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REGUB Path - Malignant Breast Disease (i) (Risk factors (genetics…
REGUB Path - Malignant Breast Disease (i)
Intro
most common non skin cancer in women
2nd most common cause of cancer death in women
incidence increasing
Ire has high incidence + mortality (lifetime risk = 1 in 9)
aetiology mainly unknown, there are some major risk factors (hormonal + genetic)
Risk factors
female gender
age (70% are over 50)
hormonal (sporadic)
nulliparity + 1st birth after 35 y/o - take reproductive hx
HRT
relative risk increased by 1.02/yr of tx
increased carc incidence, but less evidence of increased mortality
risk persists for 5 yrs after cessation
type of prep important (present/type of progestogen)
early menarche + late menopause (excess oestrogen exposure)
OCP or DepoProvera (injectable) - v small risk
mechanisms
oestrogen: prolif of pre-malignant + malignant cancers
oestrogen metabolites: mutations or generate DNA damaging free radicals
most occur in post menopausal women + are ER +ve
radiation
post-menopausal obesity
dietary fat
alcohol
race
geographic influence (migrants tend to adopt pattern of host country)
genetics (hereditary)
12%
AD but variable penetrance (% of carriers that get carc ranges from 30-90%)
BRCA1
TSG on chromo 17
high risk of ovarian carc (30%)
carriers are susceptible to other cancers (colon, prostate, pancreas)
breast carc tend to have medullary features, ER-ve, p53+ve, Her -ve, no visible on mammogram
BRCA2
TSG on chromo 13
higher risk for male breast carc
carriers are susceptible to other cancers (colon, prostate, pancreas)
breast carc tend to be similar to sporadic - seen on mammogram
Li-Fraumeni syndrome (germline p53 mutation)
Cowden's disease
multiple hamartomas
PTEN mutation on 10q
suspect familial syndrome if...
bilat breast carc
breast + ovarian carc
male breast carc
breast carc in <40y/o
multiple 1st degree relatives with breast carc
atypical epithelial hyperplasia
x1.5-2 relative risk with usual type
x4-5 relative risk with atypia
double the risk if +ve family hx
carc of contralat breast or endometrium
Cell of origin
most are ER +ve
originate from ER expressing luminal cells
precursors are ER +ve
ER -ve
myoepithelial cells or previously ER +ve luminal cells that have lost ER expression
unknown precursor
Classification
non-invasive (carc in situ)
confined to epithelium, don't penetrate BM
rarely if ever met
DCIS
increasing incidence
mammographic abnormality (micro calcifications or other changes)
DCIS component often found a/w invasive cancers
precursor lesions of invasive cancers
malignant cells in TDLU (terminal duct lobular units)
low/intermediate/high grade a/w risk of progression to invasive
architectural subtypes
comedo - high grade with central necrosis
solid
cribriform - punched out spaces, papillary, micropapillary
spectrum of disease
atypical ductal hyperplasia -> low grade DCIS -> high grade DCIS
accumulation of genetic mutations
factors predicting risk of invasion
margins
size
patient age
grade
80% of high grade become invasive after 10 yrs if untxed (compared to 40% or intermediates + 10% of low)
management
wide local excision +/- radiotx
mastectomy
chemo-prevention (tamoxifen - SERM) = use of agents for inhibition/delay/reversal of carcinogenesis before invasion
recurrence risk factors
grade
size
margins
LCIS
invasive - tumour cells penetrate BM + invade stroma
Paget's disease
malignant cells arising from DCIS + extending up the lactiferous ducts into nipple skin without crossing BM
erythematous eruption with scale crust
may be mistaken for eczema
can be detected by nipple bx or cytologic preparations of the exudate
inflamm cancer
any type of breast cancer that has infiltrate dermal lymphatics
red swollen oedematous breast
a/w poor prognosis
mammographic signs of malignancy
densities
calcifications: small, irregular, clustered, linear, branching
architectural distortion
asymmetry
angiogenesis
supports tumour growth + spread
mets to breast uncommon
lymphoma
melanoma
carc (lung, endometrium