Breast pathology 2 Flashcards
What are the metastatic tumours to the breast?
- Carcinoma
- bronchial
- ovarian serous carcinoma
- clear cell carcinoma of the kidney
- malignant melanoma
- soft tissue tumours
- leiomyosarcoma
Define breast carcinoma
A malignant tumour of breast epithelial cells
Where does breast carcinoma arise?
Glandular epithelium of the terminal duct lobular unit (TDLU)
It is an adenocarcinoma but is usually just referred to as ‘breast carcinoma’
What are the precursor lesions of breast carcinoma?
- ductal
- epithelial hyperplasia of usual type
- columnar cell change (+/- atypia)
- atypical ductal hyperplasia
- ductal carcinoma in situ
- lobular
- lobular in situ neoplasia
- atypical lobular hyperplasia
- lobular carcinoma in sity
- lobular in situ neoplasia
What is in situ carcinoma?
confined within basement membrane of acini & ducts
Cytologically malignant but non-invasice
What is in situ carcinoma a precursor for?
Non-obligate precursor of invasive carcinoma
How is in situ carcinoma classified?
Lobular
Ductal
What are the two classifications of lobular in situ neoplasia?
Atypical lobular hyperplasia (ALH) <50% of lobule involved
Lobular carcinoma in situ (LCIS) >50% of lobule involved
Describe intra-lobular proliferation of characteristic neoplastic cells
- small-intermediate sized nuclei
- solid proliferation
- intra-cytoplasmic lumens/vacuoles
- ER positive
- E-carherine negative (deletion and mutation of CDH1 gene on Chr 16q22.1)
Lobular in situ neoplasia is frequently ______ and ______.
Lobular in situ neoplasia is frequently multifocal and bilateral.
When does the incidence of lobular in situ neoplasia decrease?
After menopause
What is the significance of lobular in situ neoplasia?
relative risk of invasive carcinoma
What is the management of lobular in situ neoplasia?
LN discovered on core biopsy
- proceed to excision or vacuum biopsy to exclude higher grade lesion
LN discovered on vacuum or excison
- follow up
- clinical trials*
What is intraductal proliferation?
Epithelial hyperplasia of usual type
- Columnar cell change (lesion)
- Columnar cell change with atypia
- Atypical ductal hyperplasia
- Ductal carcinoma in situ
What is the RR of progression of intraductal proliferation to invasive carcinoma?
- epithelial hyperplasia of usual type= 2 x RR
- Atypical ductal hyperplasia = 4 x RR
- Ductal carcinoma in situ (low grade) = 10 x RR
Ductal carcinoma in situ are characteristically ________ (_____ duct system)
Ductal carcinoma in situ are characteristically unicentric (single duct system)
Describe the cytology of DCIS
Cytologically malignant epithelial cells confined within basement membrane of duct
What is cancerisation
DCIS involving lobules
What is paget’s disease of the nipple?
DCIS involving the nipple skin
Is paget’s disease invasive?
No still in situ carcinoma
How is DCIS classified?
- cytological grade
- histological type
- presence of necrosis
what is the significance of DCIS?
risk factor for progression of invasive carcinoma
How is DCIS managed?
- diagnosis
- surgery
- trials of mammographic follow-up in low risk DCIS
- adjuvant chemotherapy
- chemoprevention
- endocrine therapy
What is microinvasive carcinoma?
Rare, high grade DCIS with invasion of <1mm
How is microinvasive carcinoma treated?
as high grade DCIS
What is invasive breast carcinoma?
Malignant epithelial cells have breached the basement membrane
Infiltration of normal tissues
What is the risk with invasive breast carcinoma?
Metastasis and death
What are the risk factors for carcinoma of the breast?
- age
- reproductive history
- hormones
- previous disease
- geography
- lifestyle
- genetics
What are the reproductive history risk factors for carcinoma of the breast?
- age at menarche
- age at first birth
- parity
- breastfeeding
- age at menopause
What hormones affect risk of carcinoma of the breast?
Endogenous
Exogenous
- OCP
- HRT
How increased is the risk of breast cancer with OCP use, how long does it take to return to population risk
1.0 -> 1.24
10 years
What aspects of lifestyle contribute to risk of carcinoma of the breast?
- body weight- higher oestrogen from fatty tissue conversion
- physical activity (protective)- lowers oestrogen levels
- alcohol consumption- higher oestrogen levels
- diet- high fat intake
- NSAID- reduces risk slightly
- smoking
first degree Affected by breast cancer _______ relative risk
doubles
What are the cancer syndromes contributing to genetic risk of breast cancer?
- BRCA1- breast/ovarian predispostion
- BRCA2- breast/ovarian predisposition
- TP53- li fraumeni syndrome
- PTEN- cowden’s syndrome
- STK11/LKB1- peutz-jeghers syndrome
- ATM- ataxia telengiectasia
What is the lifetime risk of breast cancer with BRCA1 AND 2 mutations?
45-64%
What is the net 10 year survival from carcinoma of the breast??
78%
What is the commonest female cancer
Invasive breast carcinoma
Describe the natural history of invasive breast carcinoma?
- local invasion (T)
- stroma of breast
- skin
- muscles of chest wall
- lymphatics (N)
- regional draining lymph nodes
- Blood-borne (M)
- bone, liver, brain, lungs, abdominal viscera, female genital tract
Which lymph nodes does the breast drain to?
Internal mammary
Intramammary
Sentinel nodes
Axillary nodes
Atypical nodes
Infraclavicular nodes
Supraclavicular nodes
Cervical nodes
How can invasive breast cancer be classified morphologically?
Type
Grade
How can invasive breast cancer be classified through gene expression profiling?
Intrinsic sub-types
How can invasive breast cancer be classified through hormone receptor expression?
Oestrogen receptor
Progesterone receptor
HER2
How is breast carcinoma graded?
Objective assessment of;
- tubular differentiation (1-3)
- nuclear pleomorphism (1-3)
- mitotic activity (1-3)
Score 3,4 or 5 = grade 1
Score 6 or 7 = grade 2
Score 8 or 9 = grade 3
What are the intrinsic breast cancer subtypes?
- basal like: ER-, HER2-, Basal CK+
- HER2: ER-, HER2+
- Normal breast-like: ER-, non-epithelial
- Luminal A: ER+, low proliferation
- Luminal B: ER+, high proliferation
- Luminal C: ER+, high proliferation
__% of breast cancers are ER positive
__% of breast cancers are PgR positive
__% of breast cancers are HER2 positive
80% of breast cancers are ER positive
67% of breast cancers are PgR positive
14% of breast cancers are HER2 positive
What does ER expression predict?
Response to anti-oestrogen therapy
- oophorectomy
- tamoxifen
- aromatase inhibitors (letrozole)
- GnRH antagonists (goserlinin [zoladex])
What is HER2?
Human epidermal growth factor receptor 2
- HER 2 overexpression and amplification seen in ~__%
- HER 2 overexpression or amplification predict response to ________ (________)
- HER 2 overexpression and amplification seen in ~15%
- HER 2 overexpression or amplification predict response to trastuzamab (herceptin)
What are the predictive and prognostic factors for invasive carcinoma?
ER (PgR)
HER2
What is the nottingham prognostic index?
- 0.2 x tumour diameter (cm)
- Tumour grade (1-3)
- Lymph node status (1-3)
