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Cancers
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Breast Cancer: Biomarkers of Diagnosis and Prognosis
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Breast Cancer: Biomarkers of Diagnosis and Prognosis

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

Deadline for manuscript submissions: 15 November 2025 | Viewed by 7393

Special Issue Editors

Dr. Andrew R. Green

E-Mail Website
Guest Editor
Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK
Interests: breast cancer; pathology; metabolism; prognosis; biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Sarah J. Storr

E-Mail Website
Guest Editor
Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK
Interests: breast cancer

Special Issue Information

Dear Colleagues,

Breast cancer is a complex disease with high incidence rates worldwide; moreover, it has the second highest mortality in women out of all cancers and therefore remains a key global clinical challenge. However, it exhibits significant clinical and biological heterogeneity with divergent patient outcomes. Diagnostic and prognostic biomarkers are fundamental in the clinical pathway for treating breast cancer and hold great promise for personalized medicine. These can range from imaging-, tissue-, to serological-based markers.

Currently, only a few biomarkers remain decisive. This Special Issue aims to highlight key emerging biomarkers for early detection, predicting recurrence, metastatic spread, and treatment response. By exploring this diverse landscape of biomarkers, we hope to gain a deeper understanding of breast cancer heterogeneity and ultimately pave the way for personalized treatment approaches for every patient.

Dr. Andrew R. Green
Dr. Sarah J. Storr
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

  • breast cancer
  • biomarker
  • diagnosis
  • prognosis

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Published Papers (6 papers)

