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Clinical and Molecular Biomarkers in Breast Cancer Management
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Clinical and Molecular Biomarkers in Breast Cancer Management

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

Deadline for manuscript submissions: 5 November 2026 | Viewed by 2584

Special Issue Editor

Dr. Zahi I. Mitri

E-Mail Website
Guest Editor
1. Division of Medical Oncology, University of British Columbia, Vancouver, BC, Canada
2. Department of Medical Oncology, BC Cancer Agency—Vancouver Center, Vancouver, BC, Canada
3. Clinical Research Unit—BC Cancer Vancouver Center, Vancouver, BC, Canada
Interests: breast cancer

Special Issue Information

Dear Colleagues,

The treatment paradigm for breast cancer has evolved to integrate clinical, pathologic, and molecular biomarkers to guide adequate therapy selection across the spectrum of the disease. This includes but is not limited to immunohistochemistry testing and multigene assays for treatment selection in early-stage breast cancer, as well as next-generation sequencing and liquid biopsy platforms in advanced breast cancer. Further, special situations in breast cancer, such as germline mutation carriers, young women with breast cancer, and male breast cancer, present unique features that impact outcomes and therapy.

In this Special Issue, we welcome original or review articles focused on the current landscape for prognostic and predictive markers for breast cancer management, as well as emerging tools to help improve outcomes for patients. We hope this will enhance our knowledge in regard to personalizing treatment approaches in breast cancer.

Dr. Zahi I. Mitri
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 250 words) can be sent to the Editorial Office for assessment.

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

  • prognostic biomarkers
  • predictive biomarkers
  • molecular assays
  • therapeutics
  • special situations in breast cancer

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Published Papers (3 papers)

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Research

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17 pages, 1507 KB  
Article
Independent Relevance of Estrogen Receptor and Progesterone Receptor Statuses in DCIS on Risk of Subsequent Ipsilateral and Contralateral Invasive Breast Events in Absence of Endocrine Therapy
by Thomas J. O’Keefe, Audrey Guo, David R. Vera and Anne M. Wallace
Cancers 2026, 18(7), 1109; https://doi.org/10.3390/cancers18071109 - 30 Mar 2026
Viewed by 657
Abstract
Background: Patients with estrogen receptor (ER)-positive ductal carcinoma in situ (DCIS) derive a greater benefit from endocrine therapy than patients with ER-negative disease. The relevance of ER status and progesterone receptor (PR) status in DCIS to radiation therapy has not been well explored. [...] Read more.
Background: Patients with estrogen receptor (ER)-positive ductal carcinoma in situ (DCIS) derive a greater benefit from endocrine therapy than patients with ER-negative disease. The relevance of ER status and progesterone receptor (PR) status in DCIS to radiation therapy has not been well explored. Methods: Patients undergoing breast-conserving surgery with or without radiation were grouped by ER and PR status and matched using rank-based Mahalanobis optimal matching with respect to lesion size and grade and patient age and race. Cumulative incidences were estimated and competing risk regressions with subdistribution hazard ratios (sHRs) were calculated. Results: Among patients who underwent breast-conserving surgery only, 369 patients with ER-PR- disease were matched to 738 patients with ER+PR+ disease (1:2 matching). In multivariate models, patients with ER-PR- disease were at increased risk of any invasive events (sHR = 2.47, p = 0.007) and early ipsilateral invasive events (sHR = 2.64, p = 0.02 in the 0-to-4-year period) relative to patients with ER+PR+ disease. Among patients who underwent breast-conserving surgery with adjuvant radiation, 1498 patients with ER+PR+ disease were matched to 1498 patients with ER-PR- disease. No significant differences were noted with respect to cumulative incidence of any invasive event (5.6% vs. 5.6%) or ipsilateral invasive events (1.9% vs. 2.9%). In multivariate models, no significant differences were noted. Patients with ER-PR+ lesions had similar cumulative incidences of ipsilateral invasive events to patients with ER-PR- disease in the absence of radiation (5.9% vs. 5.9%) and similar cumulative incidences of contralateral invasive events to patients with ER+PR+ disease when radiation was administered (3.2% vs. 4.2%). Conclusion: The statuses of ER and PR carry independent prognostic and therapeutic implications beyond those of traditional clinicopathologic risk factors. Given that ER and PR statuses are routinely collected for patients with DCIS, incorporation of these variables into clinicopathologic risk classification systems is warranted. Full article
(This article belongs to the Special Issue Clinical and Molecular Biomarkers in Breast Cancer Management)
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13 pages, 740 KB  
Article
Comprehensive Analysis and Prediction of HER2-Targeted Therapy Insensitivity Among HER2-Positive Breast Cancer Patients Undergoing Neoadjuvant Treatment
by Qingyao Shang, Zian Lin, Jennifer Plichta, Samantha Thomas, Meishuo Ouyang, Sheng Luo and Xin Wang
Cancers 2026, 18(6), 989; https://doi.org/10.3390/cancers18060989 - 18 Mar 2026
Cited by 1 | Viewed by 630
Abstract
Purpose: HER2-targeted therapy has been incorporated into the standard neoadjuvant treatment (NAT) regimen for HER2-positive early-stage breast cancer, yet a subset of patients have shown a limited pathological response. This study aimed to evaluate clinicopathological factors associated with NAT sensitivity and to develop [...] Read more.
Purpose: HER2-targeted therapy has been incorporated into the standard neoadjuvant treatment (NAT) regimen for HER2-positive early-stage breast cancer, yet a subset of patients have shown a limited pathological response. This study aimed to evaluate clinicopathological factors associated with NAT sensitivity and to develop a predictive model. Methods: This retrospective study included 13,004 HER2-positive breast cancer patients from the National Cancer Database (2010–2022) who received neoadjuvant chemotherapy plus HER2-targeted therapy. Pathological complete response (pCR) was defined as no residual invasive carcinoma in the breast and axillary lymph nodes (ypT0/is, ypN0). NAT sensitivity was additionally defined using clinical-to-pathologic stage migration according to the AJCC 8th edition criteria. Baseline characteristics and overall survival (OS) were compared between NAT-sensitive and NAT-insensitive groups. A multivariable logistic regression model was developed based on age, clinical T stage, clinical N stage, histologic subtype, tumor grade, and hormone receptor (HR) status. Model performance was assessed using the area under the receiver operating characteristic curve and calibration curves. Results: Among the patients included, 3660 (28.1%) achieved pCR. Based on the predefined stage-based criteria, 10,451 (80.4%) were classified as NAT-sensitive and 2553 (19.6%) as NAT-insensitive. NAT-insensitive patients were older and more likely to present with clinical T1c and node-negative disease, whereas NAT-sensitive patients more frequently had higher clinical T and N stages. HR-positive and lower tumor grades were significantly associated with treatment insensitivity. NAT-insensitive patients demonstrated significantly worse OS compared with NAT-sensitive patients (p < 0.001). The predictive model showed acceptable discrimination with AUCs of 0.762 in the training cohort and 0.776 in the validation cohort, demonstrating good calibration. Conclusions: NAT sensitivity in HER2-positive early-stage breast cancer exhibited substantial biological and clinical heterogeneity in real-world practice. A younger age, higher clinical stage, invasive ductal histology, higher tumor grade, and HR-negative status were associated with improved responses. A predictive model based on routinely available baseline variables demonstrated reasonable performance for estimating treatment sensitivity, supporting its potential utility for baseline risk stratification pending external validation. Full article
(This article belongs to the Special Issue Clinical and Molecular Biomarkers in Breast Cancer Management)
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Review

