breast cancer Flashcards
what are the risk factors for breast cancer ?
previous breast cancer
family history / BRCA positive or TP53 mutation
age
oestrogen exposure:
- nulliparous / >30 first pregnancy
- early menarche/ late menopause
- HRT/ COCP
previous radiation to chest
lack of breast feeding
high fat diet, obesity, lack of exercise, high alcoholhow can breast cancers be classified ?
most cancer arise from epithelial lining of ducts
cancers can be invasive or not (in situ):
- non invasive:
1. ductal carcinoma in situ (DCIS) - unifocal or widespread but do not invade basement membrane so limited to ductal system
2. lobular carcinoma in situ (LCIS) - multifocal - invasive:
1. invasive ductal carcinoma (85%) - breaks through BM and invades
2. invasive lobular carcinoma
3. others - tubular, mucinous, papillary and medullayr
how do breast cancers present? (breast, systemic, metastatic)
breast symptoms:
- lump, asymmetry, retraction/dimpling
- skin changes: peau d’orange, redness, itching
- nipple: discharge, retraction, displacement , inversion
- mastalgia, temperature change
Systemic upset/ paraneoplastic:
- weight loss, anaemia (pallor, pale conjunctiva)
- signs of dehydration
- maybe fever/ night sweats (more lymphoma/leuk)
- thrombophlebitis/ thrombocytosis - DVT symptoms
- dermatomyositis
symptoms of metastasis
- bone pain, fractures, hypercalcaemia, vertebral collapse
- hepatomegaly and jaundice, ascites
- brain: focal neurology, memory/personality change, seizures, N&V, cranial nerve palsies and sensory deficit
- spinal cord compression
- pericardium, pericardial effusion and AF
- lung: consolidation, pleural effusion
- fundoscopy - choroidal mets
- lymphadenopathy - axillary, supraclavicular, cervical, lymphoedema
what is the referral criteria by NICE for breast cancer
2ww for those
- > 30yrs with unexplained lump without pain
- > 50yrs with unilateral nipple changes (discharge, retraction)
those <30 with lump have less urgent referral
where do breast cancers spread?
lymphatics
vasculature
locally - pericardium, pleura etc
metastasis - brain, bone, lung, liver, adrenals, ovaries
what is the arterial supply to the breast?
external mammary (lateral thoracic) internal mammary (thoracic) intercostal arteries
what is Pagets disease of the nipple?
defined as chronic eczematous change of nipple.
associated with high grade invasive cancer where malignant cells infiltrate into epidermis via mammary duct epithelium.
cells proliferate - thick skin, scaling , erythematous, discharge, itching
all eczema of breast should be investigated for breast cancer.
how do the majority of intraductal carcinomas present?
painless lump with bloody nipple discharge
how does inflammatory breast carcinoma present?
large rapidly growing mass that is painful.
red and warm overlying skin
how are breast lumps assessed/ diagnosis of breast cancer?
Triple therapy
- clinical examination
- imaging
- cytology/ histology
how are breast cancers clinically assessed in the triple assessment?
examination by inspection and palpation of the breast
palpation of axillary nodes
how are breast cancers imaged in triple assessment?
bilateral mammogram for those >35yrs
USS / MRI for those <35 yrs (because young women have dense breast)
MRI indicated for dense breasts, lobular carcinoma, <40yrs, good for BRCA associated cancers.
how is cytological / histological information obtained in triple assessment?
fine needle aspiration for cystic lumps
- quick and less uncomfortable - negative results does not exclude (false negatives are common ) but false positives are rare.
sterotactic core biopsy (sterotactic = image guided) - for solid lumps
- more pain and takes longer but can determine expression of receptors and grade of tumour
wide local excisional biopsy - complete removal of tumour (part of treatment)
incisional biopsy - part of lesion is removed if >/= 4cm
what are the features of malignancy on mammogram?
irregular
speculated
radio-opaque mass
microcalcifications - can be benign or malignant need to be confirmed by histology
what does cancer staging depend on?
type, size, margins, nodes, distant metastasis, grade, vascular/ lymphatic infiltration, receptor expression
what staging investigations are required for lung cancer?
node biopsy:
- for all patients with early invasive breast cancer but no evidence of axillary node involvement do a sentinel node biopsy.
