Cancer Flashcards
(237 cards)
1
Q
What causes cannonball lung mets?
A
- Testicular cancer
- Choriocarcinoma
- Renal carcinoma
- Thyroid cancer
- Melanoma
- Osteosarcoma
- Metastatic adenocarcinoma
2
Q
What is the difference between ionising and non-ionising radiation?
A
Ionising
- High energy
- From x-rays, gamma rays
- Has the ability to displace electrons from atoms
Non-ionising
- Lower energy
- From UV radiation (particularly B)
- Has the ability to excite electrons, leading to a chemical change in the tissue
3
Q
Which tissues are particularly susceptible to ionising radiation?
A
Breast, thyroid and bone marrow
4
Q
What is xeroderma pigmentosum?
A
A condition in which the repair pathway for non-ionising radiation is faulty, leading to multiple melanomas from UVB exposure at a very young age
5
Q
What will happen if you give a 16 year old radiotherapy for lymphoma?
A
She is likely to develop breast cancer later in life, due to the exposure to ionising radiation at a young age
6
Q
What are the 3 steps of carcinogenesis?
A
INITIATION - mutation in key regulatory pathways
PROMOTION - selective growth advantage induced in the initiated cells (NB usually without mutation)
PROGRESSION - multiple mutations from genetic instability leading to further degrees of invasiveness
7
Q
What cancers do tobacco smoke cause?
A
Anywhere!! Often lung, bladder
NOT endometrial
8
Q
What cancers do dye/rubber cause?
A
Bladder cancer
9
Q
What cancer does chemotherapy sometimes lead to?
A
AML
10
Q
What cancer is schistoma associated with?
A
Bladder cancer
11
Q
What cancer is malaria and EBV associated with?
A
Burkitts lymphoma
12
Q
Which environmental factors can cause cancer?
A
- Radiation
- Chemicals
- Infections
- Hormones
- Diet (most important RF?)
13
Q
What cancer is related to:
a) prolonged oestrogen exposure
b) more ovulatory cycles
A
a) endometrial cancer, breast cancer
b) ovarian cancer
14
Q
What is a germline mutation?
A
A mutation in a germ cell (testes/ova) at embryogenesis which can be passed on to future generations, and affects all cells.
eg. Hereditary cancer syndromes
15
Q
What is a somatic mutation?
A
A mutation in any cell except a germ cell, at any point during a persons lifetime. This mutation will only affect the direct cell lineage, and will not be passed on to future generations.
eg. Sporadic tumours
16
Q
What is Knudsons hypothesis?
A
If a gene has a faulty allele (ie. a germline mutation) , is only takes one mutation to become cancerous. In this way it is genetically predisposed to cancer
17
Q
What is an oncogene?
A
A gene that promotes cell proliferation by mimicking growth signals and should be switched on in embryonic life but switched off in adult tissue.
protoonco = switched off
18
Q
Give an example of where a ‘gain of function’ mutation has switched back on a proto-oncogene in cancer
A
RET gene on chr 10q11
If turned back on, it leads to MULTIPLE ENDOCRINE NEOPLASIA TYPE 2
NB with oncogenes only 1 gene copy needs to be affected (dominant)
19
Q
What cancers are associated with MEN2?
A
MEN2a: thyroid/parathyroid/phaeochromocytoma (adrenal gland)
MEN2b:
mucosal neuromas in eye, mouth and endocrine glands
20
Q
What is a tumour suppressor gene?
A
A gene that protects the cell from proliferating
NB with tumour suppressor genes both copies need to be affected (recessive)
21
Q
Give 3 examples of where a ‘loss of function’ mutation in a tumour suppressor gene has lead to cancer
A
Mutation in RB1 - retinoblastoma
Mutation in BRCA1/2 - breast/ovarian/prostate
Mutation in APC - FAP
22
Q
What is a mismatch repair gene?
A
A gene that produces proteins that detect mismatch and directs repair machinery towards it
23
Q
By which 3 ways can cell death occur in normal tissue ?
A
- Apoptosis
- Necrosis
- Autophagy
24
Q
Describe apoptosis
A
- Regulatory elements sense apoptotic signals (activation of cyclin E, removal of IL-3/IGF-1)
- Nuclear fragmentation
- Chromosomal condensation
- Cell shrinkage
- Bleb formation
- Phagocytosis of blebs
This is programmes cell death.
25
Describe 4 ways in which cancer cells can evade apoptosis
1. Loss of p53 tumour suppressor function
2. Increased survival signals (Bcl-2/xl)
3. Decreased bax, bim, puma
4. Short circuited ligand-induced death pathway
26
Describe autophagy
Lysosomes degrade cellular contents in response to stresses, allowing the metabolites to be recycled
27
How does cancer evade autophagy?
