Repro Session 11 Flashcards
why does breast enlarge at puberty in female?
under influence of oestrogens AT accumulates, and lactiferous ducts become much enlarged
what cells surround the lactiferous ducts in the breast?
myoepithelial cells
why can oedema and tenderness occur in the breasts within the week prior to the menses?
oestrogen peak stimulates mammary glands further in the menstrual cycle as it induces duct proliferation which causes ducts to enlarge and may cause oedema and tenderness
action of progesterone on breast in pregnancy?
influences development of secretory tissues
action of oestrogen on breast in pregnancy?
duct proliferation
where does base of mature breast extend?
from lateral border of sternum to mid-axillary line, and overlies 2nd to 6th ribs
major features of female breast?
nipple
areola
axillary tail
what does each lactiferous duct of each lobule of the breast comprise just prior to its opening onto the nipple?
a dilated lactiferous sinus
how is each lobule of glandular tissue in the breast delineated?
by CT septa extending from skin into deep fascia, known as suspensory ligaments
what does skin of areola comprise?
many tubercles produced by underlying alveolar glands
why is the breast mobile?
due to retromammary space between breast and fascia overlying the chest wall muscles
what changes to the breast may be visualised if a tumour is present?
distortion due to shortening of suspensory ligaments, and dimpling of skin due to oedema
blood supply to breast?
internal thoracic artery
intercostal artery
lateral thoracic
thoracoacromial
venous drainage of breast?
axillary vein
posterior IC veins
internal thoracic vein
lymphatic drainage of medial quadrants of breast?
parasternal nodes or opposite breast
most of lateral to axillary LNs
composition of lobes of breast?
lobules of alveoli- site of milk synthesis, and surrounded by myoepithelial cells
blood vessels
lactiferous ducts
what is secreted from the breast during the 1st week after birth?
colostrum: contains less H20 soluble vits, fat and sugar than later milk but more protein, fat-soluble vits and Igs
IgG and total protein declines over next 2-3wks, whilst fat and sugar rises to produce mature milk
where is milk fat synthesised?
smooth ER of alveolar cells and passes in membrane bound droplets towards lumen
where does milk protein pass through?
golgi apparatus and is released by exocytosis
what favours development of alveoli during preganancy?
a higher progesterone to oestrogen ratio
how do alveolar cells become responsive to prolactin at birth?
fall in progesterone levels, with fall in oestrogen less so
how does suckling maintain milk secretion?
neuro-endocrine reflex: suckling by infant stimulates receptors in nipple mechanically which results in impulses being sent up to brain stem and hypothalamus to reduce dopamine secretion and VIP so promoting prolactin secretion
what is milk ‘let down’
dramatic increase in oxytocin secretion when infant next suckles, which contracts myoepithelial cells which eject the milk
what doe maintenance of lactation depend on?
regular suckling to promote prolactin secretion, and tp remove accumulated milk
what can a mother take to suppress milk production?
steroids= -ve feedback on anter.pituitary to inhibit prolactin release?
why will milk production cease if suckling stops?
decrease in prolactin and damage to breast due to turgor-induced damage
why is a new pregnancy unlikely during the time in which an infant is suckling?
fertility is reduced due to high prolactin
physiological breast changes in menarche?
increase in no. of lobules and increase in volume of interlobular stroma
physiological breast changes in menstrual cycle?
follicular phase: lobules quiescent
after ovulation: cell proliferation and stromal oedema
menses: decrease in size of lobules
physiological breast changes in pregnancy?
increase in size (hypertrophy) and number of lobules
decrease in stroma
secretory changes
clinical presentation of breast conditions?
Pain Palpable mass Nipple discharge Skin changes Lumpiness
cause of cyclical and diffuse pain in breast?
physiological e.g. in menstrual cycle
cause of non-cyclical and focal pain in breast?
ruptured cysts, injury, inflammation
triple approach to diagnosis and investigation of breast cancer?
clinical- history, FH, examination
radiographic imaging- mammogram and USS
pathology- fine needle aspiration and cytology and core biopsy
characteristics of an in situ breast carcinoma?
