Repro Session 11 Flashcards
Where do the breasts extend to horizontally?
Horizontally from lateral border of sternum to mid axillary line
Where do the breasts extend vertically?
Between 2nd and 6th intercostal cartilages
Which muscles are the breasts superficial to?
Pec major and serratus anterior
What is the circular body of the breast?
Largest and most prominent part
What is the axillary tail of the breast?
Runs along the inferior lateral edge of pec major to the axillary fossa
What surrounds the smooth muscle nipple?
Pigmented areolae with sebaceous glands
What provides arterial supply to the medial aspect of the breast?
Internal thoracic
What branches of the axillary artery supply the breast?
Lateral thoracic and thoracoacromial
What branch of the posterior intercostal artery supplies the 2nd, 3rd and 4th intercostal spaces?
Lateral mammary branch
What branch of the anterior intercostal artery supplies the breast?
Mammary branch
What are the suspensory ligaments of Cooper?
Condensations of fibrous stroma of breast that attach and secure breast to dermis and underlying pectoral fascia and separate secretory lobules
What gives innervation to the breast?
Anterior and lateral cutaneous branches of 4th and 6th intercostal nerve
What innervation do the anterior and lateral branches of the 4th and 6th intercostal provide?
Sensory and autonomic to smooth muscle and BV tone
What is the retromammary space?
Loose CT between breast and pectoral fascia
What is the pectoral fascia?
CT associated with the pectoral fascia that provides point of attachment for Cooper’s ligament
What provides lymphatic drainage to the breast?
75% axillary, 20% parasternal, posterior intercostal
Where does lymph from the skin of the breast drain?
Axillary, inferior deep cervical and infra clavicular nodes
Where does lymph from the nipple and areola drain?
Subareolar lymphatic plexus
What are the mammary glands?
15-24 lobulated masses of fibrous tissue with adipose in between embedded in the breasts
What does each lobule seen in the mammary glands consist of?
Many alveoli drained by a single lactiferous duct and sinus behind the areola
What is the purpose of the lactiferous sinus behind the areola?
Allows for accumulation of milk
How do the lactiferous sinuses drain in the lactating mother?
Through 6-16 nipple pores in the areola
When does breast development begin?
At 6 weeks in utero
Describe breast development up until birth.
Breast bud arises at 6 weeks and grows inwards to create a few ducts that are present in both the male and female at birth
What happens to mammary tissue at puberty?
Ducts begin to sprout and branch
What are the effects of oestrogen and progesterone on mammary tissue with each menstrual cycle?
Oestrogen acts on oestrogen-alpha receptors to cause ductal sprouting; oestrogen and progesterone work together on oestrogen-beta receptors to cause ductal hypertrophy
What is mammogenesis?
Preparation of breasts by hypertrophy of ductular-lobular-alveolar system and differentiation of alveolar cells
What differentiation do alveolar cells undergo in mammogenesis?
Squamous to columnar
When can mammary tissue produce milk from during pregnancy?
T2
Why is milk not secreted from the time when the mammary tissue is developed so that it can be produced during pregnancy?
Progesterone inhibition of prolactin receptor synthesis
What favours further growth of the breast in addition to hypertrophy of the ductular-lobular-alveolar system?
Oestrogen stimulating adipose tissue formation
What process is seen in mammogenesis but only in primi gravida?
Angiogenesis
What visible breast changes are seen towards the end of pregnancy?
Nipples become erect, areolar enlarges and darkens
What is the advantages of the darkening and enlargening of the areolar towards the end of pregnancy?
Makes it easier for the neonate to identify
What are Montgomery tubercles?
Sebaceous glands that have fused with ducts around alveoli
What do Montgomery tubercles release?
Oil and pheromones
What is the function of the Montgomery tubercles secretions?
Oil hydrates skin around nipples and pheromones signal to neonate
What happens to the sensitivity of the breasts towards the end of pregnancy?
Increases
What is lactogenesis?
Synthesis of milk
What is the ultrastructure of lactocytes adapted for?
Production of fat by the SER, protein secretion by the Golgi apparatus, sugar synthesis and secretion
How is the ultrastructure of lactocytes adapted for lactogenesis?
Nucleus is positioned close to the base, hemidemosomes move to allow passage of macrophages and inflammatory cells
What does the movement of macrophages and neutrophils between cells in lactogenesis confer?
Maternal ductal system immunity and passive immunity to the neonate
What are the 5 mechanisms of entry for substances into breast milk?
Exocytosis, lipid synthesis and secretion, transmembrane secretion, transcytosis, paracellular pathway
What substances enter breast milk via exocytosis?
