This document provides an introduction to biomarkers. It defines biomarkers as measurements that can indicate exposure to toxins, disease states, or responses to treatment. Biomarkers can be molecular, histologic, radiographic, or reflect physiologic characteristics. They are categorized based on their ability to predict predisposition, diagnose, prognose, predict outcomes, monitor safety/response, or assess risk/susceptibility. The document discusses biomarkers for cancer detection, risk assessment, screening, monitoring disease progression and response to treatment. It provides examples of important biomarkers for breast cancer including ER-α, PR, HER2, p53, BRCA1, EGFR, CK20 and CK7.

1. Introduction to
biomarkers
Prepared by: Mostafa Khooshebast
Supervisor: Prof. J Haddadnia
Hakim Sabzevari University
INTRODUCTION TO BIOMARKERS 1

2. Table of context
❑ Biomarker definition
❑ Biomarker requirement
❑ Types of biomarkers
❑ Categories of biomarkers
❑ Biomarkers in cancer
❑ Biomarkers in breast cancer
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3. Biomarker Definition
1987: “indicators signaling events in biological systems or samples” that could be classified into
three categories: exposure, effect and susceptibility markers.
1990: “measurements at the molecular, biochemical, or cellular level in either wild populations
from contaminated habitats or in organisms experimentally exposed to pollutants that indicate
that the organism has been exposed to toxic chemicals, and the magnitude of the organism's
response”
1994: “a biochemical, cellular, physiological or behavioral change which can be measured in
body tissues or fluids or at the level of the whole organism that reveals the exposure at/or the
effects of one or more chemical pollutants.”
1996: a biomarker by definition should be used only to describe sublethal biochemical changes
resulting from individual exposure to xenobiotics.
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4. Biomarker Definition
1998: "a characteristic that is objectively measured and evaluated as an indicator of normal
biological processes, pathogenic processes, or pharmacologic responses to a therapeutic
intervention.’’
2000: “biochemical and/or physiological change(s) in organisms exposed to contaminants, and
thus represent initial responses to environmental perturbation and contamination".
Simple definition: biomarkers defined as “any substance, structure, or process that can be
measured in the body or its products and influence or predict the incidence of outcome or
disease”.
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5. Biomarker requirements
(FDA) ideal biomarker should be:
1. Specific for a particular disease and able to differentiate between different physiological states
2. Safe and easy to measure.
3. Rapid so as to enable faster diagnosis.
4. Cheap and Cost efficient to follow up.
5. Modifiable with treatment.
6. Able to give accurate results.
7. Consistent between different ethnic groups and genders.
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6. Types of biomarkers
1. Molecular:
➢ biophysical properties
➢ nucleic acids-based biomarkers
2. Histologic:
➢ Reflect biochemical or molecular alteration in cells, tissues or fluids
3. Radiographic:
➢ imaging studies
4. Physiologic characteristics:
➢ body processes
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7. Categories of biomarkers
1. Predisposition:
➢ Increased likelihood of developing a health disorder based on the presence of a particular
biomarker
2. Diagnostic:
➢ Detects or confirms the presence of a disease or condition of interest
3. Prognostic:
➢ Identify the likelihood of a clinical event, disease recurrence, or disease progression in patients
4. Predictive:
➢ Predicting clinical outcomes / Optimize ideal treatments
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8. Categories of biomarkers
5. Safety:
➢ Measure the safety or toxicity of a therapeutic regimen / treatment
6. Monitoring:
➢ Assess the status of a disease or medical condition
7. Response:
➢ Show that a biological response has occurred
8. Susceptibility / Risk:
➢ Associated with an increased or decreased chance of developing a disease or medical condition
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9. Categories of biomarkers
9. Complex biomarkers:
➢ Enable better predictions because multiple biomarkers each play a small role in the summative
outcome of interest
10. Digital Biomarkers:
➢ Objective, quantifiable physiological and behavioral data that are collected and measured by
means of digital devices
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10. Biomarkers applications
1. Disease prevention
2. Disease detection
3. Disease monitoring
4. Drug development
5. Cancer detection
6. Early diagnosis
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11. Biomarkers in cancer
Types:
Risk Assessment → frequently associated with a predisposition to cancer
Screening/Detection → real-time indicators of the presence of cancer
Monitoring → predict and monitor a patient's cancer recurrence of the disease after treatment
Diagnosis → aid in diagnosis and help determine the primary origin of the tumor
Prognosis → provide information about a patient's expected outcome, regardless of therapy
Prediction → predict a patient's response to treatment or to determine the optimal drug dose
or type used
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12. Biomarkers in cancer
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Cancer biomarkers can include:
▪ Proteins
▪ Gene mutations (changes)
▪ Gene rearrangements
▪ Extra copies of genes
▪ Missing genes
▪ Other molecules

13. Biomarkers in cancer
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Function of cancer biomarkers:
• Trigger Cells to Grow and Multiply Abnormally
• Support a Treatment’s Cellular or Molecular Action
• Disrupt a Treatment’s Cellular or Molecular Action

14. Biomarkers in breast cancer
1. ER-α:
▪ A nuclear protein with a ligand-dependent transcription factor function
▪ Commonly detected in both luminal A and B subtypes
2. PR:
▪ Plays a key role in ER-α protein regulation
▪ Highly expressed in luminal A-type breast cancer
▪ Associated with a good prognosis
3. ErbB2/HER2:
▪ Can be found in 20–30% of breast cancer tumors
▪ Commonly found in more aggressive types of the disease
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15. Biomarkers in breast cancer
4. p53:
▪ Can be found in 80% of triple-negative breast cancer (TNBC) cases
▪ p53 IHC stains commonly used for diagnostic purposes
5. BRCA1:
▪ Well-known breast cancer-associated protein mutations
▪ A tumor suppressor gene and one of the most commonly mutated genes
▪ A crucial biomarker in the diagnosis and prognosis of many breast cancer types
6. EGFR:
▪ A transmembrane receptor and its expression is frequently found in TNBC and IBC
▪ Associated with a poor prognosis
▪ A common biomarker for aggressive breast cancer types
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16. Biomarkers in breast cancer
7. CK20 & CK7:
▪ Can be found in 80% of triple-negative breast cancer (TNBC) cases
▪ p53 IHC stains commonly used for diagnostic purposes
8. APOBEC3B:
▪ Expressed in ER-positive breast cancers and is used as a biomarker of poor prognosis
▪ A driver for downstream genetic mutations which accelerate the progression of breast cancer
9. FOXA1:
▪ Have a unique distribution within breast cancer cells compared to other cell types
▪ Is crucial for chromatin opening and the transcriptional activation of ER-α responsive genes
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17. Biomarkers in breast cancer
10. GATA3:
▪ A zinc finger transcription factor crucial for breast luminal epithelium differentiation
▪ For both primary and metastatic breast cancer and commonly found in luminal A and B
11. CK5:
▪ Expressed in ER-positive breast cancers and is used as a biomarker of poor prognosis
▪ A driver for downstream genetic mutations which accelerate the progression of breast cancer
12. E-cadherin:
▪ Have a unique distribution within breast cancer cells compared to other cell types
▪ Is crucial for chromatin opening and the transcriptional activation of ER-α responsive genes
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18. Thesis sections
1. Abstract
2. Introduction
3. Definitions
4. Literature review
5. Research methodology
6. discussions
7. Results
THESIS 18