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Breast Cancer: Clinical Diagnosis and Personalized Therapy
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Breast Cancer: Clinical Diagnosis and Personalized Therapy

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

Deadline for manuscript submissions: 10 October 2025 | Viewed by 5680

Special Issue Editor

Dr. Edy Ippolito

E-Mail Website
Guest Editor
Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy
Interests: breast cancer; lung cancer; radiotherapy; advanced technology; radiation induced toxicity; concomitant treatments

Special Issue Information

Dear Collegues,

Breast cancer treatment has significantly changed and expanded in the last few decades, mainly due to the increased understanding of the molecular factors contributing to breast cancer pathogenesis and heterogeneity. Although overall survival has improved due to advanced diagnostic modalities as well as the introduction of tailored treatements directed at specific patient populations, there is still room for improvement.

This Special Issue addresses the topic of precision medicine and novel research in the field of diagnosis, predictive biomarkers, loco-regional treatment (radiation and surgery), and systemic treatments.

Dr. Edy Ippolito
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. Journal of Clinical Medicine 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 2600 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
  • imaging biomarkers
  • molecular biomarkers
  • precision medicine
  • loco-regional treatment
  • breast surgery
  • breast radiotherapy

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Published Papers (5 papers)

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Research

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15 pages, 2514 KiB  
Article
Sentinel Lymph Node Biopsy Predicts Non-Sentinel Lymph Node Metastases and Supports Omission of Axillary Lymph Node Dissection in Breast Cancer Patients
by Toshihiko Yoneto, Fumiko Ikiuo, Naoko Koyanagi, Takayuki Yoshimoto and Yasutaka Takeda
J. Clin. Med. 2025, 14(10), 3441; https://doi.org/10.3390/jcm14103441 - 14 May 2025
Viewed by 184
Abstract
Background: Current international guidelines recommend omitting axillary lymph node dissection (ALND) based on sentinel lymph node biopsy (SLNB) in early-stage breast cancer patients. However, the evolving landscape of axillary management highlights the need to balance diagnostic accuracy with minimizing invasiveness. The possibility of [...] Read more.
Background: Current international guidelines recommend omitting axillary lymph node dissection (ALND) based on sentinel lymph node biopsy (SLNB) in early-stage breast cancer patients. However, the evolving landscape of axillary management highlights the need to balance diagnostic accuracy with minimizing invasiveness. The possibility of omitting SLNB itself should also be considered. Methods: In this study, we have evaluated the feasibility of omitting SLNB in a total of 1044 clinically node-negative (cN (−)) breast cancer patients whose SLN status was determined by histopathology and one-step nucleic acid amplification (OSNA) after SLNB. We also analyzed SLN-positive cases to explore the association between non-SLN (NSLN) metastatic status and various biomarkers. We predicted the metastatic status of NSLNs based on patient data using a nomogram and further assessed the prevalence of macro- and micro-metastatic SLN, along with the NSLN status in SLNB cases. Results: Of the 644 cN (−) cases, approximately 70% of SLN-positive cases were NSLN negative, suggesting that ALND could be omitted. SLN (+) was detected approximately 7% more often by OSNA than by histopathology, suggesting that OSNA detection may be an overdiagnosis. Although NSLN-positive cases represented only 5.9% of the 581 cN (−) cases and, therefore, ALND could be omitted, it may be difficult to omit the SLNB itself as the SLN macro-metastasis was 12.5%. Biomarker analysis showed a significant correlation between total tumor load and metastatic SLN copy number with NSLN metastatic status. Based on these tumor characteristics, the nomogram predicted NSLN-positive rates very well. Conclusions: Thus, omitting SLNB itself carries the risk of missing high-frequency macro-metastatic SLN-positive cases and losing important SLN-related information that can predict NSLN metastases. Therefore, SLNB, which provides not only SLN status but also NSLN metastases, is necessary for reassurance in omitting ALND. Full article
(This article belongs to the Special Issue Breast Cancer: Clinical Diagnosis and Personalized Therapy)
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12 pages, 600 KiB  
Article
Clinical Outcomes in Early-Stage HER2-Low and HER2-Zero Breast Cancer: Single-Center Experience
by Jamshid Hamdard, Mehmet Haluk Yücel, Harun Muğlu, Özgür Açıkgöz, Aslı Çakır, Ahmet Bilici and Ömer Fatih Ölmez
J. Clin. Med. 2025, 14(9), 2937; https://doi.org/10.3390/jcm14092937 - 24 Apr 2025
Viewed by 335
Abstract
