L2: Solid Tumor Malignancies
Describe the pathogenesis associated with each solid tumor — lung, breast, colon, prostate CA
Identify the common risk factors associated with the development of each solid tumor discussed
Describe the signs and symptoms associated with each solid tumor discussed
Interpret cancer screening strategies for early detection and diagnosis of each solid tumor discussed
Explain the pathogenesis of Lung CA
multiple genetic lesions formed on bronchial epithelial cells → chronic inflammation → cytogenetic changes & transformations → malignancy
What control pathways are impaired in Lung CA?
cellular regulatory and growth control pathways
List the steps of Lung CA pathogenesis
Activation of Oncogenes
Inhibition/Mutation of Tumor Suppressor Genes
Production of Autocrine (self-stimulatory) Growth Factors → Cellular Proliferation & Malignant Transformation
What are the 2 types of Lung CA?
Non-Small Cell (more prevalent) & Small Cell
What are the prognosis for Lung CA?
Localized Disease vs Metastatic Disease
What are the 3 types of Non-Small Cell Lung CA?
Adenocarcinoma (Non-Squamous)
Most common subtype
Most common in non-smokers
Peripheral Lung
Large Cell (Non-Squamous)
Peripheral Lung
Squamous
Linked with smoking
Central Bronchial
Which type of Non-Small Cell Lung CA is associated with a poor prognosis?
Large Cell (Non-Squamous)
How do you calculate pack years?
# packs per day * years
How long of smoking cessation does one start experiencing gradual decrease risk in Lung CA?
5 years, however, quitting for 10-15 years still has twice the risk than a non-smoker
What are the Environmental Respiratory Carcinogens?
Radon Gas released from soil and building materials, second hand smoke, air pollution, and Diesel Exhaust
What are the Occupational Respiratory Carcinogens?
asbestos, Rubber Manufacturing, Paving, Roofing, painting, and chimney sweeping
What are Comorbidities linked with Lung CA
Emphysema, COPD, Asthma, Tuberculosis
What are genetic predisposition related to Lung CA?
First degree relative with Lung CA
What are common local symptoms of Lung CA
cough, purulent sputum, dyspnea/wheezing, hoarseness, hemoptysis (coughing blood), localized chest pain, shoulder/arm pain, recurrent bronchitis or pneumonia
How is metastatic disease Lung CA shown?
symptoms consistent with organ involvement
What are systemic symptoms shown in Lung CA ?
anorexia, unexplained weight loss
What are Paraneoplastic syndromes?
phenomenon mediated by humoral factors (hormones) excreted by tumor cells or against tumor cells; SIADH, Hypercalcemia, Pleural Effusion
What is Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
causes the body to retain too much water → decreased serum sodium
What Lung CA screening is recommended for average risk?
none recommended by the ACS or other medical/scientific organizations
What Lung CA screening is recommended for increased risk?
annual surveillance (low dose CAT scan of lungs)
What are the criteria for increased risk of Lung CA?
Ages 50-80 and > 20 Pack Year History
What imaging studies for identification are used for Lung CA workup and diagnosis?
Chest x-ray and CT scans (chest, abdomen, and pelvis)
What Biopsy/Cytology are used for Lung CA workup and diagnosis?
Tumor Biopsy for pathology review and Cytology of pleural effusion if applicable
What are Lung CA tumor markers that can help guide therapy?
Epidermal Growth Factor Receptor (EGFR mutation), Anaplastic Lymphoma Kinase-4 (ALK-4 mutation), and Programmed Cell Death Ligand-1 (PDL-1)
List the steps of COLON CA pathogenesis
Normal cells → APC Mutation → Hyper-proliferated Epithelium
COX-2 Overexpression → Small Adenoma
KRAS Mutation → Large Adenoma
p53 Mutation → Loss of Chromosome 18q (tumor suppressor gene) and Colon Carcinoma
What are the Non-Modifiable risk factors of Colon CA
> 45 age, history of Colorectal Polyps, Chronic Inflammatory Bowel Disease, Genetic Predisposition (significantly increases risk)
What are examples of chronic inflammatory bowel diseases that are colon CA risk factors?