Proteins and lactose
How do fat droplets and milk fat globules seen in breast milk differ?
Globules are droplets with a membrane for even distribution
Which substances enter breast milk via transmembrane secretion?
Water, sodium and potassium
What substances move into breast milk via transcytosis?
Intact proteins
What is colostrum?
40ml of breast milk secreted in days 0-3 that has a different composition to intermediate and mature breast milk
Describe the composition of colostrum.
Less water, fat and lactose than more mature milk but more proteins, especially IgA, IgM and IgG, white cells present
What is the purpose of immunoglobulins in colostrum?
Coat neonatal intestinal mucosa
Describe the composition of mature breast milk.
~90% water, 7% lactose, 3% fat, proteins, minerals, vitamins and endocannabinoids
Which proteins are seen in mature breast milk?
Lactoalbumin, lactoglobulin, lactoferrin
What is the purpose of endocannabinoids in breast milk?
Appetite regulation of the neonate
How does cow’s milk compare to human breast milk?
Less lactose, more indigestible casein, more lactoalbumin and other proteins, more minerals
How long does it take milk production to mature?
2 weeks
How much energy does each litre of breast milk provide?
27 MJ
How much milk is produced each day by a lactating mother?
800 ml or double if twins
What effects does oestrogen have on prolactin?
Increases prolactotroph growth but not secretion
How is prolactin controlled?
Inhibition by dopamine
Where is prolactin produced in the pregnancy female?
Anterior pituitary and decidua
What is special about the control of prolactin produced by the decidua?
Not under inhibitory control by dopamine
What is the decidua?
Endometrium of the last menstrual cycle before pregnancy
What allows milk ejection?
Let-down reflex
What happens in galactokinesis?
Nipple on back of neonatal mouth stimulate mechanoreceptors in nipples –> signal to hypothalamus causing posterior pituitary to release oxytocin –> acts on myoepithelial receptors around alveoli causing ejection
What is galactopoeisis?
Maintenance of lactation via neuroendocrine reflex
What can stimulate the neuroendocrine reflex in milk let down?
Baby crying, fondling baby, anticipation of feed
What is needed for galactopoeisis to occur?
Sufficient sucking stimulus with regular removal of accumulated fluid
What are the consequences of infrequent breast feeding?
Turgor-induced damage to to secretory cells
Why does infrequent breast feeding rapidly become painful for the mother?
Turgor-induced damage combined with increased breast sensitivity
Is prolactin release seen in anticipation of a feed?
No
What can cause cessation of lactation?
Loss of feedback, pain, menstruation, suppression of prolactin, age
What might pain in the breasts causing cessation of lactation be due to?
Incensed turgor or mastitis
How does menstruation cease lactation?
Progesterone and oestrogen stimulate alveolar growth instead of secretion, reduce sensitivity to oxytocin by decreasing receptor synthesis
How can prolactin be suppressed resulting in a cessation of lactation?
Ergot Tx, diuretics, retained placenta
How does a retained placenta cause cessation of lactation?
Produces progesterone and oestrogen
Why does age cause a cessation of lactation?
Involution of mammary tissue begins around 35 y.o.
What are the benefits of breast feeding?
Fewer infections for neonate; deceased risk of breast and ovarian cancer; further contraction of the uterus to pre pregnancy state; binding via oxytocin; loss of pregnancy weight
When are the breasts non-functional?
Throughout life except during lactation
What change in mammary tissue structure is seen at menarche?
Increased number of lobules and increased volume of interlobular stroma
Describe the lobules in the breast during the follicular phase of mesntruation.
Quiescent
What changes in mammary tissue are seen just after ovulation?
Cell proliferation and stromal oedema
What changes are seen in mammary tissue at menstruation?
Decreased lobule size
What changes are seen in mammary tissue at pregnancy?
Increased lobule size and number, decreases stroma and secretory changes in the epithelium
Why does the cytoplasm of epithelial cells in mammary tissue clear during pregnancy?
Allow for milk accumulation
What happens to the lobules after lactation?
Atrophy but do not return to previous state
Describe the changes seen in ageing mammary tissue.
Terminal duct lobular units decrease in number and stroma is replaced by adipose
Why is US imaging of the breast preferred to mammogram in younger patients?
Stroma is more fibrous therefore mammograms are hard to interpret
What are the four common clinical presentations of breast disease?
Pain, palpable mass, nipple discharge, mammographic abnormalities
What description of breast pain indicated physiological cause?
Cyclical and diffuse
What does non-cyclical and focal beast pain indicate?
Ruptured cysts, injury, inflammation
What is the non-pathological cause of a palpable breast mass?
