CAN Week 2 (breast Cancer) Flashcards
(98 cards)
1
Q
Triple approach for a breast lump
A
Clinical examination - palpating of breast to determine nature and feeling of abnormality
US +/- mammogram (sometimes MRI)
FNAC/B (sample lesion- cutting out cells into needle/ small tissue biopsy)
2
Q
What clinical features would make you suspicious of a malignant lump
A
- irregular and hard
- fixed to the chest wall
- skin above is tethered
- palpable lymph nodes in axilla
- indrawn nipple / nipple involvement
- bone tenderness / pain
3
Q
What is fibroadenoma
A
A benign breast tumour
4
Q
Describe treatment of a breast lump
A
Surgery: wide local excision
Removal of lump with 2cm margin of normal breast tissue, preserving tissue
Sampling of axillary nodes same size
- specimens sent for histology for staging and grading
5
Q
Different cancer treatments
A
Surgery
Radiotherapy
Chemotherapy
- neo-adjuvant
- adjuvant (chemo and surgery combined)
- palliative
Immunotherapy
6
Q
What are antimetabolites
A
Interfere with metabolic pathways in DNA synthesis
- folate antagonist eg methotrexate, inhibits purine and pyrimidine synthesis
7
Q
What are alkylating agents eg cyclophosphamide
A
Cause chemical, covalent cross-linking of DNA leading to defective DNA replication
- dna cant be unwinded for replication
8
Q
What is the mode of action of platinum compounds eg cisplatin
A
Inhibition of DNA synthesis by cross linking guanine residues
9
Q
What are false substrates eg 5-fluoruracil
A
Pyrimidine analogues
Inhibits thymidylate synthase
Incorporated into DNA as false metabolites and lead to damage of the DNA
10
Q
What are anthracycline antibiotics eg doxorubicin
A
Interfere with nucleotide synthesis by intercalated between DNA strands, inhibiting topoisomerase and generating free radicals
11
Q
What are topoisomerase inhibitors eg etoposide
A
Inhibition of topoisomerase II prevents ligation of DNA, leading to breaks in the DNA strand
12
Q
What are microtubule inhibitors
A
Vinca alkaloids block the formation of the mitotic spindle
- taxanes stabilise spindle fibres
13
Q
Side effects of anticancer drugs
A
- inhibit all fast growing cells (gut, epithelia, hair loss) myelosuppression (bone marrow) for all except vincristine
This causes ulcers in the mouth and diarrhoea
Myelosuppression:
- anaemia
- decreased resistance to infection (neutropenic sepsis)
- increasing bleeding
14
Q
How can some of the side effects of anticancer drugs be overcome
A
Overcome reduced white counts with colony - stimulating factors
Prevents infections with antibiotics and antifungals
15
Q
Other side effects of anti cancer drugs
A
Nausea: common esp with platinum compounds
- use of anti-emetics
Hair loss
Infertility (due to the drugs being highly damaging to rapidly dividing cells eg sperm)
Cardiotoxicity with anthracycline antibiotics
16
Q
What is palliative care for cancer
A
Pain relief
Use strong opiods
- morphine and diamorphine
- oromorph for breakthrough pain
- constipation and nausea
- fentanyl patches
- syringe drivers
- hospice care
17
Q
Symptoms of ovarian cancer
A
Abdominal pain Persistent indigestion / nausea Bloating Pain during sex Altered bowel habits Back pain Vaginal bleeding Tiredness Unintentional weight loss
18
Q
How do targeted approach exploit biological weakness in tumours
A
Faulty genes
Faulty signalling systems
Tumour growth
Angiogenesis
19
Q
What do hormonal targets do
A
May antagonise hormones responsible to promoting tumour growth eg oestrogen in breast cancer
20
Q
Describe hormone based therapy in breast cancer
A
Oestrogen can stimulate the growth of metastasised cells (proliferation)
Tamoxifen is used as it blocks oestrogen as a selective oestrogen- receptor modulator (SERM) - reduces growth of oestrogen driven breast cancer. Used in ER+ breast cancer
- prevents bone loss via oestrogenic effects
21
Q
Why is breast cancer more common in older generation
A
Over expression of oestrogen is more common in older population and oestrogen can drive proliferation of cancer cells
22
Q
What are aromatase inhibitors eg anastrozole
A
An inhibitor that prevents peripheral conversion of androgens into oestrogen in post-menopausal women by the enzyme aromatase
23
Q
How is oestrogen produced before and after menopause