Background/Objectives: The goal of this study is to characterize the survival patterns and outcomes of women with early-stage breast cancer, with a particular emphasis on the distinction between HER2-low and HER2-zero expression. There is limited real-world data on how patients with HER2-negative or [...] Read more.
Background/Objectives: The goal of this study is to characterize the survival patterns and outcomes of women with early-stage breast cancer, with a particular emphasis on the distinction between HER2-low and HER2-zero expression. There is limited real-world data on how patients with HER2-negative or HER2-low metastatic or recurrent breast cancer are treated. Methods: We retrospectively analyzed the medical records of 1500 breast cancer patients diagnosed between January 2020 and December 2024. From this cohort, 99 patients with HER2-low and 34 patients with HER2-zero early-stage breast cancer were included in our analysis. HER2 low was defined as Immunohistochemistry (IHC) 1+ or IHC 2+ with negative Silver In situ Hybridization (SISH), while HER2 zero was defined as IHC 0. Statistical analyses, including Kaplan–Meier survival analyses and log-rank tests for group comparisons, were performed using IBM SPSS Statistics. Results: The median age of patients was 55 years. The HER2-zero group exhibited a higher incidence of brain, liver, bone, and lung metastases (p < 0.001 for all) and increased use of CDK4/6 inhibitors (p < 0.001). In univariate analyses, younger age, an HER2-zero status, and the absence of metastases were associated with improved disease-free survival (DFS) and overall survival (OS). However, in multivariate analyses, an HER2-zero status independently predicted longer DFS (HR = 0.14, 95% CI: 0.05–0.41, p < 0.001) and OS (HR = 0.16, 95% CI: 0.042–0.6, p = 0.007). Conclusions: Our study revealed distinct metastatic patterns and survival outcomes between HER2-low and HER2-zero early-stage breast cancers. Despite a higher metastatic burden in univariate analyses, HER2 zero status was independently associated with longer DFS and OS in multivariate analyses, highlighting their biological heterogeneity and the need for further research to inform tailored strategies. Full article
(This article belongs to the Special Issue Breast Cancer: Clinical Diagnosis and Personalized Therapy)
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10 pages, 562 KiB  
Article
Evaluation of Dose Reduction Factors and Impact on Progression-Free Survival in Patients Treated with CDK 4/6 Inhibitors
by Ali Kaan Güren, Murad Guliyev, Özkan Alan, Kıvanç Çadırci, İpek Naz Belevi, İlkay Gültürk, Emre Özge, Erkam Kocaaslan, Yeşim Ağyol, Pınar Erel, Burak Paçacı, Mustafa Alperen Tunç, Nargiz Majidova, Nadiye Sever, Abdussamet Çelebi, Rukiye Arıkan Erdoğan, Selver Işık, Nebi Serkan Demirci, Murat Sarı, Osman Köstek and İbrahim Vedat Bayoğluadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(4), 1071; https://doi.org/10.3390/jcm14041071 - 7 Feb 2025
Cited by 1 | Viewed by 746
Abstract
Introduction: CDK 4/6 inhibitors are effectively utilized among patients with hormone-positive, HER-2-negative metastatic breast cancer. The dose reduction for these patients varies between 35% and 57% across multiple trials. We aim to clarify the characteristics of patients who had dosage reduction and the [...] Read more.
Introduction: CDK 4/6 inhibitors are effectively utilized among patients with hormone-positive, HER-2-negative metastatic breast cancer. The dose reduction for these patients varies between 35% and 57% across multiple trials. We aim to clarify the characteristics of patients who had dosage reduction and the effect of this reduction on survival outcomes. Materials and Methods: The study was designed as a retrospective, multicenter study. Patients who received CDK 4/6 inhibitors in the first-line and subsequent treatment settings were grouped based on dose reductions. Progression-free survival was compared between these groups, and factors influencing dose reduction were analyzed. Results: Multivariate logistic regression study demonstrated that patients aged 65 and older, with a Charlson CI score of 2 or higher, having metastases in three or more sites, and classed as normal weight, had greater dosage reductions. Dose reduction had no impact on progression-free survival (PFS) (p = 0.114 for first-line treatment, p = 0.528 for second and subsequent-line treatment; p > 0.05). Conclusions: Regarding the absence of disparity in progression-free survival between patients with dose reduction and those without, dose reduction should not be avoided in certain patient groups to ensure therapy continuity and mitigate potential adverse effects. Full article
(This article belongs to the Special Issue Breast Cancer: Clinical Diagnosis and Personalized Therapy)
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23 pages, 5602 KiB  
Article
Traditional Clinicopathological Biomarkers Still Determine Disease-Free and Overall Survival in Invasive Breast Cancer Patients: A Pilot Study
by Katarzyna Wrzeszcz, Katarzyna Kwiatkowska, Piotr Rhone, Dorota Formanowicz, Stefan Kruszewski and Barbara Ruszkowska-Ciastek
J. Clin. Med. 2024, 13(7), 2021; https://doi.org/10.3390/jcm13072021 - 30 Mar 2024
Viewed by 1486
Abstract
