Breast Flashcards
What risk factors result in a >4 times relative risk of breast cancer?
Gene mutation
Lobular carcinoma in situ
Ductal carcinoma in situ
Atypical hyperplasia
Who can an USS help define a solid mass particularly well in?
Young women
Women with mammographically dense breasts
What investigation is needed for definitive diagnosis of breast cancer?
Image-guided core-needle biopsy
Ductal carcinoma in situ is usually not palpable. How does it appear on screening?
Malignant calcifications:
- Pleomorphic
- Casting
How is ductal carcinoma in situ diagnosed definitively?
Stereotactic vacuum biopsy
How does invasive lobular carcinoma spread?
Diffusely
How does invasive lobular carcinoma appear histologically?
‘Indian file’ pattern (not visible or palpable early)
What is always required following breast-conserving surgery?
Radiotherapy
What is a modified radical mastectomy?
Removes entire breast including:
- Overlying skin
- Axillary lymph nodes
What is preserved in a modified radical mastectomy and why?
Pectoralis major:
- Improve wound healing
- Better reconstruction
What are the indications for post-mastectomy radiotherapy?
> 3 nodes involved
Positive surgical margins
Tumours >5cm
What is the first line targeted drug therapy for malignant breast cancer?
Bevacizumab:
- Recombinant humanised monoclonal Ab against VEGF
How does Lapatinib work?
Dual inhibitor for EGFR and HER2 tyrosine kinases
When and with what is Lapatinib prescribed?
Advanced breast cancer and metastatic disease in those with HER+ disease and who have had previous therapy including: - An anthracycline and - A taxine and - Herceptin Prescribed with Capecitabine
What is Trastuzumab?
A HER2 inhibitor
How does cyclic mastalgia present?
Diffuse
Most intense premenstrual
Usually bilateral
How does non-cyclic mastalgia present?
Localised
Often persistent
Less responsive to treatment
How is mastalgia treated?
Evening primose oil
Tamoxifen
Topical NSAIDs
How does a breast cyst feel on examination?
Clearly defined
Soft
Mobile
Smooth
When is a breast cyst usually most tender?
Before menstruation
How can a breast cyst be diagnosed and treated?
FNA
How is mastitis treated?
Flucloxacillin 500mg PO every 6 hrs for 7 days
OR
Augmentin 625mg every 8 hrs for 7 days
When should antibiotics for mastitis be administered?
As soon as signs/symptoms:
- Fever
- Erythema
- Induration
- Tenderness
- Swelling
After treating mastitis, how should examination be carried out?
Examine every 3 days:
- Ensure response to therapy
- Ensure no abscess formation
How is an abscess in mastitis treated?
Drainage
What can cause non-puerperal mastitis?
Staph. aureus
Peptostreptococcus magnus
Bacteroides fragilis
How is non-puerperal mastitis treated?
Augmentin 625mg every 8 hrs for 7 days
OR
Cephalexin 500mg PO every 6 hours
What is chronic mastitis associated with?
Subareolar abscess
What can occur in chronic mastitis?
Periareolar fistulae
What cells are seen in an apocrine metaplasia of breast epithelial cells?
Eosinophils (in the lining of a cyst)
What is a galactocoele?
Palpable milk-filled cyst
What are galactocoeles associated with?
Pregnancy
Lactation
How are galactocoeles diagnosed and treated?
FNA
How do lipomas appear on mammography?
Thin border (they are palpable)
What is Mondor’s Disease?
Phlebitis
Subsequent clot formation in superficial breast veins
How does Mondor’s Disease look and feel?
Firm, vertical, cord-like structure
What is Mondor’s Disease associated with?
Breast trauma (eg. Surgery)
How long does Mondor’s Disease take to resolve?
8-12 weeks
What is the routine screening for breast cancer?
Mammography:
- Aged 50-70
- Every 3 years
- Picks up small and impalpable tumours
How many palpable lumps (breast cancer) are operable?
84%
What triple assessment occurs at the one stop clinic?
Physical examination of the breasts Breast imaging: - Mammogram +/or - USS FNA or Needle-core biopsy if lump found
If breast cancer is confirmed, what further investigations are done?
Staging CT
Breast MRI (especially if lobular)
?Bone scan
How is a ductal carcinoma in situ treated?
Breast-conserving therapies
OR
Mastectomy
What radiotherapy follows the treatment of a DCIS?
Radiotherapy of the whole breast:
- 40Gy in 15 sessions over 3 weeks
- Using 2 tangential fields
When can the breast alone be irradiated following breast conserving surgery?
