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Cancers
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Combination Therapies in Breast Cancer Chemotherapy: Chemoradiation, Targeted Agents, and...
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Combination Therapies in Breast Cancer Chemotherapy: Chemoradiation, Targeted Agents, and Immunotherapy

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

Deadline for manuscript submissions: 30 April 2027 | Viewed by 783

Editor

Prof. Dr. Piotr J. Wysocki

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Guest Editor
Department of Oncology, Jagiellonian University Medical College, 31-007 Cracow, Poland
Interests: metronomic chemotherapy; geriatric oncology; combined treatment modalities; novel therapeutic targets; breast cancer; ovarian cancer; prostate cancer; RCC; urothelial cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The therapeutic landscape of breast cancer is undergoing a profound transformation driven by the integration of multimodal strategies that combine classical cytotoxic chemotherapy with endocrine treatment, radiotherapy, monoclonal antibodies, antibody–drug conjugates, small-molecule kinase inhibitors, metronomic chemotherapy, and emerging immunotherapies. These rational combination approaches offer the potential to enhance antitumor efficacy, delay or overcome intrinsic and acquired resistance, optimize long-term disease control, and improve survival across both early-stage and metastatic settings. Endocrine-based combinations, HER2-directed doublet and triplet strategies, ADC-containing regimens, and synergistic pairings of targeted agents with immunotherapy or radiotherapy illustrate the growing complexity and promise of modern breast cancer treatment. Despite this progress, many questions remain regarding optimal sequencing, patient selection, toxicity mitigation, and biomarker-guided personalization. This Special Issue aims to highlight the latest advances in chemoradiation, endocrine combinations, molecularly targeted therapies, metronomic chemotherapy, and innovative multi-agent strategies. We welcome original research papers and comprehensive reviews that elucidate underlying biological mechanisms, identify predictive and prognostic biomarkers, explore real-world evidence, and refine therapeutic algorithms to advance precision care for patients with breast cancer.

Prof. Dr. Piotr J. Wysocki
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-anonymized 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.

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Keywords

  • breast cancer
  • combination therapy
  • endocrine therapy
  • chemoradiation
  • monoclonal antibodies
  • antibody–drug conjugates (ADCs)
  • small-molecule kinase inhibitors
  • immunotherapy
  • predictive biomarkers
  • therapy resistance
  • precision oncology
  • translational research

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Published Papers (2 papers)

