1
Q
what is the commonest cause of cancer death in women worldwide?
A
breast cancer
2
Q
what factors increase the risk of developing breast cancer?
A
- family history
- age (30-80yrs risk increase)
- diet
- social class
- nulliparity
- exposure to oestrogens
- early menarche
- late menopause
- low parity
- HRT
3
Q
what part of the breast do most malignancies occur?
A
upper outer quadrant
4
Q
what is overdetection?
A
the identification of abnormalities that were never going to cause harm, abnormalities that don’t progress, that progress slowly to cause symptoms or harm or that resolve spontaneously
5
Q
what factors increase the chance of overdetection?
A
- Increasing use of high resolution diagnostic tool increases the risk of overdetection
- The more tests that are ordered the more likely you are to detect disease which may be problematic if early detection doesn’t improve patient outcome
6
Q
what are the 2 mechanisms that lead to over definition/
A
- Lowering the threshold for risk factor without evidence that doing so helps people long term
- Expanding disease definitions to include patients with ambiguous or very mild symptoms
7
Q
give an example of overdefinition?
A
changing what is classed as high blood pressure from being >150 to >130
8
Q
what is overselling?
A
moving the line between what is normal from abnormal so people with milder symptoms get diagnosed.
9
Q
what is overtreatment?
A
Overtreatment occurs when best scientific evidence demonstrates that a treatment provides no benefit for the diagnosed condition
10
Q
what is screening?
A
detection of pre-symptomatic disease in the ‘well’.
11
Q
what criteria must a screening programme meet?
A
- common or severe disease
- recognizable early stage that responds better to treatment
- non-harmful test which is acceptable to the screened population and has acceptable false positive and false negative rate
- cost effectiveness
12
Q
in the UK who is breast screening offered to?
A
all women aged 50-70 every 3 years
13
Q
Describe the process of mammogram imaging of the breast?
A
- 2 view mammography of each breast
- tumor identified as soft tissue density or micro calcification within the breast
14
Q
what happens at an assessment clinic for breast cancer?
A
history and examination
ultrasound and biopsy
if not benign refer to surgeon
15
Q
what affect does mammography have on breast cancer mortality?
A
reduces mortality by about 25% because of early diagnosis
16
Q
what is expected costs or benefits?
A
sum of costs/benefits weighted by their probabilities
17
Q
what is risk aversion?
A
preference for a certain but less good outcome to an uncertain but better expected outcome
18
Q
what are the benefits of mammography?
A
- less deaths from breast cancer
- more conservative surgery
- reduced need for chemotherapy
- improved breast awareness
- reassurance
- improved symptomatic breast care driven by screening
19
Q
what are the performance characteristics of screening?
A
sensitivity specificity receiver operating characteristic curve area under ROC curve positive predictive value negative predictive value
20
Q
what are the disadvantages of mammography?
A
- increased anxiety
- time off work
- transport cost
- unnecessary recalls and benign biopsies
- treatment of cancer and precancerous state in women who die prematurely from other causes
- false reassurance
- risks such as radiation exposure, pain, psychological stress, over diagnosis of benign breast conditions
21
Q
what are the reasons for delayed presentation of breast cancer in primary care?
A
- in younger women often manifests as localised nodality rather than discreet lump
- usually present 3 months after first noticing lump
- vague, non-specific symptoms
- psychological and behavioural factors: associated with pain, suffering, death, fear, anxiety
- socio-demographic and ethnicity factors: working or retired, age, culture (not enough female doctors)
22
Q
what is involved in the triple assessment of breast cancer?
A
- clinical exam and history
- imaging-mammography and/or ultrasound if over 35
- sampling-core biopsy or fine needle aspiration cytology
23
Q
describe the role of MRI in imaging breast cancer?
A
high sensitivity for breast cancer and extent of disease
low specificity and PPV
24
Q
describe the role of fine needle aspiration cytology in breast cancer diagnosis?
