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Eurasian Journal of
Medicine and Oncology NOTCH3 in CSVD and breast cancer

Table 1. Prominent genes linked to an elevated risk of breast cancer incidence
Gene Chromosome Function and degree of penetration Risk for breast cancer (%)
site
ATM 26 11q22.3 • DNA repair and cell cycle regulation 20 – 60
• Moderate penetration
BRCA1 27 17q21.31 • DNA repair and cell cycle regulation 45 – 87
• High penetration
BRCA2 28 13q13.1 • DNA repair and cell cycle regulation 50 – 85
• High penetration
BRIP1 29 17q23.2 • Participation in BRCA1 function Limited Data
• Moderate penetration
CDH1 30 16q22.1 • Cell adhesion regulation 63 – 83
• Regulate epithelial cell proliferation and mobility
• High penetration
CHEK2 31 22q12.1 • Cell cycle regulation 20 – 25
• Moderate penetration
PALB2 32 16p12.2 • DNA repair 33 – 58
• Moderate penetration
PTEN 33 10q23.31 • Cell cycle regulation 50 – 85
• High penetration
STK11 34 19p13.3 • Cell cycle regulation 32 – 54
• Upkeep of energy balance
• High penetration
TP53 35 17p13.1 • DNA repair, cell cycle regulation, triggering apoptosis, promoting senescence 20 – 85
and sustaining cellular metabolism are all crucial cellular processes
• High penetration
Note: Risk percentages reflect ranges from recent meta-analyses (2020 – 2024).
Abbreviations: ATM: Ataxia telangiectasia mutated; BRCA1: Breast cancer gene 1; BRCA2: Breast cancer gene 2; BRIP1: BRCA1 interacting protein
c-terminal helicase 1; CDH1: Cadherin 1; CHEK2: Checkpoint kinase 2; PALB2: Partner and localizer of BRCA2; PTEN: Phosphatase and tensin
homolog; STK11: Serine/Threonine kinase 11; TP53: Tumour protein 53.

as inflammatory and immune-mediated CSVD, venous a silent malignancy in up to 3% of patients. In addition,
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collagenopathies and other forms of CSVD, including non- post-mortem examinations of cancer patients show the
amyloid microvessel degeneration in Alzheimer’s disease presence of ischemic stroke in 15% of cases, with half of
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and post-radiation angiopathy. Various pathomechanisms these cases being silent or asymptomatic. Considering
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and molecular cascades have been proposed for the that CSVD could potentially serve as the initial indication
onset and progression of CSVD, and many of which are of neoplasia, in this case, BC. This necessitates a precise
interrelated across most, if not all, CSVD categories. 44-50 determination of the underlying cause to tailor treatment
appropriately and enhance clinical outcomes. 52
4. Putative clinicopathological correlates of
BC and CSVD BC and malignancies in general, share numerous risk
factors with CSVD. These risk factors are more prevalent
CSVD is a precursor for ischemic stroke, a complex among the elderly population, which also tends to have a
pathological event leading to sudden neurological damage, higher burden of vascular risk factors. Studies have indicated
with cancer being just one of the numerous associated risk that the prevalence of these vascular risk factors, including
factors. Simultaneously, it seems that the occurrence and diabetes mellitus, obesity, hypertension, hyperlipidemia,
frequency of both conditions are rising within the elderly smoking, alcoholism, and atrial fibrillation, is comparable
population. Similarly, in cancer patients, cerebrovascular between ischemic stroke patients with cancer and stroke
disease emerges as the second most prevalent neurological patients without cancer. Considering both higher
2,54
condition after metastases. However, this connection pathogenicity and prevalence of vascular risk factors, it comes
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is frequently overlooked by the clinician. CSVD or as no surprise that these factors continue to be the most
even ischemic stroke may manifest at any stage during common cause of ischemic stroke, even among individuals
malignancy and, in some cases, serve as the initial sign of with cancer, specifically BC. Alarmingly, studies have shown
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Volume 9 Issue 3 (2025) 35 doi: 10.36922/EJMO025150095