Negative sentinel node biopsy (SNB)
Micromets. (>0.2mm but <2mm) in SNB
<4 nodes involved in adequate axillary node clearance
When is there a radiotherapeutic boost to the tumour bed following breast conserving surgery?
Women under age 54 on day of surgery
Posterior margin <1mm for invasive disease after full thickness excision
When is chest wall radiotherapy carried out following mastectomy?
Tumour size >5cm
>=4 nodes involved
Involved resection margins
T4 disease
When is the ipsilateral axilla irradiated following breast surgery?
> 1 positive macrometastases in sentinel node biopsy
Extensive ECS post-axillary clearance
Following neo-adjuvant treatment, when is a node considered involved?
If there is a pathological response (scarring) in the node
Where is 5 field radiotherapy directed?
Whole breast OR Chest wall
Axilla
Supraclavicular fossa
When is tamoxifen used in breast cancer?
ER+ disease
Preferred in premenopausal women
How long can tamoxifen be given?
10yrs
When is letrozole used in breast cancer?
Preferred in postmenopausal women
How long can tamoxifen be given?
5yrs
When is trastuzumab used in breast cancer?
HER+ patients (as measured by IHC or FISH)
How many breast cancer patients are HER+?
25-30%
For locally advanced breast cancer, when is radiotherapy considered?
As initial therapy for a primary inoperable tumour
Patients still inoperable after primary systemic therapy
Post-surgery for all patients
In locally advanced breast cancer, what can be done in patients with T>4b tumours?
0.5cm bolus following mastectomy
Increase skin does
What cancers tend to metastasise to the breast?
Lung Liver Bone Brain Skin
How are the symptoms of metastatic breast cancer treated?
Bisphosphonates
Radiotherapy
Chemotherapy
When not lactating, what is the structure of the mammary gland?
Secretory lobe -? Extralobular duct -> Lactiferous duct -> Lactiferous sinus -> Nipple
How many lobes are there per breast?
15-25
What is each lobe in the breast associated with?
A compound tubulo-acinar gland
What tissue is adjacent to lobes?
Dense fibrous tissue
Adipose tissue
What is the structure of the duct system?
Terminal ductules -> Intralobular collecting duct -> Lactiferous duct
What does the lactiferous duct expand into?
Lactiferous sinus
What is the lining of larger ducts?
Columnar
In secretory acini, what is the structure of the epithelium?
Cuboidal
OR
Low-columnar
What are the epithelial cells in secretory acini surrounded by?
Myoepithelial cells
What is the potential origination of breast lobes?
Modified sweat glands
What is the epithelium covering the nipple?
High pigmented keratinised stratified squamous epithelium
What is at the core of the nipple?
Dense irregular connective tissue with smooth muscle bundles
What is the lining of the ducts near the surface?
Stratified squamoues
What is the lining of the ducts deeper than the surface?
Stratified cuboidal
What is the lining of the deepest ducts?
Cuboidal (1 cell thick)
What glands are on the surface of the nipple?
Sebaceous glands
What happens to the structure of the breast during the luteal phase of menstruation?
Epithelial cells increase in height
Lumina of ducts increase in diameter
Small secretions
What happens to the structure of the breast following menopause?
Secretory cells degenerate so only ducts are left
Reduced fibroblasts:
- Reduced collagen and elastic fibres
What happens to the structure of the breast during the 1st trimester?
Elongation and branching of smaller ducts
Proliferation of gland epithelium and myoepithelial cells
What happens to the structure of the breast during the 2nd trimester?
Differentiation of secretory alveoli
Plasma cells and lymphocytes infiltrate connective tissue
What happens to the structure of the breast during the 3rd trimester?
Secretory alveoli mature
Development of extensive RER
What are the breast changes in pregnancy accompanied by?
Reduced amount of connective and adipose tissues
What is the main component of milk?
88% water
What are the main proteins in breastmilk?
Lactalbumin
Casein
What is the main carbohydrate in breast milk?
Lactose
What is present in small amounts in breast milk?
Ions
Vitamins
IgA
How are lipids secreted into the breast milk?
Secretory cell cytoplasm contains lipid droplets
As droplets bud off they are surrounded by some:
- Cytoplasm
- Plasma membrane
Apocrine secretion
How are proteins secreted into the breast milk?
Made in rER
Packaged in golgi and released via vesicles:
- Merge with apical membrane and release contents
Merocrine secretion
What is breast FNA cytology C1?
Unsatisfactory
What is breast FNA cytology C2?
Benign
What is breast FNA cytology C3?
Atypia, probably benign
What is breast FNA cytology C4?