A
Before: produced in ovaries
After: produced via the conversion of androgens via aromatase enzyme
24
Q
What is HER2
A
Naturally present in low levels but can be over expressed in some cancers eg breast cancer
- more likely in older patients
- due to oncogene (ERBB2)
- affects gene transcription and cell cycle
25
What happens when HER2 becomes dysregulated
Over expression of some elements of DNA and dysregulation of cell cycle which leads to production of VEGF, COX2 and cyclins
26
What is trastuzumab
(MAB) large molecule approach
Selective to the HER2 receptor. (Targets it to slow down cell replication)
- manages early breast cancer and metastatic breast cancer with HER2 positive tumours
27
What is epidermal growth factor kinase eg erlotinib
- small molecule approach
| - has utility in some lung and pancreatic cancer if they over express the EGF receptor
28
Mode of action of epidermal growth factor receptor
Phosphorylates tyrosine residues which alters DNA transcription and severs the cascade signalling at that point
(Targeting the activity of the second messenger)
29
Tyrosine kinase activity
Philadelphia chromosome associated with chronic myeloid leukaemia (more than 90% of patients with myeloid leukaemia produce an abnormal Ph chromosome)
- Ph chromosome produces bcr-abl protein which has tyrosine kinase activity
30
Tyrosine kinase inhibitor
Tyrosine kinase leads to uncontrolled cell proliferation
- imatinib inhibits TK acitivity
- selective inhibitor is very effective for chronic myeloid leukaemia
- trials >90% pts with CML alive after 5 years
31
What are PARP inhibitors eg olaparib
PARP: poly (ADP-ribose) polymerase
- an enzyme which repairs DNA
- BRCA genes important in DNA repair at double strange breaks: PARP enzyme repairs single strand breaks
- BRCA gene mutations: inhibition of PARP leads to inability of cancer cells to repair double strand breaks, leading to cell death
- can be used in chemoresistant ovarian cancer
32
Proteasome inhibitor
Proteasome: cellular structures which degrade proteins
- some proteins kill cancer cells: pro-apoptosic factors
- inhibition of intracellular proteasomes alters the regulation of intracellular proteins
Eg bortezomib used in multiple myeloma
33
What is anti- VEGF
Vascular endothelial growth factor
| - VEGF secreted to promote angiogenesis (blood vessel growth to support metastasis)
34
What are the 2 anti- VEGF approaches
Bevacizumab: (MAB) - advanced colonic and breast cancer
Sunitinib: inhibits VEGF-associated receptor tyrosine kinase - advanced renal carcinoma
35
What is the cause of common genetic breast cancer
5-10% of breast cancer cases (BRCA)- due to highly penetrant germ line mutations in cancer predisposition genes
- up to half of these families will have mutations in BRCA1 or BRCA2
36
What are the different predisposition genes for inherited cancer
1) proto-oncogenes - genes whose action positively promotes cell proliferation
2) tumour suppressor genes- if not working you get uncontrolled cell growth
3) mutator genes : maintain the integrity of the genome
37
Syndromes caused by mutations in Porto-oncogenes
Multiple endocrine neoplasia type 2
MET- hereditary papillary renal carcinoma
38
Syndromes caused by mutations in tumour suppressor genes
PTEN: breast cancer, skin tumours, thyroid cancer
APC: familial, adenomatous, polposis coli
BRCA1/2: breast and ovarian cancer
TP53: young onset cancers particularly sarcoma and breast
39
What is Knudsons two hit hypothesis
Gene mutations may be inherited or acquired during a persons life
A cell can initiate a tumour only when it contains 2 mutant alleles
1st mutation: present in all the cells of the patient
2nd mutation: arises in a somatic cell in the organ in which the tumour develops (loss of heterozygosity) - tumour only develops after 2nd mutation
40
Syndromes caused by mutations in mismatch repair genes
(HMLH1 and hMSH2)
Colorectal, endometrial, ovarian, uterus or renal pelvis and brain
41
Patient groups likely to ask about cancer predisposition risk
People who present in primary care because of concerns about a family history
Affected parents about risk to siblings and offspring
42
Breast cancer clinical risk categorisation.