- for those with palpable lymph node - FNA of node and cytological examination.
- if either of the above are positive, axillary clearance is indicated (removal of 11-20 nodes)
cytogenetics: receptor expression (ER, Progesterone, HER2)
bloods - LFTs, FBC, Ca, bone profile
imaging:
- CXR, USS liver
- CT CAP if abnormal LFT, CXR, hepatomegaly, neurological signs or lymphadenopathy.
- bone scan/ scintigraphy - if bone pain, local advanced disease or lymph node involvement
- PET scan
what is a sentinel node biopsy?
inject blue dye into the tumour and the first node draining the tumour will be the first to appear blue thus the sentinel node can be identified and excised for histology.
sentinel node = first node in drainage of tumour.
what tumour markers are found in breast cancer?
CEA and CA125
describe stages 0 to 4 in breast cancer.
0= cancer only found in epithelial membrane of duct/ lobule 1 = confined to breast, mobile, <2cm 2 = confined to breast, ipsilateral axillary nodes, 2-5cm, mobile 3 = fixed to muscle, ipsilateral axillary nodes, matted, may have spread to overlying skin >5cm 4 = complete fixation to chest wall, distant metastasis.
describe the TNM staging for breast cancer.
T1 = <2cm T2 = 2-5cm T3 = >5cm T4 = fixed to chest wall/ peau d'organge
N1 = mobile ipsilateral nodes N2 = fixed nodes N3 = ipsilateral mammary nodes
M1 = distant metastasis
describe the stepwise management of treat stage 1 - 2 breast cancer
- surgery: wide local excision or massectomy to remove mass
- axillary node surgery: sentinel node biopsy +/- axillary clearance
- adjuvant radiotherapy after wide local excision to stop local recurrence. may also need radiotherapy to chest wall in high risk massectomy patients. May also use radiotherapy on axilla if lymph node positive but no axillary clearance was performed
- adjuvant chemotherapy - for advanced receptor negative disease
OR adjuvant hormonal therapy if receptor positive. e.g. tamoxifen
when may neoadjuvant chemotherapy be used in breast cancer?
neoadjuvant chemo may be used in large inflammatory carcinomas to reduce tumour size before surgery and reduce the need for massectomy. MRI can be used to monitor response to neoadjuvant chemo before surgery.
however usually treatment starts with surgical removal.
what are the complications of axillary node removal (particularly clearance)
lymphoedema
shoulder stiffness
tingling and numbness in arm
what are the complications of radiotherapy for breast cancer?
pneumonitis, rib fracture, pericarditis
for axillary radiotherapy - brachial plexopathy and lymphoedema
what is considered as a high risk massectomy patient and thus qualifies for adjuvant radiotherapy?
T3/4
>/=4 positive axillary nodes
when is wide local excision used over massectomy and vice versa?
wide local excision:
- smaller tumours <4cm diameter
- peripherally located
mastectomy:
- large >4cm
- locally advanced
- multifocal disease
- if radiotherapy is contraindicated (because needs to follow wide local excision)
wide local excision is preferred as it has better cosmetic outcomes.
how is the breast reconstructed in wide local excision and massectomy?
oncoplasty
after wide local excision there is immediate reconstruction by:
- volume replacement - latissimus dorsi myocutaneous flap for lower pole and central deposits OR TRAM flap (stomach fat into breast)
- volume displacement - transverse abdominis myocutaneous flap
massectomy - implants offered to all patients unless contraindicated
how can the tumour be better localised by the surgeon for wide local excision?
fine wire can be placed around the tumour margins (presumably with imaging) and then surgeon has a guide = wire localisation
what are the contraindications to wide local excision?
previous DXT to that area diffuse microcalcifications multifocal disease large tumour tumour behind nipples
when may implants after mastectomy be contraindicated?
comorbidities that contraindicate further surgery/ anaesthetics
need for chemo/radiotherapy
what other management is required after mastectomy?
psychological support
when can mastectomy be used prophylactically?
bilateral mastectomy for BRCA1/2 positive women
why is adjuvant systemic therapy (e.g. chemo, hormones, biologics) used after?
reduces recurrence and survival of micrometasis and thus improves 5 year survival rates
when is neoadjuvant chemotherapy indicated in breast cancer?