Ulcerative Colitis and Crohn’s Disease
What are the genetic predisposition risk factors for colon CA?
Familial Adenomatous Polyposis (FAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
What are modifiable risk factors for Colon CA?
Diet (high fat, red eat, low fruit/vegetable, low fiber), Obesity, Excessive Alcohol, Chronic Tobacco Use
What are the early symptoms of Colon CA?
Asymptomatic
What are the sign and symptoms of Colon CA?
Changes in bowel habits, Melena (Rectal Bleeding), Abdominal pain/discomfort/distention, Weight loss
How is metastatic disease Colon CA shown?
symptoms consistent with organ involvement; Pain in Upper Right Quadrant for Liver
What annual fecal tests are used for screen Colon CA?
Fecal Immunochemical Test (FIT) & Fecal Occult Blood Test (FOBT)
What colon CA screening is conducted every 5 years instead of a colonoscopy?
Flexible Sigmoidoscopy
What colon CA screening is conducted every 10 years instead of a flexible sigmoidoscopy?
Colonoscopy
At what age should people at average risk begin annual screening tests on top of the colonoscopy?
45 years of age
At what age should people with a first degree relative with colon CA should begin screenings?
35 y/o or 10 years earlier than diagnosis of affected relative
At what age should people with FAP (genetic predisposition) begin colon CA screenings?
Adolescence
At what age should people with Ulcerative Colitis begin colon CA screening?
8 years after diagnosis
What are 2 TUMOR MARKERS screened for Colon CA diagnosis
Carcinoembryonic Antigen (CEA) and KRAS
What are the 2 types of breast CA?
Invasive Lobular Carcinoma & Invasive Ductal Carcinoma (more prevalent)
What are Non-Modifiable risk factors of Breast CA?
Gender, > 40, Genetic, Endogenous Estrogen Exposure (Early Menarche < 12 y/o or Late Menopause > 55)
What are the genetic predispositions related to Breast CA?
BRCA1/BRCA2 mutation (inactivation of TUMOR SUPPRESSOR GENES) and First Degree Relative with Breast/Ovarian CA
What are Modifiable risk factors for Breast CA?
Hormonal exposure, Obesity/BMI, Sedentary Lifestyle
What are examples of Hormonal Exposure that can increase Breast CA risk factors?
Late Initial Pregnancy (> 30), Nulliparity (no children), Post-Menopausal Hormone Replacement Therapy, Oral Contraceptives (controversial)
How can Breast CA be detected if asymptomatic
Routine Mammography Screening
What are signs and symptoms of breast CA?
Painless Palpable Lump, Breast Discharge, Breast Redness or Warmth, Palpable Local-Regional Lymph Node Involvement
How is metastatic disease Breast CA shown?
Symptoms consistent with organ involvement; Upper Right Quadrant Pain/Discomfort (liver); SOB (Lung)
At what age should annual mammograms of breast CA for standard risk begin?
>45-54
How often should patients >55 receive mammograms?
Biennial (once every 2 years)
When should high risk patients of breast CA should start Mammogram +/- breast MRI screenings?
>30 annually
What are the TUMOR MARKERS used for breast CA diagnosis?
HER2-neu (Trastuzumab therapy) and Hormone/ER/PR (Tamoxifen therapy)
What are Non-Modifiable risk factors for Prostate CA?
>50, Race (African Americans > Caucasians > Asians), Genetic predisposition (1st degree relative), BPH
What are Modifiable risk factors for Prostate CA?
Diet (high fat and red meat)
What are the signs and symptoms of Prostate CA?
Urinary Urgency/Frequency, Dysuria, Weak Urinary Flow, Bloody Urine, Erectile Dysfunction
How is metastatic disease Prostate CA shown?
Symptoms consistent with organ involvement; bone pain and fractures
What are screenings used for Prostate CA?
Digital Rectal Exam (DRE) and Prostate Specific Antigen (PSA)
What is Prostate Specific Antigen (PSA)
produced by Secretory Cells and are obtained via blood test; varies with increased age, BPH, and Prostate Size