Mini Review
Volume 11 Issue 9 - 2022
Prominence of the Evolutionary and Personalized Strategy in the Breast Cancer Management: A Junction Between Cancer Cell Genetics and Clinical Oncology
Parvin Mehdipour*
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
*Corresponding Author: Parvin Mehdipour, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Received: June 23, 2022 Published: August 22, 2022


ATM has the key role in different cancers including breast. The molecular alteration of D1853N polymorphism, accompanied by the IVS 38- 63T>A and IVS38-30A>G alterations in the exon 37 and its 5’-splicing region, played the instructive role in the development of astrocytoma, as three-hit hypothesis. The D1853N polymorphism, is considered as a predisposing factor in a proband affected with primary BC.

The eight-hit event in a breast cancer patient, presented the sequential molecular alterations including the inherited D1853N predisposing factor as the first hit. The cascade of additional molecular alterations include IVS 36-8 T>C as the 2nd hit, V1833M as the 3rd hit and L1888L as the 4th- hit and the complementary somatic variants (IVS 36-46 C>T, L1842L, H1864H, and S1872R). Protein expression of ATM revealed, as a confirmative role is found to be low.

The hits with influential impact on the function of ATM was, also, confirmed by in silico analysis.

The strategic and programmed events of the breast cells are shaped through the multi-developmental processes including the programmed proliferation accompanied by different cascade of events to secure the occurrence of breast carcinoma (BC).

The major focal points of this commentary includes the evolutionary events including Five-hit and Eight-hit hypothetic personalized events in the breast cancer patients.

Key considerations: Major Concerns and the essential step in Cancer Prevention includes: 1) an early detection; 2) Considering the right of the proband’s relatives through the pedigree-based strategy; 3) considering the personalized insight; 4) application of combination of technologies including molecular and single cell-based functional assays.


Keywords: Evolution; Personalized; Hit Hypothesis; Breast Cancer; ATM Polymorphism; Predisposing Gene



  1. Tao Z., et al. “Breast cancer: epidemiology and etiology”. Cell Biochemistry and Biophysics 72 (2015): 333-338.
  2. Karami F and Mehdipour P. “A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer”. BioMed Research International (2013).
  3. Turnbull C and Rahman N. “Genetic predisposition to breast cancer: past, present, and future”. Annual Review of Genomics and Human Genetics 9 (2008): 321-345.
  4. Carranza D., et al. “Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia”. Neuromolecular Medicine (2016): 1-14.
  5. Deng Q., et al. “Genetic polymorphisms in ATM, ERCC1, APE1 and iASPP genes and lung cancer risk in a population of southeast China”. Medical Oncology 28 (2011): 667-672.
  6. Ćmielová J., et al. “Changes in the response of MCF-7 cells to ionizing radiation after the combination of ATM and DNA-PK inhibition”. Medical Oncology 32 (2015): 138.
  7. Kim JH., et al. “Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk”. Human Molecular Genetics 15 (2006): 1181-1186.
  8. Thompson D., et al. “Cancer risks and mortality in heterozygous ATM mutation carriers”. Journal of the National Cancer Institute 97 (2005): 813-822.
  9. Mehdipour P., et al. “Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer”. Medical Oncology 28 (2011): 733-737.
  10. Schrauder M., et al. “Single nucleotide polymorphism D1853N of the ATM gene may alter the risk for breast cancer”. Journal of Cancer Research and Clinical Oncology 134 (2008): 873-882.
  11. Gao LB., et al. “The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis”. Journal of Experimental and Clinical Cancer Research 29 (2010): 117.
  12. Mehdipour P., et al. “Three-hit hypothesis in astrocytoma: tracing the polymorphism D1853N in ATM gene through a pedigree of the proband affected with primary brain tumor”. Journal of Cancer Research and Clinical Oncology 134 (2008): 1173-1180.
  13. Mehdipour P and Azarnezhad A. “Five-hit hypothesis in ATM gene: An individualized model in a breast cancer patient”. Frontiers in Bioscience (2018): 375-383.
  14. Sandoval N., et al. “Characterization of ATM gene mutations in 66 ataxia telangiectasia families”. Human Molecular Genetics (1999): 69-79.
  15. Mehdipour P., et al. “Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer”. Medical Oncology (2011): 733-777.
  16. Alberts B., et al. “Cancer as a microevolutionary process (2002).
  17. Knudson AG. “Mutation and cancer: statistical study of retinoblastoma”. Proceedings of the National Academy of Sciences (1971): 820-823.
  18. Mehdipour P and Azarnezhad A. “Eight-Hit Evolutionary Pattern in ATM Gene of a Breast Carcinoma Patient: A Personalized Approach”. Journal of Cancer Research Updates 10 (2021): 23-31.
Citation: Parvin Mehdipour. “Prominence of the Evolutionary and Personalized Strategy in the Breast Cancer Management: A Junction Between Cancer Cell Genetics and Clinical Oncology”. EC Gynaecology 11.9 (2022): 46-51.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

December Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the November issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before December 21, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.