A
no longer commonly used but can assess enlarged axillary or supraventricular nodes visualised on US
differentiate between solid and cystic lesions
25
what would suggest that a breast lump is benign?
younger women
painful
enlarge before menstruation
26
what would suggest that a breast lump is malignant?
older women
| painless
27
on ultrasonography how would cysts show?
as transparent objects
28
how would a benign lesion show on ultrasonography?
tend to have well demarcated edges (cancers have indistinct outlines)
29
how can blood flow to a lesion be imaged and what would it show?
doppler
malignant lesions have greater blood flow than benign
bad specificity and sensitivity
30
what is aspiration cytology?
removal of cells by means of needle and syringe
31
describe the process of core biopsy of the breast?
- local anaesthetic containing adrenaline is put into skin and breast tissue
- 7-8 mins a small incision is done, cores of tissue removed from mass
- cutting needle technique, image guided
32
what should happen if malignancy is confirmed?
all women should proceed to surgery within 2 weeks of diagnosis
33
what factors affect breast cancer patient survival?
- tumour size
- tumour grade
- LN involvement
- lymphatic/vascular invasion
- distant spread at time of presentation
- screen detected to do better than symptomatic
34
what are the 2 pathological variants of breast cancer?
ductal (70%)
| lobular
35
what is breast cancer grading dependent on?
tubule formation
mitotic activity
nuclear pleomorphism
36
what pre-invasive changes occur in breast cancer?
ductul or lobular carcinoma in situ
37
what score is used to predict prognosis (10yr survival) in breast cancer?
nottingham prognostic index
(used following surgery)
either excellent, good, moderate or poor)
38
what is the formula of the Nottingham prognostic index?
NPI = [0.2 X S] + N + G
S=size of index lesion
N=node status
G=grade of tumour
39
describe the T part of the TMN staging system?
```
primary tumour
T0 = no detectable primary tumour
T1 = less than 2cm
T2=2-5cm
T3= >5cm
T4=tumour any size that extend into skin or chest wall
```
40
describe the N part of the TMN staging system?
```
Nodal status
N0=no nodes involved
N1=mobile axillary nodes
N2=fixed axillary nodes
N3=involved supra or infraclavicular nodes
```
41
describe the M part of TMN staging system?
metastatic status
M0=no metastases
M1=spread to distant organs
42
what increases the risk of lymphoedema?
- more lymph node removed
- multiple surgeries to chest
- radiation therapy-greater the therapy area greater the risk
- chemotherapy?
- overweight
- infection of injury->inflammation
43
what are the 4 common genes that can lead to increased risk?
BRCA 1 and 2
CHEK2
FGFR2
44
what is BRCA1 and BRCA2
tumour suppressor gene, involved in cell cycle regulation
mutation to BRCA allow damage to DNA to go unrepaired and an accumulation of DNA mutations leading to cancer
BRCA2 has a role in DNA repair
45
describe the pathology of breast cancer?
arises from epithelial cells of the milk ducts and reproduce their histological features in a variety of patterns
identifiable precursor in situ stage, confined within the basement membrane and is truly localised and detected by micro calcification on screening mammogram
most common: infiltrating ductal carcinoma
10% have familial breast cancer
3% have detectable mutations in BRCA1, BRCA2 and TP53
46
histologically what are the benign features of a breast lump?
- cells retain features similar to normal tissue
- normal mitosis-cells not dividing rapidly
- cells retain cohesion-no spread into normal tissue or metastasis
- expanding pattern of growth
47
histologically what are the malignant features of a breast lump?
- continuous growth - cells lose features of normal tissue
- abnormal rapid mitosis-DNA loss pleomorphism
- loss of cohesion and spread via lymphatics or blood vessels
- invasive growth
- neoangiogenesis
48
what are the types of pre-invasive tumours?