Cancers can survive stress (such as chemo/radio) and can shrink to a reversible dormancy, enabling regrowth after removal of stress
28
Describe necrosis
Unprogrammed chaotic cell death from noxious stimuli, involving inflammatory immune cells
29
How do cancer cells use necrosis to their selective advantage?
Necrosis of tumour cells leads to angiogenesis, cellular proliferation and tissue invasion, as it stimulates neighbouring cells in an uncontrolled way
30
How do tumour suppressor genes affect the cell cycle?
They inactivate cyclin-CDK complexes, which halts the cell cycle
31
Which cell cycle checkpoint is sometimes lost in cancer?
G1 checkpoint- this means that there is no 'checking' of the damaged cancerous genome before DNA synthesis (S phase)
32
Give an example of where cancer can cause increased expression of growth factor receptors
EGFR overexpression in GI/lung cancer
HER2 overexpression in breast cancer
This both activate Ras-Raf-MAP kinase causing cell proliferation
33
Give an example of where cancer can cause 'ligand independent signalling'
RAS mutations - activate MAP kinase in the absence of a binding of a growth factor ligand
34
Give 3 ways in which cancer cells can evade growth suppression
1. Lack of response to p53 and Rb inhibitory signals
2. Loss of contact inhibition
3. Mutations in tumour suppressor genes (Rb, tp53, tp21/27)
35
How do cancer cells enable replicative immortality?
They possess a telomerase enzyme that adds nucleotides to telomeres to allow continued cell division
36
How do cancer cells induce and maintain angiogenesis? How are these blood vessels different to normal ones?
1. Production of growth factors (VEGF, PDGF)
2. Suppression of angio inhibitors (TSP1)
3. Maintenance of vasculature by pericytes and myeloid cells (although vessels are much more leaky and likely to haemorrhage)
Tumour cells cannot grow beyond 1mm cubed without their own blood supply
37
Name 2 therapies that target cancer-induced angiogenesis
Bevacizumab - VEGF antibody
| Sunitinib - PDGF inhibitor
38
What does cadherin-1 do, and how is this involved in metastasis?
What is the name of this transition?
Cadherin-1 is a protein that usually organises cell tissue sheets.
In cancer, a mutation or downregulation of CDH1 gene means the cell becomes more disorganised and more motile, invasive and aggressive.
This is known as the epithelial-mesenchymal transition
39
Following the epithelial-mesenchymal transition, how do the new mesenchymal cells stimulate invasive behaviour?
They produce CCLs, which together with IL2 and IFNgamma, induce WBC infiltration.
Macrophages degrade the matrix with enzymes, allowing for invasion of the basement membrane
40
What is aerobic glycolysis and how is it involved in cancer?
ie. how do cancer cells reprogram energy metabolism?
It is the ability to to limit energy production to glycolysis, even when oxygen is present. (Usually cells use oxidative phosphorylation when oxygen is present)
This is helpful because the intermediates from glycolysis are necessary for production of new cancer cells
41
How can inflammation influence tumour development?
Once leucocytes have moved into tissue, they release reactive oxygen species, which are mutagenic to surrounding tissue.
42
How do tumour cells evade immune destruction?
They can recruit T helper and suppressor cells that enable them to not be recognised by immune cells.
43
Why are HIV patients predisposed to cancer?
Deficiency of CD4 cells means that their immune systems will not be strong enough to identify and destroy cancerous cells
44
What is the pathology of familial adenomatous polyposis?
Mutation in the APC gene, involved in the tumour suppressor pathway. This leads to a cascade of mutations leading to a 'multistep carcinogenesis'
45
What are the two main types of FAP?
1. Classical - 1000s of adenomas, 100% risk of malignancy (do colectomy)
2. Attenuated - 100s of adenomas, increased but not certain risk of malignancy
46
What are the symptoms of FAP?
Blood in stool
Change in bowel habits >6wks
Abdo pain
47
What are the extracolonic features of FAP?
- You get polyps all over the gut
- Retinal pigmentation
- Childhood hepatoblastoma
- Thyroid cancer
- Sebaceous/jaw cysts
48
A patient has retinal pigmentation, bloody stools and change in bowel habits. His dad had to have a colectomy when he was young. What condition are you worried about, and what screening should they have?
FAP
Annual screening (colonoscopy) from age 11
49
A patient with known FAP presents with an osteoma and a soft tissue tumour. What are you worried about?
Gardners syndrome
50
A patient with known FAP presents with confusion and CT scan shows brain tumour. What are you worried about?
