Table of Contents
HORMONES AND CANCER – H. DEPYPERE ................................................................... 3
Molecular Action and Systemic Regulation ................................................................................... 3
Skeletal Health and Osteoporosis ................................................................................................ 3
Obesity and Menopause Management .......................................................................................... 4
Breast Anatomy and Cancer Subtypes .......................................................................................... 4
Therapeutic Approaches for Hormone-Related Cancers ................................................................ 5
SCREENING AND PREVENTION OF GYNECOLOGICAL CANCERS – H. DEPYPERE ............ 8
Breast Cancer Development and Prevention ................................................................................. 8
Risk Factors for Breast Cancer ..................................................................................................... 8
Obesity, Metabolic Syndrome, and Cancer.................................................................................... 9
Hereditary Breast Cancer and BRCA Mutations ............................................................................. 9
Epigenetics and Breast Cancer ..................................................................................................... 9
Hormone Replacement Therapy and Prevention .......................................................................... 10
Breast Cancer Screening............................................................................................................ 10
Endometrial Cancer Prevention .................................................................................................. 11
Ovarian Cancer Prevention......................................................................................................... 11
Conclusion................................................................................................................................ 11
PATHOLOGY OF THE CERVIX – H. DEPYPERE............................................................... 12
Molecular Pathogenesis, Transformation Zone and HPV Structure................................................ 12
Clinical Progression, Natural History and Statistics ..................................................................... 12
Detailed Screening and Triage in Belgium .................................................................................... 13
Bethesda Classification and Cytological Interpretation ............................................................... 14
Diagnostic Visualization by Colposcopy ...................................................................................... 14
Surgical Management of CIN ...................................................................................................... 14
HPV Vaccination ........................................................................................................................ 15
CLINICAL ASPECTS OF CANCER (1) – WIM CEELEN ..................................................... 16
Epidemiological Foundations and Risk Factors ........................................................................... 16
Principles of Cancer Screening ................................................................................................... 16
The TNM Staging System ............................................................................................................ 17
Critical Appraisal of Clinical studies in Cancer ............................................................................ 18
CLINICAL ASPECTS OF CANCER (2) – WIM CEELEN ..................................................... 19
Guidelines and Specialized Trial Designs .................................................................................... 19
Defining Clinical Outcomes and Endpoints ................................................................................. 19
Bias Mitigation, Randomization, and Participant Analysis Sets ..................................................... 20
Advanced Trial Designs and Evidence Synthesis .......................................................................... 21
IMAGING IN CANCER – WIM CEELEN.......................................................................... 23
Module 1: Fundamental Principles and Spatial Resolution in Imaging ........................................... 23
Module 2: Endoscopic Diagnostics and Tumor Morphology.......................................................... 23
Module 3: Comprehensive Endoscopic Resection Techniques ..................................................... 23
Module 4: Disease Progression and Advanced Endoscopic Interventions ..................................... 23
Module 5: Palliative Stenting and Enhanced Optical Technologies ................................................ 24
Module 6: The Physics of Radiology and Computed Tomography .................................................. 24
Module 7: Magnetic Resonance Imaging (MRI) Principles and Oncological Use ............................. 25
Module 8: Nuclear Medicine and Treatment Response Assessment ............................................. 25
ROLE OF SURGERY IN CANCER TREATMENT – WIM CEELEN ........................................ 27
Diagnosis and staging of cancer ................................................................................................. 27
Treatment of cancer: resection ................................................................................................... 28
NEOPLASIA PART 1 - CREYTENS ................................................................................. 30
, Fundamentals of Clinical Pathology ........................................................................................... 30
The Clinical Workflow and Specimen Collection.......................................................................... 30
How to deliver the specimen to the pathology department? ......................................................... 31
Laboratory Processing: From Tissue to Slide ............................................................................... 31
Standard Staining and Processing Times ..................................................................................... 32
Histology versus Cytology .......................................................................................................... 32
Advanced Diagnostic and Molecular Techniques ......................................................................... 32
NEOPLASIA PART 2 – CREYTENS ................................................................................ 34
