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Biomedicines
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Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches
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Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 13064

Special Issue Editors

Dr. Stefania Cocco

E-Mail Website
Guest Editor
Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
Interests: breast cancer; oncology; pharmacology
Dr. Vincenzo Quagliariello

E-Mail Website
Guest Editor
Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Division of Cardiology, Napoli, Italy
Interests: cardio-oncology; inflammation; chemoresistance; radioresistance; nanotechnology; endocrine disruptor
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breast cancer is a heterogeneous disease characterized by variant pathological features, disparate responses to therapeutics. During recent years, several new therapies such as PARP inhibitors, immune checkpoint inhibitors, CDK-4/6 inhibitors, and new HER-2 blocking agents, have been integrated into clinical practice, significantly improving the survival of breast cancer patients. However, many patients could early relapse due to the absence of predictive biomarkers of response and resistance to these new agents. This Special Issue welcomes the field of personalizing medicine in breast cancer, covering interdisciplinary health research, preclinical models, translational and clinical research.

Dr. Stefania Cocco
Dr. Vincenzo Quagliariello
Guest Editors

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Keywords

  • breast cancer
  • biomarkers
  • prognostic and predictive medicine
  • biochemical pathways
  • gene signature
  • precision medicine
  • target therapy
  • immunotherapy

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Published Papers (6 papers)