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Research

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17 pages, 1121 KiB  
Article
Predictors of Recurrence and Overall Survival in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy and Surgery: A Comprehensive Statistical Analysis
by Vlad Bogdan Varzaru, Roxana Popescu, Daliborca Cristina Vlad, Cristian Sebastian Vlad, Aurica Elisabeta Moatar, Andreas Rempen and Ionut Marcel Cobec
Cancers 2025, 17(6), 924; https://doi.org/10.3390/cancers17060924 - 8 Mar 2025
Viewed by 861
Abstract
Background/Objectives: This study evaluates the impact of clinical, pathological, and treatment-related factors on breast cancer recurrence and overall survival following neoadjuvant chemotherapy and surgery. Patients and Method: A total of 298 patients treated at Diakoneo Diak Klinikum, Schwäbisch Hall, Germany (2010–2021) were [...] Read more.
Background/Objectives: This study evaluates the impact of clinical, pathological, and treatment-related factors on breast cancer recurrence and overall survival following neoadjuvant chemotherapy and surgery. Patients and Method: A total of 298 patients treated at Diakoneo Diak Klinikum, Schwäbisch Hall, Germany (2010–2021) were analyzed. Key variables included hormone receptor status, molecular subtypes, tumor grade, treatment protocols, and metastatic disease at diagnosis. Results: Recurrence was strongly associated with metastatic disease (p < 0.001) but not with hormone receptor status or molecular subtypes. Platinum/taxane-based chemotherapy was linked to a lower recurrence risk (p = 0.05) compared to anthracycline-based regimens. Patients with recurrence had significantly lower overall survival (27.91% vs. 8.24%, p < 0.001). Logistic regression suggested a trend toward increased recurrence in ER-positive and PR-negative patients, though not statistically significant. These findings emphasize the importance of personalized treatment strategies and highlight the need for future studies incorporating genomic data and residual disease analysis to refine recurrence risk prediction and therapy selection. Full article
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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23 pages, 9726 KiB  
Article
Comparing 68Ga-Pentixafor,18F-FDG PET/CT and Chemokine Receptor 4 Immunohistochemistry Staining in Breast Cancer: A Prospective Cross Sectional Study
by Bawinile Hadebe, Lerwine Harry, Lerato Gabela, Thembelihle Nxasana, Nontobeko Ndlovu, Venesen Pillay, Siphelele Masikane, Maryam Patel, Dineo Mpanya, Ines Buccimaza, Mpumelelo Msimang, Colleen Aldous, Mike Sathekge and Mariza Vorster
Cancers 2025, 17(5), 763; https://doi.org/10.3390/cancers17050763 - 24 Feb 2025
Viewed by 625
Abstract
Background. CXCR4 is a chemokine receptor that is frequently overexpressed in invasive breast cancer and plays a major role in tumor proliferation, aggressiveness and metastasis. The aim of this prospective study was to establish the value of CXCR4-directed PET imaging in patients [...] Read more.
Background. CXCR4 is a chemokine receptor that is frequently overexpressed in invasive breast cancer and plays a major role in tumor proliferation, aggressiveness and metastasis. The aim of this prospective study was to establish the value of CXCR4-directed PET imaging in patients with breast cancer using the novel CXCR4-targeted PET probe 68Ga-Pentixafor by comparing it with 18F-FDG PET/CT (n = 40). Materials and methods. In this prospective cross-sectional study, fifty-one patients with breast cancer aged 36–81 (median (Q1-Q3) 51 (42.5–63)), n = 47 (92%) with initially diagnosed and n = 4 (8%) patients with recurrent breast cancer, underwent CXCR4-targeted PET imaging using 68Ga-Pentixafor. Maximum standardized uptake values (SUVmax), total lesion glycolysis (TLG) or total lesion uptake (TLU), metabolic tumor volume (MTV) and tumor-to-background ratios (TBR) of tumor lesions were measured and correlated with pathological prognostic factors, molecular subtypes and CXCR4 immunohistochemistry (IHC) staining. 18F-FDG PET/CT images were available in 40 of 51 cases (82%) and were compared semi-quantitatively. The patients were followed up for a median of 11 months (range 4–80 months) to determine whether CXCR4 expression correlated with survival. Results. 68Ga-Pentixafor-PET/CT was visually positive in 49/51 (96%) of the cases; in addition, [18F]FDG demonstrated a higher SUVmax compared to 68Ga-Pentixafor. The mean SUVmax was 7.26 ± 2.84 and 18.8 ± 9.1 for 68Ga-Pentixafor and [18F]FDG, respectively. Thirty-seven percent (18/51) of patients had triple-negative breast cancer and 25/51 (49%) had estrogen receptor (ER+) disease. There was a statistically significant correlation between tumor grade, proliferative index (Ki-67) and SUVmax obtained from 68Ga-Pentixafor PET p = 0.002. There was no correlation between the SUVmax obtained from 68Ga-Pentixafor and PET molecular subtypes, estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status; however, triple-negative breast cancers had more avid 68Ga-Pentixafor accumulation compared to luminals A and B. The median (Q1–Q3) 68Ga-Pentixafor TLU was significantly higher in HIV-positive (376 (219–881)) compared to HIV-negative (174 (105–557)) breast cancer patients. Conclusions. In conclusion, 68Ga-Pentixafor had a sensitivity of 96% and a specificity of 100% for detecting primary breast cancer; in addition, 68Ga-Pentixafor exhibited significantly higher uptake in patients with higher tumor grade, high proliferative index and triple-negative breast cancer (TNBC), as well as HIV-infected breast cancer patients, highlighting the potential clinical utility and prognostic role of CXCR4-targeted PET imaging in aggressive breast cancer. Notably, 68Ga-Pentixafor complements 18F-FDG by detecting more metastasis in the brain and the skull where FDG has limitations, while 18F-FDG remains superior for detecting skeletal metastasis. Future research should further explore the potential of CXCR4-targeted PET imaging in selecting patients with triple-negative breast cancer and high-grade breast cancer who may benefit from CXCR4-targeted therapies, particularly in the context of HIV co-infection. Full article
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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14 pages, 871 KiB  
Article
Are All Prognostic Stage IB Breast Cancers Equivalent?
by Stephanie M. Yoon, Shengyang Wu, Amanda Schwer, Scott Glaser, Todd DeWees and Jose G. Bazan
Cancers 2024, 16(22), 3830; https://doi.org/10.3390/cancers16223830 - 14 Nov 2024
Viewed by 1046
Abstract
Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research [...] Read more.
Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research shows that increased nodal involvement is a critical predictor of worse prognosis, raising questions about whether biological subtype or anatomic stage has a greater influence on outcomes in these discordant cases. We hypothesized that overall survival (OS) remains worse for LA-HR+/HER2- BC compared to ES-TNBC, despite both being classified as PPS IB. Methods: Using the National Cancer Database, we identified patients with LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1–2) and ES-TNBC (T1N0, grade 2–3) treated between 2004 and 2017. Patients without complete primary tumor stage, biomarker status, grade, TNM staging, or treated with neoadjuvant therapy were excluded. The primary endpoint was OS. Multivariable Cox regression evaluated OS between LA-HR+/HER2- BC and ES-TNBC. Results: Among 45,818 patients (17,359 LA-HR+/HER2- BC and 28,459 ES-TNBC), LA-HR+/HER2- BC had significantly worse 6-year OS (86.1% vs. 90.4%; HR = 1.63; p < 0.0001). Among patients receiving appropriate therapies, patients with LA-HR+/HER2- BC had 35% relatively higher risk of death (HR = 1.35; 1.24–1.48; p < 0.0001). These results highlight that LA-HR+/HER2- breast cancer has worse survival compared to ES-TNBC, despite both being classified as PPS IB and receiving all appropriate treatments. Conclusions: Anatomic disease extent remains an important factor in patients with discordant AS and PPS. Future iterations of PPS should re-classify LA-HR+/HER2- breast cancer from PPS IB to ensure more accurate prognostic and survival information. Full article
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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12 pages, 1468 KiB  
Article
Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with Clinical Outcome
by Kate Lacey, Megan R. Greener, Tangkam R. Marak, Emad A. Rakha, Andrew R. Green, Ian O. Ellis, Stewart G. Martin and Sarah J. Storr
Cancers 2024, 16(18), 3206; https://doi.org/10.3390/cancers16183206 - 20 Sep 2024
Cited by 1 | Viewed by 2151
Abstract
Protein tyrosine kinase 7 (PTK7), originally known as colon carcinoma kinase (CCK4), is an evolutionary conserved, catalytically defective transmembrane receptor involved in Wnt signalling. PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has [...] Read more.
Protein tyrosine kinase 7 (PTK7), originally known as colon carcinoma kinase (CCK4), is an evolutionary conserved, catalytically defective transmembrane receptor involved in Wnt signalling. PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer. PTK7 protein expression was evaluated in 1136 early-stage invasive breast tumours by immunohistochemistry. In addition, PTK7 mRNA expression in the METABRIC (n = 1980) and the TCGA breast cancer cohorts (n = 1082) was evaluated. Associations between PTK7 expression and clinicopathological criteria and patient outcome were determined. No association between PTK7 protein expression and breast cancer-specific survival was observed; however, PTK7 mRNA expression in the METABRIC cohort was associated with breast cancer-specific survival (p < 0.001). PTK7 protein and mRNA expression were associated with breast cancer-specific survival of patients with a poor prognostic Nottingham Prognostic Index (NPI) and a moderate prognostic NPI, respectively. Taken together, these data indicate that PTK7 expression is associated with patient outcome in subgroups of breast cancer patients. Full article
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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Review