Turcot syndrome
51
What is the pathology of Lynch Syndrome (aka HNPCC)
Mutation in MLH1 mismatch repair gene, leading to a cascade of mutations that cannot be repaired.
This will occur at areas of repeated DNA sequences known as microsatellites.
This leads to a frameshift mutation and a new truncated peptide.
This has two actions:
1. Generation of adenomas
2. The body mounts an inflammatory response against this foreign peptide
52
What is micro satellite instability?
Failure to repair repetitive sequences of DNA, due to faulty mismatch repair genes. This is characteristic of lynch syndrome and is rarely seen in sporadic colorectal cancer
53
What are the symptoms of lynch syndrome?
Usually none!!
54
What are the complications of lynch syndrome?
Colorectal cancer
| Endometrial cancer
55
What is the Amsterdam Criteria (321)?
It says that lynch syndrome is likely if there are
3 colorectal tumours
across 2 generations
with at least 1 diagnosed before 50
If it fulfils this, do colonoscopy every 2 years after the age of 25
56
How can biopsy differentiate between Lynch syndrome and sporadic colon cancer?
Do a biopsy of tumour tissue and do MSI and BRAF test.
MSI high - lynch syndrome
BRAF high - sporadic cancer
57
How is lynch syndrome managed?
1. Surveillance
2. Chemoprophylaxis with low dose aspirin
3. Surgical prophylaxis (colectomy)
4. Family cascade testing
58
A person with known lynch syndrome presents with sebaceous skin tumours. What are you worried about?
Miur Torre Syndrome
59
A patient presents with mucosal neuromas on the tongue, long fingers and skin pigmentation. Her father had to have his adrenal gland removed. What are you worried about?
MEN2b - mutation of RET gene associated with those features + phaemochromocytoma + thyroid cancer
60
What exam finding would in hereditary retinoblastoma give you?
White pupillary reflex
Two different coloured eyes with 'flash'
Hereditary - more likely to be bilateral
61
What are Wilsons Criteria for evaluating a screening programme?
- Important health problem
- Understood natural history of condition
- Easy to perform test
- Recognised treatment
- Treatment more effective if started early
- Policy on who should be treated
- Diagnosis and treatment cost effective
- Continuous case-finding
62
What are the features of Peutz-Jeghers syndrome?
Wine coloured lip staining
| Cancers of pancreas, lungs, liver, breast ovary and uterus
63
How are people with known PJ syndrome screened?
Screening every 6 months by OGD/capsule, from 8 years
64
Describe the genetics of PJ syndrome
Mutation of STK11 gene tumour suppressor
65
What is a CUP and why is it difficult to manage?
Cancer of unknown primary
- More aggressive
- Early dissemination
- Unpredictable metastatic pattern
66
What approach do you use to manage a CUP?
1. Search for primary site
2. Rule out potentially treatable/curable cancers
3. Treat with curative or palliative intent
67
What is the gold standard for a diagnostic work up of a CUP?
Immunohistochemistry
68
What are the five main subtypes of CUP?
1. Moderately well differentiated adenocarcinoma (better prognosis)
2. Poorly or undifferentiated adenocarcinoma
3. Squamous cell carcinoma
4. Undifferentiated carcinoma
4. Carcinoma of neuroendocrine differentiation
69
What is the main predictor of suitability for chemo?
Performance status
70
What are the symptoms of lung cancer?
Respiratory - Cough, dyspnoea, chest pain, haemoptysis, recurrent chest infections
Systemic - fever, weight loss, fatigue
Specific - dysphagia, hoarsness
71
Why do you get dysphagia in some lung cancers?
Extrinsic oesophageal compression by the primary tumour
72
Why do you get hoarseness in some lung cancers?
Invasion of the recurrent laryngeal nerve
73
What are the 4 characteristcs of clubbing?
1. Increased curvature
2. Soft tissue swelling
3. Nail fluctuance
4. Loss of nail bed angle
74
What are the signs of lung cancer?
Nicotine staining, clubbing, retention flap
Pulmonary collapse/effusion/consolidation
Lymphadenopathy, SVC obstruction
75
For a pleural effusion what is the:
a) expansion
b) mediastinum
c) vocal fremitus
d) percussion
e) breath sounds
f) air entry
And what other 2 features do you often hear?
a) reduced
b) central
c) reduced
d) reduced
e) dull
f) reduced
Whispering pectoliruquy - loud on whispering
Pleural rub
76
What is acanthosis nigricans?
A paraneoplastic syndrome causing velvety dark patches, particularly under the arms, associated with lung cancer
77
What is Pancoats syndrome, and what 4 features does it cause?
