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Cancers
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Metastatic Breast Cancers
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Metastatic Breast Cancers

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

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 24757

Special Issue Editor

Prof. Dr. Vesna Bjelic-Radisic

E-Mail Website
Guest Editor
Breast Unit, Helios University Hospital Wuppertal, University Witten/Herdecke, 58455 Witten, Germany
Interests: breast cancer; quality of life
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metastatic breast cancer remains an incurable disease with a median overall survival of approximately 3 years and 5-year survival of about 25%.

In the last few years, the outcome of the MBC has changed due to new therapy options.

The most important advance in the therapy of hormone-receptor-positive, HER2-negative metastatic breast cancer was the introduction of CDK 4/6 inhibitors. The results of studies conducted in the last five years showed a substantial benefit in DFS. More recently, some studies seem to indicate an improvement in OS.

Due to the introduction of the dual blockade, as well as T-DM1 and tucatinib, the prognosis of HER2-positive MBC has changed and patients can live a long time with the disease, especially if they achieve complete remission.

Triple-negative BC (TNBC) remains the biggest “problem” within metastatic breast cancer. Some new therapies such as PARP inhibitors in patients with a germline BRCA mutation, as well as PDL-1 Inhibitors have proven to be effective for metastatic TNBC.

The determination of specific biomarkers as possible targets for therapy and determination of biomarkers that are predictive and/or prognostic factors for the outcome of breast cancer is one of the most important issues for the near future.

This Special Issue focuses on new promising therapies for metastatic breast cancer, as well as quality of life as an outcome parameter in this population.

Prof. Vesna Bjelic-Radisic
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • metastatic breast cancer
  • quality of life in MBC
  • PARP Inhibitors
  • germline BRCA mutation
  • CDK 4/6 inhibitors
  • breast cancer biomarkers
  • immune therapy in the breast cancer

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Published Papers (7 papers)

