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Pathogens
Special Issues
Role of Microorganisms in Breast Cancer
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Role of Microorganisms in Breast Cancer

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: 30 May 2024 | Viewed by 18838

Special Issue Editors

Dr. María Leonor Fernández-Murga

E-Mail Website1 Website2
Guest Editor
Medical Oncology Department, Hospital Arnau de Vilanova, Fundación para el Fomento de la Investigación Sanitaria i Biomédica de la Comunidad Valenciana (FISABIO), 46020 Valencia, Spain
Interests: Breast cancer; microbioma; metagenomic; probiotic; immunoteraphy; estrobolome; metabolomic
Dr. Antonio Llombart-Cussac

E-Mail Website
Guest Editor
Medical Oncology Department, Hospital Arnau de Vilanova, Fundación para el Fomento de la Investigación Sanitaria i Biomédica de la Comunidad Valenciana (FISABIO), 46020 Valencia, Spain
Interests: Breast cancer; microbioma; metagenomic;endocrine-sensitivity; immunotherapy; estrobolome; metabolomics

Special Issue Information

Dear Colleagues,

Breast cancer remains among the most frequent causes of death in young women in developed countries. Anatomically, the breast tissue conforms a complex microenvironment. In addition, humans coexist with a vast bacterial, fungal, and viral microbiome with which we have coevolved for millions of years. Several epidemiological associations have been established between specific microorganisms and cancer. With the advent of next-generation sequencing, we have an unprecedented ability to study tumor and host genomes as well as those of the vast array of microorganisms that exist within living organisms. Evidence now suggests that these microbes and their metabolites may confer susceptibility to certain cancers, such as breast cancer, and may also influence response to therapeutics. These studies have revealed causal mechanisms for both microbes within the tumor environment and microbes in other host niches separated from tumors, mediated through direct metabolites and proteins, and immunological mechanisms.

It is therefore timely and relevant for Pathogens to publish this Special Issue. We will provide insights into the effect and behavior of pathogens and human microbiota on breast cancer disease. Such knowledge can be derived from a vast amount of publicly available microorganism data (beneficial, probiotic, and pathogens) and through well-designed population-based studies.

The objective of this Special Issue is to compile the most recent research targeting the complex interaction between breast cancer, the gut microbiome, and pathogenic microorganisms. All types of articles will be considered for publication, including communication, original research, and review articles. 

References

  1. Fernández, M.F.; Reina-Pérez, I.; Astorga, J.M.; Rodríguez-Carrillo, A.; Plaza-Díaz, J.; Fontana, L. Breast Cancer and Its Relationship with the Microbiota. Int. J. Environ. Res. Public Heal. 2018, 15, 1747, doi:10.3390/ijerph15081747.
  2. Picardo, S.L.; Coburn, B.; Hansen, A.R. The microbiome and cancer for clinicians. Crit. Rev. Oncol. 2019, 141, 1–12, doi:10.1016/j.critrevonc.2019.06.004.
  3. Yang, L.; Liu, Q.; Zhang, X.; Liu, X.; Zhou, B.; Chen, J.; Huang, D.; Li, J.; Li, H.; Chen, F.; et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nat. Cell Biol. 2020, 583, 133–138, doi:10.1038/s41586-020-2394-6.
  4. Ojo-Okunola, A.; Nicol, M.; Du Toit, E. Human Breast Milk Bacteriome in Health and Disease. Nutr. 2018, 10, 1643, doi:10.3390/nu10111643.
  5. Bodai, B. Breast Cancer: Lifestyle, the Human Gut Microbiota/Microbiome, and Survivorship. Perm. J. 2020, 24, doi:10.7812/tpp/19.129.
  6. Vergara, D.; Simeone, P.; Damato, M.; Maffia, M.; Lanuti, P.; Trerotola, M. The Cancer Microbiota: EMT and Inflammation as Shared Molecular Mechanisms Associated with Plasticity and Progression. J. Oncol. 2019, 2019, 1–16, doi:10.1155/2019/1253727.
  7. Banerjee, S.; Tian, T.; Wei, Z.; Shih, N.; Feldman, M.D.; Peck, K.N.; DeMichele, A.M.; Alwine, J.C.; Robertson, E.S. Distinct Microbial Signatures Associated With Different Breast Cancer Types. Front. Microbiol. 2018, 9, 951, doi:10.3389/fmicb.2018.00951.

