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Combination Therapy for the Treatment of Breast Cancer
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Combination Therapy for the Treatment of Breast Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1540

Special Issue Editor

Dr. Xin Wang

E-Mail Website
Guest Editor
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Interests: breast cancer; precision surgery; liquid biopsy; artificial intelligence in oncology; prognostic model; clinical translational research

Special Issue Information

Dear Colleagues,

Breast cancer is the most commonly diagnosed malignancy among women worldwide and remains a leading cause of cancer-related mortality. Although substantial progress has been achieved with surgery, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, therapeutic resistance, tumor heterogeneity and disease recurrence continue to pose major clinical challenges. Combination therapy has emerged as a critical strategy to enhance treatment efficacy, overcome resistance mechanisms and improve patient outcomes across breast cancer subtypes.

This Special Issue aims to highlight recent advances in combination therapeutic strategies for breast cancer, spanning basic, translational and clinical research. We welcome original research articles and reviews that investigate the biological rationale, clinical effectiveness, safety and predictive biomarkers of combination treatments. Particular interest is placed on innovative approaches integrating systemic and local therapies, novel targeted agents, immunotherapy, antibody–drug conjugates and radiotherapy.

Topics include, but are not limited to, the following: combination strategies in different molecular subtypes; mechanisms of synergy and resistance; biomarkers for patient stratification; neoadjuvant and adjuvant combination therapies; clinical trial and real-world evidence and emerging combination treatment paradigms.

Dr. Xin Wang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • breast cancer
  • combination therapy
  • targeted therapy
  • immunotherapy
  • endocrine therapy
  • chemotherapy
  • anti-body–drug conjugates
  • treatment resistance
  • biomarkers

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Published Papers (2 papers)

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Research

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13 pages, 1763 KB  
Article
Exploration of Optimal Synergistic Treatment Strategies of Postoperative Radiotherapy and Immunotherapy in Early-Stage Breast Cancer
by Qingyao Shang, Hanyu Wang, Yan Zhuang, Jennifer K. Plichta, Samantha M. Thomas, Meishuo Ouyang, Sheng Luo and Xin Wang
Cancers 2026, 18(7), 1145; https://doi.org/10.3390/cancers18071145 - 2 Apr 2026
Viewed by 277
Abstract
Background: The optimal sequencing of radiotherapy and immunotherapy in early-stage breast cancer remains uncertain. Although synergistic interactions between radiotherapy and immunotherapy have been widely reported, most available evidence derives from advanced disease with high tumor burden. Whether treatment sequencing influences outcomes in [...] Read more.
Background: The optimal sequencing of radiotherapy and immunotherapy in early-stage breast cancer remains uncertain. Although synergistic interactions between radiotherapy and immunotherapy have been widely reported, most available evidence derives from advanced disease with high tumor burden. Whether treatment sequencing influences outcomes in postoperative adjuvant therapy has not been well defined. Methods: Patients with stage I–III human epidermal growth factor receptor 2 (HER2)-negative breast cancer who underwent surgery followed by both adjuvant radiotherapy and immunotherapy were identified from the National Cancer Database. According to treatment initiation dates, patients were classified into immunotherapy-first and radiotherapy-first groups. Overall survival was compared using Kaplan–Meier analysis and weighted Cox regression. Baseline imbalances were adjusted using inverse probability of treatment weighting. Prespecified subgroup analyses were conducted based on adjuvant chemotherapy status and radiotherapy fractionation regimen. A sensitivity analysis was performed in an independent cohort of stage IV inoperable patients. Results: A total of 3813 patients were included. Immunotherapy-first sequencing was associated with improved overall survival compared with radiotherapy-first sequencing after weighted (HR 0.71; 95% CI 0.56–0.89). The survival benefit was most evident among patients receiving adjuvant chemotherapy (HR 0.63; 95% CI 0.48–0.84), whereas no significant difference was observed in patients without chemotherapy (HR 1.01; 95% CI 0.71–1.44). Subgroup analysis according to radiotherapy fractionation demonstrated a significant advantage of immunotherapy-first sequencing in patients treated with conventional fractionation radiotherapy (HR 0.58; 95% CI 0.36–0.92), but not in those receiving hypofractionated radiotherapy (HR 0.44; 95% CI 0.17–1.13). In stage IV inoperable patients, no survival difference was detected between sequencing strategies (HR 1.04; 95% CI 0.88–1.23). Conclusions: For postoperative patients with low residual tumor burden, particularly those receiving adjuvant chemotherapy, immunotherapy-first strategy may provide stronger synergistic effects and lead to improved survival. In addition, conventional fractionation radiotherapy with lower doses per fraction appears to facilitate more effective interaction with immunotherapy compared with hypofractionated regimens. Prospective trials are needed for further validation. Full article
(This article belongs to the Special Issue Combination Therapy for the Treatment of Breast Cancer)
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Review

