11) The breast Flashcards
Describe the structure of a normal breast
Glandular & supporting fibrous tissue embedded within fatty matrix, together with blood vessels, lymphatics & nerves
Where is the location of mammary glands in the breast?
Subcutaneous tissue overlying pectoralis major & minor
Consist of 15-20 lobulated masses of tissues
Fibrous tissue connecting the lobes & adipose tissue between them
What is each lobe of the breast made up of?
Lobules of alveoli, blood vessels & lactiferous ducts
Alveoli - site of milk synthesis
Myoepithelial cells, smooth muscle cells responsible for milk let down surround the alveoli
What determines the size of the non-lactating breast?
The amount of fat surrounding the glandular tissue
Roughly circular body of breast rests in a bed that extends from:
Lateral sternal edge to midaxillary line
2nd rib to 6th rib
List the constituents of human milk in the first week after birth
Up to 40ml/day of Colostrum secreted
Colostrum contains less water soluble vitamins, fat & sugar than later milk but much more protein, fat soluble vitamins & immunoglobulins
Over the following 2-3 weeks, IgG & total protein declines, fat & sugar rise to produce mature milk
What constitutes mature human milk?
Mature milk is produced for as long as the baby suckles (from week 2/3 breastfeeding)
Energy value of 27MJ/litre, pH 7.0
Composition: 90% water, 7% Lactose, 2% Fat
Proteins: Lactoglobulin (maternal IgG), Lactalbumin, Minerals, Vitamins
How is milk produced in the lactating breast?
Synthesis of milk takes place in Alveolar cells
Fats: synthesised in SER, then membrane bound droplets towards lumen
Protein: Passes through Golgi, secreted by exocytosis
Sugar: Synthesised & secreted
What hormones control the growth & development of mammary tissues?
Birth, few lactiferous ducts are present, breast remains this way until puberty
Puberty, oestrogens cause ducts to sprout & branch, the ends form masses of cells, later become alveoli
With each menstrual cycle, changes in breast tissue with changes in oestrogen & progesterone levels
What happens to mammary tissue during pregnancy?
High progesterone:oestrogen ratio favours development of alveoli, but not secretion
Hypertrophy of ductular-lobular-alveolar system
Prominent lobules form
Alveolar cells differentiate to be capable of milk production from mid gestation
What happens to milk production if an infant does not suckle?
Birth, progesterone falls sharply, less sharp fall of oestrogen
Breast becomes responsive to prolactin secreted from anterior pituitary
If infant doesn’t suckle, prolactin levels fall
How does suckling help to maintain breast milk production?
Suckling initiates & maintains secretion by neuro-endocrine reflex by mechanically stimulating receptors in nipple
Impulses pass to brain stem & hypothalamus to reduce dopamine secretion & vaso-active intestinal peptide, promoting prolactin
Amount of milk produced before next feed depends on suckling stimulus
Milk continuously produced between feeds, accumulates in ducts, increases turgor of breast
How is milk ‘let down’ controlled by hormones?
Caused by dramatic increase in secretion of Oxytocin from posterior pituitary
Oxytocin causes myoepithelial cells surrounding alveoli to contract
Infants don’t suck from breast, must learn from bottle
As suckling causes release of oxytocin, suckling also important, keeps uterus clamped down on open placenta blood vessels
‘Let down’ reflex can be conditioned, often begins before baby reaches nipple
How is the cessation of lactation produced?
Lactation maintenance dependent on suckling, to promote prolactin & oxytocin to remove milk
Suckling stops, production of milk stops
Due to lower prolactin levels & turgor-induced damage to breast
A reduction in prolactin helps the cessation of lactation. What else does it do?
Prolactin secretion also reduces fertility
New pregnancy less likely until infant stops suckling
What are common breast diseases?
Inflammatory conditions
Benign epithelial lesions
Stromal tumours
Breast carcinoma
What are the differences between physiological & pathological changes of the breast?
Physiological - Changes or symptoms that come about due to normal breast physiology
Pathological - Changes or symptoms that come about due to underlying breast pathology
Name some physiological breast changes
Prepubertal breast - few lobules
Menarche (first cycle/onset of puberty) - Increased number lobules, increased volume of interlobular stroma
Menstrual cycle - Follicular phase - lobules inactive, After ovulation - cell proliferation & stromal oedema, Menstruation - Decrease in size of lobules
What physiological breast changes take place during pregnancy?