Apical malignant neoplasm (usually sq) that invades the brachial plexus and cervical sympathetic nerves causing:
1. Chest/shoulder pain at T1
2. Horners syndrome
3. Atrophy of hand and arm muscles
4. SVC obstruction
78
What are the features of Horners syndrome?
1. Meiosis
2. Anhydrosis
3. Ptosis
4. Enopthalmous
79
Why is T1 level significant?
It is the most common place for NSCLC to metastasize and will cause chest/shoulder pain
80
What investigations should be done in someone with suspected lung cancer?
BEDSIDE - sputum, sats
BLOODS - FBC (can get anaemia), CRP, LFTs, U&Es, bone profile, LDH
IMAGING - CXR, bronchoscopy, transthoracic needle biopsy, CT (always couple imagine with biopsy)
SPECIAL - pleural tap (exudative)
81
What further investigations should be done in someone with confirmed lung cancer?
```
Pulmonary function tests
V/Q
MRI
USS
Scope
```
These are to assess metastatic spread and operability of cancer/performance status
82
What blood test should always be done in a patient with unexplained confusion?
CRP - most common cause of confusion in the elderly is UTI
| Calcium
83
What is the main type of lung cancer? What are the subtypes?
Non small cell carcinoma (85%)
- Adenocarcinoma (40%)
- Squamous (30%)
- Large cell carcinoma
- Broncheoalveolar carcinoma
84
Describe an adenocarcinoma NSCLC
- Peripheral lung
- Slow growing but metastatic
- Asbestos
85
Which NSCLC is most common in non-smokers and women?
Adenocarcinoma
86
Describe a squamous NSCLC
- Central, cavitating lesion (can haemorrhage)
- Proximal bronchi
- Slow growing
- Smoking association
87
Describe some CXR changes with lung cancer
Mass lesion (nb if patient has pneumonia, repeat in a month)
Pleural Effusion
Diaphragm
88
Describe a large cell NSCLC
- Very large peripheral mass
- Subtle initital symptoms (due to peripheral location)
- Fast -growing
- Incurable once LN are involved
- Mucus secreting
89
What is the fastest growing NSCLC?
Large cell
90
Describe a broncheolaveolar carcinoma NSCLC
- Multiple bilateral nodules
- Non-invasive
- Frothy pink sputum
- Drug resistant
91
A patient has drug resistant lung cancer with frothy pink sputum. What is the mst likely diagnosis?
Broncheoalveloar carcinoma
92
Describe a small cell carcinoma
- Found all over the lung
- Hilar/mediastinal lymphadenopathy
- Highly metastatic
- Fast-growing
- Responds well to therapy
OFTEN PARANEOPLASTIC (as they originate from neuroendocrine cells)
93
A patient with lung cancer has an xray showing mediastinal/hilar lymphadenopathy. What is the diagnosis? What paraneoplastic syndrome are you worried about?
Small cell carcinoma
Cushings (ACTH)
SIADH (ADH)
94
Describe a malignant mesothelioma
- Arises from the pleura (of any organ!)
- Manifests as unilateral pleural effusion
- Restrictive defect
- Asbestos
95
What CXR finding is seen in malignant mesothelioma?
Unilateral pleural effusion
96
What are the complications of local invasion of lung cancer?
- SVC obstruction
| - Pleural effusion
97
What are the features of SVC obstruction?
- Facial oedema
- Non pulsative JVP
- Demarcations around the nipples
- Aggravated by bending down
98
What causes SVC obstruction?
Compression of superior mediastinum, most commonly by lung cancer
99
Where do lung cancers metastatize?
1. Brain
2. Liver
3. Bones
4. Adrenals
100
What are some signs of brain mets ? How can they be investigated? How can they be treated?
Headache, cognitive impairment, seizures
Do CT/PET
```
Surgery most effective
Steroids for oedema
Anticonvulsants
Radio
Chemo (rarely passes BBB)
```
101
What are the 2 reasons that you get hypercalcemia in lung cancer?
1. Bony mets
| 2. Ectopic production of PTH, particularly from NSCLC (squamous)
102
How is hypercalcemia diagnosed?
Ca > 2.7
Increased phosphate
Decreased PTH/Cl
103
How is hypercalcemia managed?
IV fluids
| IV bisphosphonates
104
What is the most common endocrine paraneoplastic syndrome?
SIADH
| cause by lung, prostate, thymic, pancreatic cancers and lymphoma
105
What
| paraneoplastic conditions do you get with lung cancer?