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22 pages, 339 KB  
Review
The Evolution of Targeted Therapies in Early Hormone Receptor-Positive, HER2-Negative Breast Cancer
by Hyejee Ohm, Caroline Lohrisch, Nathalie LeVasseur, Christine Simmons and Zahi I. Mitri
Cancers 2026, 18(7), 1130; https://doi.org/10.3390/cancers18071130 - 1 Apr 2026
Viewed by 911
Abstract
Breast cancer is the second most common malignancy worldwide, and over 70% of new diagnosis are of the hormone receptor-positive (HR+) and HER2-negative (HER2−) subtype. The cornerstone in management of early stage HR+ breast cancer has historically consisted of chemotherapy and endocrine therapies. [...] Read more.
Breast cancer is the second most common malignancy worldwide, and over 70% of new diagnosis are of the hormone receptor-positive (HR+) and HER2-negative (HER2−) subtype. The cornerstone in management of early stage HR+ breast cancer has historically consisted of chemotherapy and endocrine therapies. Genomic assays in early stage HR+HER2− breast cancer has provided a prognostic tool for recurrence and a predictive tool to select patients for adjuvant chemotherapy. The introduction of bone-modifying agents and adjuvant CDK 4/6 inhibitors into early stage disease represents new therapeutic modalities aimed at reducing risk in high-risk HR+HER2− cancers. This manuscript aims to provide a comprehensive overview of the evidence behind endocrine therapy and recommended duration of treatment, genomic assays to guide chemotherapy delivery, data guiding use of bisphosphonate therapy to reduce bone recurrence, and indications for incorporating CDK 4/6 inhibitors. In addition, novel endocrine agents and targeted therapies under investigation are highlighted. Full article
(This article belongs to the Special Issue Clinical and Molecular Biomarkers in Breast Cancer Management)
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