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26 pages, 1788 KB  
Review
Cannabinoids in Combination with Conventional Breast Cancer Therapies: Mechanistic Insights and the Gap to Clinical Translation
by Anja Bizjak, Uroš Potočnik and Helena Čelešnik
Cancers 2026, 18(5), 761; https://doi.org/10.3390/cancers18050761 - 27 Feb 2026
Viewed by 1068
Abstract
Current treatments for breast cancer (BC) include surgery, radiation, chemotherapy, targeted therapy, hormonal therapy, and immunotherapy. However, adverse effects such as pain, nausea, cardiotoxicity, and neuropathy have prompted interest in complementary approaches. Cannabinoids (CBS), particularly cannabidiol and delta-9-tetrahydrocannabinol, are already used by cancer [...] Read more.
Current treatments for breast cancer (BC) include surgery, radiation, chemotherapy, targeted therapy, hormonal therapy, and immunotherapy. However, adverse effects such as pain, nausea, cardiotoxicity, and neuropathy have prompted interest in complementary approaches. Cannabinoids (CBS), particularly cannabidiol and delta-9-tetrahydrocannabinol, are already used by cancer patients for symptom relief, and preclinical studies in cell culture and mouse models suggest additional therapeutic potential at the cellular level: combining CBS with chemotherapy may sensitize tumour cells to chemotherapeutic agents, inhibit tumour proliferation, and increase apoptosis. In murine models, such combinations may also mitigate chemotherapy-induced cardiotoxicity by enhancing antioxidant activity, modulating cannabinoid receptor signalling to reduce pro-inflammatory markers, and restoring mitochondrial function in myocytes. In addition, CBS may augment hormonal therapy in estrogen receptor-positive (ER+) BC cells, primarily via aromatase inhibition and modulation of ER and EGR3 signalling. Notably, evidence on combining CBS with targeted therapies in BC is lacking, while studies of CBS–immunotherapy combinations have been conducted in non-BC cancers; in BC, they are scarce and limited to in vitro models. This represents a key area for future research, particularly given the heterogeneity across non-BC cancers, where CBS–immunotherapy combinations have demonstrated mixed effects, both beneficial and detrimental (e.g., reduced response rates and overall survival), with the underlying mechanisms remaining unclear. Translation of these findings into clinical practice faces several challenges. Although over 120 CBS have been identified, only a few are well-characterized. CBS exhibit diverse mechanisms and effects, including potential adverse outcomes and interactions with conventional therapies (e.g., effects on chemotherapeutic drug metabolism). Variability among BC cells may also result in differing responses to the same therapeutic combinations. Future research should delineate the effects of individual CBS in combination strategies and prioritize well-controlled, standardized clinical studies to build on in vitro and animal data, while also exploring genetically informed personalized approaches. Ultimately, clinical guidelines specifying CBS type, formulation, and delivery are needed. Full article
(This article belongs to the Special Issue Combination Therapy for the Treatment of Breast Cancer)
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