Breast Disease Flashcards
What are the normal histological features of normal breast tissue?
- Ducts and acini arranged into lobules
- Dual layer of epithelium
- Inner layer cuboidal
- Outer layer of myoepthilium to allow contraction
- Surrounded by adipose tissue
What physiologial changes are seen in breast tissue throughout a womans life?
Pre-puberty: few lobules (identical to male)
Menarche: increased number of lobules, increased volume of interlobular stroma
Menstrual cycle: follicular lobules develop to prepare for pregnancy, after ovulation see proliferation and stromal oedema, with menstruation a decrease in lobule size
What does breast tissue look like in pregnancy?
- Less fibromuscular stroma
- Lobules contain colostrum - white + fluffy
- Will go back to normal afterwards
What physiological changes are seen in breast tissue with increasing age?
- Decrease in number and size of terminal duct lobular units
- Interlobular stroma is replaced by adipose tissue - fattier breast compared with younger woman
- makes examining breasts easier if older
How can breast conditions present?
- Pain
- Palpable mass
- Nipple dicharge
- Skin changes
- Lumpiness
- Mammographic abnormalities (picked up on screening)
What does cyclical and diffuse breast pain suggest?
Often phsycological or linked to periods, can’t do much to treat the pain
What does non-cyclical and focal breast pain suggest?
could be:
- ruptured cysts
- injury
- inflammation
- only occasionally would cancer cause pain
What breast conditions can cause a palpable mass?
- Normal nodularity
- Invasive carcinoma
- Fibroadenomas
- Cysts
Most worrying if hard, craggy and fixed
What would densities on a mammmogram suggest?
- Invasive carcinoma
- Fibroadenoma
- Cysts
What would calcification on a mammogram suggest?
- Ductal carcinoma in situ (DCIS)
- May be benign
Briefly explain the principles of the breast screening programme (UK)
Mammogram performed on wome aged 47-73 invited every 3 years
Increases detection of small invasive tumours and in situ carcinomas
What is the most common type of benign breast tumour?
Fibroadenoma
What age group do breast fibroadenomas most commonly appear in?
<30 years
What is a phyllodes tumour?
A very rare breast neoplasm
Although very similar to a fibroadenoma, the stromal component is hypercellular with increased pleomorphism and mitotic activity
Presents mostly in women in 6th decade
What is acute mastitis?
- Usually a Staphylococcus aureus infection from cracked nipples from breastfeeding
- Breast is erythematous and often pyrexic
- May produce abscesses
How is acute mastitis treated?
Expressing milk and antibiotics
What occurs in breast fat necrosis?
- Destruction of fatty tissue surrounded by macrophages and inflammatory cells
- Often have a history of trauma or surgery
- Can mimic carcinoma clinically and on mammograms
What is the most common type of breast lesion?
Fibrocystic change
What changes are seen in benign epithelial fibrocystic breast disease?
- May present as a mass or on mammogram
- Often dissapears after fine needle aspiration
- but can come back as cyst refills
- Histology - see cysts, fibrosis and apocrine metaplasia (pink cells) and large dilated ducts
What are breast fibroadenomas? a.k.a breast mouse
- Present as a mass, usually mobile or mammographic abnormality
- Can be multiple and bilateral
- Can grow very large and replace msot of the breast
How do fibroadenomas appear macroscopically?
Well circumscribed, rubbery, greyish/white
Can easily be scooped out in surgery without removing surrounding tissue
What do brest fibroadenomas look like histologically?
A mix of stromal and epithelial elements
What is gynaecomastia?
- Enlargement of male breast
- Unilateral or bilateral
- Often seen at puberty and the elderly
- Caused by relative decrease in androgen effect or increase in oestrogen
- Can mimic male breast cancer if unilateral
- No increased risk of cancer
Why does gynaecomastia occur in most neonates?
Due to circulating maternal and placental oestrogens and progresterone
What are some of the causes of gynaecomastia?
- Transiet gynaecomastia: affects more than 1/2 boys in puberty as oesterogen production peaks earlier than testosterone
- Klinefelter’s syndrome: XXY chromosome
- Oestrogen excess: if patient has liver cirrohosis oestrogen cannot be effectively metabolised
- Gonadotrophin excess: functioning testicular tumour e.g. Leydig and Sertoli tumours, germ cell tumours
- Drug related: spironolacton,e chlorpromazine, digitalise, cimetidine, alcohol, marijuana, heroin, anabolic steroids
What is the most common type of breast cancer?
