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Cancers
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Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer
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Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer

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

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 14990

Special Issue Editors

Dr. Mireia Margeli Vila

E-Mail Website
Guest Editor
B-ARGO (Badalona Applied Research group in Oncology) Group, IGTP (Germans Trias I Pujol Research Institute), Depertment of Medical Oncology, ICO Badalona, Autonomous University of Barcelona, Badalona, Spain
Interests: breast cancer
Dr. Eudald Felip Falgas

E-Mail Website
Guest Editor
B-ARGO (Badalona Applied Research group in Oncology) Group, IGTP (Germans Trias I Pujol Research Institute), Depertment of Medical Oncology, ICO Badalona, Badalona, Spain
Interests: breast cancer; genomics; transcriptomics
Dr. Bergamino Sirven Milana Arantza

E-Mail Website
Guest Editor
B-ARGO (Badalona Applied Research group in Oncology) Group, IGTP (Germans Trias I Pujol Research Institute), Depertment of Medical Oncology, ICO Badalona, Badalona, Spain
Interests: breast cancer; genomic; transcriptomics

Special Issue Information

Dear Colleagues,

The treatment of HER2-positive breast cancer has been an example of constant development and incorporation of new therapies for the last two decades. We have experienced the rapid incorporation of drugs such as trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) that are part of our daily therapeutic arsenal, expanding their use to different therapeutic settings on many occasions.

The deeper knowledge of this disease, as well as the mechanisms of drug resistance, has allowed the development of new drugs that include tucatinib, fam-trastuzumab deruxtecan-nxki (DS-8201a), neratinib and margetuximab-cmkb, and others. We are going incorporating some of these drugs into our clinical practice according to the results obtained from ongoing clinical trials. Thus, the landscape of treating HER2-positive disease is constantly changing.

However, there are still new opportunities for improvement in the treatment of HER2-positive breast cancer, in the field of diagnosis, the development of new biomarkers. and the incorporation of new therapies, with the ultimate goal of approaching an increasingly personalized treatment of patients.

Some of the questions we ask ourselves are:

  • Is there a place for anti-HER2 strategies without chemotherapy?
  • What are the candidates for descaling therapies?
  • What are the candidates for escalation therapies?
  • What is the optimal treatment algorithm for early breast cancer?
  • What is the optimal algorithm for metastatic configuration?
  • What are the most promising new drugs?
  • What is the role of new biomarkers or platforms in HER2-positive diseases?
  • How can we help patients with specific needs and with brain metastases?

In this issue, we will collate data in relation to HER2-positive disease, which will help us to reflect on where we should direct our efforts in the treatment of this disease.

Dr. Mireia Margeli Vila
Dr. Eudald Felip Falgas
Dr. Bergamino Sirven Milana Arantza
Guest Editors

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 short 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

  • breast cancer
  • HER2-positive

Published Papers (3 papers)

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Review

50 pages, 1300 KiB  
Review
Emerging Targeted Therapies for HER2-Positive Breast Cancer
by María Florencia Mercogliano, Sofía Bruni, Florencia Luciana Mauro and Roxana Schillaci
Cancers 2023, 15(7), 1987; https://doi.org/10.3390/cancers15071987 - 26 Mar 2023
Cited by 18 | Viewed by 5985
Abstract
Breast cancer is the most common cancer in women and the leading cause of death. HER2 overexpression is found in approximately 20% of breast cancers and is associated with a poor prognosis and a shorter overall survival. Tratuzumab, a monoclonal antibody directed against [...] Read more.
Breast cancer is the most common cancer in women and the leading cause of death. HER2 overexpression is found in approximately 20% of breast cancers and is associated with a poor prognosis and a shorter overall survival. Tratuzumab, a monoclonal antibody directed against the HER2 receptor, is the standard of care treatment. However, a third of the patients do not respond to therapy. Given the high rate of resistance, other HER2-targeted strategies have been developed, including monoclonal antibodies such as pertuzumab and margetuximab, trastuzumab-based antibody drug conjugates such as trastuzumab-emtansine (T-DM1) and trastuzumab-deruxtecan (T-DXd), and tyrosine kinase inhibitors like lapatinib and tucatinib, among others. Moreover, T-DXd has proven to be of use in the HER2-low subtype, which suggests that other HER2-targeted therapies could be successful in this recently defined new breast cancer subclassification. When patients progress to multiple strategies, there are several HER2-targeted therapies available; however, treatment options are limited, and the potential combination with other drugs, immune checkpoint inhibitors, CAR-T cells, CAR-NK, CAR-M, and vaccines is an interesting and appealing field that is still in development. In this review, we will discuss the highlights and pitfalls of the different HER2-targeted therapies and potential combinations to overcome metastatic disease and resistance to therapy. Full article
(This article belongs to the Special Issue Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer)
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19 pages, 340 KiB  
Review
Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends
by Kreina Sharela Vega Cano, David Humberto Marmolejo Castañeda, Santiago Escrivá-de-Romaní and Cristina Saura
Cancers 2023, 15(1), 51; https://doi.org/10.3390/cancers15010051 - 22 Dec 2022
Cited by 8 | Viewed by 2147
Abstract
Approximately 20% of breast cancers (BC) overexpress human epidermal growth factor receptor 2 (HER2). This subtype of BC is a clinically and biologically heterogeneous disease that was associated with an increased risk for the development of systemic and brain metastases and poor overall [...] Read more.
Approximately 20% of breast cancers (BC) overexpress human epidermal growth factor receptor 2 (HER2). This subtype of BC is a clinically and biologically heterogeneous disease that was associated with an increased risk for the development of systemic and brain metastases and poor overall survival before anti-HER2 therapies were developed. The standard of care was dual blockade with trastuzumab and pertuzumab as first-line followed by TDM-1 as second-line. However, with the advent of new HER2-targeted monoclonal antibodies, tyrosine kinase inhibitors and antibody- drug conjugates, the clinical outcomes of patients with HER2-positive BC have changed dramatically in recent years, leading to a paradigm shift in the treatment of the disease. Notably, the development of new-generation ADCs has led to unprecedented results compared with T-DM1, currently establishing trastuzumab deruxtecan as a new standard of care in second-line. Despite the widespread availability of HER2-targeted therapies, patients with HER2-positive BC continue to face the challenges of disease progression, treatment resistance, and brain metastases. Response rate and overall life expectancy decrease with each additional line of treatment, and tumor heterogeneity remains an issue. In this review, we update the new-targeted therapeutic options for HER2-positive BC and highlight the future perspectives of treatment in this setting. Full article
(This article belongs to the Special Issue Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer)
23 pages, 905 KiB  
Review
Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer
by Angelica Ferrando-Díez, Eudald Felip, Anna Pous, Milana Bergamino Sirven and Mireia Margelí
Cancers 2022, 14(14), 3305; https://doi.org/10.3390/cancers14143305 - 06 Jul 2022
Cited by 12 | Viewed by 6171
Abstract
Despite the improvement achieved by the introduction of HER2-targeted therapy, up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the [...] Read more.
Despite the improvement achieved by the introduction of HER2-targeted therapy, up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown a significant improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). In ER+ HER2+ patients, target therapies such as phosphoinositide-3-kinase (PI3K) pathway inhibition or cyclin-dependent kinases 4/6 blocking may be effective in controlling downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies. Multiple trials have explored these strategies with some promising results, and probably, in the next years conclusive results will succeed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents such as HER-2 therapy plus checkpoint inhibitors, or new vaccines approaches have been investigated in this setting, with promising but controversial results obtained to date. Full article
(This article belongs to the Special Issue Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer)
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