Low risk- less than 2x population lifetime risk of br ca
Moderate risk 2-3x population lifetime risk of br ca
High risk - greater than 3x population lifetime risk of br ca
43
Bowel cancer clinical risk categorisation
Low risk- risk of developing bowel ca <1 in 10
Moderate risk - risk of developing bowel ca 1 in 6 to 1 in 10
High risk - risk of developing bowel ca > 1 in 6
44
What is malignancy
Disordered growth and differentiation of normal tissues
- arises from genetic damage
- arises due to increases proliferation or reduced apoptosis
45
2 types of haematological malignancy
1) myeloid: including myeloproliferative disorders
- myelodysplasia
2) lymphoid : including lymphomas and immunosecretory disorders
46
Myeloid disorders (series of malignancies)
- acute myeloid leukaemia
- chronic myeloid leukaemia
- myeloproliferative disorders:
* essential thrombocythaemia
- polycythaemia rubra Vera
* myelofibrosis
* idiopathic hypereosinophilic syndrome
* systemic mastocytosis
- myelodysplasic syndromes
47
Lymphoid disorders
- acute lymphoblastic leukaemia
- chronic lymphocytic leukaemia
- plasma cell disorders eg myeloma
Non Hodgkin’s lymphomas eg
- Hodgkin’s disease
- diffuse large B NHL
- follicular lymphoma
- mantle cell lymphoma
- marginal zone lymphoma
- burkitts lymphoma
- T cell lymphomas
48
Myeloproliferative disorders
Present with an excess of mature cells in the blood:
- polycythaemia rubra Vera: excess red cells
- essential thrombocythaemia: excess platelets
- both PRV and ET may progress to myelofibrosis or acute leukaemia
- both PRV and ET have an underlying problem with the Janus kinase gene JAK2 (may cause stroke or heart attack due to abnormal clotting)
49
What is myelofibrosis
Excess bone marrow scarring due to abnormal megakaryocyte activity- leading to bone marrow failure
50
What is acute leukaemia
Leukaemia is malignancy of the bone marrow
- very rapid cell growth
- may fill marrow before spilling out into blood
- high WBC not always present
- present with bone marrow failure : anaemia, thrombocytopenia, neutropenia
- may arise from pre existing conditions eg myelodysplasia
51
Treating acute leukaemia
Delay in treatment makes infective complications worse
- commence chemo immediately
AML: strong iv chemo in short sharp bursts
- younger patients have better prognosis as can tolerate high dose better
- elderly may receive palliative chemo (gentler)
ALL= mix of strong chemo and persisting milder tablets ( for 3 years) to prevent relapse
52
Acute lymphoblastic leukaemia
Commonest malignancy of children
- peak incidence age 4-5
- may present with cytopenias or chest masses
- 90% can be brought into remission with infection chemo
- 85% cured
- higher replapse rates in older children and boys (testes and CNS are ‘sanctuary sites’)
53
Chronic myeloid leukaemia
Chronic leukaemias present with high white cells but not usually with bone marrow failure
- CML presents with:
- high WBC
- splenomegaly
- priapism
Due to t(9:22) = Philadelphia chromosome
- gene fusion produces BCR- ABL fusion protein
- treatment now involves specific inhibition of this tumour cell specific enzyme by the drug IMANTINIB
54
Chronic lymphocytic leukaemia
Relatively common (3000 cases/year in UK)
- increases with age
- majority of patients die of unrelated conditions