Increase in size & number of follicles
Decrease in stroma
Secretory changes
Cessation of lactation - Atrophy of lobules but not to former levels
What physiological breast changes take pace with increasing age?
Terminal duct lobular units (TDLUs) decrease in number & size
Interlobular stroma replaced by adipose tissue (mammograms easier to interpret)
Name some pathological breast changes that take place
Disorders of development - Milk line remnants (3rd nipples). accessory axillary breast tissue
Inflammatory conditions - Acute mastitis, duct ectasia, fat necrosis
Benign epithelial lesions - Fibrocystic change, epithelial hyperplasia, papilloma
Stromal tumours - Fibroadenoma, phyllodes tumours, lipoma, hamartoma
Gynaecomastia
Breast carcinoma
Describe the clinical presentation of breast pain
Cyclical & diffuse - often physiological
Non-cyclical & focal - ruptured cysts, injury, inflammation
Occasionally the presenting complaint in breast cancer
Describe the clinical presentation of a palpable mass in the breast
May represent normal nodularity
Worrying if hard, craggy & fixed
Invasive carcinomas, fibroadenomas, cysts
Describe the clinical presentation of nipple discharge
Most concerning if spontaneous or unilateral
Milky - endocrine disorders (e.g. pituitary adenoma), side effect of medication (e.g. OCP)
Bloody or serous - benign lesions (e.g. papilloma), duct ectasia, occasionally malignant
What breast changes may occur and present clinically?
Pain Palpable mass Nipple discharge Skin changes Lumpiness Mammographic abnormalities
Describe the clinical use of mammographies
Breast screening programme
Easier to detect lesions in older women (more adipose)
50-70 year olds invited every 3 years
Currently being extended 47-73
Densities - invasive carcinomas, fibroadenomas, cysts
Calcifications - Ductal Carcinoma In Situ (DCIS), benign changes
Describe the incidence of fibroadenomas, phyllodes tumours & breast cancer
Fibroadenomas - Any age in reproductive period, often < 30yrs, most common benign tumour
Phyllodes tumour - Most present in 6th decade
Breast cancer - Rare before 25yrs except familial, incidence increases with age, 77% in women >50yrs, average age of diagnosis is 64yrs
Most common non-skin malignancy in women
How are breast lesions (incl. breast cancer) investigated & diagnosed?
Triple approach:
Clinical: Hx, FHx, examination
Radiographic imaging: Mammogram & USS
Pathology: Fine needle aspiration cytology (FNAC) & core biopsy
What is acute mastitis?
Usually Staphylococcus aureus infection from nipple cracks & fissures Almost always during lactation (benign) Erythematous painful breast, often fever May produce breast abscesses Treated by expressing milk & antibiotics
What is duct ectasia?
Dilation & inflammation of lactiferous duct
Often patient’s in 50’s & 60’s
May have peri-areolar mass and/or nipple discharge
Can mimic carcinoma clinically
What is fat necrosis?
Presents as a mass, skin changes or mammographic abnormality
Often history of trauma or surgery
Can mimic carcinoma clinically & mammographically
What is gynaecomastia?
