S. Tran
Communications Psychology.2026;[Epub] CrossRef
Fulvestrant versus capecitabine as maintenance therapy in hormone receptor-positive, HER2-negative metastatic breast cancer after first-line chemotherapy (FAMILY): a multicenter, open-label, randomized, phase 3 trial
Wenjing Wu, Yaping Yang, Haizhu Chen, Yongkui Lu, Yinduo Zeng, Jianli Zhao, Caiwen Du, Ying Lin, Peijian Peng, Mei Huang, Ying Zhang, Quchang Ouyang, Linxiaoxiao Ding, Ziliang Cheng, Yuanyu Wen, Zhiyong Wu, Jinhui Ye, Li Ling, Kun Wang, Ying Lu, Guorong Z
Signal Transduction and Targeted Therapy.2026;[Epub] CrossRef
6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7)
Fatima Cardoso, Shani Paluch-Shimon, Eva Schumacher-Wulf, Leonor Matos, Karen Gelmon, Matti S. Aapro, Jyoti Bajpai, Carlos H. Barrios, Jonas Bergh, Elizabeth Bergsten-Nordström, Laura Biganzoli, Maria João Cardoso, Lisa A. Carey, Mariana Chavez-MacGregor,
The Breast.2024; 76: 103756. CrossRef
Maintenance endocrine therapy plus bevacizumab for advanced or metastatic breast cancer
Stanislas Quesada, William Jacot
The Lancet Oncology.2022; 23(5): 557. CrossRef

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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

Abstract PDF PubReader ePub

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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