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Research

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19 pages, 4655 KiB  
Article
Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods
by Rafat Ali, Armiya Sultan, Romana Ishrat, Shafiul Haque, Nida Jamil Khan and Miguel Angel Prieto
Biomedicines 2023, 11(5), 1271; https://doi.org/10.3390/biomedicines11051271 - 25 Apr 2023
Cited by 7 | Viewed by 2536
Abstract
Breast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene [...] Read more.
Breast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene expression datasets are widely used to discover the new biomarkers and molecular therapeutic targets in diseases. In the present study, we analyzed four datasets using R packages with accession number GSE29044, GSE42568, GSE89116, and GSE109169 retrieved from NCBI-GEO and differential expressed genes (DEGs) were identified. Protein–protein interaction (PPI) network was constructed to screen the key genes. Subsequently, the GO function and KEGG pathways were analyzed to determine the biological function of key genes. Expression profile of key genes was validated in MCF-7 and MDA-MB-231 human breast cancer cell lines using qRT-PCR. Overall expression level and stage wise expression pattern of key genes was determined by GEPIA. The bc-GenExMiner was used to compare expression level of genes among groups of patients with respect to age factor. OncoLnc was used to analyze the effect of expression levels of LAMA2, TIMP4, and TMTC1 on the survival of breast cancer patients. We identified nine key genes, of which COL11A1, MMP11, and COL10A1 were found up-regulated and PCOLCE2, LAMA2, TMTC1, ADAMTS5, TIMP4, and RSPO3 were found down-regulated. Similar expression pattern of seven among nine genes (except ADAMTS5 and RSPO3) was observed in MCF-7 and MDA-MB-231 cells. Further, we found that LAMA2, TMTC1, and TIMP4 were significantly expressed among different age groups of patients. LAMA2 and TIMP4 were found significantly associated and TMTC1 was found less correlated with breast cancer occurrence. We found that the expression level of LAMA2, TIMP4, and TMTC1 was abnormal in all TCGA tumors and significantly associated with poor survival. Full article
(This article belongs to the Special Issue Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches)
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11 pages, 1665 KiB  
Article
Suppression of Platelet-Derived Growth Factor Receptor-Alpha Overcomes Resistance to Trastuzumab through STAT3-Dependent IL-6 Reduction in HER2-Positive Breast Cancer Cells
by Sangmin Kim, Hyungjoo Kim, Yisun Jeong, Daeun You, Sun Young Yoon, Eunji Lo, Seok Jin Nam, Jeong Eon Lee and Seok Won Kim
Biomedicines 2023, 11(3), 675; https://doi.org/10.3390/biomedicines11030675 - 23 Feb 2023
Cited by 1 | Viewed by 1773
Abstract
Platelet-derived growth factor receptor (PDGFR) plays an essential role in the proliferation and invasion of malignant cancer cells. However, the functional role of PDGFR alpha (PDGFRA) in HER2-positive (HER2+) breast cancer has not been fully clarified yet. Thus, the objective of this study [...] Read more.
Platelet-derived growth factor receptor (PDGFR) plays an essential role in the proliferation and invasion of malignant cancer cells. However, the functional role of PDGFR alpha (PDGFRA) in HER2-positive (HER2+) breast cancer has not been fully clarified yet. Thus, the objective of this study was to investigate the clinical significance of PDGFRA and the therapeutic potential of PDGFR inhibitors as part of an effort to overcome trastuzumab (TRZ) resistance. Aberrant PDGFRA expression is closely associated with decreased survival in HER2+ breast cancers. Therefore, we established BT474 trastuzumab-sensitive (TRZ_S) and trastuzumab-resistant (TRZ_R) cells to investigate the association between PDGFR signaling and TRZ resistance. We found that PDGFRA was significantly upregulated in the BT474 TRZ_R cells. In addition, IL-6 expression, which was also found to be upregulated in the TRZ_R cells, was induced by PDGFC, a ligand of PDGFR. Next, we investigated the effects of ponatinib and sunitinib, PDGFR inhibitors, on the BT474 TRZ_R and HCC1954 (TRZ-resistant cell line) cells. These inhibitors decreased cell viability and migration in a dose-dependent manner. Additionally, IL-6 expression was decreased by ponatinib in both the BT474 TRZ_R and HCC1954 cells. In contrast, IL-6 was not suppressed by TRZ, implying that the PDGFRA/STAT3/IL-6 axis is associated with resistance to TRZ. In addition, we found that STAT3 and ERK phosphorylation were increased in the BT474 TRZ_R cells. IL-6 expression was suppressed by a STAT3 inhibitor, indicating that IL-6 expression is modulated downstream of STAT3. Taken together, these results suggest that PDGFRA could serve as a therapeutic target to overcome TRZ resistance. Full article
(This article belongs to the Special Issue Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches)
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18 pages, 2358 KiB  
Article
Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses
by Alaa Siddig, Wan Faiziah Wan Abdul Rahman, Siti Norasikin Mohd Nafi, Sarina Sulong, Maya Mazuwin Yahya, Tengku Ahmad Damitri Al-Astani Tengku Din, Rozaimi Razali and Kamarul Imran Musa
Biomedicines 2023, 11(1), 200; https://doi.org/10.3390/biomedicines11010200 - 12 Jan 2023
Cited by 3 | Viewed by 2140
Abstract
Background: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial. Methods: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from [...] Read more.
Background: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial. Methods: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from 13 fresh estrogen receptor (ER)-positive primary breast cancer tissues of untreated patients (7 = young age ≤45 years and 6 = old age ≥55 years). In silico validation for the differentially expressed genes (DEGs) by young-age patients was conducted using The Cancer Genome Atlas (TCGA) database. Next, we analyzed the protein expression encoded by two of the significantly down-regulated genes by young-age patients, Glycine N-acyltransferase-like 1 (GLYATL-1) and Ran-binding protein 3 like (RANBP3L), using immunohistochemical analysis in an independent cohort of 56 and 74 ER-positive pre-therapeutic primary breast cancer tissues, respectively. Results: 12 genes were significantly differentially expressed by young-age breast cancers (fold change >2 or <2- with FDR p-value < 0.05). TCGA data confirmed the differential expression of six genes. Protein expression analysis of GLYATL-1 and RANBP3L did not show heterogeneous expression between young and old-age breast cancer tissues. Loss of expression of GLYATL-1 was significantly (p-value 0.005) associated with positive lymph node status. Higher expression of RANBP3L was significantly associated with breast cancers with lower histopathological grades (p-value 0.038). Conclusions: At the transcriptomic level, breast cancer developed in young and old age patients seems homogenous. The variation in the transcriptomic profiles can be attributed to the other clinicopathological characteristics rather than the age of the patient. Full article
(This article belongs to the Special Issue Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches)
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13 pages, 1155 KiB  
Article
The Role of Matrix Metalloproteinase Single-Nucleotide Polymorphisms in the Clinicopathological Properties of Breast Cancer
by Agnė Bartnykaitė, Aistė Savukaitytė, Justina Bekampytė, Rasa Ugenskienė, Danguolė Laukaitienė, Erika Korobeinikova, Jurgita Gudaitienė and Elona Juozaitytė
Biomedicines 2022, 10(8), 1891; https://doi.org/10.3390/biomedicines10081891 - 4 Aug 2022
Cited by 8 | Viewed by 1788
Abstract
(1) Background. Breast cancer is the leading cancer type among women. Despite convenient diagnostics at early stages, there is a need for continuous monitoring to predict more aggressive or recurring breast cancer forms. The evidence suggests that the detection of genetic biomarkers could [...] Read more.
(1) Background. Breast cancer is the leading cancer type among women. Despite convenient diagnostics at early stages, there is a need for continuous monitoring to predict more aggressive or recurring breast cancer forms. The evidence suggests that the detection of genetic biomarkers could help in improving disease management and reduce mortality. Matrix metalloproteinases (MMPs) are a large family of enzymes that perform physiologically relevant functions and have the potential properties to be biomarkers for cancer assessment. We aimed to evaluate the contribution and association of single-nucleotide polymorphisms (SNPs) in MMP genes (MMP1, MMP2, MMP3, MMP7, MMP8, MMP9) with clinicopathological breast-cancer features. (2) Methods. In this study, 100 breast cancer patients were genotyped by polymerase chain reaction–restriction fragment length polymorphism methodology (PCR–RFLP). (3) Results. The presence of the MMP7 rs11568818 A allele was associated with lower chances for poorly differentiated breast cancer. The lower possibility for HER2-positive breast cancer was associated with the presence of the MMP9 rs3918242 C allele. (4) Conclusions. These results indicate that MMP7 rs11568818 and MMP9 rs3918242 are potential biomarkers for the anticipation of breast cancer aggressiveness. Full article
(This article belongs to the Special Issue Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches)
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Review

