Update in Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 13852

Special Issue Editor


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Guest Editor
1. Oxford Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK 2. Department of Oncology, University of Oxford, Oxford OX1 2JD, UK
3. Discipline of Medical Oncology, Post-Graduation Programme in Medicine, Faculty of Medicine, Nine of July University (UNINOVE), São Paulo 04101-000, Brazil
Interests: medical oncology; immunotherapy; biomarkers; EGFR insertion 20; MET inhibitors; Alk inhibitors; target therapies; lung cancer
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Special Issue Information

Dear Colleagues,

Breast cancer is a very aggressive disease when diagnosed in the advanced setting. A multidisciplinary approach involving medical oncologists, breast surgeons, radiation oncologists, nuclear medicine specialists, breast radiologists, and other health care professionals is essential to acquire the best clinical outcomes. Personalizing medicine plays a main role in clinical practice since it provides the best treatment for breast cancer (BC). To fully understand the molecular mechanisms of BC is very important to the development of new drugs and biomarkers through inhibiting driver mutations responsible for the disease pathogenesis. Molecular testing, tumor boards, and predictive models play a key role in treatment decisions. Thus, we believe that this Special Issue will be important for publishing the last updated research in BC regarding future trends in prognostic and predictive biomarkers to help oncologists in the provision of best care. All type of articles will be considered, such as narrative review, meta-analysis, cost-effective analysis, original articles, commentaries, and editorials.

Sincerely,

Prof. Dr. Ramon Andrade De Mello
Guest Editor

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Keywords

  • CDK inhibitors
  • PIK3CA inhibitors
  • Breast cancer
  • Nano string
  • ctDNA
  • PET CT scan
  • Breast MRI
  • Breast imaging
  • Breast roll techniques
  • Breast surgery
  • Targeted therapies
  • Immunetherapy
  • Predictive biomarkers
  • Prognostic biomarkers.

Published Papers (6 papers)