Conventional Morphology as the Basis of Oncopathology ............................................................ 34
Benign and Malignant Tumors .................................................................................................... 34
Diberentiation and Anaplasia ..................................................................................................... 34
Histological Grading .................................................................................................................. 35
Metastasis and TNM Classification ............................................................................................. 35
Dysplasia and Carcinogenesis ................................................................................................... 36
Teratomas and Hamartomas ...................................................................................................... 36
PALLIATIVE CARE – MARTINE DE LAAT ........................................................................ 37
PRINCIPLES OF CHEMOTHERAPY – SYLVIE ROTTEY .................................................... 40
Module 1: The Biological Foundation of Malignancy and Growth Kinetics ...................................... 40
Module 2: Clinical Assessment, Dosing, and Treatment Logistics ................................................. 40
Module 3: Objectives and Specialized Terminology of Chemotherapy ........................................... 41
Module 4: Alkylating Agents and Platinum Complexes ................................................................. 42
Module 5: Anti-metabolites, Plant-Derived Agents, and Immunotherapy....................................... 43
Module 6: Drug Resistance and Evaluation of Treatment Ebicacy ................................................. 43
NON-CHEMO TARGETED THERAPIES – SYLVIE ROTTEY ................................................ 45
The Genetic and Evolutionary Nature of Cancer .......................................................................... 45
The Shift from Traditional to Precision Medicine .......................................................................... 45
Mechanisms of Targeted Therapy and Growth Signaling ............................................................... 45
Antibody-Drug Conjugates (ADCs) .............................................................................................. 46
Mechanism of Action of ADCs .................................................................................................... 47
Advantages of ADCs .................................................................................................................. 48
Important ADC Examples ........................................................................................................... 48
Resistance Mechanisms ............................................................................................................ 48
Limitations and Future Directions ............................................................................................... 49
ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER – OST ............................... 50
Physiological Basis of Androgen Production ................................................................................ 50
Methods of Androgen Deprivation............................................................................................... 50
Complications of ADT and Their Management ............................................................................. 52
Sarcopenia and Loss of Muscle Mass ......................................................................................... 52
Metabolic Syndrome and Cardiovascular Risk............................................................................. 53
Osteoporosis and Bone Health ................................................................................................... 53
TEAM Approach ......................................................................................................................... 53
RADIOTHERAPY – OST ............................................................................................... 54
The Multi-Step Process of Radiotherapy ...................................................................................... 54
Radiotherapy Toxicity and the Therapeutic Ratio .......................................................................... 55
The Evolution Toward Hypofractionation ..................................................................................... 56
,HORMONES AND CANCER – H. DEPYPERE
Molecular Action and Systemic Regulation
Steroid hormones such as 17β-estradiol function as powerful agonists that can di9use
through cell membranes and enter the nucleus. There, they bind to estrogen receptors
(ERs). This binding activates the receptor, leading to receptor dimerization and
recruitment of coactivator proteins through the receptor domains AF1 and AF2. The
activated receptor complex then binds to specific DNA sequences known as Estrogen
Response Elements (EREs), stimulating the transcription of estrogen-responsive genes.
This process promotes the production of proteins involved in tissue maintenance,
growth, and repair, including structural proteins such as collagen and elastin.
Beyond their reproductive functions, estrogens are important regulators of multiple
organ systems. They play a particularly important role in cardiovascular health by
interacting with endothelial cells lining blood vessels. Through activation of signaling
pathways such as Ras, Src, and MAP kinase, estrogens stimulate nitric oxide (NO)
production, resulting in vasodilation and improved vascular function. In
postmenopausal women, declining estrogen levels contribute to vascular sti9ness,
increased peripheral resistance, and elevated blood pressure.
Skeletal Health and Osteoporosis
The adult skeleton consists of approximately 80% compact (cortical) bone and 20%
spongy (trabecular) bone. Cortical bone provides biomechanical strength and rigidity,
whereas trabecular bone contributes flexibility and metabolic activity.
Bone homeostasis is maintained through a balance between osteoclasts and
osteoblasts. Osteoclasts resorb old or damaged bone, while osteoblasts synthesize
collagen and form new bone tissue. Estrogen is crucial for maintaining this balance by
limiting excessive bone resorption. Bone mass generally reaches its peak around the
age of 25–30 years, after which it gradually declines. In women, this decline accelerates
markedly during menopause because of the sharp reduction in estrogen levels.
This accelerated bone loss can lead to osteoporosis, an often underestimated disease
characterized by reduced bone strength and an increased risk of fractures.
Approximately 1 in 3 women over the age of 50 will experience an osteoporotic fracture.