Ductal carcinoma in situ (DCIS)
| lobular carcinoma in situ/lobular neoplasia (LCIS)
49
what is DCIS?
doesn't usually present with clinical findings
detected on screening mammogram (calcification)
incidental finding on biopsy
high, intermediate or low grade predicts rate of progress to invasive cancer
50
what is rate of progression of LCIS?
Rate of progression uncertain
| usually slow
51
what are the types of invasive tumours?
```
invasive ductal (90%)
invasive lobular (8%)
rare: mucinous, tubular. secondary tumours presenting as breast lumps-malignant melanoma, renal, lymphoma
```
52
describe invasive ductal tumour?
hard lump, skin tethering
easily seen on mammogram
histological grade 1,2,3
53
describe invasive lobular tumour?
may be thickening or skin tethering but may have minimal symptoms
often difficult to see on mammogram and often multiple tumours in same or both breasts
histological grade 1 or 2
54
give examples of causes of benign lumps?
cyst
fibroadenoma
phylloides tumours (rare)
55
describe cysts?
- very common 40-50yrs
- flat, smooth, fluctuant, tense and painful
- frequently multiple and bilateral
- common with HRT
- rare >60yrs
- Rx-US scan aspirate if painful
- natural history-most resolve with time or menopause
56
describe fibroadenoma?
- mobile discrete nodule most frequent in 15-30yrs
- evolution 5% get bigger 30% smaller over 2 yrs
- need good core WBN sample to be sure of diagnosis
- only remove >30mm or if patient wishes
57
describe phylloides tumours?
rare
resembles fibroadenoma
locally aggressive/borderline malignant
58
what are the clinical features of breast cancer?
symptomatic rather than screen detected cancer present with:
- 80% painful
- if painless-cyclical/noncyclical
- increasing mass
- nipple discharge
- dimpling
- skin tethering
- oedema/erythema
59
What should you ask as part of a breast history?
- lump site and size
- deformity
- nipple inversion
- nipple discharge
- nipple itch
- pain related to menstruation, oral contraceptive, HRT
- FH of breast or ovary cancer
- last mammogram
60
what should you look for on examination?
- size of lump
- shape of lump (round, oval, sausage/ridge)
- surface of lump (smooth, lobulated, bi lobed, hard, nodular)
- consistency (soft, tense, fluctuant, hard, rubbery)
- contour of lump edge (well, poorly defined)
- colour of overlying skin (normal, inflamed, thickened, P de orange, puckering)
- temperature of skin
- tethered-overlying skin or deep structures
- lymph nodes (axillary, supra-clavicular)
61
what are the 2 referral routes to breast clinic?
- by GP-2 week referral
| - recalled by breast screening
62
describe the process of GP referral to treatment?
- patient aware of symptoms
- GP visit
- GP examines and history
- urgent referral with 2 week wait
- seen by surgical staff
- investigation and biopsy
- MDT discussion
- admit for surgery
- findings discussed again at postop MDT
- oncologist appointment for radiotherapy, chemotherapy, hormonal therapy
- follow up
63
describe the principles of treatment of metastatic breast cancer?
- may require endocrine therapy, CT, RT
- not curative
- consistent with good quality of life
- little benefit added by endocrine therapy and CT combination
- inclusion of anti-HER2 antibodies in CT has produced an advantage
- prolonging treatment can delay relapse but at expense of toxicity
- serial use of intermittent courses of the different endocrine and CT starting with least toxic and most effective treatment is most consistent
64
what patients is chemotherapy used in?
patients who lack features of hormone responsive disease who fail to respond to endocrine therapy
65
what is used as part of adjuvant chemotherapy?
cyclophosphamide
methotrexate
fluorouracil
66
describe other receptor targeting therapy?
more intensive therapy using FEC: 5-FU, epirubicin, cycloposphamide=more effective
third generation therapy combines FEC and docetaxel is standard
a quarter of breast cancers express epidermal growth factor receptor 2 (EGFR) target for monoclonal antibody trastuzumab (herceptin)
67
describe adjuvant hormonal therapy in premenopausal women?