Suspicious of malignancy
What is breast FNA cytology C5?
Malignant
What is the benefit of a vacuum assisted biopsy over a needle-core biopsy?
Large volume/mammotome
What is breast needle-core biopsy B1?
Unsatisfactory/Normal
What is breast needle-core biopsy B2?
Benign
What is breast needle-core biopsy B3?
Atypia, probably benign
What is breast needle-core biopsy B4?
Suspicious of malignancy
What is breast needle-core biopsy B5a?
Malignant:
- Carcinoma in situ
What is breast needle-core biopsy B5b?
Invasive carcinoma
What breast developmental diseases are benign?
Hypoplasia
Juvenile hypertrophy
Accessory breast tissue
Accessory niple
What inflammatory breast diseases are benign?
Fat necrosis
Duct ectasia
Acute mastitis/abscess
What non-neoplastic breast diseases exist?
Gynaecomastia Fibrocystic change Hamartoma Fibroadenoma Sclerosing lesions
How does sclerosing adenosis appear?
Radial scar/Complex sclerosing lesions
What breast tumours are benign?
Phyllodes tumours
Intraduct papilloma
What prescription drugs can cause gynaecomastia?
Cimetidine
5-alpha-reductase inhibitors
Spironolactone
Calcium channel blockers
Apart from prescription drugs, what else can cause gynaecomastia?
Exogenous/Endogenous hormones
Cannabis
Liver disease
When do the majority of breast fibrocystic changes occur?
Between the ages of 40-50
How do fibrocystic breast changes affect menstruation?
Menstrual abnormalities
Early menarche
Late menopause
How do fibrocystic breast changes present?
Smooth discrete lumps Sudden pain Cyclical pain Lumpiness Incidental finding/Screening
How do the cysts appear in fibrocystic breast changes?
1mm - Several cm
Blue domed with pale fluid
Usually multiple
Associated with other benign changes
How do fibrocystic cysts appear microscopically?
Cysts:
- Thin walled (maybe fibrotic)
- Lined by apocrine epithelium
Fibrosis
How are fibrocystic breast changes treated?
Exclude malignancy
Reassure
Excise (if necessary)
What is the following describing:
A circumscribed lesion composed of cell types normal to the breast but present in an abnormal pattern or distribution?
Hamartoma
How does a breast fibroadenoma present?
Screening
Painless, firm, discrete, mobile mass:
- “Breast mouse”
In who is a breast fibroadenoma most common?
African women
Peak incidence in 3rd decade
How does a breast fibroadenoma appear on USS?
Solid
How does a breast fibroadenoma appear macroscopically?
Circumscribed Rubbery Grey-white colour Biphasic tumour/lesion: - Epithelium - Stroma
How is a breast fibroadenoma treated?
Diagnose
Reassure
Excise
What are sclerosing breast lesions?
Benign, disorderly proliferation of acini and stroma
How does sclerosing adenosis present?
Pain, Tenderness Lumpiness/Thickening OR Asymptomatic
Between what ages does sclerosing adenosis present?
20-70 years
How big are radial scars?
1-9mm
How big are complex sclerosing lesions?
> =10mm
What is the pathology of a radial scar?
Stellate architecture
Central puckering
Radiating fibrosis
How do radial scars appear on histology?
Fibroelastic core
Radiating fibres containing distorted ductules
Fibrocystic change
Epithelial proliferation
Radiologically, what does a radial scar mimic?
Carcinoma
How is a radial scar treated?
Excise
Sample extensively by vacuum biopsy
What can cause breast fat necrosis?
Local trauma:
- Seat belt injury
- Frequently no history
Warfarin therapy
What is the pathology behind fat necrosis?
Damage and disruption of adipocytes
Infiltration by acute inflammatory cells
“Foamy” macrophages
Subsequent fibrosis and scarring
How can fat necrosis be treated?
Confirm diagnosis
Exclude malignancy
What do the following clinical features describe:
- Affects subareolar ducts (dilatation)
- Pain
- Acute episodic inflammatory changes (Periductal)
- Blood +/or purulent discharge
- Fistulation
- Nipple retraction and distortion
Duct ectasia
What is duct ectasia associated with?
Smoking
How is duct ectasia managed?
Treat acute infections
Exclude malignancy
Stop smoking
Excise ducts
What organisms are indicated in mastitis/abscess in duct ectasia?
Mixed organisms
Anaerobes
What organisms are indicated in mastitis/abscess during lactation?
Staph. aureus
Strep. pyogenes
What are the clinical features of a Phyllodes Tumour?