The consequences can be severe: nearly 20% of patients die within the first year after a
hip fracture, and more than half are unable to walk independently one year later.
, Obesity and Menopause Management
The menopausal transition is associated with major changes in body composition,
including an increase in fat mass and a reduction in lean body mass. As a result,
obesity becomes more prevalent in postmenopausal women.
Obesity contributes to breast cancer risk through several mechanisms.
Insulin resistance often develops, causing the pancreas to produce higher levels of
insulin. Elevated insulin levels can stimulate cell proliferation and activate signaling
pathways that support tumor growth.
In addition, adipose tissue expresses the enzyme aromatase, which converts
androgens into estrogens. Consequently, adipose tissue becomes an important source
of estrogen production after menopause, providing hormonal stimulation that can
promote the growth of estrogen receptor-positive breast cancers.
Modern pharmacological management of obesity includes GLP-1 receptor agonists
such as semaglutide.
Normally: GLP-1 is released in response to food intake and increases satiety and
reduces hunger.
Semaglutide is approximately 94% homologous to native human GLP-1 and has a half-
life of about one week. It acts on appetite-regulating centers in the hypothalamus and
hindbrain, increasing satiety and reducing hunger.
This results in sustained weight loss and improvements in cardiovascular risk factors
such as blood pressure, cholesterol levels, and insulin sensitivity.
Breast Anatomy and Cancer Subtypes
The breast is a modified apocrine gland consisting of 15–20 lobes, each containing
multiple lobules, with up to 40 lobules per lobe. The breast also contains adipose
tissue, connective tissue, blood vessels, and an extensive lymphatic network. These
lobules undergo substantial changes throughout life, particularly during puberty,
pregnancy, lactation, and menopause.
Pregnancy has a protective e9ect against breast cancer. A first full-term pregnancy
before the age of 20 can reduce long-term breast cancer risk by approximately 50%.
This protection is thought to result from terminal diAerentiation of breast epithelial
cells, shifting them into a more quiescent and less proliferative state compared with
the highly proliferative breast tissue observed in women who have never been pregnant.
Breast cancer is staged according to the TNM classification system.
• "T" = the size and extent of the primary tumor,
• "N" = lymph node involvement, and
• "M" = the presence or absence of distant metastases.
HORMONES AND CANCER – H. DEPYPERE ................................................................... 3
Molecular Action and Systemic Regulation ................................................................................... 3
Skeletal Health and Osteoporosis ................................................................................................ 3
Obesity and Menopause Management .......................................................................................... 4
Breast Anatomy and Cancer Subtypes .......................................................................................... 4
Therapeutic Approaches for Hormone-Related Cancers ................................................................ 5
SCREENING AND PREVENTION OF GYNECOLOGICAL CANCERS – H. DEPYPERE ............ 8
Breast Cancer Development and Prevention ................................................................................. 8
Risk Factors for Breast Cancer ..................................................................................................... 8
Obesity, Metabolic Syndrome, and Cancer.................................................................................... 9
Hereditary Breast Cancer and BRCA Mutations ............................................................................. 9
Epigenetics and Breast Cancer ..................................................................................................... 9
Hormone Replacement Therapy and Prevention .......................................................................... 10
Breast Cancer Screening............................................................................................................ 10
Endometrial Cancer Prevention .................................................................................................. 11
Ovarian Cancer Prevention......................................................................................................... 11
Conclusion................................................................................................................................ 11
PATHOLOGY OF THE CERVIX – H. DEPYPERE............................................................... 12
Molecular Pathogenesis, Transformation Zone and HPV Structure................................................ 12
Clinical Progression, Natural History and Statistics ..................................................................... 12
Detailed Screening and Triage in Belgium .................................................................................... 13
Bethesda Classification and Cytological Interpretation ............................................................... 14
Diagnostic Visualization by Colposcopy ...................................................................................... 14
Surgical Management of CIN ...................................................................................................... 14
HPV Vaccination ........................................................................................................................ 15
CLINICAL ASPECTS OF CANCER (1) – WIM CEELEN ..................................................... 16
Epidemiological Foundations and Risk Factors ........................................................................... 16
Principles of Cancer Screening ................................................................................................... 16
The TNM Staging System ............................................................................................................ 17
Critical Appraisal of Clinical studies in Cancer ............................................................................ 18
CLINICAL ASPECTS OF CANCER (2) – WIM CEELEN ..................................................... 19
Guidelines and Specialized Trial Designs .................................................................................... 19
Defining Clinical Outcomes and Endpoints ................................................................................. 19
Bias Mitigation, Randomization, and Participant Analysis Sets ..................................................... 20
Advanced Trial Designs and Evidence Synthesis .......................................................................... 21
IMAGING IN CANCER – WIM CEELEN.......................................................................... 23
Module 1: Fundamental Principles and Spatial Resolution in Imaging ........................................... 23
Module 2: Endoscopic Diagnostics and Tumor Morphology.......................................................... 23