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Research

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13 pages, 1174 KiB  
Article
Clinical Significance of Ultrasound Elastography and Fibrotic Focus and Their Association in Breast Cancer
by Na-Rang Lee, Hoon-Kyu Oh and Young-Ju Jeong
J. Clin. Med. 2022, 11(24), 7435; https://doi.org/10.3390/jcm11247435 - 15 Dec 2022
Cited by 1 | Viewed by 1908
Abstract
(1) Background: Ultrasound (US) elastography is an imaging technology that reveals tissue stiffness. This study aimed to investigate whether fibrotic focus (FF) affects elastographic findings in breast cancer, and to evaluate the clinical significance of US elastography and FF in breast cancer. (2) [...] Read more.
(1) Background: Ultrasound (US) elastography is an imaging technology that reveals tissue stiffness. This study aimed to investigate whether fibrotic focus (FF) affects elastographic findings in breast cancer, and to evaluate the clinical significance of US elastography and FF in breast cancer. (2) Methods: In this study, 151 patients with breast cancer who underwent surgery were included. Strain elastography was performed and an elasticity scoring system was used to assess the findings. The elasticity scores were classified as negative, equivocal, or positive. FF was evaluated in the surgical specimens. Medical records were reviewed for all patients. (3) Results: Elastographic findings were equivocal in 30 patients (19.9%) and positive in 121 patients (80.1%). FF was present in 68 patients (46.9%). There was no correlation between elastographic findings and FF. Older age, larger tumor size, lymph node metastasis, and higher tumor stage were associated with positive elastographic results. FF showed a positive correlation with age, postmenopausal status, tumor size, lymphovascular invasion, lymph node metastasis, tumor stage, and intratumoral and peritumoral inflammation. (4) Conclusions: Our study showed that positive elastographic results and FF were associated with poor prognostic factors for breast cancer. FF did not affect the elastographic findings of this study. Full article
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18 pages, 1395 KiB  
Article
Tissue Plasminogen Activator as a Possible Indicator of Breast Cancer Relapse: A Preliminary, Prospective Study
by Katarzyna Wrzeszcz, Artur Słomka, Elżbieta Zarychta, Piotr Rhone and Barbara Ruszkowska-Ciastek
J. Clin. Med. 2022, 11(9), 2398; https://doi.org/10.3390/jcm11092398 - 25 Apr 2022
Cited by 4 | Viewed by 1590
Abstract
(1) Background: The fundamental causes of breast cancer mortality are the cancer spread and hypercoagulability state. The study aimed to evaluate the prognostic efficacy of the fibrinolytic profile concerning 5-year follow-up. (2) Methods: We investigated the predictive potential of the plasma activity of [...] Read more.
(1) Background: The fundamental causes of breast cancer mortality are the cancer spread and hypercoagulability state. The study aimed to evaluate the prognostic efficacy of the fibrinolytic profile concerning 5-year follow-up. (2) Methods: We investigated the predictive potential of the plasma activity of urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) as well as antigen of tissue plasminogen activator (t-PA), u-PA, PAI-1, and PAI-1/t-PA and PAI-1/u-PA complexes in 41 breast cancer patients. The median follow-up was 66 months, with full evidence of the first event. (3) Results: A significantly lower level of PAI-1 antigen was noted in IBrC patients with lymph node involvement (N1) than in patients with free lymph node metastases (N0). According to ROC curve analysis, a t-PA antigen was the strongest predictor of disease relapse (the area under the curve, AUC = 0.799; p < 0.0006). Patients with PAI-1 activity < 3.04 U/mL had significantly better disease-free survival (DFS) compared to those with PAI-1 activity > 3.04 U/mL. Patients with both t-PA antigen lower than 1.41 ng/mL (cut-off according to median value) and lower than 1.37 ng/mL (cut-off according to ROC curve) had significantly shorter DFS (p = 0.0086; p = 0.0029). (4) Conclusions: The results suggest that a higher plasma t-PA antigen level or lower PAI-1 activity are linked to better outcomes in breast cancer patients. Full article
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25 pages, 14939 KiB  
Article
Analysis of Yes-Associated Protein-1 (YAP1) Target Gene Signature to Predict Progressive Breast Cancer
by Gomathi Venkatasubramanian, Devaki A. Kelkar, Susmita Mandal, Mohit Kumar Jolly and Madhura Kulkarni
J. Clin. Med. 2022, 11(7), 1947; https://doi.org/10.3390/jcm11071947 - 31 Mar 2022
Cited by 2 | Viewed by 2536
Abstract
Breast cancers are treated according to the ER/PR or HER2 expression and show better survival outcomes with targeted therapy. Triple-negative breast cancers (TNBCs) with a lack of expression of ER/PR and HER2 are treated with systemic therapy with unpredictable responses and outcomes. It [...] Read more.
Breast cancers are treated according to the ER/PR or HER2 expression and show better survival outcomes with targeted therapy. Triple-negative breast cancers (TNBCs) with a lack of expression of ER/PR and HER2 are treated with systemic therapy with unpredictable responses and outcomes. It is essential to investigate novel markers to identify targeted therapies for TNBC. One such marker is YAP1, a transcription co-activator protein that shows association with poor prognosis of breast cancer. YAP1 transcriptionally regulates the expression of genes that drive the oncogenic phenotypes. Here, we assess a potential YAP target gene signature to predict a progressive subset of breast tumors from METABRIC and TCGA datasets. YAP1 target genes were shortlisted based on expression correlation and concordance with YAP1 expression and significant association with survival outcomes of patients. Hierarchical clustering was performed for the shortlisted genes. The utility of the clustered genes was assessed by survival analysis to identify a recurring subset. Expression of the shortlisted target genes showed significant association with survival outcomes of HER2-positive and TNBC subset in both datasets. The shortlisted genes were verified using an independent dataset. Further validation using IHC can prove the utility of this potential prognostic signature to identify a recurrent subset of HER2-positive and TNBC subtypes. Full article
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9 pages, 1194 KiB  
Article
Plasma Levels of Decorin Increased in Patients during the Progression of Breast Cancer
by Tokuko Hosoya, Goshi Oda, Tsuyoshi Nakagawa, Iichiroh Onishi, Tadashi Hosoya, Megumi Ishiguro, Toshiaki Ishikawa and Hiroyuki Uetake
J. Clin. Med. 2021, 10(23), 5530; https://doi.org/10.3390/jcm10235530 - 26 Nov 2021
Cited by 5 | Viewed by 1612
Abstract
Decorin (DCN), an extracellular matrix proteoglycan found in tumor surrounding tissues, is a natural inhibitor of tumor cell proliferation and invasion. We conducted a cross-sectional observation study to evaluate the association of the pathological stage with the levels of DCN in plasma or [...] Read more.
Decorin (DCN), an extracellular matrix proteoglycan found in tumor surrounding tissues, is a natural inhibitor of tumor cell proliferation and invasion. We conducted a cross-sectional observation study to evaluate the association of the pathological stage with the levels of DCN in plasma or tumor surrounding tissue. Among 118 patients who underwent breast surgery, 35 were designated as carcinoma in situ (Stage 0), 39 were Stage I, and 44 were Stage II or III. The stromal expression of DCN was quantified using a semiquantitative digital image analysis after immunohistochemical staining. The concentration of DCN was evaluated with a specific ELISA. As we have previously shown, stromal DCN expression was attenuated in the patients with Stage I, whereas stromal and plasma DCN was elevated paradoxically in those with Stage II/III. The elevated plasma DCN is an independent predictive factor of Stage II/III by the multivariate logistic regression analysis. The plasma level of DCN was negatively correlated with stromal DCN expression only in patients with advanced disease (Stage II/III). The plasma level of DCN could become a useful biomarker for patients in the advanced stages. Extensive studies and further assessments are warranted for evaluating the prognostic significance and tumor characteristics to understand the clinical significances of stromal and systemic DCN. Full article
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9 pages, 550 KiB  
Article
Superparamagnetic Iron Oxide for Identifying Sentinel Lymph Node in Breast Cancer after Neoadjuvant Chemotherapy: Feasibility Study
by Andrzej Kurylcio, Zuzanna Pelc, Magdalena Skórzewska, Karol Rawicz-Pruszyński, Radosław Mlak, Katarzyna Gęca, Katarzyna Sędłak, Piotr Kurylcio, Teresa Małecka-Massalska and Wojciech Polkowski
J. Clin. Med. 2021, 10(14), 3149; https://doi.org/10.3390/jcm10143149 - 16 Jul 2021
Cited by 8 | Viewed by 2078
Abstract
Sentinel lymph node biopsy (SLNB) is a well-established procedure for staging clinically node-negative early breast cancer (BC). Superparamagnetic iron oxide (SPIO) demonstrated efficacy for nodal identification using a magnetic probe after local retroaeroal interstitial injection. Its benefits lie in its flexibility, which is [...] Read more.
Sentinel lymph node biopsy (SLNB) is a well-established procedure for staging clinically node-negative early breast cancer (BC). Superparamagnetic iron oxide (SPIO) demonstrated efficacy for nodal identification using a magnetic probe after local retroaeroal interstitial injection. Its benefits lie in its flexibility, which is an essential property in the global setting, where access to the isotope is difficult. To the best of our knowledge, this is the first study to evaluate the feasibility and safety of the SPIO for SLNB in BC patients treated with neoadjuvant chemotherapy (NAC). Seventy-four female patients were included. The median time of lymph node retrieval was 20 min. The median number of resected sentinel nodes (SNs) was 4. SN was detected in all patients. No serious adverse event was observed. SPIO in identifying SN in BC patients after NAC is feasible and oncologically safe. Full article
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Review