Age 40-50
Slow growing unilateral breast mass
What is the alternative name for a Phyllodes Tumour?
Cystosarcoma phyllodes
How does a Phyllodes Tumour appear?
Biphasic
Stromal overgrowth
What dictates the behaviour of a Phyllodes Tumour?
Stromal features
How does a Phyllodes Tumour tend to behave?
Local recurrence (if not adequately excised) Rarely metastasise
How does an intraduct papilloma present?
Age 35-60
Nipple discharge +/- blood
How does an asymptomatic intraduct papilloma appear at screening?
Nodules
Calcification
What size are intraduct papillomas?
2-20mm
How do intraduct papillomas appear?
Papillary fronds containing a fibrovascular core
Covered by myoepithelium and epithelium
Where do breast carcinomas arise?
Glandular epithelium of the terminal duct lobular unit
What type of cancer are breast carcinomas?
Adenocarcinomas
How is an in situ carcinoma confined?
Within basement membrane of acini and ducts
How much of the lobule is involved in atypical lobular hyperplasia?
<50%
How much of the lobule is involved in lobular carcinoma in situ?
> 50%
How does the intralobular proliferation of lobular in situ neoplasms appear?
Small-intermediate sized nuclei
Solid proliferation
Intracytoplasmic lumens/vacuoles
What receptors are lobular in situ neoplasms positive for?
ER+
Lobular in situ neoplasms are E-cadherin negative. What does this mean?
Deletion and mutation of CDH1 gene on Chromosome 16q22.1
When does the incidence of a lobular in situ neoplasm decline?
After menopause
How is a lobular in situ neoplasm managed if discovered on core biopsy?
Excision/Vacuum biopsy to exclude higher grade lesion
How is a lobular in situ neoplasm managed if discovered on vacuum/excision biopsy?
Follow up
Clinical trials
Ductal carcinomas in situ are unicentric. What does this mean?
Single duct system
What is the cytological appearance of a ductal carcinoma in situ?
Malignant epithelial cells
Where are ductal carcinomas in situ confined to?
Basement membrane of duct
What is Paget’s Disease of the Nipple?
High grade ductal carcinoma in situ extending along ducts to reach epidermis of nipple (still in situ)
How can ductal carcinoma in situ be classified?
Cytological grade
Histological type
Presence of necrosis (comedo)
What is the significance of a ductal carcinoma in situ?
Risk factor for invasive carcinoma
True precursor lesion
How is a ductal carcinoma in situ managed?
Diagnosis Surgery: - Mammographic follow-up in low risk DCIS - Adjuvant radiotherapy - Chemoprevention (trial)
What is a microinvasive breast carcinoma?
A ductal carcinoma in situ with invasion <1mm
How is a microinvasive breast carcinoma treated?
Treat as high grade ductal carcinoma in situ
What are the low grade breast carcinomas?
Tubular carcinoma
Lobular carcinoma
G1 ductal carcinoma
What are the intermediate grade breast carcinomas?
G2 ductal carcinoma
Pleo Lobular carcinoma
What is the main high grade breast carcinoma?
G3 ductal carcinoma
How is an invasive breast carcinoma generally defined?
Malignant epithelial cells which have breached the basement membrane
In terms of the UK population, how common is invasive breast carcinoma?
Most commonly diagnosed UK cancer
What reproductive history features increase the risk of breast carcinoma?
Early menarche (younger than 12 years) Late pregnancy (First pregnancy at age >30) Low/No parity Not breastfeeding Late menopause (Older than 55)
What lifestyle features increase the risk of breast carcinoma?
Overweight Low physical activity Alcohol Poor diet Smoking
How do NSAIDs affect the risk of breast carcinoma?
Lower it
In what populations is breast carcinoma more common?
White populations
Western Europe >
How does a first degree relative of breast carcinoma affect the risk?
Doubles risk
What syndrome is the TP53 gene associated with?
Li Fraumeni Syndrome
What cancers does TP53 mutation predispose to?
Childhood sarcoma Brain Leukaemia Adrenocortical carcinoma Early-onset breast
What cancers does BRCA2 predispose to?
Breast (inc. male)
Ovarian
Prostate
Pancreatic
What cancers does BRCA1 predispose to?
Breast
Ovarian
Bowel
Prostate
What syndrome does PTEN mutation cause?
Cowden’s Syndrome
What cancers does PTEN mutation predispose to?
Breast
GI
Thyroid (benign and malignant)
What syndrome does STK11/LKB1 predispose to?
Peutz-Jeghers Syndrome
What cancers does STK11/LKB1 mutation predispose to?
