Breast Cancer: Molecular Mechanisms, Diagnosis Techniques and Therapeutic Targets

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Molecular Targeted Therapy".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 3245

Special Issue Editor


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Guest Editor
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
Interests: breast cancer; Triple Negative Breast Cancer (TNBC); metastatic breast cancer

Special Issue Information

Dear Colleagues,

Breast cancer remains one of the most common cancers affecting women. Its molecular mechanism involves the growth, migration and invasion of cancerous cells due to dysfunctional proteins and pathways at a genetic level. The main subtypes include Luminal A, Luminal B, HER2-enriched and triple-negative breast cancers. Each has different biomarkers and therapeutic responses. Diagnosis techniques include self-examination, mammography, ultrasound, biopsy and genetic testing. These methods help to identify the stage, type and spread of the cancer. The advancements in molecular biology have led to the formation of therapeutic targets such as hormone receptors (estrogen and progesterone receptors), HER2 proteins and BRCA1 and BRCA2 genes. Targeted therapies based on these receptors and genes have shown better results in treatment. Hormone therapy, radiation therapy, chemotherapy, immunotherapy and surgery are some standard treatment options. However, many novel therapeutic strategies are being developed and tested. Although significant progress has been made over the years, continued research is necessary to improve the survival rate and personalized treatment plans.

This Special Issue aims to present a collection of original research articles and reviews that address the use of modern molecular diagnosis techniques and targeted therapies in breast cancer.

Dr. Shipra Gandhi
Guest Editor

Manuscript Submission Information

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Keywords

  • breast cancer
  • triple-negative breast cancer
  • biomarker
  • molecular mechanism
  • diagnosis technique
  • therapeutic target
  • genetic
  • targeted therapies

Published Papers (3 papers)

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Editorial

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3 pages, 196 KiB  
Editorial
Novel Biomarkers to Guide Immunotherapy De-Escalation in the Neoadjuvant Setting in Triple-Negative Breast Cancer
by Shipra Gandhi
J. Pers. Med. 2023, 13(9), 1313; https://doi.org/10.3390/jpm13091313 - 27 Aug 2023
Cited by 1 | Viewed by 982
Abstract
Triple-negative breast cancer (TNBC) has the highest incidence of disease recurrence and distant metastases among breast cancer subtypes, leading to significant rates of morbidity and mortality [...] Full article

Research

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13 pages, 913 KiB  
Article
Immunologic Factors Associated with Differential Response to Neoadjuvant Chemoimmunotherapy in Triple-Negative Breast Cancer
by Robert J. Seager, Heidi Ko, Sarabjot Pabla, Maria-Fernanda Senosain, Pawel Kalinski, Erik Van Roey, Shuang Gao, Kyle C. Strickland, Rebecca Ann Previs, Mary K. Nesline, Stephanie Hastings, Shengle Zhang, Jeffrey M. Conroy, Taylor J. Jensen, Marcia Eisenberg, Brian Caveney, Eric A. Severson, Shakti Ramkissoon and Shipra Gandhi
J. Pers. Med. 2024, 14(5), 481; https://doi.org/10.3390/jpm14050481 - 30 Apr 2024
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Abstract
Background: KEYNOTE-522 resulted in FDA approval of the immune checkpoint inhibitor pembrolizumab in combination with neoadjuvant chemotherapy for patients with early-stage, high-risk, triple-negative breast cancer (TNBC). Unfortunately, pembrolizumab is associated with several immune-related adverse events (irAEs). We aimed to identify potential tumor microenvironment [...] Read more.
Background: KEYNOTE-522 resulted in FDA approval of the immune checkpoint inhibitor pembrolizumab in combination with neoadjuvant chemotherapy for patients with early-stage, high-risk, triple-negative breast cancer (TNBC). Unfortunately, pembrolizumab is associated with several immune-related adverse events (irAEs). We aimed to identify potential tumor microenvironment (TME) biomarkers which could predict patients who may attain pathological complete response (pCR) with chemotherapy alone and be spared the use of anti-PD-1 immunotherapy. Methods: Comprehensive immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on matched FFPE tumor samples from 22 stage I-III TNBC patients (14 patients treated with neoadjuvant chemotherapy alone (NAC) and 8 treated with neoadjuvant chemotherapy combined with pembrolizumab (NAC+I)). Results: Differential gene expression analysis revealed that in the NAC group, IL12B and IL13 were both significantly associated with pCR. In the NAC+I group, LCK and TP63 were significantly associated with pCR. Patients in both treatment groups exhibiting pCR tended to have greater tumor inflammation than non-pCR patients. In the NAC+I group, patients with pCR tended to have greater cell proliferation and higher PD-L1 expression, while in the NAC group, patients with pCR tended to have lower cancer testis antigen expression. Additionally, the NAC+I group trended toward a lower relative dose intensity averaged across all chemotherapy drugs, suggesting that more dose reductions or treatment delays occurred in the NAC+I group than the NAC group. Conclusions: A comprehensive understanding of immunologic factors could potentially predict pCR to chemotherapy alone, enabling the avoidance of the unnecessary treatment of these patients with checkpoint inhibitors. Full article
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7 pages, 4612 KiB  
Communication
Divergent Cellular Expression Patterns of PD-L1 and PD-L2 Proteins in Breast Cancer
by Julie M. Jorns, Yunguang Sun, Sailaja Kamaraju, Yee Chung Cheng, Amanda Kong, Tina Yen, Caitlin R. Patten, Chandler S. Cortina, Christopher R. Chitambar, Hallgeir Rui and Lubna N. Chaudhary
J. Pers. Med. 2024, 14(5), 478; https://doi.org/10.3390/jpm14050478 - 29 Apr 2024
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Abstract
PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression [...] Read more.
PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression patterns of PD-L1 and PD-L2. PD-L1-positivity was higher in immune cells than in cancer cells (median = 5.0% vs. 0.0%; p = 0.001), whereas PD-L2-positivity was higher in cancer cells than immune cells (median = 30% vs. 5.0%; p = 0.001). Percent positivity of PD-L1 and PD-L2 were not correlated, neither in cancer cells nor immune cells. Based on a cut-point of ≥1% positivity, ER+ tumors (n = 23) were frequently PD-L2-positive (73.9%), whereas only 40.9% were PD-L1-positive. These data suggest differential control of cellular PD-L1 and PD-L2 expression in BC and a potential role for PD-L2 IHC as a complementary marker to PD-L1 to improve selection of aggressive ER+ BC that may benefit from anti-PD-1 therapy. Full article
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