Module 3: Comprehensive Endoscopic Resection Techniques ..................................................... 23
Module 4: Disease Progression and Advanced Endoscopic Interventions ..................................... 23
Module 5: Palliative Stenting and Enhanced Optical Technologies ................................................ 24
Module 6: The Physics of Radiology and Computed Tomography .................................................. 24
Module 7: Magnetic Resonance Imaging (MRI) Principles and Oncological Use ............................. 25
Module 8: Nuclear Medicine and Treatment Response Assessment ............................................. 25
ROLE OF SURGERY IN CANCER TREATMENT – WIM CEELEN ........................................ 27
Diagnosis and staging of cancer ................................................................................................. 27
Treatment of cancer: resection ................................................................................................... 28
NEOPLASIA PART 1 - CREYTENS ................................................................................. 30
, Fundamentals of Clinical Pathology ........................................................................................... 30
The Clinical Workflow and Specimen Collection.......................................................................... 30
How to deliver the specimen to the pathology department? ......................................................... 31
Laboratory Processing: From Tissue to Slide ............................................................................... 31
Standard Staining and Processing Times ..................................................................................... 32
Histology versus Cytology .......................................................................................................... 32
Advanced Diagnostic and Molecular Techniques ......................................................................... 32
NEOPLASIA PART 2 – CREYTENS ................................................................................ 34
Conventional Morphology as the Basis of Oncopathology ............................................................ 34
Benign and Malignant Tumors .................................................................................................... 34
Diberentiation and Anaplasia ..................................................................................................... 34
Histological Grading .................................................................................................................. 35
Metastasis and TNM Classification ............................................................................................. 35
Dysplasia and Carcinogenesis ................................................................................................... 36
Teratomas and Hamartomas ...................................................................................................... 36
PALLIATIVE CARE – MARTINE DE LAAT ........................................................................ 37
PRINCIPLES OF CHEMOTHERAPY – SYLVIE ROTTEY .................................................... 40
Module 1: The Biological Foundation of Malignancy and Growth Kinetics ...................................... 40
Module 2: Clinical Assessment, Dosing, and Treatment Logistics ................................................. 40
Module 3: Objectives and Specialized Terminology of Chemotherapy ........................................... 41
Module 4: Alkylating Agents and Platinum Complexes ................................................................. 42
Module 5: Anti-metabolites, Plant-Derived Agents, and Immunotherapy....................................... 43
Module 6: Drug Resistance and Evaluation of Treatment Ebicacy ................................................. 43
NON-CHEMO TARGETED THERAPIES – SYLVIE ROTTEY ................................................ 45
The Genetic and Evolutionary Nature of Cancer .......................................................................... 45
The Shift from Traditional to Precision Medicine .......................................................................... 45
Mechanisms of Targeted Therapy and Growth Signaling ............................................................... 45
Antibody-Drug Conjugates (ADCs) .............................................................................................. 46
Mechanism of Action of ADCs .................................................................................................... 47
Advantages of ADCs .................................................................................................................. 48
Important ADC Examples ........................................................................................................... 48
Resistance Mechanisms ............................................................................................................ 48
Limitations and Future Directions ............................................................................................... 49
ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER – OST ............................... 50
Physiological Basis of Androgen Production ................................................................................ 50
Methods of Androgen Deprivation............................................................................................... 50
Complications of ADT and Their Management ............................................................................. 52
Sarcopenia and Loss of Muscle Mass ......................................................................................... 52
Metabolic Syndrome and Cardiovascular Risk............................................................................. 53
Osteoporosis and Bone Health ................................................................................................... 53
TEAM Approach ......................................................................................................................... 53
RADIOTHERAPY – OST ............................................................................................... 54
The Multi-Step Process of Radiotherapy ...................................................................................... 54
Radiotherapy Toxicity and the Therapeutic Ratio .......................................................................... 55
The Evolution Toward Hypofractionation ..................................................................................... 56
,HORMONES AND CANCER – H. DEPYPERE
Molecular Action and Systemic Regulation
Steroid hormones such as 17β-estradiol function as powerful agonists that can di9use
through cell membranes and enter the nucleus. There, they bind to estrogen receptors
(ERs). This binding activates the receptor, leading to receptor dimerization and
recruitment of coactivator proteins through the receptor domains AF1 and AF2. The
activated receptor complex then binds to specific DNA sequences known as Estrogen
Response Elements (EREs), stimulating the transcription of estrogen-responsive genes.