Endocrine -
1. SIADH (SCLC)
2. Ectopic ACTH (SCLC)
3. Raised gonadotrophins
4. Hypercalcemia
Dermatological
- Dermatomyositis
Neuro
- Lambert Eaton
- Encephalomyopathy
106
A patient has loss of short term memory and hallucinations. He was diagnosed with SCLC a few months ago. What is going on? How can this complication be diagnosed?
He is suffering from an encephalomyopathy.
| Diagnosis with raised protein in CSF and anti-HUantibody in serum
107
A patient has proximal muscle weakness and symptoms like myasthenia gravis, without any bulbar involvement. He was diagnosed with SCLC a few months ago. What is going on? How can this complication be diagnosed?
Lambert-Eaton syndrome - reduced calcium dependent Ach release at the neuromuscular junction
Diagnosis with low amplitude muscle action potential on EMG
108
What are the complications of chemotherapy?
- Neutropenic sepsis
| - Anaemia
109
What is the definition of neutropenic sepsis?
```
Pyrexia >38C or >37.5 twice in one hour
OR
Rigors
OR
Unexplained tachycardia/hypotension
```
in a patient with neutrophils <1 x 10^9/L
110
How is neutropenic sepsis managed?
1. Do blood cultures
2. COMPENCE BROAD ABX (TAZOCIN)
2. Do further investigations
111
What are the components of a sepsis/infection screen?
Cultures, MSU, CXR, swabs
112
What should not be done in suspected neutropenic sepsis?
What are the signs of poor prognosis?
PV/PR - infection dissemination
Paracetamol - may affect fever
Diarrhoea
Hypotension
Coagulopathy
Organ failure
113
What is radiation pneumonitis?
Shortness of breath, dry cough, fever, chest tightness and pain, secondary to radiotherapy for chest malignancies
114
In germ cell tumours, markers can be diagnostic. Which tumour markers should be done in suspected germ cell tumour?
AFP
b-HCG
(these are also good for monitoring)
LDH
115
What cancers give a raised AFP?
Germ cell tumour
Hepatocellular carcinoma
NB - it is normally present in very low levels as it is made my the liver and intestine
116
What could give you a false positive AFP?
Alcohol
117
What could give a raised b-HCG?
Germ cell tumour (high sensitivity for NSGCT and choriocarcinoma)
Pregnancy
Molar pregnancy
118
What could give you a false positive bHCG?
Cannabis
119
Why do you get raised LDH?
It is an enzyme released from cell necrosis, so represents a high cell turnover
120
High levels of LDH are a predictor of...
Tumour lysis syndrome
121
When should AFP. bHCG and LDH be measured?
At diagnosis - if high they can be used to measure outcome
Pre-orchidectomy, 24hr after and weekly after until normal
When normal, the cancer has likely gone.
122
Other than tumour markers, what investigations should be done in a patient with suspected testicular cancer?
Scrotal USS
Bloods
Imaging
123
What are the risk factors for testicular cancer?
```
Klinefelters syndrome (47XXY)
Downs syndrome (trisomy 21)
Testicular maldescent
Infertility
Infant hernia
Genetics
```
124
What are the 2 main subtypes of testicular cancer?
Seminoma
| Non seminomatous germ cell tumour
125
Describe the pathology of a seminoma
Cancer of sheets of uniform cells that resemble primitive germ cells
126
Describe the spread of a seminoma
Spreads locally to rete testis
Lympathically to para-aortic nodes
Rarely haematogenously
127
Describe the pathology of NSGCT.
| Give 2 examples
Cancers of a variety of appearances
- teratoma
- choriocarcinoma
These have an earlier onset and lower survival rate
128
Describe the spread of an NSGCT
Spreads locally to rete testis
Lymphatically to para-aortic nodes
Haematogenously to the lungs
129
What therapy do seminoma and NSGCT respond to?
Seminoma - responds well to chemo/radio
NSCGT - responds to cisplatin
They have a good prognosis generally!!
130
What are the complications of testicular cancer:
a) local
b) metastatic
c) non-metastatic
a) SVC obstruction, ureteric obstruction
b) brain, lung, liver, nodes
c) tumour lysis, pulmonary emboli
131
A 20yo male undergoing chemo presents with vomiting, diarrhoea, muscle cramps and weakness. What is happening?
Tumour lysis syndrome - rapid cell turnover causing rapid release of urate which is toxic (corresponds with high LDH)
132
What are the RF for tumour lysis syndrome?
Large, sensitive tumours eg. burkitts, sarcoma, germ cell
Renal impairment
Male <25
133
What electrolyte abnormalities are seen in tumour lysis syndrome?
Hyper K/urea/phosphate
| Hypo calcemia
134
What are the complications of tumour lysis syndrome?
- cardiac arrest
- renal failure
- DIC
135
How can tumour lysis syndrome be prevented?