Background: Molecular classification, tumor diameter, Ki67 expression, and brachytherapy administration still act as the most potent potential predictors of breast cancer recurrence and overall survival. Methods: Over the period of 23 months, we included in the study 92 invasive breast cancer (IBrC) patients [...] Read more.
Background: Molecular classification, tumor diameter, Ki67 expression, and brachytherapy administration still act as the most potent potential predictors of breast cancer recurrence and overall survival. Methods: Over the period of 23 months, we included in the study 92 invasive breast cancer (IBrC) patients initially diagnosed at the Clinical Ward of Breast Cancer and Reconstructive Surgery, Oncology Center in Bydgoszcz, Poland. The probability of disease-free survival (DFS) and overall survival (OS) in relation to potential prognostic factors for the patients were determined using a Kaplan–Meier analysis, and univariate and multivariate Cox regression analyses evaluated the predictive factors of IBrC patients. The investigation of the potential prognostic model’s accuracy was analyzed using the ROC curve. Results: Patients with tumor size < 2 cm, Ki67 expression < 20%, luminal-A molecular subtype, and extra-dose brachytherapy boost administration displayed the most favorable prognosis according to breast cancer disease-free survival and overall survival. The estimated 5 year probability of DFS and OS rates in women with tumor diameter < 2 cm were 89% and 90%, respectively. In tumor diameter > 2 cm, the estimated 5 year probability of DFS was 73% and OS was 76%. Interestingly, the tumor diameter of 1.6 cm with a specificity of 60.5% and a sensitivity of 75% occurred as the best threshold point to differentiate patients with cancer recurrence from those without cancer progression. Conclusions: Our study provides essential information on the clinicopathological profile and future outcomes of early stage IBrC patients. Furthermore, the tumor diameter cut-off value of 1.6 cm discriminating between disease recurrence and those without disease progression patients represents an innovative direction for further research. Full article
(This article belongs to the Special Issue Breast Cancer: Clinical Diagnosis and Personalized Therapy)
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12 pages, 2068 KiB  
Systematic Review
A Systematic Review to Evaluate the Barriers to Breast Cancer Screening in Women with Disability
by Huda I. Almohammed
J. Clin. Med. 2024, 13(11), 3283; https://doi.org/10.3390/jcm13113283 - 2 Jun 2024
Cited by 2 | Viewed by 2242
Abstract
Background: Breast cancer (BC) is one of the leading causes of mortality worldwide. There are observed disparities in patients with disability as compared to those without disability, which leads to poor BC screening attendance, thereby worsening disease management. Aim: The aim of this [...] Read more.
Background: Breast cancer (BC) is one of the leading causes of mortality worldwide. There are observed disparities in patients with disability as compared to those without disability, which leads to poor BC screening attendance, thereby worsening disease management. Aim: The aim of this systematic review is to investigate if there are disparities in screening rates in women with disability as compared to those without disability, as well as the different factors that pose barriers to patients with disability for enrolment in BC screening programs. Method: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed published articles between 2008 and 2023, which assessed different factors that contributed to poor attendance in BC screening programs held across different countries. Detailed study characteristics were obtained, and methodological quality assessment was performed on the individual studies included in this review. Result: A total of fifty-three articles were identified as eligible studies based on the pre-defined inclusion and exclusion criteria. These included 7,252,913 patients diagnosed with BC (913,902 patients with disability/6,339,011 patients without disability). The results revealed there are demographic, clinical, financial, and service-related barriers that contributed to lower screening rates in disabled patients as compared to non-disabled. Patient age is the most common factor, with the highest effect observed for 80 years (vs. 30–44 years) [odds ratio (OR) = 13.93 (95% confidence interval (CI) = 8.27–23.47), p < 0.0001], followed by race/ethnicity for Hispanic (vs. non-Hispanic white) [OR = 9.5 (95%CI = 1.0–91.9), p < 0.05]. Additionally, patients with multiple disabilities had the highest rate of dropouts [OR = 27.4 (95%CI = 21.5–33.3)]. Other factors like education, income, marital status, and insurance coverage were essential barriers in screening programs. Conclusions: This study presents a holistic view of all barriers to poor BC screening attendance in disabled patients, thereby exacerbating health inequalities. A standardized approach to overcome the identified barriers and the need for a tailored guideline, especially for disability groups, is inevitable. Full article
(This article belongs to the Special Issue Breast Cancer: Clinical Diagnosis and Personalized Therapy)
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