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Cancers
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Research on Early-Stage Breast Cancer: Management and Treatment
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Research on Early-Stage Breast Cancer: Management and Treatment

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

Deadline for manuscript submissions: 15 August 2025 | Viewed by 6741

Special Issue Editor

Dr. Ernyu Tan

E-Mail Website
Guest Editor
1. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
2. Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
Interests: breast cancer

Special Issue Information

Dear Colleagues,

Many cancers are now being diagnosed early. Small tumors, often without nodal involvement, have an excellent prognosis after surgery. Some women will develop recurrent and metastatic disease, which is perhaps even more psychologically devastating given the expectations of excellent survival. For this reason, adjuvant treatments are still recommended. Genomic testing in ER-positive HER2-negative disease now shows that chemotherapy can be limited to high-risk individuals. The challenge is similar for triple-negative and HER2-positive disease forms, where some data suggest limited benefits of systemic therapy for T1ab tumors. Some groups have also explored the omission of radiation post-wide excision regarding in situ disease. The ongoing challenge is to reduce the burden of over-treatment without compromising survival. More precise risk stratification is needed to identify high-risk individuals who will benefit most from adjuvant treatment.

Dr. Ernyu Tan
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 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

  • early-stage breast cancer
  • adjuvant treatment
  • systemic therapy
  • risk stratification
  • survival

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Published Papers (5 papers)