Dr. María Leonor Fernández-Murga
Dr. Antonio Llombart-Cussac
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. Pathogens is an international peer-reviewed open access monthly 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 2700 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

  • Microorganism
  • Pathogens
  • Microbiota and dysbiosis
  • Antibiotics
  • Estrobolome
  • Probiotics
  • Multidrug resistance and microbiota
  • Breast milk bacteriome
  • Cathelicidin antimicrobial protein in breast cancer
  • Inflammation and dysbiosis and breast cancer

Published Papers (9 papers)

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Research

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31 pages, 8591 KiB  
Article
The Bio-Diversity and the Role of Gut Microbiota in Postmenopausal Women with Luminal Breast Cancer Treated with Aromatase Inhibitors: An Observational Cohort Study
by Angioletta Lasagna, Mara De Amici, Chiara Rossi, Valentina Zuccaro, Marta Corbella, Greta Petazzoni, Francesco Comandatore, Lucia Sacchi, Giorgia Testa, Elisa Ferraris, Gianpiero Rizzo, Richard Tancredi, Alessandra Ferrari, Marco Lucioni, Paolo Sacchi, Raffaele Bruno and Paolo Pedrazzoli
Pathogens 2022, 11(12), 1421; https://doi.org/10.3390/pathogens11121421 - 26 Nov 2022
Cited by 2 | Viewed by 1492
Abstract
The interactions between aromatase inhibitors (AI) in breast cancer (BC) and gut microbiota (GM) have not been completely established yet. The aim of the study is to evaluate the bio-diversity of GM and the relationship between GM, inflammation and tumor-infiltrating lymphocytes (TILs) in [...] Read more.
The interactions between aromatase inhibitors (AI) in breast cancer (BC) and gut microbiota (GM) have not been completely established yet. The aim of the study is to evaluate the bio-diversity of GM and the relationship between GM, inflammation and tumor-infiltrating lymphocytes (TILs) in postmenopausal women with BC during adjuvant AI treatment compared to women with disease relapse during or after one year of AI therapy (“endocrine-resistant”). We conducted a monocenter observational case-control study. Eighty-four women with BC (8 cases, 76 controls) were enrolled from 2019 to 2021. We observed a significant difference in the mean microbial abundance between the two groups for the taxonomic rank of order (p 0.035) and family (p 0.029); specifically, the case group showed higher diversity than the control group. Veillonella reached its maximum abundance in cases (p 0.022). Cytokine levels were compared among the groups created considering the TILs levels. We obtained a statistically significant difference (p 0.045) in IL-17 levels among the groups, with patients with low TILs levels showing a higher median value for IL-17 (0.15 vs. 0.08 pg/mL). Further studies about the bio-diversity in women with BC may lead to the development of new biomarkers and targeted interventions. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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Review

