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Advances in Breast Cancer: From Pathogenesis to Therapy
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Advances in Breast Cancer: From Pathogenesis to Therapy

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

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 12065

Special Issue Editors

Prof. Dr. Ana Isabel Torres-Suárez

E-Mail Website
Guest Editor
Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
Interests: breast cancer; chemotherapy; drug delivery; drug targeting; gynecological cancers; microparticles; nanocarriers; nanomedicine; nanotheranostics
Special Issues, Collections and Topics in MDPI journals
Dr. Ana Isabel Fraguas-Sánchez

E-Mail Website
Guest Editor
Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
Interests: antimicrobial agents; breast cancer; cannabinoids; drug delivery; drug targeting; in situ-forming implants; nanomedicine; ovarian cancer; polymers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breast cancer is the most frequent neoplasm in women worldwide, showing a mortality-to-incidence ratio of around 15%. In fact, it is the second leading cause of cancer death in the female population. According to the World Health Organization, the breast cancer incidence is expected to increase from 2.26 million diagnoses in 2020 to 3.03 million cases in 2040, representing an important global health problem. This is a very heterogenous disease that can be clinically grouped according to the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER-2) into three main subtypes: luminal ER and PR positive tumors, HER-2 positive tumors, and triple negative breast cancer (TNBC) that does not express any of these receptors. Breast cancer treatment depends on the tumor subtype and disease stage and includes local treatments such as surgery and radiotherapy; and systemic therapies such as hormonotherapy, immunotherapy and chemotherapy.

This Special Issue aims to compile the latest advances made in breast cancer research from its pathogenesis to the discovery of new treatments and the development of new formulations of all breast cancer subtypes. Manuscripts reporting original data or updated literature reviews covering some of these issues are welcome.

Prof. Dr. Ana Isabel Torres-Suárez
Dr. Ana Isabel Fraguas-Sánchez
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 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

  • antibody-drug-conjugates
  • breast cancer exosomes
  • chemotherapy
  • drug resistance
  • endocrine therapy
  • HER-2 positive tumors
  • immunotherapy
  • nanomedicine
  • targeted therapies
  • TNBC

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Published Papers (6 papers)