Breast
GI
Pancreatic
Ovarian
What syndrome does ATM mutation predispose to?
Ataxia telangiectasia
What cancers does ATM mutation predispose to?
NHL
Ovarian
Breast (in heterozygote carriers)
Where do breast carcinomas invade locally?
Stroma of breast
Skin
Muscles of chest wall
Where do breast carcinomas spread haematogenously?
Bone Liver Brain Lungs Abdominal viscera Female genital tract
What percentage of breast carcinomas are ER+?
80%
What percentage of breast carcinomas are progesterone receptors +?
67%
What percentage of breast carcinomas are HER+?
14%
What is the most common histopathological type of breast carcinoma?
Ductal
What intrinsic breast cancer sub-type is ER-, HER2- and Basal CK+?
Basal-like
What intrinsic breast cancer sub-type is ER- and HER2+?
HER2
What intrinsic breast cancer sub-type is ER- and non-epithelial?
Normal breast-like
What does ER receptor expression in breast cancer predict?
Response to anti-oestrogen therapy:
- Oophorectomy
- Tamoxifen
- Aromatase inhibitors (Letrozole)
- GnRH antagonists (Goserelin)
What is HER2?
Human Epidermal GF Receptor 2
What does HER2 expression in breast cancer predict?
Response to Trastuzumab (Herceptin)
What is the Nottingham Prognostic Index?
A histopathological prognostic index:
- 0.2 x tumour diameter (cm)
- Tumour grade (1 - 3)
- LN status (1 - 3)
What factors does the Adjuvant! Online prognostic index take into account?
Histopathology
ER
Clinical features
What factors does the PREDICT prognostic index take into account?
Histopathology ER Clinical features HER2 Mode of detection
How is a breast mass imaged in women ages <40 years?
USS
How is a breast mass imaged in women aged >40 years?
Mammography +/- USS
What is mammography designed to do?
Maximise contrast between the breast tissues whilst minimising radiation dose
What is the only method of breast imaging that reliably visualises microcalcifications (<0.5mm)?
Mammography
When is digital mammography better?
Dense breasts
Younger women
What are the advantages of digital mammography?
Better contrast Faster Fewer technical repeats Fewer films Easier image storage and transfer
How does glandular tissue appear on a normal mammogram?
Higher density
How do trabeculae appear on a normal mammogram?
Thin
Sharply defined
How do lymph nodes appear on a normal mammogram?
Oval/Horseshoe
Fatty hilum
25% have intramammary nodes (upper outer quadrant)
How do calcifications appear on a normal mammogram?
Bright white:
- Arterial
- Sebaceous glands (polo mints)
- Eggshell curvilinear (oil cysts)
What views are taken in mammograms?
Mediolateral oblique
Craniocaudal
Extended craniocaudal
What is the best single view in mammography?
Mediolateral oblique:
- Least foreshadowing
What does a craniocaudal view allow visualisation of?
Retromammary fat
Medial and most of lateral tissue
What do paddle view mammograms allow demonstration of?
Borders of mass
What are the BIRADS parenchymal patterns on a normal mammogram?
a = Nearly all fat b = Scattered fibroglandular densities c = Heterogeneously dense d = Extremely dense
If calcifications on a mammogram are in a cluster or segmental, what does this suggest?
Suspicious
If calcifications on a mammogram are scattered or diffuse, what does this suggest?
Benign
What MRI sequences help determine breast cancer morphology?
High resolution T1 and T2
What MRI sequences help determine breast cancer vascularity?
Dynamic contrast enhancement kinetics
What MRI sequences help determine breast cancer cellularity?
Diffusion-weighted imaging
What MRI sequences help determine breast cancer metabolism?
Spectroscopy
What MRI sequences help determine breast cancer oxygenation?
Intrinsic susceptibility-weighted MRI
What can cause false negatives on MRI?
Invasive lobular carcinoma
DCIS
Mucinous carcinoma
What can cause false positives on MRI?
Normal BBC Fibroadenomas Post-therapy changes Fat necrosis Intramammary nodes
In breast conservation surgery, how big do the margins need to be for equivalent disease free and overall survival when compared to mastectomy?
Clear margins >=1mm
What is the standard chemotherapy treatment following breast surgery?
Standard FEC100: - Fluorouracil, Epirubicin + Cyclophosphamide AND Taxane (eg. Docetaxel) \+/- Herceptin
What free-flap options are available for breast reconstruction?
Latissimus dorsi pedicled flap
Deep inferior epigastric artery perforator
Inferior gluteal artery perforator