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15 pages, 297 KiB  
Review
Radiomics in Triple Negative Breast Cancer: New Horizons in an Aggressive Subtype of the Disease
by Camil Ciprian Mireștean, Constantin Volovăț, Roxana Irina Iancu and Dragoș Petru Teodor Iancu
J. Clin. Med. 2022, 11(3), 616; https://doi.org/10.3390/jcm11030616 - 26 Jan 2022
Cited by 6 | Viewed by 3193
Abstract
In the last decade, the analysis of the medical images has evolved significantly, applications and tools capable to extract quantitative characteristics of the images beyond the discrimination capacity of the investigator’s eye being developed. The applications of this new research field, called radiomics, [...] Read more.
In the last decade, the analysis of the medical images has evolved significantly, applications and tools capable to extract quantitative characteristics of the images beyond the discrimination capacity of the investigator’s eye being developed. The applications of this new research field, called radiomics, presented an exponential growth with direct implications in the diagnosis and prediction of response to therapy. Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with a severe prognosis, despite the aggressive multimodal treatments applied according to the guidelines. Radiomics has already proven the ability to differentiate TNBC from fibroadenoma. Radiomics features extracted from digital mammography may also distinguish between TNBC and non-TNBC. Recent research has identified three distinct subtypes of TNBC using IRM breast images voxel-level radiomics features (size/shape related features, texture features, sharpness). The correlation of these TNBC subtypes with the clinical response to neoadjuvant therapy may lead to the identification of biomarkers in order to guide the clinical decision. Furthermore, the variation of some radiomics features in the neoadjuvant settings provides a tool for the rapid evaluation of treatment efficacy. The association of radiomics features with already identified biomarkers can generate complex predictive and prognostic models. Standardization of image acquisition and also of radiomics feature extraction is required to validate this method in clinical practice. Full article
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