- treatment is only required for troublesome symptoms, bulk disease or marrow failure
- reproductive rate of most CLL is less than ordinary blood cells, but defective apoptosis means they don’t die normally
- usually present incidentally on a routine FBC for other reasons, but may present with lymphadenopathy
55
How do you diagnose chronic lymphocytic leukaemia
High lymphocyte count
- smudge cells on blood film
- appropriate cell surface markers on lymphocytes
- hypogammaglobulinaemia (low antibody levels) common association but not diagnostic
- may have lymphadenopathy or splenomegaly
- may have immune disturbance
- may have marrow suppression
56
Chronic lymphocytic leukaemia prognosis (using Binet staging system)
Stage A: lymphocytes is only: 10 years
Stage B: lymphocytosis + 3 areas lymphadenopathy : 5 years
Stage C: lymphocytosis +LN + Hb<10 : 2 years
57
Non Hodgkin’s lymphoma
Grouping of a variety of different disease entities all showing tumour growth of lymphoid cells
- 30% occur outside lymph nodes
- more common in the elderly
- some may be related to viruses eg EBV, HTLV, HHV8, HIV
- some related to chemical exposure
- some related to sunlight exposure
- B symptoms pr lymphadenopathy are the usual clue to lymphoma
58
What are lymph nodes
The police stations of the bodies immune system
- they may swell as part of the normal immune response
- they may swell if the lymph system is invaded by the metastatic solid tumour
- they can swell in lymphoid malignancy
59
What are B symptoms
Weight loss > 10% in 6 months
Drenching night sweats - enough to change clothes
- fevers >38c
60
What is Hodgkin’s disease
A subtype of the non Hodgkin’s lymphomas
- related to EBV infection
- 2 age peaks - teens / early twenties and elderly
- age peaks may be related to where the EBV has integrated in the lymphocyte DNA- closer or further away from the proto- oncogenes
- presents with B symptoms + continuous nodal spread
- the bulk of the tumour in HD are ‘normal’ white cells reacting to the presence of tumour cells
61
What is stage of lymphoma
Defines the extent
- spread is not the death sentence it is in other tumours as lymphocytes naturally circulate
- worse stage implies but does not guarantee worse prognosis
- assess stage by CT scan to locate lymphadenopathy and extra lymphatic spread + bone marrow to assess marrow involvement
- bone marrow biopsy is not a diagnostic test for lymphoma
62
What is grade of lymphoma
Non Hodgkin’s lymphoma is a diverse group of diseases
Grade is a shorthand way of telling how aggressive the condition is in a particular patient
Low grade = slow, grumbling
High grade = fast, aggressive
63
Immunosecretory disorders
Myeloma
Asymptomatic myeloma
MGUS (monoclonal gammopathy of uncertain significance)
Localised plasmacytoma
Waldenstroms macroglobulinaemia
Cold haemagglutin disease (CHAD)
Amyloidosis
64
List some normal antibodies
IgD is expressed by newly mature B lymphocytes
IGM clears pathogens from circulation
IgG clears pathogens from tissue fluid
IgA prevents pathogens invading mucosal surfaces
IgE protects against parasites
65
What are paraproteins
Normal plasma proteins can be analysed by electrophoresis
Normal antibodies occur as a polyclonal smear on EP
Paraprotein = monoclonal antibody, causing a spike in the normal globulin pattern