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Research

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15 pages, 2033 KiB  
Article
Ethanol Ablation Therapy Drives Immune-Mediated Antitumor Effects in Murine Breast Cancer Models
by Corrine A. Nief, Adam M. Swartz, Erika Chelales, Lauren Y. Sheu, Brian T. Crouch, Nirmala Ramanujam and Smita K. Nair
Cancers 2022, 14(19), 4669; https://doi.org/10.3390/cancers14194669 - 25 Sep 2022
Cited by 3 | Viewed by 2415
Abstract
Ethanol ablation is a minimally invasive, cost-effective method of destroying tumor tissue through an intratumoral injection of high concentrations of cytotoxic alcohol. Ethyl-cellulose ethanol (ECE) ablation, a modified version of ethanol ablation, contains the phase-changing polysaccharide ethyl-cellulose to reduce ethanol leakage away from [...] Read more.
Ethanol ablation is a minimally invasive, cost-effective method of destroying tumor tissue through an intratumoral injection of high concentrations of cytotoxic alcohol. Ethyl-cellulose ethanol (ECE) ablation, a modified version of ethanol ablation, contains the phase-changing polysaccharide ethyl-cellulose to reduce ethanol leakage away from the tumor. Ablation produces tissue necrosis and initiates a wound healing process; however, the characteristic of the immunologic events after ECE ablation of tumors has yet to be explored. Models of triple-negative breast cancer (TNBC), which are classically immunosuppressive and difficult to treat clinically, were used to characterize the immunophenotypic changes after ECE ablation. In poorly invasive TNBC rodent models, the injury to the tumor induced by ECE increased tumor infiltrating lymphocytes (TILs) and reduced tumor growth. In a metastatic TNBC model (4T1), TILs did not increase after ECE ablation, though lung metastases were reduced. 4T1 tumors secrete high levels of granulocytic colony stimulating factor (G-CSF), which induces a suppressive milieu of granulocytic myeloid-derived suppressor cells (gMDSCs) aiding in the formation of metastases and suppression of antitumor immunity. We found that a single intratumoral injection of ECE normalized tumor-induced myeloid changes: reducing serum G-CSF and gMDSC populations. ECE also dampened the suppressive strength of gMDSC on CD4 and CD8 cell proliferation, which are crucial for anti-tumor immunity. To demonstrate the utility of these findings, ECE ablation was administered before checkpoint inhibitor (CPI) therapy in the 4T1 model and was found to significantly increase survival compared to a control of saline and CPI. Sixty days after tumor implant no primary tumors or metastatic lung lesions were found in 6/10 mice treated with CPI plus ECE, compared to 1/10 with ECE alone and 0/10 with CPI and saline. Full article
(This article belongs to the Special Issue Metastatic Breast Cancers)
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11 pages, 1249 KiB  
Article
Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals
by Clelia Chalumeau, Matthieu Carton, Alexandre Eeckhoutte, Stelly Ballet, Anne Vincent-Salomon, Perrine Vuagnat, Audrey Bellesoeur, Jean-Yves Pierga, Marc-Henri Stern, Francois-Clement Bidard and Florence Lerebours
Cancers 2022, 14(9), 2114; https://doi.org/10.3390/cancers14092114 - 24 Apr 2022
Cited by 4 | Viewed by 1878
Abstract
Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined [...] Read more.
Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated. Methods: Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available. Results: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4–4.7]) and 11.3 months (95% CI [8.3–25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a TOP2A/ERBB2 co-amplification. No statistically significant correlation was found between outcome and TOP2A/ERBB2 co-amplification. Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC. Full article
(This article belongs to the Special Issue Metastatic Breast Cancers)
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15 pages, 1925 KiB  
Article
Next-Generation Sequencing-Directed Therapy in Patients with Metastatic Breast Cancer in Routine Clinical Practice
by Simona Bruzas, Sherko Kuemmel, Hakima Harrach, Elisabeth Breit, Beyhan Ataseven, Alexander Traut, Anna Rüland, Athina Kostara, Ouafaa Chiari, Christine Dittmer-Grabowski and Mattea Reinisch
Cancers 2021, 13(18), 4564; https://doi.org/10.3390/cancers13184564 - 11 Sep 2021
Cited by 10 | Viewed by 3681
Abstract
Next-generation sequencing (NGS) followed by matched therapy has opened up new therapeutic options to patients with metastatic breast cancer (mBC). Here we report our experience with this approach in everyday clinical practice. This retrospective study included 95 patients with mBC who were genotyped [...] Read more.
Next-generation sequencing (NGS) followed by matched therapy has opened up new therapeutic options to patients with metastatic breast cancer (mBC). Here we report our experience with this approach in everyday clinical practice. This retrospective study included 95 patients with mBC who were genotyped with the FoundationOne® (CDx) assay in a commercial molecular pathology laboratory. Genetic alterations were identified in all tumor specimens, and 83 patients (87.4%) had a median of 2 (range, 1–6) potentially actionable alterations. A multidisciplinary tumor board recommended genomically guided therapy to 63 patients, 30 of whom received such treatment. Everolimus (n = 15) and anti-human epidermal growth factor receptor 2 (HER2) therapy (n = 6) were most frequently administered. The ratio of progression-free survival (PFS) under NGS-based therapy to PFS under the last line of standard therapy prior to NGS was >1.3 in 13 (43.3%) patients, indicative of a clinical benefit to NGS-directed therapy. One-year overall survival rates were 22.7% (95% CI, 6.5–44.4) in 65 patients allocated to the standard therapy versus 62.9% (95% CI, 41.6–78.2) in 30 patients receiving the matched therapy. In conclusion, NGS-matched treatment improved the clinical outcomes in a subgroup of mBC patients. Full article
(This article belongs to the Special Issue Metastatic Breast Cancers)
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14 pages, 1435 KiB  
Article
Clinical Impact of FDG-PET/CT Compared with CE-CT in Response Monitoring of Metastatic Breast Cancer
by Mohammad Naghavi-Behzad, Hjalte Rasmus Oltmann, Tural Asgharzadeh Alamdari, Jakob Lykke Bülow, Lasse Ljungstrøm, Poul-Erik Braad, Jon Thor Asmussen, Marianne Vogsen, Annette Raskov Kodahl, Oke Gerke and Malene Grubbe Hildebrandt
Cancers 2021, 13(16), 4080; https://doi.org/10.3390/cancers13164080 - 13 Aug 2021
Cited by 9 | Viewed by 2023
Abstract
We compared response categories and impacts on treatment decisions for metastatic breast cancer (MBC) patients that are response-monitored with contrast-enhanced computed-tomography (CE-CT) or fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). A comparative diagnostic study was performed on MBC patients undergoing response monitoring by CE-CT ( [...] Read more.
We compared response categories and impacts on treatment decisions for metastatic breast cancer (MBC) patients that are response-monitored with contrast-enhanced computed-tomography (CE-CT) or fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). A comparative diagnostic study was performed on MBC patients undergoing response monitoring by CE-CT (n = 34) or FDG-PET/CT (n = 31) at the Odense University Hospital (Denmark). The responses were assessed visually and allocated into categories of complete response (CR/CMR), partial response (PR/PMR), stable disease (SD/SMD), and progressive disease (PD/PMD). Response categories, clinical impact, and positive predictive values (PPV) were compared for follow-up scans. A total of 286 CE-CT and 189 FDG-PET/CT response monitoring scans were performed. Response categories were distributed into CR (3.8%), PR (8.4%), SD (70.6%), PD (15%), and others (2.1%) by CE-CT and into CMR (22.2%), PMR (23.8%), SMD (31.2%), PMD (18.5%), and others (4.4%) by FDG-PET/CT, revealing a significant difference between the groups (P < 0.001). PD and PMD caused changes of treatment in 79.1% and 60%, respectively (P = 0.083). PPV for CE-CT and FDG-PET/CT was 0.85 (95% CI: 0.72–0.97) and 0.70 (95% CI: 0.53–0.87), respectively (P = 0.17). FDG-PET/CT indicated regression of disease more frequently than CE-CT, while CE-CT indicated stable disease more often. FDG-PET/CT seems to be more sensitive than CE-CT for monitoring response in metastatic breast cancer. Full article
(This article belongs to the Special Issue Metastatic Breast Cancers)
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Review