Adenocarcinoma
In what location do approximately 50% of breast cancers occur?
Upper outer qudrant
List some risk factors for developing breast cancer
- Female
- Uninterrupted menses
- Early menarche (<11 yrs)
- Late menopause
- Reproduction - parity and age of 1st full term pregnancy >30 years higher risk
- Breast feeding though to be protective
- Obesity and high fat diet
- Exogenous oestrogens (HRT, long term OCP use)
- Breast density - harder to detect if more fibrous
- Geography - high incidence in US and Europe
- Previous breast cancer or atypical change
- Radiation
Which genes are associated with 25% of familiar breast cancers? Explain how they can cause cancer?
BRCA1 and BRCA2
Both are tumour suppressor genes - repair damaged DNA therefore mutation in gene allows proliferation of tumour
What gene is mutated in Li-Fraumeni syndrome?
p53
(The guardian of the genome)
What is an in situ carcinoma?
A neoplastic population of cells limited to ducts and lobules by the basement membrane
Does not invade into surrounding vessels, so cannot metastasise or kill the patient
What is ductal carcinoma in situ a problem if it doesn’t have ability to metastasise?
- Non obligate precursor of invasive carcinoma
- Presents as mammographic calcifications or a mass
- Can spread through ducts and lobules extensively (without invading other tissues)
- Shows central necrosis with calclification (comedo)
What is Paget’s disease?
- Unilateral red and crusing nipple
- Atypical and malignant cells can grow up the epidermis extending to the nipple
- Suggests malignanc elsewhere in breast
- Eczematous or inflammatory conditions of nipple need biopsy to exclude Paget’s
How does invasive carcinoma differ from DCIS?
Neoplastic cells have extended beyond the basement membrane into the stroma, can invade into vessels and metastasise to lymph nodes and other sites
What is peau d’orange?
A symptom of malignant tumour causing the skin of the breast to pull in
Suggests involvement of lymphatic drainage of skin
What are the classifications of invasive breast carcinoma?
Invasive Ductal Carcinoma:
- 70-80%
- Well differentiated - tubules lined by atypical cells
- Poorly differentated type - sheets of pleomorphic cells
- 25-50% survival 10 years
Invasive Lobular Carcinoma:
- 5-15%
- Inflitrating cells in single file, lack cohesion
Other types: tubular, mucinous
What does invasive ductal carcinoma look like histologically?
No organisation
Lots of tubules and glands in stroma
What does invasive lobular carcinoma look like histologically?
- Single banded line
- Can be hard to spot
- Doesn’t create much change to the stroma
What does a mucinous carcinoma look like histologically?
Lots of island cells floating in mucin
How can breast cancer spread?
- Lymphatics to lymph nodes, usually the ipsilateral axilla
- Blood vessels spread causes distant metastases
- Invasive lobular carcinoma can spread to: peritoneaum, retroperitoneum, leptomeninges, GI tract, ovaries, uterus
What are the most frequent sites for breast cancer to metastasise to?
- Bones
- Lungs
- Liver
- Brain
What factors determine prognosis in breast disease?
- In situ or invasive
- Tumour Stage (TNM)
- Tumour Grade
- Histological subtype (Invasive ductal poorer prognosis)
- Molecular classifcation and gene expression profile
Explain the molecular classifications of breast cancer
Either Oestrogen receptor +/- or HER2 +/-
What is the triple approach to investigating and diagnosis breast cancer?
- Clinical: history, family history, examination
- Radiographic imaging: mammogram and ultrasound
- Pathology: core biopsy and fine needle aspiration cytology
What is sentinel lymph node biopsy?
- Reduced risk of post-op morbidity
- Intra-operative mapping of lymph nodes with dye to identify sentinal node (most likely to contain metastases)
- If sentinel node is negative, axillary dissection can be avoided
Which receptor does tamoxifen target?
Oestreogen receptor if patient is ER +
What receptor does Herceptin target?
HER2 (a tyrosine kinase receptor)
Herceptin = trastuzumab = humanised antibodies against the HER2 protein
What is mammary duct ectasia?
- Dilation of the major ducts, filled with creamy secretion and inflammation
- May be asymptomatic or symptoms
- nipple discharge
- retracted nipple
- acute inflammation
- recurrent chronic inflammation/ abscess
What symtpoms can suggest breast cancer?
- Lump
- Nipple retraction
- Dimples
- Weight loss
- Axillary node enlargement
- Discharge
