Breast ca Flashcards
definition of breast ca
Primary invasive breast cancer
malignancy originating in the breasts and nodal basins
invasive indicates that the malignancy has penetrated past the basement membrane of the duct or lobule of the breast and has spread to the surrounding tissues - but has not spread to other organs
RF for breast ca
related to FH 5-10%
age
uninterrupted oestrogen exposure
- (nulliparity ie never pregnant
- 1st preg >30yrs
- early menarche
- late menopause,
- HRT after being on for 3-5yrs
- not breastfeeding
lifestyle
- obesity in post-menopausal women (androgens converted to oestrogens in fat)
- low fibre and high fat diet
- smoking
- alcohol
genetic BRCA1/2 mutation
- autosomal dominant inherited gene mutation
- increased risk of breast acncer (70%) and ovarian cancer
- BRCA +Ve women develop breast cancer approx 15-20 years earlier than women w/o mutation
- BRCA mutations found un 5-10% of all women with breast cancer
past breast cancer - metachronous rate = 2%, synchrononous rate = 1%
positive history of breast conditions (eg fibrocystic change, fibroadenoma), with cellular atypia
previous radiation treatment in childhood
positive FH - affected 1st degree relative
ethnic origin
radiation exposure
high socioeconomic class
benign breast disease
increased breast density
pathophysiology of breast ca
non-invasive ductal carcinoma in situ (DCIS) is premalignant - seen as microcalcification on mammograph (unifocal/wide-spread)
non-invasive lobular CIS rarer and multifocal
medullary affect younger people
colloid/mucoid effect elderly
60-70% breast cancers are oestrogen receptor positive = better prognosis
approx 30% over express HER2 = aggressive disease and poor prognosis
histology of breast ca
in situ carcinoma - ductal or lobular carcinoma in situ
invasive - most common is ductal carcinoma or no special type
others - lobular (10-15%), mucinous, medullary papillary, adenoid cystic, tubular and Paget’s disease of nipple
genetic diseases associated with breast ca
Li-Fraumeni syndrome (Sarcoma, Breast, Leukemia and Adrenal Gland cancer syndrome (SBLA))
- Autosomal dominant inherited mutation of the p53 tumor suppressor gene (TP53)
- Loss of heterozygosity: one abnormal copy of the TP53 gene is inherited → second allele is somatically mutated or deleted → unregulated cell proliferation and cancer
- Multiple malignancies at an early age: breast cancer, osteosarcoma, leukemia, lymphoma, brain tumor, adrenocortical carcinoma
Peutz-Jeghers syndrome
epidemiology of breast ca
non-invasive lobular carcinoma in situ (CIS) is rarer than non-invasive ductal carcinoma in situ (DCIS)
invasive ductal carcinoma is most common
most common malignancy in women - 30% of all malignancies in women
lifetime risk of developing BC in USA is 12% (1in8 women in USA will develop invasive breast cancer)
peak incidence - post menopausal
2nd leading cause of cancer death of women in the US
rare in men
peak incidence 40-70yr
incidence increasing, mortality falling
sx of breast ca
can be benign things
concerned if
- spontaneous
- single duct
- blood stained
breast lump - usually painless
change in breast shape
axillary lump
nipple inversion
weigh loss, bone pain, paraneoplastic syndromes - metastatic
confusion - metastatic - from brain abscesses, raised Ca secondary to bone met or malignant meningitis (cancer met to meninges)
inflammatory breast ca
Rapid onset breast warmth
erythema
peau d’orange
w/o definite mass
early involvement of the axillary nodes
The characteristic pathological finding is dermal lymphatic invasion by carcinoma, which can lead to obstruction of lymphatic drainage causing the clinical appearance of erythema and oedema.
can occur in association with infiltrating ductal or lobular, medullary and large cell carcinomas
signs of breast ca
Notes
firm breast mass - may be associated with axillary lymphadenopathy, skin changes, and nipple discharge
breast mass - elicit whether the mass is tender, if changes in size/character of the mass and whether the character of the mass have been affected by the menstrual cycle
dont always present with a new breast mass - many cancers are diagnosed on the basis of mammographic abnormalities eg linear or pleomorphic microcalcifications
occult breast cancer is found in approx 0.3% of women diagnosed with axillary lympadenopathy
nipple discharge may be watery, serous, milky or bloody. Bloody is classically associated with neoplasm, may be related to intraductal papilloma. Relation of nipple discharge to malignancy appears to be affected by age
Axillary nodal involvement is the most reproducible prognostic factor for primary invasive breast cancer. Clinical assessment of nodal status can often be inaccurate; therefore, imaging (e.g., CT scan) can be used to evaluate lymph node involvement
brief signs of breast ca
breast lump - hard, irregular, may be fixed
peau d’orange
skin tethering
fixed to chest wall
skin ulceration
paget’s disease of nipple (DCIS infiltrating the nipple) - eczematous, ulcerated, discharging nipple
Ix for breast ca
asymptomatic pts may be diagnosed after abnormal calcifications and/or architectural distortion are noted on a routine screening program
Edit
1st investigation to order
mammogram
for initial screening and diagnosis of breast cancer
screening starts at 40yrs
they use XR, breast compressed between 2 plates, 2 views: oblique and craniocaudal
Diagnostic mammography should be used to evaluate symptomatic adult patients or as follow-up to evaluate abnormal findings on screening mammography.