Neoplastic population of cells limited to ducts and lobules by BM, myoepithelial cells are preserved
Does not invade into vessels so can’t metastasise
how does a ductal carcinoma in situ most commonly present?
mammographic calcifications- clusters or linear and branching, but can present as a mass
histological appearance of a ductal carcinoma in situ?
central necrosis with calcification
how does invasive breast carcinoma commonly present?
mass or mammographic abnormality
over 50% will have metastasised to axillary LNs by time lump is found
why is breast turgor increased between feeds?
milk accumulates in alveoli and ducts as suckling at 1 feed promotes prolactin release which causes production of next feed
define physiological breast changes
changes or symptoms that come about due to normal breast physiology
physiological breast changes in menarche?
increase in lobule number, increase vol of interlobular stroma
describe cessation of lactation as a physiological breast change
atrophy of lobules but not to former levels
what happens to the breast with increasing age?
terminal duct lobular units decrease in no. and size, interlobular stroma replaced by AT- makes mammograms easier to interpret as less fibrous stroma which can make calcification more difficult to see
palpable breast mass most worrying if…?
hard, craggy, fixed
causes of palpable breast mass?
invasive carcinomas
fibroadenomas
cysts
when is nipple discharge most concerning?
spontaneous and unilateral
occasionally malignant lesions can cause bloody or serous discharge
why might nipple discharge be milky?
endocrine disorders e.g. pit adenoma, SE of med. e.g. OCP
when are women invited to screening by mammograms?
age 50-70 yrs every 3 yrs, but extending age to 47-73 yrs
most common benign tumour of breast?
fibroadenoma
aim of mammographic screening?
detect small invasive tumours and in situ carcinomas- not gone through BM, so therefore can treat before metastasis
does an in situ ductal cell carcinoma metastasise?
no, as doesn’t go through BM so can’t invade into blood vessels
only benign lesion to cause skin dimpling?
fat necrosis
how does fat necrosis usually result?
from skin trauma
common age of fibroadenoma occurrence?
<30yrs
but can occur at any age during repro. period
when do most phyllodes tumours present?
6th decade
average age of diagnosis of breast cancer?
64 yrs
incidence increases with age
pathological conditions of breast?
disorders of development inflammatory conditions benign epithelial lesions stromal tumours gyanecomastia breast carcinoma= malignant neoplasm of epithelial cells
examples of disorders of devleopment?
milk line remnants- polythelia= accessory nipple, accessory axillary breast tissue
inflammatory conditions of breast?
acute mastitis- almost always occurs during lactation
duct ectasia
fat necrosis
characteristics of breast affected by acute mastitis?
red warm painful often pyrexia may produce breast abscesses
common causative agent of acute mastitis?
staphylococcus aureus- infection from nipple cracks and fissures
how is acute mastitis usually treated?
by expressing milk- flush out infection, and antibiotics
what can duct ectasia mimic clinically?
carcinoma
characteristics of duct ectasia?
duct dilatation and inflammation- inflammatory cells seen under microscope
may have periareolar mass and/or nipple discharge
presentation of fat necrosis?
mass, skin changes e.g. dimpling or mammpgraphic abnormality
can mimic carcinoma clinically and mammographically
commonest benign breast condition?
fibrocystic changes
presentation of fibrocystic change?
mass or mammographic abnormality
but mass often disappears after fine needle aspiration
histological fibrocystic change?
fibrosis- collagen deposition
cyst formation
apocrine metaplasia (mammary gland cells change from 1 differentiated cell type to another but the change is reversible)
can mimic carcinoma clinically and mammographically
common site for distant metastases of breast cancer?
bone, liver, lung, brain
what might densities on a mammogram be due to?
invasive carcinomas
fibroadenomas
cysts
describe epithelial hyperplasia
proliferation of epithelial cells distending ducts and lobules
assoc with slight increased risk of carcinoma
if atypical, higher risk of carcinoma
often detected as mammographic abnormality or incidental finding in biopsies
how might papillomas present?
nipple discharge as ductal epithelium irritated, may be bloody, small palpable mass, mammographic abnormality
histology of a papilloma?
intraduct lesion consisting of multiple branhcing fibrovascular cores covered by myoepithelial and epithelial cells
what cells should always be present on breast histology to indicate normal breast?
epithelial and myoepithelial cells
examples of stromal tumours?
fibroadenoma phyllodes tumour lipoma leimyoma hamartoma
how do fibroadenomas typically present?
mobile mass or mammographic abnormality
can be multiple and bilateral
can grow very largw and replace most of breast
macroscopic appearance of fibroadenoma?
well circumscribed, rubbery, greyinsh/white
histology of fibroadenoma?
mixture of stromal and epithelial elements
histology of phyllodes tumour?
nodules of proliferating stroma covered by epithelium
stroma more cellular and atypical than that in fibroadenomas
presentation of phyllodes tumour?