Normal nodularity
What does a hard, craggy and fixed palpable breast mass indicate?
Invasive carcinoma, fibroadenoma, cyst
What presentation of nipple discharge is most concerning?
Spontaneous and unilateral
What does milky nipple discharge indicate?
Endocrine disorder e.g. Pituitary adenoma, OCP S/E
What does bloody/serous nipple discharge indicate?
Benign lesion e.g. Papilloma, duct ectasia
What are the three changes looked for on mammography?
Densities, calcification sand deformities
What do densities on mammogram indicate?
Invasive carcinomas, cysts, fibroadenoma
What do calcifications on mammogram indicate?
DCIS, benign change
What is the most common benign breast tumour?
Fibroadenoma
At what age does Fibroadenoma typically present?
Describe the incidence of breast cancer.
Most common non-skin malignancy in women, rare 50 y.o.
What can often be confused with Fibroadenoma but tends to affect older pts?
Phyllodes tumour
Why is phyllodes tumour more concerning than Fibroadenoma?
Can be malignant
What is polythelia/axillary breast tissue?
Breast tissue found anywhere on the milk line
How might a breast tumour be identified in a location other than the breast?
Tumour on milk line that enlarges before menstruation
When is acute mastitis almost always seen?
During lactation
What is the usual pathogenesis of acute mastitis?
Staph aureus infection from nipple cracks and fissures
How does acute mastitis present?
Erythematous painful breast with pyrexia +/- breast abscess
How is acute mastitis treated?
Expression of milk and Abx
What history indicates fat necrosis in the breast?
Trauma or surgery
How does fat necrosis in the breast present?
Mass, skin change, mammographic abnormality
How does fat necrosis appear on histological examination?
Ail yes surrounded by macrophages and inflammatory cells
What is the commonest breast lesion that is almost invariably present in older women?
Fibrocystic change
How does fibrocystic change present?
Mass or mammographic change
What does histology show on fibrocystic change of the breast?
Cyst formation (dilated acini), fibrosis and apocrine metaplasia lining the acini
What often happens to the mass seen in fibrocystic change when aspirated with a fine needle?
Disappears
What types of stromal tumours may be seen in the breast?
Fibroadenoma, phyllodes tumour, lipoma, leiomyoma, harmatoma
What is a breast mouse?
Elusive, mobile mass seen in Fibroadenoma
Describe the tumour size and location that may be seen in Fibroadenoma.
Multiple, bilateral, very large replacing majority of breast
How does Fibroadenoma appear histologically?
With stromal and epithelial elements
How does Fibroadenoma appear macroscopically?
Well circumscribed, rubbery and grey-White
Is Fibroadenoma true neoplasm?
No, localised hyperplasia
How do Phyllodes tumours appear histologically?
Nodules of atypical cellular stroma covered by epithelium with visible mitoses
Describe the incidence of the types of phyllodes tumours.
Majority are benign, some borderline and
How does malignant phyllodes tumour progress?
Aggressive, recur locally and metastasise via blood
Why do phyllodes tumours metastasise via the blood?
Stromal origin
What is required when phyllodes tumours are excised?
Wide margin
Describe the pathogenesis of gynaecomastia.
Relative reduced androgen effect/increased oestrogen effect –> uni/bilateral enlargement of male breast
What are some causes of gynaecomastia?
Secondary to circulating maternal and placental oestrogens in the neonate, earlier oestrogen peak in normal puberty, drugs e.g. Spironolactone, Klinefelter’s syndrome, liver cirrhosis, testicular tumours causing gonadotrophin excess
What types of testicular tumour may lead to gynaecomastia?
Leydgig cell tumour, Sertoli cell tumour, germ cell tumour
What proportion of malignancies in women are breast cancer?
20%
How many women will develop breast cancer at some point in their lifetime?
1 in 12
What is the distribution of tumour types making up all cases of breast cancer?
~95% adenocarcinomas, primary sarcomas e.g. Angiosarcoma make up rest
Which area of the breast are cancers usually seen?
Upper outer quadrant
What proportion of breast cancer cases are male?
1%
What increases the risk of male breast cancer?
Klinefelter’s syndrome, male–>female, oestrogen Tx for prostate cancer
What are risk factors for breast cancer?
Gender, uninterrupted menses, prolonged oestrogen exposure, obesity, geographic location, exogenous oestrogens, older age at first pregnancy, therapeutic radiation
What proportion of breast cancers are hereditary?
10%
What are 3% of all breast cancer cases attributed to?
BRCA1/2 mutation
What are the consequences of a BRCA1/2 mutation?