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13 pages, 556 KiB  
Review
The Prognostic and Predictive Value of Genomic Assays in Guiding Adjuvant Breast Radiation Therapy
by Sasha J. Beyer, Miranda Tallman, Sachin R. Jhawar, Julia R. White and Jose G. Bazan
Biomedicines 2023, 11(1), 98; https://doi.org/10.3390/biomedicines11010098 - 30 Dec 2022
Cited by 2 | Viewed by 1762
Abstract
Many patients with non-metastatic breast cancer benefit from adjuvant radiation therapy after lumpectomy or mastectomy on the basis of many randomized trials. However, there are many patients that have such low risks of recurrence after surgery that de-intensification of therapy by either reducing [...] Read more.
Many patients with non-metastatic breast cancer benefit from adjuvant radiation therapy after lumpectomy or mastectomy on the basis of many randomized trials. However, there are many patients that have such low risks of recurrence after surgery that de-intensification of therapy by either reducing the treatment volume or omitting radiation altogether may be appropriate options. On the other hand, dose intensification may be necessary for more aggressive breast cancers. Until recently, these treatment decisions were based solely on clinicopathologic factors. Here, we review the current literature on the role of genomic assays as prognostic and/or predictive biomarkers to help guide adjuvant radiation therapy decision-making. Full article
(This article belongs to the Special Issue Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches)
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Other

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10 pages, 2574 KiB  
Case Report
Synchronous Breast and Cervical Carcinoma: A Genetic Point of View
by Maya Mazuwin Yahya, Mohd Pazudin Ismail, Shogeta Ramanathan, Muhammad Nashriq Kadir, Azzahra Azhar, Noorul Balqis Che Ibrahim, Chee Lee Wee, Zahiah Mohd Amin, Seng Kong Tham, Shuhaila Mat-Sharani and Nik Soriani Yaacob
Biomedicines 2023, 11(2), 525; https://doi.org/10.3390/biomedicines11020525 - 11 Feb 2023
Cited by 2 | Viewed by 2136
Abstract
Breast carcinoma is the most common cancer of women in Malaysia. The most common sites of metastasis are the lung, liver, bone and brain. A 45-year-old lady was diagnosed with left invasive breast carcinoma stage IV (T4cN1M1) with axillary lymph nodes and lung [...] Read more.
Breast carcinoma is the most common cancer of women in Malaysia. The most common sites of metastasis are the lung, liver, bone and brain. A 45-year-old lady was diagnosed with left invasive breast carcinoma stage IV (T4cN1M1) with axillary lymph nodes and lung metastasis. She was noted to have a cervical mass through imaging, and biopsy showed CIN III. Post chemotherapy, the patient underwent left simple mastectomy with examination under anaesthesia of the cervix, cystoscopy and staging. The cervical histopathological examination (HPE) showed squamous cell carcinoma, and clinical staging was 2A. The breast tissue HPE showed invasive carcinoma with triple receptors positivity. The patient was given tamoxifen and put on concurrent chemoradiotherapy (CCRT) for the cervical cancer. The management of each pathology of this patient involved a multi-disciplinary team that included surgeons, oncologists, gynaecologists, pathologists and radiologists. Due to the complexity of the case with two concurrent cancers, the gene expression profiles may help predict the patient’s clinical outcome. Full article
(This article belongs to the Special Issue Breast Cancer: Future Biomarkers and Personalizing Treatment Approaches)
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