Special Issue "Brain Metastases in Breast Cancer"

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

Deadline for manuscript submissions: 15 May 2022.

Special Issue Editors

Prof. Dr. Renata Duchnowska
E-Mail Website
Guest Editor
Department of Oncology, Military Institute of Medicine, Szaserów 128 St., 04-141 Warsaw, Poland
Interests: breast cancer; brain metastases; genetics; targeted therapy
Prof. Dr. Philippe Métellus
E-Mail Website
Guest Editor
Department of Neurosurgery Clairval Hospital Center, Generale de Santé, 317 Boulevard du Redon 1009, 13009 Marseille, France
Interests: Neurosurgery; brain tumor

Special Issue Information

Dear Colleagues,

Breast cancer is the second most frequent cause of brain metastases after lung cancer, with an estimated occurrence of 10-30%. Paradoxically, increased efficacy of breast cancer treatment allows more time for the development of brain metastases. In consequence, this problem is becoming increasingly important and remains an unmet need.

The prognosis of breast cancer patients with brain metastases is generally poor. Their management includes neurosurgery, radiotherapy, and systemic therapies. Most anticancer agents show limited penetrance through the blood-brain barrier, making the brain a “sanctuary site.” Recently, there has been a shift from combating established brain metastases to preventive strategies. The knowledge on the mechanisms of brain-specific metastatic process and on the role of the unique brain microenvironment is still limited. Currently available molecular techniques allow analysis of thousands of genes, and researchers have hopes they can pave the way to new preventive and therapeutic strategies.

This Special Issue includes reviews that highlight biological and clinical aspects of brain metastases in breast cancer. It is our hope that this endeavor will attract great interest from a wide range of researchers and clinicians dealing with this malignancy.

Prof. Dr. Renata Duchnowska
Prof. Dr. Philippe Métellus
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 papers will be 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 2400 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
  • brain metastases
  • gene signature
  • targeted therapy
  • radiotherapy

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
Landscape of Epidermal Growth Factor Receptor Heterodimers in Brain Metastases
Cancers 2022, 14(3), 533; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030533 - 21 Jan 2022
Viewed by 160
Abstract
HER2+ breast cancer patients have an elevated risk of developing brain metastases (BM), despite adjuvant HER2-targeted therapy. The mechanisms underpinning this reduced intracranial efficacy are unclear. We optimised the in situ proximity ligation assay (PLA) for detection of the high-affinity neuregulin-1 receptor, HER2-HER3 [...] Read more.
HER2+ breast cancer patients have an elevated risk of developing brain metastases (BM), despite adjuvant HER2-targeted therapy. The mechanisms underpinning this reduced intracranial efficacy are unclear. We optimised the in situ proximity ligation assay (PLA) for detection of the high-affinity neuregulin-1 receptor, HER2-HER3 (a key target of pertuzumab), in archival tissue samples and developed a pipeline for high throughput extraction of PLA data from fluorescent microscope image files. Applying this to a large BM sample cohort (n = 159) showed that BM from breast, ovarian, lung and kidney cancers have higher HER2-HER3 levels than other primary tumour types (melanoma, colorectal and prostate cancers). HER2 status, and tumour cell membrane expression of pHER2(Y1221/1222) and pHER3(Y1222) were positively, but not exclusively, associated with HER2-HER3 frequency. In an independent cohort (n = 78), BM had significantly higher HER2-HER3 levels than matching primary tumours (p = 0.0002). For patients who had two craniotomy procedures, HER2-HER3 dimer levels were lower in the consecutive lesion (n = 7; p = 0.006). We also investigated the effects of trastuzumab and pertuzumab on five different heterodimers in vitro: HER2-EGFR, HER2-HER4, HER2-HER3, HER3-HER4, HER3-EGFR. Treatment significantly altered the absolute frequencies of individual complexes in SKBr3 and/or MDA-MB-361 cells, but in the presence of neuregulin-1, the overall distribution was not markedly altered, with HER2-HER3 and HER2-HER4 remaining predominant. Together, these findings suggest that markers of HER2 and HER3 expression are not always indicative of dimerization, and that pertuzumab may be less effective at reducing HER2-HER3 dimerization in the context of excess neuregulin. Full article
(This article belongs to the Special Issue Brain Metastases in Breast Cancer)
Show Figures

Figure 1

Review

Jump to: Research

Review
Patient Eligibility and Results for Brain Metastasis in Phase 3 Trials of Advanced Breast Cancer: A Scoping Review
Cancers 2021, 13(21), 5306; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215306 - 22 Oct 2021
Viewed by 484
Abstract
Background: Although brain metastases (BM) affect 5% of all breast cancer patients and 14% of those with metastatic disease, patients with BM are often excluded from participation in clinical trials. We conducted a structured assessment of the contemporary restrictions to enrolment of, and [...] Read more.
Background: Although brain metastases (BM) affect 5% of all breast cancer patients and 14% of those with metastatic disease, patients with BM are often excluded from participation in clinical trials. We conducted a structured assessment of the contemporary restrictions to enrolment of, and results for, patients with BM in phase 3 trials published over a period of 23 years in advanced breast cancer. Methods: We used PubMed to search for completed randomized trials published between 01/98 and 12/20. For all eligible trials, two authors independently abstracted data on general characteristics of the studies and detailed information on patient eligibility regarding the presence of BM. Results: We analyzed 210 trials, which enrolled 92,409 eligible patients. Of that total, 162 (77.1%) publications explicitly mentioned eligibility criteria related to the presence of BM and 75 (35.7%) trials reportedly allowed patients with BM, usually with restrictions related to prior brain treatment or stability of lesions. There was a significant increase over time in the percentages of trials allowing patients with BM (p < 0.001), and these trials were more frequently dedicated to HER2-positive or triple-negative disease (p = 0.001). Only 11 trials reported separate results for patients with BM at baseline. The direct treatment activity on BM was usually not reported, although in subgroup analyses the treatment effect in relative terms was usually better among patients with BM than in overall populations. Conclusion: Nearly 36% of phase 3 trials in advanced breast cancer over a 23-year period allowed patients with BM, and this practice is increasing over time. More research is needed to establish the activity of current and promising therapies in patients with BM. Full article
(This article belongs to the Special Issue Brain Metastases in Breast Cancer)
Show Figures

Figure 1

Back to TopTop