Urine paraprotein = isolated light chains - bence-jones protein
66
What are the 2 out of 3 conditions that must be met to diagnose myeloma
1) plasma cells in marrow >10%
2) detectable paraprotein in blood or urine
3) lyric lesions on skeletal survey
Skeletal survey = series of plain XR. It is not the same as a bone scan
67
Diagnosing myeloma
```
Disease of the elderly
Think of this diagnosis whenever you see a patient with:
- anaemia
- high ESR
- back pain
- unexpected renal failure
- unusual fractures
```
3000 cases per year in uk, poor prognosis
68
What is waldenstroms macroglobulinaemia
Disease of the elderly
- clue is IgM paraprotein
- marrow shows sparse infiltrate of lymphoplasmacytoid lymphocytes. Ie midway between lymphocytes and plasma cells
- disease bulk is not normally a problem - health risk is hyper viscosity due to paraprotein
- if IgM paraprotein has haemolytic activity the disease is CHAD (cold HaemAgglutinin disease)
69
What is hyperviscosity syndromes
Due to excess plasma proteins (fibrinogen, IgM, IgA etc) or extreme polycythaemia
- blood is stickier so does not flow as easily (treacle compared to water)
Symptoms are: fatigue, headaches, confusion
May progress to stroke , heart attack
- anaemia lowers viscosity (less RBC to impede blood flow) so correcting this with transfusion is dangerous
- severe cases treated by plasmapheresis to remove protein
70
What is myelodysplasia
Disordered maturation of blood cells in bone marrow
- any or all cell lines may be affected eg isolated thrombocytopenia or pancytopenia
- easy to diagnose if a chromosomal abnormality is detected or if disorganisation of marrow is severe
- may be hard to distinguish from reactive marrow changes eg from rheumatoid arthritis, chronic infection or other systemic illness
Can progress to acute leukaemia with time
71
Dietary factors causing cancer
Obesity / weight gain (insulin and insulin related growth factors)
Red and processed meat (nitrates + AA = nitrosamines; N-nitroso compounds; high cooking temperatures - heterolytic amines)
Saturated and animal fats- lung, colorectal, prostate and breast
Alcohol- aerodigestive tract, liver and breast
Protective: fruit, veg, phytochemicals, fibre, dairy, calcium and vit D
72
Describe undernutrition in cancer patients
At the time of diagnosis approx 75% of cancer patients are undernourished with a significantly lower fat free mass than healthy controls
- patients with highest weight loss are those with cancer of oesophagus, stomach and larynx
73
What is cachexia
Chronic hypermetabolic state characterised by rapid weight loss and anorexia
Generally seen in cancer patients, certain infectious disease and chronic alcoholics
Prevalence depends on type of malignancy seen in up to 85% of gastrointestinal, pancreatic, colorectal and lung cancer patients at diagnosis
Duration, malignancy and number of anatomic sites tend to cause hyper metabolism
74
What is nutrition therapy for cancer patients
Essential to increase the likelihood of completion of cancer treatment and improve quality of life
Support adequate energy and nutrient intake with the aim to:
- reverse undernutrition and weight loss that have already occurred
- prevent weight loss and promote weight gain
- enhance immune function.