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13 pages, 661 KiB  
Review
The Microbiome in the Obesity-Breast Cancer Axis: Diagnostic and Therapeutic Potential
by Dimiter Avtanski, Varun Reddy, Radoslav Stojchevski, Nikola Hadzi-Petrushev and Mitko Mladenov
Pathogens 2023, 12(12), 1402; https://doi.org/10.3390/pathogens12121402 - 29 Nov 2023
Viewed by 1142
Abstract
A growing body of evidence has demonstrated a relationship between the microbiome, adiposity, and cancer development. The microbiome is emerging as an important factor in metabolic disease and cancer pathogenesis. This review aimed to highlight the role of the microbiome in obesity and [...] Read more.
A growing body of evidence has demonstrated a relationship between the microbiome, adiposity, and cancer development. The microbiome is emerging as an important factor in metabolic disease and cancer pathogenesis. This review aimed to highlight the role of the microbiome in obesity and its association with cancer, with a particular focus on breast cancer. This review discusses how microbiota dysbiosis may contribute to obesity and obesity-related diseases, which are linked to breast cancer. It also explores the potential of the gut microbiome to influence systemic immunity, leading to carcinogenesis via the modulation of immune function. This review underscores the potential use of the microbiome profile as a diagnostic tool and treatment target, with strategies including probiotics, fecal microbiota transplantation, and dietary interventions. However, this emphasizes the need for more research to fully understand the complex relationship between the microbiome, metabolic disorders, and breast cancer. Future studies should focus on elucidating the mechanisms underlying the impact of the microbiome on breast cancer and exploring the potential of the microbiota profile as a biomarker and treatment target. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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22 pages, 2294 KiB  
Review
A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target
by M. Leonor Fernández-Murga, Fernando Gil-Ortiz, Lucía Serrano-García and Antonio Llombart-Cussac
Pathogens 2023, 12(9), 1086; https://doi.org/10.3390/pathogens12091086 - 26 Aug 2023
Cited by 2 | Viewed by 1561
Abstract
Breast cancer (BC) is the most frequently occurring malignancy and the second cancer-specific cause of mortality in women in developed countries. Over 70% of the total number of BCs are hormone receptor-positive (HR+), and elevated levels of circulating estrogen (E) in the blood [...] Read more.
Breast cancer (BC) is the most frequently occurring malignancy and the second cancer-specific cause of mortality in women in developed countries. Over 70% of the total number of BCs are hormone receptor-positive (HR+), and elevated levels of circulating estrogen (E) in the blood have been shown to be a major risk factor for the development of HR+ BC. This is attributable to estrogen’s contribution to increased cancer cell proliferation, stimulation of angiogenesis and metastasis, and resistance to therapy. The E metabolism–gut microbiome axis is functional, with subjacent individual variations in the levels of E. It is conceivable that the estrobolome (bacterial genes whose products metabolize E) may contribute to the risk of malignant neoplasms of hormonal origin, including BC, and may serve as a potential biomarker and target. It has been suggested that β-glucuronidase (GUS) enzymes of the intestinal microbiome participate in the strobolome. In addition, it has been proposed that bacterial GUS enzymes from the gastrointestinal tract participate in hormone BC. In this review, we discuss the latest knowledge about the role of the GUS enzyme in the pathogenesis of BC, focusing on (i) the microbiome and E metabolism; (ii) diet, estrobolome, and BC development; (iii) other activities of the bacterial GUS; and (iv) the new molecular targets for BC therapeutic application. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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15 pages, 663 KiB  
Review
Control of Redox Homeostasis by Short-Chain Fatty Acids: Implications for the Prevention and Treatment of Breast Cancer
by Carmen González-Bosch, Patricia A. Zunszain and Giovanni E. Mann
Pathogens 2023, 12(3), 486; https://doi.org/10.3390/pathogens12030486 - 19 Mar 2023
Cited by 4 | Viewed by 2097
Abstract
Breast cancer is the leading cause of death among women worldwide, and certain subtypes are highly aggressive and drug resistant. As oxidative stress is linked to the onset and progression of cancer, new alternative therapies, based on plant-derived compounds that activate signaling pathways [...] Read more.
Breast cancer is the leading cause of death among women worldwide, and certain subtypes are highly aggressive and drug resistant. As oxidative stress is linked to the onset and progression of cancer, new alternative therapies, based on plant-derived compounds that activate signaling pathways involved in the maintenance of cellular redox homeostasis, have received increasing interest. Among the bioactive dietary compounds considered for cancer prevention and treatment are flavonoids, such as quercetin, carotenoids, such as lycopene, polyphenols, such as resveratrol and stilbenes, and isothiocyanates, such as sulforaphane. In healthy cells, these bioactive phytochemicals exhibit antioxidant, anti-apoptotic and anti-inflammatory properties through intracellular signaling pathways and epigenetic regulation. Short-chain fatty acids (SCFAs), produced by intestinal microbiota and obtained from the diet, also exhibit anti-inflammatory and anti-proliferative properties related to their redox signaling activity—and are thus key for cell homeostasis. There is evidence supporting an antioxidant role for SCFAs, mainly butyrate, as modulators of Nrf2-Keap1 signaling involving the inhibition of histone deacetylases (HDACs) and/or Nrf2 nuclear translocation. Incorporation of SCFAs in nutritional and pharmacological interventions changes the composition of the the intestinal microbiota, which has been shown to be relevant for cancer prevention and treatment. In this review, we focused on the antioxidant properties of SCFAs and their impact on cancer development and treatment, with special emphasis on breast cancer. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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13 pages, 5607 KiB  