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24 pages, 3328 KiB  
Review
Exosome-Mediated Cellular Communication in the Tumor Microenvironment Imparts Drug Resistance in Breast Cancer
by RamaRao Malla, Priyamvada Bhamidipati, Anuveda Sree Samudrala, Yerusha Nuthalapati, Vasudevaraju Padmaraju, Aditya Malhotra, Annah S. Rolig and Sanjay V. Malhotra
Cancers 2025, 17(7), 1167; https://doi.org/10.3390/cancers17071167 - 30 Mar 2025
Viewed by 596
Abstract
Globally, breast cancer (BC) is the leading cause of cancer-related death for women. BC is characterized by heterogeneity, aggressive behavior, and high metastatic potential. Chemotherapy, administered as monotherapy or adjuvant therapy, remains a cornerstone of treatment; however, acquired drug resistance is a significant [...] Read more.
Globally, breast cancer (BC) is the leading cause of cancer-related death for women. BC is characterized by heterogeneity, aggressive behavior, and high metastatic potential. Chemotherapy, administered as monotherapy or adjuvant therapy, remains a cornerstone of treatment; however, acquired drug resistance is a significant clinical challenge. Deciphering mechanisms of drug resistance will be central to developing more efficient treatment options and improving patient outcomes. The current review examines the multifaceted nature of exosomes in conferring drug resistance in BC through complex communication networks within the tumor microenvironment. We further explore recent advances in understanding how exosomes contribute to resistance against established chemotherapeutic agents such as tamoxifen, paclitaxel, doxorubicin, platinum-based drugs, trastuzumab, and newer immunotherapies, such as immune checkpoint inhibitors. Moreover, we discuss existing systematic approaches to investigating the exosome–drug resistance relationship in BC. Finally, we explore promising therapeutic approaches to overcome exosome-dependent drug resistance in BC, highlighting potential avenues for improved treatment efficacy. Investigating the distinct functions and cargo of exosomes offers potential for developing innovative approaches to overcoming treatment resistance. Full article
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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11 pages, 464 KiB  
Review
Predictive Factors of Antibody–Drug Conjugate Treatment in Metastatic Breast Cancer: A Narrative Review
by Gennaro Gadaleta-Caldarola, Laura Lanotte, Anna Natalizia Santoro, Antonello Pinto, Arianna Gadaleta-Caldarola, Luca Giacomelli and Palma Fedele
Cancers 2024, 16(23), 4082; https://doi.org/10.3390/cancers16234082 - 5 Dec 2024
Viewed by 1437
Abstract
Antibody–drug conjugates (ADCs) have revolutionized the treatment landscape for metastatic breast cancer, offering targeted delivery of cytotoxic agents with improved efficacy and tolerability compared to conventional chemotherapy. This narrative review explores key predictive factors influencing the efficacy of ADCs, focusing on HER2-targeted therapies, [...] Read more.
Antibody–drug conjugates (ADCs) have revolutionized the treatment landscape for metastatic breast cancer, offering targeted delivery of cytotoxic agents with improved efficacy and tolerability compared to conventional chemotherapy. This narrative review explores key predictive factors influencing the efficacy of ADCs, focusing on HER2-targeted therapies, such as trastuzumab emtansine and trastuzumab deruxtecan, as well as sacituzumab govitecan for triple-negative breast cancer. HER2 expression, TROP-2 levels, hormone receptor status, and the tumor microenvironment emerge as critical biomarkers for patient selection and therapeutic outcomes. Additionally, we discuss resistance mechanisms, such as antigen loss, impaired drug internalization, and the role of circulating tumor DNA in predicting ADC response. Finally, future perspectives on the sequential use of ADCs and potential combination therapies are highlighted, along with emerging agents targeting alternative antigens like HER3 and LIV-1. Overall, identifying predictive biomarkers and overcoming resistance mechanisms are essential for optimizing the use of ADCs in metastatic breast cancer, thereby improving patient outcomes. Full article
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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