1. Adequate hydration
2. Allopurinol and raspuricase
3. Alkalise urine
136
How can tumour lysis syndrome be managed?
1. Electrolyte replenishment
2. Haemodialysis
3. Allopurinol oral/IV
137
What are some complications of treatment for germ cell tumours?
- Tumour lysis syndrome
- Neutropenic sepsis
- Infertility
- Psychosexual issues
- Secondary malignancies
- Pulmonary fibrosis from belomycin
- CVS risk from nephrotoxic chemo
138
How might a testicular tumour present?
- Dragging sensation
- Scrotal pain
- Painless, unilateral mass
- Decreased testicular size
- Systemic (weight loss, fatigue etc)
- Advanced disease (urinary changes, mets)
139
Describe the ways in which breast cancer might present?
- Discolouration
- Oedema
- Peau d'orange (skin puckering from local invasion)
- Pagets disease (eczematous rash, bloody discharge)
- Nipple retraction
- Discharge
- Assymetry
140
What proportion of breast cancer pts have a family history?
10%
141
In terms of family history, what presentation is the strongest indicator of familial breast cancer?
First degree relative with bilateral breast disease for breast cancer
142
What are the RF for breast cancer?
- Family hx
- Oestrogen exposure (not COCP!)
- Previous benign breast disease
- Smoking/alcohol/obesity
143
What lymph node involvement indicated poor prognosis in breast cancer?
Supraclavicular
144
What examination findings may be present in someone with breast cancer?
- Breast changes
- Lymphadenopathy
- Respiratory compromise - consolidation
- Distant mets
145
What are the components of the 2WW triple assessment for breast cancer?
1. Clinical exam
2. Mammography (or MRI/USS)
3. FNA/core biopsy
146
What features on mammography would be suggestive of malignancy?
- Asymmetry
- Microcalcifications
- Mass (can detect before palpable)
- Architectural distortion
147
When is USS imaging helpful for breast cancer diagnosis?
Can distinguish between solid and cystic, especially if the lesion is non-palpable
148
When is MRI imaging useful for breast cancer diagnosis?
Patients who already have fibroadenomas or excessive lumpiness, in which palpation is very difficult
Used especially in high risk or younger patients
149
Why is FNA used as part of the triple assessment?
Allows doctor to obtain matieral for cytology and aspirate masses to look for blood
150
When is breast biopsy indicated? Describe the two types?
If FNA shows blood, or unsure about diagnosis
1. Excisional biopsy - removes entire abnormal area
2. Wire excision biopsy
151
What tumour marker can be done in suspected breast cancer? How useful is it?
What other cancer is it elevated in?
CA-153 - low specificity and sensitivity so not suitable for screening/diagnosis but can be good for risk of recurrence
Gynae cancers
152
What are the main pathological subtypes of breast cancer?
```
Ductal carcinoma (70%)
Lobular carcinoma (30%)
```
Both can be in situ or invasive
153
What is the most common location for breast cancer?
Left breast
| Upper outer quadrant and retroareolar region
154
What are BRCA1/2?
Tumour suppressor genes that have 'loss of function' mutations in familial breast cancer
155
What cancers involve BRCA1 mutation?
Breast cancer (most common in younger women)
Peritoneal cancer
Pancreatic cancer
Prostate cancer
156
What population have a high rate of BRCA1/2 mutations?
Ashkenazi Jews
157
What cancers involve BRCA2 mutation?
Male breast cancer
Prostate cancer
Pancreatic cancer
158
What are the characteristics of BRCA associated cancer?
- Younger age of onset
- Frequent bilateral occurence
- Worse histological features (aneuploidy, higher grade, proliferation)
159
Describe the ER status of BRCA1 and what this means for management
ER negative - this means tamoxifen won't work as its a hormone therapy for people with ER+ cancer
160
Describe the ER status of BRCA2 and what this means for management
ER positive so responds to tamoxifen
161
Describe breast screening for people with BRCA mutations
Annual screening from age 30
162
What is Li Fraumeni syndrome?
Autosomoal dominant mutation in p53 tumour suppresor gene, causing 100% risk of breast cancer
163
Describe breast screening for people with Li Fraumeni syndrome
Annual screening from age 20 to at least 49, followed by annual mammography
164
A patient has multiple hamartomas all over her skin. What is she at risk of?
Breast cancer
| patient has Cowden Syndrome
165
What is the name of the condition that give you 'spider veins', loss of motor control and an increased risk of breast cancer?
Ataxia telangectasia
166
What is HER2 status?
Presence of human epidermal growth factor 2. Overexpression of this receptor can lead to breast cancer and it is an indication of severity
167
How do you determine someones HER2 status?
