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Molecular Advances in Breast Cancer
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Molecular Advances in Breast Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 10820

Special Issue Editor

Prof. Dr. Fabio Puglisi

E-Mail Website
Guest Editor
1. Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
2. Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
Interests: breast cancer; translational research; precision oncology; anticancer therapy; liquid biopsy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The prevalence of breast cancer in Western countries is extremely high and tends to increase with age. It is the first leading cause of cancer-related death in women worldwide.

Understanding the cancer biology of patients suffering from breast cancer is key for making progress in the treatment of these patients. Recent technical developments that allow better resolution have increased our understanding of the molecular mechanisms that are important for breast cancer biology and disease evolution.

We would like to invite manuscripts that decipher the molecular and biochemical development and progression of breast cancer. We are particularly interested in the mechanism of drug delivery and gene therapy in breast cancer. This Special Issue will focus on the current status of and challenges in treating early and progressive breast cancer and attempts to understand it at a molecular, biochemical, and genetic level.

Prof. Dr. Fabio Puglisi
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 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 tissue
  • breast cancer
  • tumor
  • genetics
  • diagnosis
  • therapeutics
  • predictive factors
  • prognosis
  • target therapy

Published Papers (4 papers)

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Research

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17 pages, 5746 KiB  
Article
PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression
by Duaa Alkaabi, Kholoud Arafat, Shahrazad Sulaiman, Aya Mudhafar Al-Azawi and Samir Attoub
Int. J. Mol. Sci. 2023, 24(7), 6420; https://doi.org/10.3390/ijms24076420 - 29 Mar 2023
Cited by 3 | Viewed by 2314
Abstract
Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed [...] Read more.
Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed death-ligand 1 (PD-L1) is an immunosuppressive protein that inactivates T cells by binding to the inhibitory receptor programmed death-1 (PD-1). PD-L1 overexpression in cancer cells contributes to immune evasion and, subsequently, poor survival and prognosis in several cancers, including breast cancer. Apart from its inhibitory impact on T cells, this ligand is believed to have an intrinsic role in cancer cells. This study was performed to clarify the PD-1 independent role of PD-L1 in TNBC MDA-MB-231 cells by knocking out the PD-L1 using three designs of CRISPR-Cas9 lentiviral particles. Our study revealed that PD-L1 knockout significantly inhibited MDA-MB-231 cell proliferation and colony formation in vitro and tumor growth in the chick embryo chorioallantoic membrane (CAM) model in vivo. PD-L1 knockout also decreased the migration and invasion of MDA-MB-231 cells in vitro. We have shown that PD-L1 knockout MDA-MB-231 cells have low levels of p-Akt and p-ERK in addition to some of their downstream proteins, c-Fos, c-Myc, p21, survivin, and COX-2. Furthermore, PD-L1 knockout significantly decreased the expression of Snail and RhoA. This study shows the intrinsic role of PD-L1 in TNBC independently of its binding to PD-1 receptors on T cells. It may pave the way for developing novel therapeutic strategies using PD-L1 inhibitors alone and in combination to treat TNBC more effectively. Full article
(This article belongs to the Special Issue Molecular Advances in Breast Cancer)
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17 pages, 1170 KiB  
Article
Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting
by Ramona Erber, Miriam Angeloni, Robert Stöhr, Michael P. Lux, Daniel Ulbrich-Gebauer, Enrico Pelz, Agnes Bankfalvi, Kurt W. Schmid, Robert F. H. Walter, Martina Vetter, Christoph Thomssen, Doris Mayr, Frederick Klauschen, Peter Sinn, Karl Sotlar, Katharina Stering, Albrecht Stenzinger, Marius Wunderle, Peter A. Fasching, Matthias W. Beckmann, Oliver Hoffmann, Rainer Kimmig, Nadia Harbeck, Rachel Wuerstlein, Fulvia Ferrazzi and Arndt Hartmannadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(15), 8716; https://doi.org/10.3390/ijms23158716 - 05 Aug 2022
Cited by 4 | Viewed by 2157
Abstract
In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric [...] Read more.
In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B. Full article
(This article belongs to the Special Issue Molecular Advances in Breast Cancer)
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Review

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14 pages, 314 KiB  
Review
Extended Adjuvant Endocrine Treatment in Luminal Breast Cancers in the Era of Genomic Tests
by Mariarosaria Saponaro, Luigi Annunziata, Antonella Turla, Ilaria Viganò, Michele De Laurentiis, Mario Giuliano, Lucia Del Mastro, Filippo Montemurro, Fabio Puglisi, Carmine De Angelis, Giuseppe Buono, Francesco Schettini and Grazia Arpino
Int. J. Mol. Sci. 2022, 23(21), 13604; https://doi.org/10.3390/ijms232113604 - 06 Nov 2022
Cited by 1 | Viewed by 2115
Abstract
In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond [...] Read more.
In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice. Full article
(This article belongs to the Special Issue Molecular Advances in Breast Cancer)
22 pages, 1367 KiB  
Review
The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90
by Giusi Alberti, Giuseppe Vergilio, Letizia Paladino, Rosario Barone, Francesco Cappello, Everly Conway de Macario, Alberto J. L. Macario, Fabio Bucchieri and Francesca Rappa
Int. J. Mol. Sci. 2022, 23(14), 7792; https://doi.org/10.3390/ijms23147792 - 14 Jul 2022
Cited by 15 | Viewed by 3556
Abstract
Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can [...] Read more.
Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can be predicted to be a crucial factor in these mechanisms. The chief components of the CS are the molecular chaperones, and here we discuss four of them, Hsp27, Hsp60, Hsp70, and Hsp90, focusing on their pro-carcinogenic roles in BC and potential for developing anti-BC therapies. These chaperones can be targets of negative chaperonotherapy, namely the elimination/blocking/inhibition of the chaperone(s) functioning in favor of BC, using, for instance, Hsp inhibitors. The chaperones can also be employed in immunotherapy against BC as adjuvants, together with BC antigens. Extracellular vesicles (EVs) in BC diagnosis and management are also briefly discussed, considering their potential as easily accessible carriers of biomarkers and as shippers of anti-cancer agents amenable to manipulation and controlled delivery. The data surveyed from many laboratories reveal that, to enhance the understanding of the role of the CS in BS pathogenesis, one must consider the CS as a physiological system, encompassing diverse members throughout the body and interacting with the ubiquitin–proteasome system, the chaperone-mediated autophagy machinery, and the immune system (IS). An integrated view of the CS, including its functional partners and considering its highly dynamic nature with EVs transporting CS components to reach all the cell compartments in which they are needed, opens as yet unexplored pathways leading to carcinogenesis that are amenable to interference by anti-cancer treatments centered on CS components, such as the molecular chaperones. Full article
(This article belongs to the Special Issue Molecular Advances in Breast Cancer)
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