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16 pages, 366 KiB  
Review
Targeted Therapy in HR+ HER2− Metastatic Breast Cancer: Current Clinical Trials and Their Implications for CDK4/6 Inhibitor Therapy and beyond Treatment Options
by Constanze Elfgen and Vesna Bjelic-Radisic
Cancers 2021, 13(23), 5994; https://doi.org/10.3390/cancers13235994 - 29 Nov 2021
Cited by 14 | Viewed by 4351
Abstract
A metastatic state of breast cancer (MBC) affects hundreds of thousands of women worldwide. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) MBC, cyclin-dependent kinase (CDK)4/6 inhibitors can improve the progression-free survival (PFS), as well as the overall survival (OS), in [...] Read more.
A metastatic state of breast cancer (MBC) affects hundreds of thousands of women worldwide. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) MBC, cyclin-dependent kinase (CDK)4/6 inhibitors can improve the progression-free survival (PFS), as well as the overall survival (OS), in selected patients and have been established as first- and second-line therapies. However, as MBC remains uncurable, resistance to CDK4/6 inhibitors occurs and requires alternative treatment approaches. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. This review provides a summary and update on the clinical relevance, patient selection, ongoing trials of CDK4/6 inhibitors, and further targeted therapy options. It focuses on clinical aspects and practicability, as well as adverse events and patient-reported outcomes. Full article
(This article belongs to the Special Issue Metastatic Breast Cancers)
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27 pages, 4446 KiB  
Review
Currently Used Laboratory Methodologies for Assays Detecting PD-1, PD-L1, PD-L2 and Soluble PD-L1 in Patients with Metastatic Breast Cancer
by Seri Jeong, Nuri Lee, Min-Jeong Park, Kibum Jeon and Wonkeun Song
Cancers 2021, 13(20), 5225; https://doi.org/10.3390/cancers13205225 - 18 Oct 2021
Cited by 11 | Viewed by 3185
Abstract
Approximately 20% of breast cancer (BC) patients suffer from distant metastasis. The incidence and prevalence rates of metastatic BC have increased annually. Immune checkpoint inhibitors are an emerging area of treatment, especially for metastatic patients with poor outcomes. Several antibody drugs have been [...] Read more.
Approximately 20% of breast cancer (BC) patients suffer from distant metastasis. The incidence and prevalence rates of metastatic BC have increased annually. Immune checkpoint inhibitors are an emerging area of treatment, especially for metastatic patients with poor outcomes. Several antibody drugs have been developed and approved for companion testing of the programmed death protine-1 (PD-1) axis. We reviewed currently used laboratory methodologies for assays determining PD-1 axis to provide a comprehensive understanding of principles, advantages, and drawbacks involved in their implementation. The most commonly used method is immunohistochemistry (92.9%) for PD-L1 expression using tissue samples (96.4%). The commonly used anti-PD-L1 antibody clone were commercially available 22C3 (30.8%), SP142 (19.2%), SP263 (15.4%), and E1L3N (11.5%). Enzyme-linked immunosorbent assay and electrochemiluminescent immunoassay that target soluble PD-ligand (L)1 were developed and popularized in 2019–2021, in contrast to 2016–2018. Easy accessibility and non-invasiveness due to the use of blood samples, quantitative outputs, and relatively rapid turnaround times make them more preferable. Regarding scoring methods, a combination of tumor and immune cells (45.5% in 2016–2018 to 57.1% in 2019–2021) rather than each cell alone became more popular. Information about antibody clones, platforms, scoring methods, and related companion drugs is recommended for reporting PD-L1 expression. Full article
(This article belongs to the Special Issue Metastatic Breast Cancers)
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17 pages, 1203 KiB  
Review
Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer
by Francesco Schettini, Mario Giuliano, Matteo Lambertini, Rupert Bartsch, David James Pinato, Concetta Elisa Onesti, Nadia Harbeck, Diana Lüftner, Sylvie Rottey, Peter A. van Dam, Khalil Zaman, Giorgio Mustacchi, Joseph Gligorov, Ahmad Awada, Mario Campone, Hans Wildiers, Alessandra Gennari, Vivianne C. G. Tjan-Heijnen, Javier Cortes, Mariavittoria Locci, Ida Paris, Lucia Del Mastro, Sabino De Placido, Miguel Martín, Guy Jerusalem, Sergio Venturini, Giuseppe Curigliano and Daniele Generaliadd Show full author list remove Hide full author list
Cancers 2021, 13(17), 4421; https://doi.org/10.3390/cancers13174421 - 1 Sep 2021
Cited by 15 | Viewed by 6173
Abstract
Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed [...] Read more.
Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m2. Following three pivotal first-line phase III trials in HER2-negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2-negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms. Full article
(This article belongs to the Special Issue Metastatic Breast Cancers)
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