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Research

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17 pages, 20325 KiB  
Article
Prognostic Evaluation of Piezo2 Channels in Mammary Gland Carcinoma
by Raquel Martín-Sanz, Aline Rodrigues-Françoso, Yolanda García-Mesa, Francisco Javier García-Alonso, María Asunción Gómez-Muñoz, Sandra Malmierca-González, Rocío Salazar-Blázquez, Olivia García-Suárez and Jorge Feito
Cancers 2024, 16(13), 2413; https://doi.org/10.3390/cancers16132413 - 29 Jun 2024
Viewed by 1061
Abstract
In the last decade, a group of Ca2+ channels called Piezo were discovered, demonstrating a decisive role in the cellular response to mechanical stimuli and being essential in the biological behavior of cells regarding the extracellular compartment. Several investigations have suggested a [...] Read more.
In the last decade, a group of Ca2+ channels called Piezo were discovered, demonstrating a decisive role in the cellular response to mechanical stimuli and being essential in the biological behavior of cells regarding the extracellular compartment. Several investigations have suggested a potential role in carcinogenesis, with a tumor suppressor role in some cases but increased expression in several high-grade neoplasms. Regarding Piezo2 expression in mammary gland neoplasms, a protective role for Piezo2 was initially suggested, but a subsequent study demonstrated a relationship between Piezo2 expression and the highly aggressive triple-negative phenotype of breast carcinoma. A cohort of 125 patients with clinical follow-up was chosen to study Piezo2 expression and clarify its clinical implications using the same immunohistochemical evaluation performed for other breast carcinoma parameters. Fisher’s exact test was chosen to identify potential relationships between the different variables. A significant association was found with the Ki67 proliferation index, but not with mitoses. The tendency of most proliferative tumors was to have an increased score for Piezo2. A similar association was found between Piezo2 expression and perineural invasion. Full article
(This article belongs to the Special Issue Advances in Breast Cancer: From Pathogenesis to Therapy)
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10 pages, 1225 KiB  
Article
CT-Guided Percutaneous Cryoablation of Breast Cancer: A Single-Center Experience
by Thomas J. Vogl, John Bielfeldt, Ulrich Kübler and Hamzah Adwan
Cancers 2024, 16(13), 2373; https://doi.org/10.3390/cancers16132373 - 28 Jun 2024
Viewed by 1049
Abstract
This study shall retrospectively evaluate the efficacy and safety of liquid-nitrogen based CT-guided cryoablation (CA) as a minimal-invasive technique for the curative treatment of primary breast cancer. A total of 45 female patients with 56 tumors were treated by CT-guided CA in analgosedation [...] Read more.
This study shall retrospectively evaluate the efficacy and safety of liquid-nitrogen based CT-guided cryoablation (CA) as a minimal-invasive technique for the curative treatment of primary breast cancer. A total of 45 female patients with 56 tumors were treated by CT-guided CA in analgosedation as an outpatient procedure. We used a liquid-nitrogen based system with a single cryoprobe and performed two freeze cycles with an intermediate thawing. The mean tumor diameter was 1.6 ± 0.7 cm. Follow-up was conducted via contrast-enhanced MR images of the breast. No complications were observed in all 56 ablations. Initial complete ablation was achieved in 100% of cases. Four cases of local tumor progression were reported, resulting in a rate of 8.9%, and 6 cases of intramammary distant recurrence at a rate of 13.3%. The extramammary tumor progression was observed in 7 patients at a rate of 15.6%. The mean overall survival was 4.13 years (95% CI: 3.7–4.5). The mean overall progression-free survival was 2.5 years (95% CI: 1.8–3.2) and the mean local progression-free survival was 2.9 years (95% CI: 2.3–3.6). Cryoablation is a safe and effective treatment for primary breast cancer tumors, which can be performed in analgosedation and as an outpatient procedure. However, potential for improvement exists and further evidence is necessary. Full article
(This article belongs to the Special Issue Advances in Breast Cancer: From Pathogenesis to Therapy)
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15 pages, 2477 KiB  
Article
Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes—Obesity as a Crucial Player
by Carla Luís, Fernando Schmitt, Rute Fernandes, Nuno Coimbra, Joana Rigor, Paula Dias, Dina Leitão, Rúben Fernandes and Raquel Soares
Cancers 2023, 15(20), 4936; https://doi.org/10.3390/cancers15204936 - 11 Oct 2023
Cited by 1 | Viewed by 1654
Abstract
Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was [...] Read more.
Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine. Full article
(This article belongs to the Special Issue Advances in Breast Cancer: From Pathogenesis to Therapy)
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19 pages, 2875 KiB  
Article
Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo
by Paulo George Cavalcante de Freitas, Bruno Rodrigues Arruda, Maria Gabriela Araújo Mendes, João Vito Barroso de Freitas, Mateus Edson da Silva, Tiago Lima Sampaio, Raquel Petrilli and Josimar O. Eloy
Cancers 2023, 15(10), 2802; https://doi.org/10.3390/cancers15102802 - 17 May 2023
Cited by 7 | Viewed by 2394
Abstract
Resveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines. However, RSV [...] Read more.
Resveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines. However, RSV is a lipophilic drug, and its therapeutic effect could be improved through nanoencapsulation. Functionalizing polymeric nanoparticles based on polycaprolactone (PCL) with polyethylene glycol 1000 tocopheryl succinate (TPGS) has been reported to prolong drug circulation and reduce drug resistance. However, the effect of TPGS on the physicochemical properties and biological effects of breast cancer cells remains unclear. Therefore, this study aimed to develop RSV-loaded PCL nanoparticles using nanoprecipitation and investigate the effect of TPGS on the nanoparticles’ physicochemical characteristics (particle size, zeta potential, encapsulation efficiency, morphology, and release rate) and biological effects on the 4T1 breast cancer cell line (cytotoxicity and cell uptake), in vitro and in vivo. The optimized nanoparticles without TPGS had a size of 138.1 ± 1.8 nm, a polydispersity index (PDI) of 0.182 ± 0.01, a zeta potential of −2.42 ± 0.56 mV, and an encapsulation efficiency of 98.2 ± 0.87%, while nanoparticles with TPGS had a size of 127.5 ± 3.11 nm, PDI of 0.186 ± 0.01, zeta potential of −2.91 ± 0.90 mV, and an encapsulation efficiency of 98.40 ± 0.004%. Scanning electron microscopy revealed spherical nanoparticles with low aggregation tendency. Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) identified the constituents of the nanoparticles and the presence of drug encapsulation in an amorphous state. In vitro release studies showed that both formulations followed the same dissolution profiles, with no statistical differences. In cytotoxicity tests, IC50 values of 0.12 µM, 0.73 µM, and 4.06 µM were found for the formulation without TPGS, with TPGS, and pure drug, respectively, indicating the potentiation of the cytotoxic effect of resveratrol when encapsulated. Flow cytometry and confocal microscopy tests indicated excellent cellular uptake dependent on the concentration of nanoparticles, with a significant difference between the two formulations, suggesting that TPGS may pose a problem in the endocytosis of nanoparticles. The in vivo study evaluating the antitumor activity of the nanoparticles confirmed the data obtained in the in vitro tests, demonstrating that the nanoparticle without TPGS significantly reduced tumor volume, tumor mass, maintained body weight, and improved survival in mice. Moreover, the biochemical evaluation evidenced possible hepatotoxicity for formulation with TPGS. Full article
(This article belongs to the Special Issue Advances in Breast Cancer: From Pathogenesis to Therapy)
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19 pages, 15718 KiB  
Article
Myo-Inositol Reverses TGF-β1-Induced EMT in MCF-10A Non-Tumorigenic Breast Cells
by Noemi Monti, Simona Dinicola, Alessandro Querqui, Gianmarco Fabrizi, Valeria Fedeli, Luisa Gesualdi, Angela Catizone, Vittorio Unfer and Mariano Bizzarri
Cancers 2023, 15(8), 2317; https://doi.org/10.3390/cancers15082317 - 15 Apr 2023
Cited by 4 | Viewed by 2125
Abstract
Epithelial-Mesenchymal Transition (EMT), triggered by external and internal cues in several physiological and pathological conditions, elicits the transformation of epithelial cells into a mesenchymal-like phenotype. During EMT, epithelial cells lose cell-to-cell contact and acquire unusual motility/invasive capabilities. The associated architectural and functional changes [...] Read more.
Epithelial-Mesenchymal Transition (EMT), triggered by external and internal cues in several physiological and pathological conditions, elicits the transformation of epithelial cells into a mesenchymal-like phenotype. During EMT, epithelial cells lose cell-to-cell contact and acquire unusual motility/invasive capabilities. The associated architectural and functional changes destabilize the epithelial layer consistency, allowing cells to migrate and invade the surrounding tissues. EMT is a critical step in the progression of inflammation and cancer, often sustained by a main driving factor as the transforming growth factor-β1 (TGF-β1). Antagonizing EMT has recently gained momentum as an attractive issue in cancer treatment and metastasis prevention. Herein, we demonstrate the capability of myo-inositol (myo-Ins) to revert the EMT process induced by TGF-β1 on MCF-10A breast cells. Upon TGF-β1 addition, cells underwent a dramatic phenotypic transformation, as witnessed by structural (disappearance of the E-cadherin–β-catenin complexes and the emergence of a mesenchymal shape) and molecular modifications (increase in N-cadherin, Snai1, and vimentin), including the release of increased collagen and fibronectin. However, following myo-Ins, those changes were almost completely reverted. Inositol promotes the reconstitution of E-cadherin–β-catenin complexes, decreasing the expression of genes involved in EMT, while promoting the re-expression of epithelial genes (keratin-18 and E-cadherin). Noticeably, myo-Ins efficiently inhibits the invasiveness and migrating capability of TGF-β1 treated cells, also reducing the release of metalloproteinase (MMP-9) altogether with collagen synthesis, allowing for the re-establishment of appropriate cell-to-cell junctions, ultimately leading the cell layer back towards a more compact state. Inositol effects were nullified by previous treatment with an siRNA construct to inhibit CDH1 transcripts and, hence, E-cadherin synthesis. This finding suggests that the reconstitution of E-cadherin complexes is an irreplaceable step in the inositol-induced reversion of EMT. Overall, such a result advocates for the useful role of myo-Ins in cancer treatment. Full article
(This article belongs to the Special Issue Advances in Breast Cancer: From Pathogenesis to Therapy)
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Review

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21 pages, 2728 KiB  
Review
Natural Products for the Prevention, Treatment and Progression of Breast Cancer
by Fabiano Svolacchia, Sergio Brongo, Alessia Catalano, Agostino Ceccarini, Lorenzo Svolacchia, Alessandro Santarsiere, Carmen Scieuzo, Rosanna Salvia, Francesca Finelli, Luigi Milella, Carmela Saturnino, Maria Stefania Sinicropi, Tommaso Fabrizio and Federica Giuzio
Cancers 2023, 15(11), 2981; https://doi.org/10.3390/cancers15112981 - 30 May 2023
Cited by 11 | Viewed by 2860
Abstract
In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, [...] Read more.
In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy. Full article
(This article belongs to the Special Issue Advances in Breast Cancer: From Pathogenesis to Therapy)
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