Review
Role of Gut Microbiota in Breast Cancer and Drug Resistance
by Sathiyapriya Viswanathan, Sheetal Parida, Bhuvana Teja Lingipilli, Ramalingam Krishnan, Devendra Rao Podipireddy and Nethaji Muniraj
Pathogens 2023, 12(3), 468; https://doi.org/10.3390/pathogens12030468 - 16 Mar 2023
Cited by 8 | Viewed by 4521
Abstract
Breast cancer is the most common malignancy in women worldwide. The cause of cancer is multifactorial. An early diagnosis and the appropriate treatment of cancer can improve the chances of survival. Recent studies have shown that breast cancer is influenced by the microbiota. [...] Read more.
Breast cancer is the most common malignancy in women worldwide. The cause of cancer is multifactorial. An early diagnosis and the appropriate treatment of cancer can improve the chances of survival. Recent studies have shown that breast cancer is influenced by the microbiota. Different microbial signatures have been identified in the breast microbiota, which have different patterns depending on the stage and biological subgroups. The human digestive system contains approximately 100 trillion bacteria. The gut microbiota is an emerging field of research that is associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain disease, rheumatoid arthritis, and cancer. In this review article, we discuss the impact of the microbiota on breast cancer, with a primary focus on the gut microbiota’s regulation of the breast cancer microenvironment. Ultimately, updates on how immunotherapy can affect the breast cancer-based microbiome and further clinical trials on the breast and microbiome axis may be an important piece of the puzzle in better predicting breast cancer risk and prognosis. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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12 pages, 690 KiB  
Review
The Role of Microorganisms in the Development of Breast Implant-Associated Anaplastic Large Cell Lymphoma
by Mario Alessandri-Bonetti, Tiffany Jeong, Luca Vaienti, Carolyn De La Cruz, Michael L. Gimbel, Vu T. Nguyen and Francesco M. Egro
Pathogens 2023, 12(2), 313; https://doi.org/10.3390/pathogens12020313 - 14 Feb 2023
Cited by 9 | Viewed by 2537
Abstract
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a variant of anaplastic large cell lymphoma (ALCL) associated with textured-surface silicone breast implants. Since first being described in 1997, over 1100 cases have been currently reported worldwide. A causal relationship between BIA-ALCL and textured [...] Read more.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a variant of anaplastic large cell lymphoma (ALCL) associated with textured-surface silicone breast implants. Since first being described in 1997, over 1100 cases have been currently reported worldwide. A causal relationship between BIA-ALCL and textured implants has been established in epidemiological studies, but a multifactorial process is likely to be involved in the pathogenesis of BIA-ALCL. However, pathophysiologic mechanisms remain unclear. One of the hypotheses that could explain the link between textured implants and BIA-ALCL consists in the greater tendency of bacterial biofilm in colonizing the surface of textured implants compared to smooth implants, and the resulting chronic inflammation which, in predisposed individuals, may lead to tumorigenesis. This review summarizes the existing evidence on the role of micro-organisms and rough surface implants in the development of BIA-ALCL. It also provides insights into the most updated clinical practice knowledge about BIA-ALCL, from clinical presentation and investigation to treatment and outcomes. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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17 pages, 373 KiB  
Review
HPV-Associated Breast Cancer: Myth or Fact?
by Erik Kudela, Eva Kudelova, Erik Kozubík, Tomas Rokos, Terezia Pribulova, Veronika Holubekova and Kamil Biringer
Pathogens 2022, 11(12), 1510; https://doi.org/10.3390/pathogens11121510 - 09 Dec 2022
Cited by 7 | Viewed by 2129
Abstract
Some estimates place the proportion of human malignancies attributable to viruses at between 15 and 20 percent. Viruses including the human papillomavirus are considered an interesting but controversial etiological risk factor for breast cancer. HPV infection is anticipated to be an early trigger [...] Read more.
Some estimates place the proportion of human malignancies attributable to viruses at between 15 and 20 percent. Viruses including the human papillomavirus are considered an interesting but controversial etiological risk factor for breast cancer. HPV infection is anticipated to be an early trigger in breast cancer carcinogenesis, followed by cumulative alterations over time (“hit and run” mechanism) through synergy with other environmental factors. The association between HPV and breast cancer has not yet been verified. There are very conflicting data on the presence of HPV DNA in breast cancer samples, and we lack a clarified, exact mode of HPV transmission to the breast. In our review article we analyzed the up-to-date knowledge about the association of HPV and breast cancer. Furthermore, we summarized the available original research published since 2010. In conclusion, the complexity and inconsistency of the available results together with the relatively low prevalence of HPV infection requires extensive research with much larger studies and exact and unified diagnostic methods are required to better understand the role of the HPV in breast carcinogenesis. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)