This process promotes the production of proteins involved in tissue maintenance,
growth, and repair, including structural proteins such as collagen and elastin.
Beyond their reproductive functions, estrogens are important regulators of multiple
organ systems. They play a particularly important role in cardiovascular health by
interacting with endothelial cells lining blood vessels. Through activation of signaling
pathways such as Ras, Src, and MAP kinase, estrogens stimulate nitric oxide (NO)
production, resulting in vasodilation and improved vascular function. In
postmenopausal women, declining estrogen levels contribute to vascular sti9ness,
increased peripheral resistance, and elevated blood pressure.
Skeletal Health and Osteoporosis
The adult skeleton consists of approximately 80% compact (cortical) bone and 20%
spongy (trabecular) bone. Cortical bone provides biomechanical strength and rigidity,
whereas trabecular bone contributes flexibility and metabolic activity.
Bone homeostasis is maintained through a balance between osteoclasts and
osteoblasts. Osteoclasts resorb old or damaged bone, while osteoblasts synthesize
collagen and form new bone tissue. Estrogen is crucial for maintaining this balance by
limiting excessive bone resorption. Bone mass generally reaches its peak around the
age of 25–30 years, after which it gradually declines. In women, this decline accelerates
markedly during menopause because of the sharp reduction in estrogen levels.
This accelerated bone loss can lead to osteoporosis, an often underestimated disease
characterized by reduced bone strength and an increased risk of fractures.
Approximately 1 in 3 women over the age of 50 will experience an osteoporotic fracture.
The consequences can be severe: nearly 20% of patients die within the first year after a
hip fracture, and more than half are unable to walk independently one year later.
, Obesity and Menopause Management
The menopausal transition is associated with major changes in body composition,
including an increase in fat mass and a reduction in lean body mass. As a result,
obesity becomes more prevalent in postmenopausal women.
Obesity contributes to breast cancer risk through several mechanisms.
Insulin resistance often develops, causing the pancreas to produce higher levels of
insulin. Elevated insulin levels can stimulate cell proliferation and activate signaling
pathways that support tumor growth.
In addition, adipose tissue expresses the enzyme aromatase, which converts
androgens into estrogens. Consequently, adipose tissue becomes an important source
of estrogen production after menopause, providing hormonal stimulation that can
promote the growth of estrogen receptor-positive breast cancers.
Modern pharmacological management of obesity includes GLP-1 receptor agonists
such as semaglutide.
Normally: GLP-1 is released in response to food intake and increases satiety and
reduces hunger.
Semaglutide is approximately 94% homologous to native human GLP-1 and has a half-
life of about one week. It acts on appetite-regulating centers in the hypothalamus and
hindbrain, increasing satiety and reducing hunger.
This results in sustained weight loss and improvements in cardiovascular risk factors
such as blood pressure, cholesterol levels, and insulin sensitivity.
Breast Anatomy and Cancer Subtypes
The breast is a modified apocrine gland consisting of 15–20 lobes, each containing
multiple lobules, with up to 40 lobules per lobe. The breast also contains adipose
tissue, connective tissue, blood vessels, and an extensive lymphatic network. These
lobules undergo substantial changes throughout life, particularly during puberty,
pregnancy, lactation, and menopause.
Pregnancy has a protective e9ect against breast cancer. A first full-term pregnancy
before the age of 20 can reduce long-term breast cancer risk by approximately 50%.
This protection is thought to result from terminal diAerentiation of breast epithelial
cells, shifting them into a more quiescent and less proliferative state compared with
the highly proliferative breast tissue observed in women who have never been pregnant.
Breast cancer is staged according to the TNM classification system.
• "T" = the size and extent of the primary tumor,
• "N" = lymph node involvement, and
• "M" = the presence or absence of distant metastases.