- anti-oestrogen drugs (reduction can be achieved via pituitary downregulation using GnRH such as goserelin or leuprorelin)
- tamoxifen (mixed agonist and antagonist of oestrogen action on the oestrogen reception. selective ER alpha antagonist. effects progesterone receptor)
- SERM-fulvestrant
- no advantage in oestrogen receptor negative tumours
- synthetic progesterone such as megestrol acetate have effect on breast tumour cells through PR and impact on pituitary/ovarian, adrenal/pituitary axis (pre and post menopausal)
68
describe adjuvant hormonal therapy in post menopausal women?
- aromatase inhibitors-block aromatase enzymes which are responsible for circulating oestrogens derived from adrenal precursors. limit synthesis of oestrone and oestrone sulphate.
- sequential therapy-tamoxifen then aromatase inhibitor for 5 yrs
69
when is adjuvant radiotherapy given?
after lumpectomy
large high grade primary tumour
proximity to surgical margins
LN mets
70
what is the purpose of adjuvant radiotherapy?
reduce risk of local recurrence of tumour
without radiation this risk is between 40-60%
with radiation risk is 4-6%
71
what treatment would follow surgery due to invasive cancer who have had local excision?
radiotherapy
72
what treatment would a woman who has had surgery with lymph node involvement have?
further surgery or radiotherapy to the axilla
73
after surgery what treatment would follow for oestrogen receptor positive tumours?
endocrine therapy
74
after surgery what treatment would follow for HER2 positive tumour?
trastuzumab for 12 months
75
after surgery what treatment would follow for women with large or high grade tumours?
Chemotherapy
76
what causes peau d'orange?
lymphoedema of the skin tethering of the sweat ducts giving a dimpled appearance to the swollen skin
77
what is the usual course of action in younger women with breast cancer?
neoadjuvant chemotherapy to reduce tumour size followed by surgery and radiotherapy
78
What is the usual treatment for older women
may be treated with hormonal therapy alone if cancer expresses oestrogen receptor and/or progesterone receptor
79
what is oncoplastic breast reduction?
removal of a quarter or more of the breast tissue with rearrangement of residual tissue to a normal cosmetic shape
80
what is the surgical option for a breast lump >5cm?
mastectomy
81
what is a sentinel node?
the node to which a cancer first drains to
82
how is lymph node staging carried out?
removing sentinel node, axillary sampling or clearance for all invasive tumours
83
what is the surgical option for a lump with a mas of <5cm and not fixed?
remove lump plus a border of normal tissue (lumpectomy/wide local excision)
84
what is a breast abscess?
painful build-up of pus in the breast caused by an infection. It mainly affects women who are breastfeeding
85
what age group of women are most affected by breast infection (abscess and infection)?
15-45 especially those lactating
86
what is the most frequent pathogenic cause of breast infection?
staphylococcus aureus
87
what is fibrocystic disease of the breast?
benign (noncancerous) condition in which the breasts feel lumpy. Fibrocystic breasts aren't harmful or dangerous, but may be bothersome or uncomfortable for some women
88
what is intraductal papilloma?
small, benign tumor that forms in a milk duct in the breast. These tumors are made of gland and fibrous tissue as well as blood vessels. They most commonly occur in women between ages 35 and 55. There are no known risk factors
89
what is lipoma of the breast?
A lipoma is a benign tumor of the breast. fat tissue is the main component of a lipoma.
a lipoma is a pocket of fat that is encapsulated by a thin fibrous capsule.
90
what is duct ectasia?
Duct ectasia of the breast, mammary duct ectasia or plasma cell mastitis is a condition in which occurs when a milk duct beneath the nipple widens, the duct walls thicken and the duct fills with fluid.
This is the most common cause of greenish discharge. Mammary duct ectasia can mimic breast cancer.
Block 32 GI and surgery
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