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14 pages, 939 KB  
Article
Adverse Events as a Surrogate of Sufficient Pharmacological Exposure in Metronomic Combination Chemotherapy: Extended Real-World Cohort Analysis of the FulVEC Regimen in Metastatic ER+/HER2− Breast Cancer
by Anna Buda-Nowak, Maciej Lubaś, Michał Jurczyk, Łukasz Kwinta, Anna Michałowska-Kaczmarczyk, Agnieszka Przywara-Sikora, Kamil Konopka, Maciej Koniewski, Joanna Kadłuczka, Olga Szczerbak and Piotr J. Wysocki
Cancers 2026, 18(14), 2303; https://doi.org/10.3390/cancers18142303 - 17 Jul 2026
Abstract
Background: Metronomic chemo-endocrine therapy combining fulvestrant with metronomic VEC (vinorelbine, cyclophosphamide, and capecitabine)—the FulVEC regimen—demonstrated promising activity in an initial cohort of 38 patients with advanced ER+/HER2− breast cancer (JCM 2023). Here, we present an extended analysis of 72 consecutive patients, with a [...] Read more.
Background: Metronomic chemo-endocrine therapy combining fulvestrant with metronomic VEC (vinorelbine, cyclophosphamide, and capecitabine)—the FulVEC regimen—demonstrated promising activity in an initial cohort of 38 patients with advanced ER+/HER2− breast cancer (JCM 2023). Here, we present an extended analysis of 72 consecutive patients, with a focus on a novel hypothesis: that treatment-emergent adverse events (AEs) requiring dose modification serve as a surrogate for sufficient pharmacological exposure in metronomic combination chemotherapy. Methods: Retrospective analysis of 72 consecutive patients with metastatic ER+/HER2− breast cancer treated with FulVEC at Jagiellonian University Hospital between 2018 and 2024. Efficacy endpoints included progression-free survival (PFS), overall survival (OS), and biochemical response, as assessed by CA15-3 dynamics. Patients were stratified by AE severity requiring intervention (grade 0: no modification; grade 1: dose reduction; and grade 2: treatment delay). The association between AE grade and efficacy outcomes was assessed using Spearman’s correlation, the log-rank test, and the chi-square test. Results: The median PFS was 8.5 months, and the median OS was 18.0 months. The biochemical benefit rate (any CA15-3 decline) was 81.6%. No statistically significant differences in efficacy were observed according to prior exposure to CDK4/6 inhibitors, fulvestrant, or cytotoxic components of the FulVEC regimen. A monotonic dose–response relationship was observed across AE grade categories: non-progression rates increased from 73.2% (grade 0) to 84.2% (grade 1) and 91.7% (grade 2); biochemical benefit rates from 68.4% to 90.9% and 100.0%; and median CA15-3 reduction deepened from −34% to −44% and −52%, respectively (Spearman r = 0.258 and p = 0.043 for AE grade vs. treatment duration). Formal log-rank comparisons of PFS and OS across the three AE-grade categories did not reach statistical significance (p = 0.583 and p = 0.743, respectively), reflecting the limited size of the treatment-delay subgroup (n = 12); the dose–response signal should, therefore, be regarded as exploratory. No patient required permanent treatment discontinuation due to toxicity. Conclusions: The extended FulVEC cohort confirms durable activity and a reproducible, manageable safety profile in a heavily pretreated population, including CDK4/6i-refractory patients. The exploratory, hypothesis-generating observation of a dose–response gradient between AE severity and clinical outcomes raises the possibility that treatment-emergent AEs may, in some patients, reflect adequate pharmacological exposure to the metronomic regimen. Given confounding by treatment duration and survivor bias, and the absence of pharmacokinetic data, this hypothesis requires prospective validation and does not, at this stage, support any change to current treatment practice. Full article
(This article belongs to the Special Issue Combination Therapies in Breast Cancer Chemotherapy: Chemoradiation, Targeted Agents, and Immunotherapy)
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21 pages, 2136 KB  
Conference Report
Hermione Exchange Educational Program: How to Integrate Multidisciplinary Approaches to Manage HR+/HER2- Metastatic Breast Cancer
by Marina Elena Cazzaniga, Nicola Fusco, Alessandra Fabi, Umberto Malapelle and Paolo Vigneri
Cancers 2026, 18(13), 2087; https://doi.org/10.3390/cancers18132087 - 27 Jun 2026
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Abstract
Background/objective: Given the increasing complexity of the luminal breast cancer landscape, a proper characterization is required in everyday clinical practice, and the recurrence after the standard first-line treatment with CDK4/6 inhibitors with/without endocrine therapy should be managed. Method: The Hermione Exchange Educational Program [...] Read more.
Background/objective: Given the increasing complexity of the luminal breast cancer landscape, a proper characterization is required in everyday clinical practice, and the recurrence after the standard first-line treatment with CDK4/6 inhibitors with/without endocrine therapy should be managed. Method: The Hermione Exchange Educational Program was held in Milan, Italy, between September 2024 and January 2025. Two questionnaires were proposed regarding the use of targeted treatment or chemotherapy after progression from CDK4/6 inhibitors. The lecture and use cases enhanced the discussion during the workshops. Results: From the surveys, it emerged that most participants (69%) considered liver metastases at CDK4/6-inhibitor progression as a key reason to initiate chemotherapy, while lung progression influenced this choice for 50% of participants. Liver involvement guided the use of targeted therapy for 56%, and attitudes were divided on whether the duration of first-line CDK4/6 therapy should affect decisions (44% in agreement vs. 38% in disagreement). The willingness of patients to receive chemotherapy (88%) and comorbidities (81%) were significant drivers. Almost all participants agreed that both the duration of response and the molecular status were key aspects to consider when choosing a second line of therapy, along with the general clinical condition of the patient. In the lecture, tissue and liquid biopsy are considered powerful tools to describe tumor molecular features over time; such complexity should be harnessed by a close dialogue between oncologists, molecular biologists, and pathologists to optimize the therapeutic choice according to the mutational status of patients. The use cases illustrate three patients with visceral progression, non-visceral progression within 12 months, and non-visceral progression after 12 months following CDK4/6 inhibitors. Conclusion: Genomic testing should be considered at diagnosis and repeated during treatment to monitor the disease. The clinical experience acquired over the years must be integrated with new molecular knowledge. Full article
(This article belongs to the Special Issue Combination Therapies in Breast Cancer Chemotherapy: Chemoradiation, Targeted Agents, and Immunotherapy)
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