- reduce mental and physical fatigue
75
What is enteral nutrition support
Provided when patients are expected to or have not received adequate nutrition for 7 days
Small bowel feeding administered with pump over 8-20 hours
Formulas come in a variety of energy densities
76
What is parenteral nutrition support
Used when GI tract is not functional, accessible or safe to use eg colon cancer
Central or peripheral vein
Energy requirement predicted from estimated daily energy expenditure
77
What is the lymphatic system
Part of immune system
Have both superficial and deep lymphatic vessels and nodes
Superficial drains into deep vessels
78
What is the lymphatic system composed of
Lymphatic vessels (thin walled and have valves) found throughout the body. They emerge from the:
- lymphatic plexuses (small lymphatic vessels)
- lymphatic capillaries (in extracellular space)
- lymph nodes (filter the lymph)
- lymphocytes (circulating cells)
- lymphoid organs (where lymphocytes are produced eg spleen, thymus)
79
What is the role of the lymphatic system
- part of immune system
- drains interstitial fluid from the tissues of the body and empties it into venous system
- absorbs and transports fat from food (so via intestines)
80
Describe lymphatics of breast
Most lymph of the lateral breast drains into axillary lymph nodes
Most lymph of the medial breast drains into parasternal lymph nodes or to other breast
Most lymph of the inferior breast drains into abdominal lymph nodes
81
What does postural drainage involve
Person is placed in a number of different positions - so each lobe of the lung is drained
- requires gravity so in some positions the lungs need to be lower than the hips
- chest physiotherapist involves gentle banging or percussion of the lungs whilst in a drainage position
- removes mucus etc from the lungs
- helps relieve some of the symptoms in someone with eg COPD, cystic fibrosis
- potential problems are eg acid reflux - if that leads to someone choking and getting it in their lungs, can then lead to infection
82
Difference between differentiation of benign and malignant
Benign: resembles cell of origin
Malignant: failure of differentiation
83
Difference between behaviour of benign and malignant
Benign: expansive; grows locally
Malignant: expansile and invasive; may metastasise
84
What are the 2 main groups of lymphomas
Hodgkin’s disease
- non Hodgkin’s lymphoma : the most common and important of these are the lymphocytic lymphomas
85
Clinical features and behaviour of lymphoma
Most present clinically with lymphadenopathy : lymph node enlargement, localised or generalised
Some may also infiltrate liver (hepatomegaly), spleen (splenomegaly) or bone marrow
Bad prognosis types may diffusely infiltrate other organs
86
Define myeloma
A tumour of mature plasma cells. Presents with bone tumours, osteolytic, painful but with interesting systemic effects
87
Summarise lymphomas
Lymphomas are malignant diseases derived from lymphoid cells
- 2 main types: Hodgkin’s disease and non hodgkins lymphomas
- main effects are replacement of lymph nodes and infiltration of other tissues
- myeloma is a bone marrow disease based on plasma cells
88
What are astrocytomas
Brain tumours that behave in a malignant manner by local invasion but do not metastasise
89
What are embryonal tumours
Derived from embryonic remnants of primitive ‘blast’ tissue
Mainly in young children
Highly malignant
Spread early and widely by lymphatic and veins
Sensitive to chemo
Formerly rapidly fatal, chemo has revolutionised prognosis
90
Name some different embryonal tumours
Nephroblastoma (Wilms tumour) - in kidney, most common
Neuroblastoma - in adrenal gland, derived from primitive adrenal medullary precursors
Rarer:
Retinoblastoma - retina; often bilateral; genetic basis
Medulloblastoma - cerebellum
Hepatoblastoma- liver
91
What are teratomas
Tumours derived from primitive germ cells which retain the capacity to differentiate along all 3 primitive embryological lines. Hence teratomas should contain representative of ectoderm, mesoderm and endoderm
As they are of germ cell origin, they mainly occur in the ovary and testis
92
Describe teratomas of the ovary
Young women
Benign
Invariably cystic (benign cystic teratoma)
Cyst contains keratin (dermoid cyst of ovary)
Skin, hair, bronchial and gut epithelium, thyroid, neuroglia, bone, cartilage
Good prognosis
93
Describe teratomas of the testis
Young men
Painless swelling of testis
Malignant
Malignancy varies according to type
Spreads early via blood stream (lung and liver etc)
Chemo has revolutionised prognosis
Tumour markers are important in management
94
What suggests a mass might be malignant rather than benign
Fixation of the mass to deep tissues
95
What 4 things are true about benign tumours
1) can cause illness and death
2) can increase pressure on adjacent vital structures in the brain
3) can secrete hormones
4) can convert to malignant tumours
96
What can colorectal cancers present as
1) intestinal obstruction
2) fresh bleeding per rectum
3) severe anaemia of unknown cause
4) weight loss
5) hepatomegaly
97
Which tumours produce the tumour marker: alpha-fetoprotein
1) hepatocellular carcinoma
| 2) germ cell tumours
98
Which tumours produce harbour alterations in the MYC oncogene
1) burkitts lymphoma
| 2) neuroblastoma