FISH test
168
How are HER2 cancers treated?
Herceptin
169
What staging system is used in breast cancer?
TNM
170
What investigations for mets should be done:
a) in all patients
b) if suspected mets
a) CXR, USS, bone scan
| b) CT, MRI
171
What treatment is used for breast cancer?
Premenopausal - Tamoxifen (depending on ER status)
Postmenopausal - Aromatoase inhibitors (anastrozole)
Radiotherapy
Chemotherapy
SURGERY DOESNT HELP DUE TO MICROCALCIFICATIONS
172
What are the side effects of tamoxifen?
Increased risk of DVT and endometrial cancer
173
How can breast cancer be prevented in those with known risk factors?
Masectomy
Ovarian ablation (no oestrogen production)
Tamoxifen??
Surveillance and screening
174
What are the local complications of breast cancer?
Lymphoedema
| Pleural effusion
175
Where does breast cancer metastasise?
- Bones - do radioisotope scan
- Brain - do CT/PET (second most common after lung cancer)
- Liver
- Lung
176
What are the four components in management of bony mets?
1. Pain relief
2. Preservation of function
3. Skeletal stabilization
4. Local tumour control (release impingement)
177
What cancer is the main cause of spinal cord compression?
Breast cancer
178
What is the investigation of choice for spinal cord compression?
MRI (diagnosis is clinical but confirmation by MRI)
179
In SCC, what is the strongest predictor of treatment outcome?
Degree of pre-treatment neurological dysfunction
180
What cancer is most likely to give brain mets?
Lung cancer
181
How is spinal cord compression managed?
Steroids, etc etc
182
What are the symptoms of ovarian cancer?
```
ASYMPTOMATIC 'the silent killer'
Bloating, ascites and abdo pain
Vaginal bleeding after menopause
GORD
Early satiety
```
183
Why do patients with ovarian cancer sometimes present with PE?
Many of the ovarian cancers, particularly clear cell, are pro-thrombotic. This is known as Trousseaus syndrome
184
What are the RF for ovarian cancer?
MORE OVULATORY CYCLES (low parity, IVF, HRT)
Chemicals (talc, smoking)
Diet (lactose, fatty foods)
Family history
185
What is the biggest RF for ovarian cancer?
Family history
186
Which genetic mutations are involved in ovarian cancer?
BRCA1
BRCA2
HNPCC (mutation in MLH1/2)
187
What are some protective factors for ovarian cancer?
- Combined pill
- High parity
- Breastfeeding
- Hysterectomy
188
What investigations should be done for a patient with suspected ovarian cancer?
Bedside - urine dip, obs
Bloods - FBC, U&E, LFT, bone profile TFTs, tumour markers
Imaging - USS, CXR
189
Which tumour markers are used in ovarian cancer?
Ca-125
CEA
bHCG, AFP and LDH in younger women
190
How effective is Ca-125 as a tumour marker? When is it best used?
It is sensitive but non specific, as it released from inflammation of any peritoneal surface.
Best used in presentation of a women with a pelvic mass
191
What is the first line imaging for ovarian cancer and what does it show?
USS diagnosis:
- Cyst >5cm in perimenopausal women
- Any cyst in postmenopausal
192
What extra imaging can be done if USS is not adequate, and why are they each useful?
CT - determines operability
MRI - cyst surveillance
Explorative laparotomy
Endometrial sampling
193
Which investigation is contraindicated in ovarian cancer?
Paracentesis/needle biopsy - could cause seeding
194
How do you calculate the risk of malignancy index?
Ultrasound appearance x menopausal status x Ca-125
USS - max 3 of (multilocular, solid areas, bilateral, ascites, mets)
Men status - (perimenopausal 1, postmenopausal 3)
195
What RMI would give you high risk for ovarian cancer?
>250 (if >200 refer to specialist centre)
196
Why do more ovulatory cycles increase the risk of ovarian cancer?
Increased rate of ovarian repair by dividing cells, translating to an increased mutation rate
197
What are the two main types of ovarian cancer?
```
Type 1 (low histological grade)
Type 2 (high histological grade)
```
198
Give some examples of Type 1 ovarian cancer
Endometrioid
Mucinous
Clear cell
199
Give some examples of Type 2 ovarian cancer?
Serous
| Carcinosarcoma
200
Name 5 types of epithelial ovarian cancer (most common)
```
Serous
Mucinous
Endometrioid
Clear cell
Transitional (brenner)
```
201
Which epithelial ovarian cancer type is associated with:
a) UTI
b) endometriosis
c) colon cancer
d) beginning in fallopian tube
e) very aggressive course with no raised Ca125
a) Transitional
b) Endometrioid
c) Mucinous
d) Serous
e) Clear cell
202
90% of ovarian cancers are epithelial. What are the other 10%?