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Research

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17 pages, 3437 KiB  
Article
Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment
by Eva Schmidt, Luitpold Distel, Ramona Erber, Maike Büttner-Herold, Marie-Charlotte Rosahl, Oliver J. Ott, Vratislav Strnad, Carolin C. Hack, Arndt Hartmann, Markus Hecht, Rainer Fietkau and Sören Schnellhardt
Cancers 2024, 16(18), 3160; https://doi.org/10.3390/cancers16183160 - 15 Sep 2024
Viewed by 847
Abstract
Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage [...] Read more.
Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage hormone-receptor-positive breast cancer as part of an Accelerated Partial Breast Irradiation (APBI) phase II trial. Resection samples from multiple locations were processed into tissue microarrays and sections thereof immunohistochemically stained for CD66b+ neutrophils. CD66b+ neutrophil density was measured separately in the stromal and intraepithelial compartment. Results: High stromal and intraepithelial CD66b+ TAN density was a negative prognostic factor in central tumor samples. In addition, neutrophil density in adjacent normal breast tissue and lymph node samples also correlated with reduced disease-free survival. TAN density correlated with CD163+ M2-like tumor-associated macrophage (TAM) density, which we analyzed in a previous study. TANs were a negative prognostic factor in tumors with an elevated M1/M2 TAM ratio, while this impact on patient outcome was lost in tumors with a low M1/M2 ratio. A combined multivariate analysis of TAM and TAN density revealed that only TAM polarization status was an independent prognostic factor. Conclusions: CD66b+ neutrophils were a negative prognostic factor in early-stage luminal breast cancer in single-marker analysis. Combined analysis with TAMs could be necessary to correctly evaluate their prognostic impact in future studies. TAN recruitment might act as a compensatory mechanism of immunoevasion and disease progression in tumors that are unable to sufficiently attract and polarize TAMs. Full article
(This article belongs to the Special Issue Research on Early-Stage Breast Cancer: Management and Treatment)
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9 pages, 719 KiB  
Article
Risk Factors for Positive Resection Margins in Breast-Conserving Surgery for Breast Cancer—Retrospective Analysis
by Rares Georgescu, Flavian Tutuianu, Orsolya Bauer, Anca Toganel, Zalan Benedek, Eugeniu Darii, Sabin Turdean and Cristina Tutuianu Radoi
Cancers 2024, 16(17), 2930; https://doi.org/10.3390/cancers16172930 - 23 Aug 2024
Viewed by 646
Abstract
The primary objective of this study was to identify preoperative factors that could be associated with positive resection margins. We also tried to analyze the local recurrence and overall survival in patients who received conservative treatment for early-stage breast cancer and correlate these [...] Read more.
The primary objective of this study was to identify preoperative factors that could be associated with positive resection margins. We also tried to analyze the local recurrence and overall survival in patients who received conservative treatment for early-stage breast cancer and correlate these parameters with preoperative factors. A retrospective examination was conducted on the medical records and pathological reports of 143 patients who underwent breast-conserving surgery (BCS) for breast cancer in our department from 2009 to 2017. Postoperative outcomes were assessed through phone contact and statistical analyses, including GraphPad Prism, and Fisher’s exact test, the Chi-square test, and the log-rank test were employed. The results revealed positive resection margins in 7.69% (11 cases) of the 143 patients, with an overall mortality rate of 16.66% for those with positive margins and 6.59% for those with negative margins. Statistical analysis indicated no significant differences in the overall (p = 0.5) or specific (p = 0.53) survival between the positive and negative margin groups. The positive margins were significantly associated with neoadjuvant chemotherapy (p < 0.0001) and the presence of ductal carcinoma in situ (DCIS) (p = 0.01). Among the analyzed factors, two out of sixteen were significantly linked to positive resection margins in BCS, emphasizing their importance in surgical management planning for early-stage breast cancer. Full article
(This article belongs to the Special Issue Research on Early-Stage Breast Cancer: Management and Treatment)
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21 pages, 3095 KiB  
Article
Clinical and Analytical Validation of Two Methods for Ki-67 Scoring in Formalin Fixed and Paraffin Embedded Tissue Sections of Early Breast Cancer
by Snežana Đokić, Barbara Gazić, Biljana Grčar Kuzmanov, Jerca Blazina, Simona Miceska, Tanja Čugura, Cvetka Grašič Kuhar and Jera Jeruc
Cancers 2024, 16(7), 1405; https://doi.org/10.3390/cancers16071405 - 3 Apr 2024
Cited by 4 | Viewed by 1858
Abstract
Proliferation determined by Ki-67 immunohistochemistry has been proposed as a useful prognostic and predictive marker in breast cancer. However, the clinical validity of Ki-67 is questionable. In this study, Ki-67 was retrospectively evaluated by three pathologists using two methods: a visual assessment of [...] Read more.
Proliferation determined by Ki-67 immunohistochemistry has been proposed as a useful prognostic and predictive marker in breast cancer. However, the clinical validity of Ki-67 is questionable. In this study, Ki-67 was retrospectively evaluated by three pathologists using two methods: a visual assessment of the entire slide and a quantitative assessment of the tumour margin in 411 early-stage breast cancer patients with a median follow-up of 26.8 years. We found excellent agreement between the three pathologists for both methods. The risk of recurrence for Ki-67 was time-dependent, as the high proliferation group (Ki-67 ≥ 30%) had a higher risk of recurrence initially, but after 4.5 years the risk was higher in the low proliferation group. In estrogen receptor (ER)-positive patients, the intermediate Ki-67 group initially followed the high Ki-67 group, but eventually followed the low Ki-67 group. ER-positive pN0-1 patients with intermediate Ki-67 treated with endocrine therapy alone had a similar outcome to patients treated with chemotherapy. A cut-off value of 20% appeared to be most appropriate for distinguishing between the high and low Ki-67 groups. To summarize, a simple visual whole slide Ki-67 assessment turned out to be a reliable method for clinical decision-making in early breast cancer patients. We confirmed Ki-67 as an important prognostic and predictive biomarker. Full article
(This article belongs to the Special Issue Research on Early-Stage Breast Cancer: Management and Treatment)
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27 pages, 1489 KiB  
Article
A Preliminary Evaluation of Advanced Oxidation Protein Products (AOPPs) as a Potential Approach to Evaluating Prognosis in Early-Stage Breast Cancer Patients and Its Implication in Tumour Angiogenesis: A 7-Year Single-Centre Study
by Marta Napiórkowska-Mastalerz, Tomasz Wybranowski, Maciej Bosek, Stefan Kruszewski, Piotr Rhone and Barbara Ruszkowska-Ciastek
Cancers 2024, 16(5), 1068; https://doi.org/10.3390/cancers16051068 - 6 Mar 2024
Cited by 2 | Viewed by 1329
Abstract
Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This [...] Read more.
Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan–Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice. Full article
(This article belongs to the Special Issue Research on Early-Stage Breast Cancer: Management and Treatment)
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Review

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13 pages, 261 KiB  
Review
De-Escalating Treatment Strategies for Patients with Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Early-Stage Breast Cancer
by Hikmat Abdel-Razeq
Cancers 2024, 16(20), 3478; https://doi.org/10.3390/cancers16203478 - 14 Oct 2024
Viewed by 931
Abstract
Almost one-fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumors and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, [...] Read more.
Almost one-fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumors and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved an adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling. Full article
(This article belongs to the Special Issue Research on Early-Stage Breast Cancer: Management and Treatment)
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