> 1cm
ER negative
axillary node positive
mainly for advanced disease
what chemotherapies can be used in breast cancer
anthracycline + flurouracil + cyclophosphamide (sometimes methotrexate)
what endocrine therapy is offered after treatment for breast cancer?
5 year treatment with tamoxifen/ aromatase
helps eradicate micrometastasis
(also LHRH analogues)
how does aromatase work and who is it indicated for?
blocks aromatase enzyme which is responsible for production of oestrogen in peripheral tissues in post menopausal women.
therefore only works in post menopause.
how does tamoxifen work?
tamoxifen blocks ER receptor to block tumour growth
can be used both pre and post menopause
what are the side effects of aromatase and tamoxifen?
tamoxifen:
- positive effect on endometrial ER - uterine polyps, endometrial cancer
- DVT
- visual disturbances
- protects bones from osteoporosis
aromatase inhibitors:
- less risk of DVT
- increases osteoporosis
- joint pain.
how is stage 3 -4 breast cancer treated?
bone metastasis: external beam radiotherapy , bisphosphonates (protect against fractures and pain)
tamoxifen in ER positive and if relapse consider chemo
Trastuzumab - HER2 positive in combo with chemo
radiation for brain metastasis
for palliative patients - psychological support
how are biologics / immunotherapy used in breast cancer?
HER2 positive tumours can be treated by Herceptin (monoclonal antibody) e.g. Trastuzumab
however tumour cell adapt by dimerising the HER2 to avoid blockage by Herceptin so Pertuzumab can be used in combo with Herceptin by blocking dimerization so Herceptin is effective.
given every week for 1 year
what are the complications of breast cancer?
psychological distress from diagnosis and treatment
side effects from radiotherapy, chemotherapies and hormones
post op complications
complications of mets: path fracture, hypercalcaemia, spinal cord compression, pleural effusion
what are the poor prognostic factors for breast cancer?
ER negative HER2 positive - aggressive, fast growth, early mets young age large tumour size high grade, lymph nodes
what is the Nottingham prognostic index?
NPI = 0.2xtumour size (cm) + nodes involves (1-3) + histological grade (1-3)
used to predict relapse and survival
what is the breast cancer screening programme?
2 view mammogram in those aged 47-73 years - every 3 yearly high risk (FHx or BRCA) are offered MRI if <40yrs or USS >40yrs
overall screening has improved mortality and prognosis
disadvantage = false positives and distress
list some benign breast conditions
fibroadenoma/ phylloides tumour breast cyst breast infection duct ectasia mastalgia sclerotic / fibrotic lesions fibromatosis
what are phylloide tumours?
benign common breast tumour in young women <30
firm, smooth, painless and mobiles
excision recommended if growing
what are breast cysts?
benign and usually multiple common in >35yrs not fixed can be apocrine or non-apocrine on mammogram appear as holes and USS can be cystic or solid. if large can be aspirated
what type of breast infections can occur?
mainly S.aureus and mainly in breast feeding
treated with Abx and drainage of pus
what is duct ectasia?
duct becomes blocked and secretions stagnate
nipple discharge - brown, green and bloody
nipple retraction with lump
what do you need to find out from someone with nipple discharge?
unilateral/ bilateral?
frequency
colour, consistency?
associated symptoms?
which age group is HER2 positive breast cancers mainly seen in?
younger women
what is the use of ovarian ablation in breast cancer?
inhibits ovaries to stop them producing oestrogen in ER positive breast cancer
can be chemical (zolidex), radiotherapy or surgical (oophorectomy)
what side effect does Herceptin have and how do we monitor for this?
cardiomyopathy
monitor by ECHO
why do majority of HER2 positive breast cancers relapse with brain mets?
Herceptin (monoclonal Ab) is a big molecule and cant cross the BBB
which breast cancers are not picked up well by mammogram?
young women
lobular