masses or mammographic abnormalities
most benign, but can be borderline or malignant
can be very large and involve entire breast
malignant type aggressive, recur locally and metastasise via blood
why do phyllodes tumours need to be excised with a large margin?
to prevent recurrence
what is gynaecomastia caused by?
relative decrease in androgen effect or increase in oestrogen effect
why can liver cirrhosis cause gynaecomastia?
oestrogen not metabolised effectively so oestrogen excess
drugs that can cause gynaecomastia?
spironolactone
cimetidine
alcohol
anabolic steroids
why might men with prostate cancer be more susceptible to breast cancer?
tment of prostate cancer with oestrogen, oestrogen stimulates ductal cell proliferation
what type of carcinoma are most breast cancers?
adenocarcinoma
whereabouts in the breast is breast cancer most common?
upper outer quadrant
RFs for breast cancer?
gender
uninterrupted menses
early menarche (<11yrs)
late menopause, longer expos to oestrogens
not many babies and old at first full term pregnancy
brast-feeding
obesity and high fat diet- peripheral oestrogen prod.
HRT, LT users of OCP
higher incidence in US and Europe- diet, exercise, breast-feeding, environ?
atypical changes on prev. biopsy
previous breast cacner
radiation
FH
what may carriers of BRCA mutations undergo to prevent breast cancer?
prophylactic mastectomies
why do BRCA1 and 2 gene mutations increase breast cancer risk?
tumour suppressor genes so their proteins repair damaged DNA hence mutations compromise this function and cells can continue proliferating with damaged DNA
what is Paget’s disease of breast?
type of breast cancer that can result from DCIS cells extending to nipple skin without crossing BM
unilateral red and crusting nipple
eczematous or inflammat conditions of nipple suspicious, should perform biopsy
what does peau d’orange mean in reference to an invasive carcinoma of breast?
involvement of lymphatic drainage of skin, blocked so diffuse oedema ensues
name another gene other than BRCA that may be involved in hereditary breast cancer?
p53
characterisitcs of Invasive Ductal Carcinoma, no specific type (IDC-NST)?
o 70-80% of invasive carcinomas
o Well-differentiated type – tubules lined by atypical cells
o Poorly differentiated type – sheets of pleomorphic cells
characteristics of invasive lobular carcinoma?
Infiltrating cells in a single file, cells lack cohesion
how might invasive carcinoma appear macroscopically?
firm tissue
parenchymal deformity as tumour pulls inward on tissue
types of invasive carcinoma?
ductal
lobular
tubular
mucinous
what sites might an invasive lobular carcinoma spread to?
peritoneum retroperitoneum GI tract ovaries uterus leptomeninges
factors determining prognosis in breast cancer?
in situ or invasive
histologic subtype
tumour grade and stage- size, locally advanced- into skin or skeletal muscle, LN metastses, distant metastases
gene expression profile
aim of mammographic screening?
detect small impalapable cancers and pre-invasive cancer, look for asymmetric densities, parenchymal deformities and caclcifications, can then assess with further imaging, fine needle aspiration cytology and core biopsy
local and regional control of breast cancer?
o Breast Surgery
Mastectomy or breast conserving surgery
o Axillary Surgery
Extent depending on whether there are nodes involved
o Post-operative radiotherapy to chest and axilla
function of sentinel LN biopsy?
can determine extent of axillary LN involvement in breast cancer and reduce risk of post op morbidity e.g. lymphoedema predisposing to arm malignancy e.g. sarcoma. Nodes are 1st draining LNs which are most likely to contain metastases and if not present, highly likely no other LNs involved so LN dissection can be avoided. intraoperative lymphatic mapping with dye and/or radioactivity of sentinel LNs
systemic control of breast cancer?
chemotherapy, can be neoadjuvant
tamoxifen if oestrogen receptor +ve- nuclei stained brown
herceptin if Her2 positive: encodes a transmembrane tyrosine kinase receptor, herceptin= antibodies against Her2 protein, brown stain on membrane if +ve. herceptin can also treat gastric cancer. gene is a protoncogene that controls cell growth.
how can survival from breast cancer be improved?
early detection- FH importance, self-exam, screening- 2 view mammograms every 3 yrs for women between 47 and 73 yrs
neoadjuvant chemo- early tment of metastatic disease as these cells that cause death
newer therapies e.g. herceptin
gene expression profiles
prevention in familial cases- genetic screening, prophylactic mastectomies