Sex cord stromal tumours (granulosa)
Sarcoma
Germ cell tumours (teratomas)
203
Which ovarian cancer subtype is most likely to occur in young women?
Teratoma
204
What is a krukenburg tumour?
A secondary tumour, usually met from GI tract, with a poor prognosis
205
Describe some local effects of ovarian cancer
```
Pleural effusion
Vaginal discharge
Bowel obstruction
Lymphoedema
Malignant ascites
```
206
What is malignant ascites?
Ascites that indicates malignant peritoneal involvement, aka a poorer prognosis
207
How is malignant ascites diagnosed and managed?
Diagnosis - clinical, USS/CT/MRI, cytology
Management - drainage
DO NOT USE DIURETICS
208
Which cancers are likely to cause dermatomyositis/polymyositis?
NSCLC, SCLC, breast, ovary, GI tract
209
A patient presents with gottrans papules, proximal myopathy and joint pain. What investigations should be done to diagnose this condition?
Dermatomyositis
BLOODS - LDH, CK, aldolase high
SPECIAL - muscle biopsy and EMG
210
How do you treat malignant dermatomyositis?
Treat tumour
Steroids
Azathioprine (immunosuppresant)
211
How can ovarian cancer be treated?
Surgical
Chemo - usually adjuvant, cisplatin
Radiation - localised
212
What is lead time bias?
The length of time between disease detection and its usual clinical presentation
ie. early diagnosis may not prolong life but it will seem like it because it is being picked up earlier
213
What is length time bias?
The fact that screening is more likely to detect slow growing tumours (as aggressive ones are not asymptomatic for long), and therefore it will seem like screening appears to improve survival
214
What are the 3 cancer screening programmes in the UK?
Breast cancer
Colon cancer
Cervical cancer
215
Describe breast cancer screening
| age, when, how?
Ages 50-70, every 3 years, mammography
216
Describe colon cancer screening
| age, when, how?
Ages 60-74, every 2 years, faecal occult blood and flexi sig
217
Describe cervical cancer screening
| age, when, how?
Age 25-29 every 3 years, biopsy for CIN
| Age 30-64 every 5 years
218
What is Meigs syndrome?
Triad of
- Benign ovarian tumour
- Ascites
- Pleural effusion
219
What is lights criteria?
A pleural effusion is likely to be exudative if
Pleural protein/plasma protein >0.5 (or LDH >0.6)
220
Describe the aspirate of an exudate?
```
Straw coloured/turbid
High protein content (>3g/dl)
High lymphocytes/neutrophils (malignancy/infection)
Low glucose
ph <7.2
```
221
Describe the aspirate of a transudate?
```
Clear
Few lymphocytes
Low protein (<3g/dl)
High glucose (>40mg/dl)
ph normal
```
222
What causes raised calcitonin?
Medullary thyroid
223
What causes raised ALP?
Osteosarcoma/bone mets/myeloma
224
What causes raised CEA?
Colorectal, ovarian
225
What causes a raised Ca199?
Pancreatic cancer
226
Patient >60 with symptoms of bowel cancer, what investigation?
Urgent 2WW colonoscopy
227
What is adjuvant therapy?
Chemo/radio given AFTER surgery
228
What is neoadjuvant therapy?
Chemo/radio given BEFORE surgery
229
What is radical therapy?
Chemo/radio with curative intent
230
What is brachytherapy?
Chemo/radio which is placed within or adjacent to the area requiring treatment.
231
Which cancers are the most metastatic?
BLT PR
| Breast, lung, thyroid, prostate, renal
232
Which cancer patients are particularly at risk of hypercalcemia and how do you treat it?
Multiple myeloma - give saline + pamidronate
233
How do you treat hypercalcemia generally?
SALINE
| If there is a metastatic cause, also give IV bisphosphates (eg. pamidronate)
234
A patient has a bad headache and is vomiting. They were diagnosed with small cell lung cancer 3 months ago. What investigation is the most urgent?
CT head - might have brain mets
235
If you suspect colon cancer, what is the next step?
ENDOSCOPY + COLONOSCOPY
| you need to do both if you are unaware where the bleeding/malignancy is coming from
236
What is extravasation of chemotherapy?
Accidentally putting chemo into the surrounding tissues rather than the vein, causing an erythematous rash around the injection site
237
What causes acanthosis nigricans?
- GI cancer
- PCOS
- Diabetes
- Thyroid dysfunction