Other

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17 pages, 1251 KiB  
Systematic Review
Microorganisms and Breast Cancer: An In-Depth Analysis of Clinical Studies
by Naghmeh Naderi, Afshin Mosahebi and Norman R. Williams
Pathogens 2024, 13(1), 6; https://doi.org/10.3390/pathogens13010006 - 19 Dec 2023
Cited by 1 | Viewed by 939
Abstract
Breast cancer is a multifactorial disease that affects millions of women worldwide. Recent work has shown intriguing connections between microorganisms and breast cancer, which might have implications for prevention and treatment. This article analyzed 117 relevant breast cancer clinical studies listed on ClinicalTrials.gov [...] Read more.
Breast cancer is a multifactorial disease that affects millions of women worldwide. Recent work has shown intriguing connections between microorganisms and breast cancer, which might have implications for prevention and treatment. This article analyzed 117 relevant breast cancer clinical studies listed on ClinicalTrials.gov selected using a bespoke set of 38 search terms focused on bacteria, viruses, and fungi. This was supplemented with 20 studies found from a search of PubMed. The resulting 137 studies were described by their characteristics such as geographic distribution, interventions used, start date and status, etc. The studies were then collated into thematic groups for a descriptive analysis to identify knowledge gaps and emerging trends. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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10 pages, 4816 KiB  
Case Report
Non-Response of Epstein–Barr Virus-Associated Breast Cancer after Primary Chemotherapy: Report of Two Cases
by Ewgenija Gutjahr, Carlo Fremd, Johanna Arnscheidt, Roland Penzel, Jürgen Wacker and Peter Sinn
Pathogens 2023, 12(12), 1387; https://doi.org/10.3390/pathogens12121387 - 24 Nov 2023
Cited by 1 | Viewed by 1111
Abstract
Based on epidemiological evidence and molecular findings, a possible association of Epstein–Barr virus (EBV) with the carcinogenesis of breast cancer has been described. However, the frequency of EBV in breast cancer and the role of EBV regarding tumor progression or therapeutic results is [...] Read more.
Based on epidemiological evidence and molecular findings, a possible association of Epstein–Barr virus (EBV) with the carcinogenesis of breast cancer has been described. However, the frequency of EBV in breast cancer and the role of EBV regarding tumor progression or therapeutic results is largely unexplored. Here, we report on two cases of advanced, lymph node-positive invasive breast cancer of no special type (NST), histologically showing no clinical or histological evidence of tumor regression as an equivalent of a lack of response to primary systemic therapy. Both tumors were considered to be EBV-associated due to their positivity in EBV-encoded RNA (EBER) in situ hybridization (ISH) and their immunoreactivity against EBV Epstein–Barr nuclear antigen 1 (EBNA1). We hypothesize that the unusual non-response to chemotherapy in these cases of breast cancer classified as triple-negative and HER2-positive may be linked to the EBV co-infection of tumor cells. Therefore, EBV tumor testing should be considered in patients with breast cancer presenting with resistance to chemotherapy. This hypothesis may provide a new aspect in the context of EBV-associated mechanisms of tumor progression. Full article
(This article belongs to the Special Issue Role of Microorganisms in Breast Cancer)
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