Digital breast tomosynthesis (DBT) is a mammographic technique - decreases number of false-positives
If a mammogram does not discover an abnormality in patients who have a clinically detected breast mass, additional imaging (e.g., ultrasound, or MRI in high-risk patients) should be performed for further evaluation.
mammogram findings in breast ca
an irregular spiculated mass
clustered microcalcifications
linear branching calcifications
parenchymal distortion
overlying skin thickening
enlarged axillary nodes
US for breast ca
adjunct to mammography - differentiate cysts from solid masses, evaluate masses that are not sufficiently assessed by mammogram, eval axillary lymph node involvement, monitor for tumour response during neoadjuvant chemo
provide more accurate measurements
if breast US confirms cancer - do axilla US to help guide treatment
US findings of malignancy
hypoechoic mass
irregular mass with internal calcifications
enlarged axillary lymph nodes
distal acoustic shadowing - sound distortion and diffraction by tumour
surrounding halo - from oedema and tumour infiltration
MRI for breast ca
recommended as supplementary to screening mammography in high risk pts eg BRCA carriers
can be useful for cases which are equivocal on mammogram and ultrasound and where there is a clinical concern that the disease may be multifocal
findings suggestive of malignancy
- heterogeneously enhancing area and significant architectural distortion
biopsy for breast ca
required for definite diagnosis
core biopsy preferred - enables differentiation between pre-invasive and invasive disease, less likely to be associated with inadequate sampling and enables assessment of receptor status
fine needle aspiration - obtain rapid diagnosis of breast malignancy, minimally invasive - cytology of discrete breast lumps and drainage of cysts
Trucut needle biopsy: Core biopsy with a spring-loaded firing device with a wide-bore needle. This allows for a histological diagnosis.
histology for invasive ductal carcinoma - cords of tumour cells among associated glandular formation, include varying degrees of fibrotic response
histology for invasive lobular carcinoma - small tumour cells that invade past the basement membrane of the lobules and form an ‘indian file’ between collagen bundles; typically appears as well differentiated tumour cells that exhibit tubule formation
medullary carcinoma - well delineated border surrounding high grade tumour cells and a prominent lymphocytic infiltrate
mucinous carcinoma - histology shows cords of epithelial cells that are dispersed in mucinous matrix
metaplastic carcinoma - histology shows well-defined border and mixture of poorly differentiated ductal, mesenchymal, and other epithelial (such as squamous) elements
hormone receptor testing for breast ca
determination of the oestrogen receptor and progesterone receptor status should be performed once a diagnosis of invasive breast cancer has been made
OR and PR status is assayed using immunohistochemistry assay
HER2 receptor testing for breast ca
determination of the oestrogen receptor and progesterone receptor status should be performed once a diagnosis of invasive breast cancer has been made
OR and PR status is assayed using immunohistochemistry assay
HER2 receptor testing
Patients diagnosed with breast cancer (early stage or metastatic disease) should have at least one tumour sample tested for HER2 expression
Immunohistochemistry (IHC) assay is used for HER2 testing, in combination with fluorescence in situ hybridisation (ISH) assay to detect HER2 gene amplification.
IHC scoring ranges from 0 to + 3+ as determined by intensity of staining, and percentage (>10%) of contiguous and homogeneous positive tumour cells. HER2 status can be classified as follows, based on the IHC score: HER2 negative (IHC score 0 or 1+); equivocal (IHC score 2+ [requires reflex testing with ISH assay]); or HER2 positive (IHC score 3+)
Assuming no apparent histopathological discordance observed by the pathologist, HER2 status can be classified as negative or positive, based on concurrent IHC and ISH results.
sentinal node biopsy in breast ca
radioactive tracer injected into tumour - nuclear scan identifies sentinal node and node is biopsied to detect spread
diagnostic not treatment
decreases needless axillary clearances in lymph node -ve patients
Patent blue dye and/or radiocolloid injected into periareolar area or tumour.•A gamma probe/visual inspection is used to identify the sentinel node.•The sentinel node is biopsied and sent for histology ± immunohisto chemistry; further clearance only if sentinel node +ve. Sentinel node identified in 90%. False -ve rates <5% for experienced surgeons.
tests to order if confirmed breast ca
CT chest, abdo, pelvis - look for metastasis
bone scan - for bone met - breast cancer likes to go to bone
pre-invasive cancer, ie ductal carcinoma in situ, wont spread so dont have to sample the lymph nodes.
triple assessment for breast ca
history/examination
radiology - US for <35yrs, mammography and US for >35yrs
histology/cytology - fine needle aspiration/core biopsy - US guided core biopsy is best for new breast lumps
- cystic lump
- residual mass - core biop
- clear fluid - discharge and reassure
- bloody fluid - cytology
- solid lump
- malignant - plan radiotherapy
- clear fluid - disgard and reassure
need concordance between the 3 forms of assessment - if you feel something that is too dense to be a cyst but radiologist doesnt find anything, you need to go and tell them where you felt it, or do a clinical core biopsy
staging and bloods for breast ca
staging - CXR, liver US, consider isotope bone scan, CT (brain or thorax)
bloods - FBC, UE, Ca, bone profile, LFT, ESR
Ix for inflammatory breast ca
aggressive and often have involved nodes, these patients are staged to assess whether they have metastases.
o First line investigations will include blood tests to assess liver function and bone health. Ca 15-3 is a tumour marker which can be used to assess response to treatment.