Enlargement of the male breast
Unilateral or bilateral
Seen at puberty & in elderly
Can indicate hormonal abnormality, cirrhosis of liver (oestrogen not metabolised effectively), functioning testicular tumour
Can occur with drugs - alcohol, marijuana, heroin, anabolic steroids
Can mimic male breast cancer, especially if unilateral
Describe the features of fibrocystic changes of the breast
Benign epithelial lesions, very common
May present as mass/mammographic abnormality
Mass often disappears after fine needle aspiration
Histology - cyst formation, fibrosis, apocrine metaplasia
Can mimic carcinoma clinically & mammographically
Describe the features of epithelial hyperplasia
Benign epithelial lesions
Proliferation of epithelial cells which fill & distend ducts & lobules
Associated with slight increased risk of carcinoma
If atypical, higher increased risk of carcinoma
Describe the features of papilloma
Benign epithelial lesions
Benign tumours, growing finger-like projections outwards
Large duct papillomata usually in lactiferous ducts, near nipple
Smaller duct papillomata deeper in breast
May present with nipple discharge (+/-blood) or small palpable mass
Histology - Intraduct lesion consisting of multiple branching fibrovascular cores covered by myoepithelia & epithelial cells
Describe the features of fibroadenoma
Stromal tumour, can be mulitple & bilateral
Presents with mass, usually mobile/mammographic abnomality
Can grow v large, replace most of breast
Macroscopically - well defined boundaries, rubbery, greyish/white
Histology - mixture, stromal & epithelial elements
Can mimic carcinoma
Describe the features of a phyllodes tumour
Stromal tumour
Mass/mammographic abnormality
Benign (most), borderline & malignant types
Can be v large, involve entire breast
Histology - nodules of proliferating stroma covered by epithelium (phullon = leaf), stroma more cellular & atypical than fibroadenomas
Need to be excised with wide margin or may recur
Malignant - aggressive, recur local & metastasise via bloodstream
What are the risk factors for breast cancer?
Most related to oestrogen exposure
Gender (^ females), Longer interval between menarche & menopause (longer exposure), Reproductive history (age at 1st pregnancy & no.), Breast feeding, Obesity & high fat diet, Exogenous risks (HRT), Geographic influence (USA/Europe high), atypical changes on previous biopsy, Radiation exposure, Genetics
What are the genetic risk factors for breast cancer?
3% all breast cancers & 25% familial cancers attributed to mutations in BRCA1 or BRCA2 tumour suppressor genes
Lifetime risk for female carriers is 60-85%
Median age at diagnosis ~20yrs earlier than sporadic cases
Carriers may undergo prophylactic mastectomies
p53 may also be involved
How are breast carcinomas classified?
~90% adenocarcinomas
Divided into in situ & invasive
Can be ductal or lobular
What are the features of an in situ carcinoma?
Neoplastic population of cells limited to ducts & lobules by basement membrane
Myoepithelial cells preserved
Does not invade into vessels, cannot metastasise
Cells can extend to nipple skin without crossing basement membrane
- Paget’s disease
- Unilateral red & crusting nipple
What are the features of a ductal carcinoma in situ (DCIS)?
Mammographic calcifications, clusters or linear & branching or presents with mass
can spread through ducts & lobules & be very extensive
Histologically - central (comedo) necrosis with calcification
Can progress to invasive carcinoma
What are the features of an invasive carcinoma?
Carcinoma invaded beyond basement membrane into stroma
Can invade vessels & metastasise to lymph nodes & other sites
Usually presents as mass/mammographic abnormality
By time cancer is palpable, >50% pts will have axillary lymph node metastases
What are the features of an invasive ductal carcinoma, no specific type (IDC-NST)?
70-80% of invasive carcinomas
Well-differentiated type - tubules lined by atypical cells
Poorly-differentiated type - sheets of pleomorphic cells
What are the features of an invasive lobular carcinoma?
Inifiltrating cells in a single file, cells lack cohesion
What other types of invasive carcinomas are there?
Tubular
Mucinous
Medullary
Papillary
Where does breast cancer usually metastasise to?
Via lymphatics, usually in ipsilateral axilla
Distant spread via blood vessels:
Lungs, Liver, Bones, Brain
Invasive lobular carcinomas can spread to odd sites such as where?
Peritoneum Retroperitoneum Leptomeninges GI tract Ovaries Uterus
What factors determine breast cancer prognosis?
In situ disease or invasive carcinoma
Histological subtype - IDC-NST has poorer prognosis
Tumour grade
Tumour stage - TMN
What local & regional approaches are there for treating breast cancer?
Breast surgery - Mastectomy or breast conserving surgery
Axillary surgery - Extent depending on whether there are nodes involved
Post-operative radiotherapy to chest & axilla
What systemic approaches are there for controlling/treating breast cancer?
Chemotherapy
Hormonal treatment - Tamoxifen if a high amount of oestrogen receptors found on assessment
Herceptin treatment - Depends on amount of Her2 receptors found on assessment