Dysfunctional tumour suppressor genes –> lifetime risk of 60-85% for female carriers
Who does the presenting age of hereditary breast cancer compare to that of spontaneous cases?
~20 years earlier
What is Li Fraumeni syndrome?
p53 mutation –> hereditary breast cancer
How are breast carcinomas classified?
In situ or invasive
Describe the neoplasm seen in in situ carcinoma of the breast.
Limited by BM to ducts and lobules, preserving myoepithelial cells and cannot metastasise
What causes the cluster/linear mammographic calcification seen in in situ breast carcinoma?
Comedo necrosis causing linear calcification through ducts and lobules
Why are ducts affected by in situ carcinoma of the breast dilated?
Cell proliferation
Why is it beneficial to identify in situ carcinoma early?
Non-obligate precursor to invasive carcinoma
What is Paget’s disease of the breast?
In situ carcinoma where neoplastic cells track up ducts to the nipple skin without crossing the BM
How does Paget’s disease of the breast present?
Unilateral red crusting nipple (like eczema)
Describe the neoplasm seen in invasive breast carcinoma.
Invaded beyond BM into stroma so can metastasise via lymph of blood vessels
What is the implication of invasive carcinoma presenting as a palpable mass?
Must’ve grown to ~2cm by which time 50% have axillary lymph node involvement
What is peau D’orange?
Blockage of lymphatic drainage to the skin except for fixed hair follicles indicating invasive breast carcinoma
What is the most common type of invasive breast carcinoma?
Invasive ductal carcinoma, no special type
What is the 10 yr survival rate for IDC NST?
35-50%
How do well differentiated IDC NST appear histologically?
Tubules line with atypical cells
How do poorly differentiated IDC NST appear histologically?
Sheets of pleomorphic cells
Why does the stroma also appear abnormal in IDC NST despite not being neoplastic?
Under influence of substances released by malignancy
What type of invasive breast carcinoma has a similar prognosis to IDC NST but only accounts for 5-15% of cases?
Invasive lobular carcinoma
How does invasive lobular carcinoma appear histiologically?
Infiltrating line of single file cells lacking E-cadherin
Which two types of incpvasive breast carcinoma have very good prognosis but only account for a small proportion of cases?
Tubular and mucinous
Which population are mucinous breast carcinomas more commonly seen in?
Older women
How do mucinous breast carcinomas appear histologically?
Lacked of mucin with epithelial cells floating within
How can invasive breast carcinoma metastasise?
Lymph, usually to ipsilateral axillary nodes; blood to bone, lungs, liver or brain; invasion to peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries or uterus
What is gene expression profiling, used in breast carcinoma?
Examination of 17 marker genes to identify metastatic potential for appropriate treatment plan
How can breast carcinomas be profiled molecularly?
By oestrogen receptor then by Her2 receptor
Which molecular profile types are associated with poor prognosis in breast carcinoma?
Oestrogen receptor -ve
What age are oestrogen receptor -ve Brest tumours more commonly seen in?
70 y.o.
What age are oestrogen receptor +ve Brest tumours more commonly seen in?
50 y.o.
Which molecular profile are BRCA1 mutations causing breast carcinoma associated with?
Oestrogen receptor -ve, Her2 -ve
What is the triple approach used in breast carcinoma investigation and diagnosis?
Clinical: Hx, FHx, examination
Radiography: mammogram or US
Pathology: fine needle aspiration cytology and core biopsy
What local and regional control approaches can be used in breast carcinoma therapy?
Mastectomy, breast conserving surgery, axillary dissection, post-operative radiotherapy to axilla and chest
Why should axillary dissection be avoided where possible?
Risk of oedema and Fibroadenoma
What is sentinel lymph node biopsy?
Examination of the draining lymph nodes for metastasis to indicate whether axillary dissection is necessary
What systemic control approaches can be used in breast carcinoma?
Chemotherapy, including neoadjuvant; hormonal Tx; Herceptin
What proportion of breast carcinomas are oestrogen receptor +ve?
80%
What proportion of breast carcinomas are Her2 +ve?
20%
Why does the nucleus stains darker in oestrogen receptor positive tumours?
This is where the receptors are located
What stains darker in a Her2 receptor +ve tumour?
CSM
What is Herceptin?
Monoclonal antibody against Her2 protein
What is Her2?
Human epidermal growth factor encoding transmembrane tyrosine kinase receptor
What improves survival of breast carcinoma?
Early detection, neoadjuvant chemotherapy, use of neve therapies e.g. Herceptin, gene expression profiles, genetic screening and prophylactic mastectomies
