Breast Disease Flashcards
Normal findings in breast exam
ANDI- aberrations of normal development and involution
ANDI
Group of conditions that are so common they should be considered as normal variations of these physiological processes
Changes seen throughout life from menarche –> after menopause
Breast development
Occurs in both sexes from age 10
May be asymmetrical initially
Surgery on developing breast
May significantly damage breast bud with consequent long term deformity:
Juvenile hypertrophy
Accessory breast tissue
Fibroadenoma
Menstruation
Breast undergoes regular changes associated with menstrual cycle
Fibroadenoma
Cyclical nodularity
Localized benign nodularity
Involution
Process begins from 30 in nulliparous women
Fat replaces breast tissue, and lobular stroma replaced by fibrous tissue
Breast cyst
Fibrocystic change
Sclerosing lesions
Duct ectasia
Fibroadenoma
Mainly women early 20s
Arise from lobular units
Consists of stromal tissue + proliferatory epithelium
Well defined, mobile, rubbery mass
Most commonly found upper outer quadrant
Management depends on age, size and anxiety about it
Fibroadenoma management
Young patient, painless, small –> conservative
Older patient, large mass, anxiety –> surgical excision
Phyllodes tumour
Rare fibroepithelial tumour commonly confused with fibroadenoma
Must be excluded in older women by core biopsy
Cysts
Usually found in pre and postmenopausal women due to falling hormones
Fluid filled sac found within the breast that are formed when breast ducts become dilated + filled with fluid
May have one or multiple in both breasts
Round or oval lumps with distinct edges + feel like soft grape
Can increase in size + become tender before menstruation, + decrease in size + become o=painless after menstruation
Cysts management
Usually conservative with reassurance OR aspiration if cyst causing symptoms
Complex radiologically indeterminate cysts should be core biopsied
No malignant potential so surgical excision rare
Multi-duct nipple discharge
Occurs when woman squeezes breast + notes discharge from multiple spots on nipple
If non-spontaneous + from multiple ducts on nipple surface –> normal
Not normal discharge
Blood stained, spontaneous, unilateral + uniductal
–> further investigation
Cyclical mastalgia
Cyclical breast pain is related to menstrual cycle + not associated with specific underlying breast disease
Affects 2/3 of women- 1 in to have moderate/severe pain
Cyclical breast pain clinical features
Starts during luteal phase (2 weeks before period), increases until menstruation begins, improves after period
Dull, heavy, aching
Usually bilateral
May be poorly localised + extend into axilla
Cyclical breast pain reassurance + advise
Reassure no underlying pathology Wear soft-fitting bra Take pain relief Keep pain diary Severe pain- primrose oil, progesterone only contraceptive, low fat diet
Radial scar + complex sclerosing lesion
Areas of benign myoepithelial proliferation
Complex sclerosing lesion>1cm
Radial scar<1cm
Asymptomatic- detected on mammography screening
Require careful investigation (core biopsy) as can radiologically appear similar to carcinoma
Mammographic surveillance continued after diagnosis
Mammography
Highly sensitive for all breast lesions in women over 40 where breast tissue less dense
Used as screening method for BC for women >50 every 3 years
Plain X Ray of breast done with 2 views- craniocaudal and medial-lateral-oblique)
Mammogram- advantages
Gold standard due to high sensitivity for symptomatic BCs (around 95%)
Good for localisation of breast lesions, especially those that are impalpable
Can visualise micro-calcifications
Can exclude multiple lesions before surgery on one lesion
Valuable to compare to old images as they are standardised
Mammogram- disadvantages
Breast compressed between two plates –> uncomfortable
Less sensitive in <40 as tissue more dense + lesions harder to identify
Ultrasound
High frequency sound waves directed through breast, and reflections from different tissue components are detected + turned into images
Ultrasound- advantages
Specificity of distinguishing a cyst from solid lesion almost 100%
Best imaging <40 with dense breast tissue
Allows guidance for FNA or core biopsy
No radiation
Not uncomfortable
Can distinguish discrete lumps from areas of nodularity in young women
Can also visualise axilla for nodes
Ultrasound- disadvantages
Operator dependent
Poor visualisations of micro-calcifications
Poor screening tool as less sensitive than mammography
Less valuable to compare to old images as user dependent + live images
Fine needle aspiration (FNA)
Sample of cells taken from lesion + examined under microscope
FNA Advantages
Quick and easy
Results available fast (30mins)
Samples large area
FNA Disadvantages
Information limited to malignant or benign –> no differentiation between malignant lesions)
Results dependent on person performing the FNA + cytologist interpreting it
Cannot assess micro-calcifications
Core biopsy
Sample of cells within the breast architecture using a wide bore needle which can then be examined under microscopy
Core biopsy advantages
Larger sample so more of the lesion is samples
Cells are within the breast architecture so more information on morphology, grading, receptor status is available
Core biopsy disadvantages
More bruising and pain
Results take longer (24-48hrs)
Distant disease
Cause of 90% of deaths from breast cancer
Most common site of metastasis
Bone
Severe and progressive pain
Pathological features
Erythema over affected bone
Metastasis Lungs
Chronic cough
Dyspnoea
Abnormal CXray
Chest pain
Metastasis Brain
Persistent, progressively worsening headache Visual changes Seizures Nausea or vomiting Vertigo Behavioural + personality changes Increased intracranial pressure
Metastsis liver
Jaundice Elevated liver enzymes Abdo pain Loss of appetite Nausea + vomiting
Systemic symptoms of metastatic disease
Fatigue
Malaise
Weight loss
Poor appetite
Scoring system using 3x assessment- modalities
Clinical assessment (palpation)- P Mammography- M Ultrasound- U Biopsy- B Cytology- C
Modality scoring 1
Normal appearance (or inadequate assessment e.g. needle doesn’t hit its target in FNA)
Modality scoring 2
Consistent with a benign lesion
Modality scoring 3
Atypical or indeterminate but probably benign
Modality scoring 4
Suspicious of malignancy
Modality scoring 5
Consistent with a malignant lesion
Evidence of role of breast screening programmes
Mammograms every 3 years women 50-70
Mammograms sensitive enough to pick up breast lesions that may be asymptomatic and impalpable
Prolongs life of 1 person for every 2000 ppl screened
Incidence BC
Most common cancer in UK (men and women combined)
1 in 8 women diagnosed in life
Incidence increases with age with half being diagnosed 65+
BC mortality
3rd most common cause of cancer death
5 year survival 77%
65% ppl with breast cancer will survive 20 years or more
BC RFs
Female Increasing age PH of breast cancer FH of breast cancer Increased oestrogen exposure Diet and lifestyle Radiation exposure before 40 Prior benign or premalignant breast disease
Risk reduction strategies
CHildbirth before 30
Exercise 3-5 hours per week
Normal weight
Limit alcohol
No smoke
Avoid prolonged hormone therapy
Preventative mastectomy for those with genes
Tamoxifen can be used as primary prevention
Aromatase inhibitors (postmenopausal)–> anastrozole, exemestane, letrozole
Anastrozole, exemestane, letrozole
Aromatase inhibitors
Aromatase inhibitors
Anastrozole, exemestane, letrozole
Non invasive carcinoma in situ
Has not progressed beyond basement membrane
Non invasive carcinoma in situ examples
Ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ (LCIS)
Ductal carcinoma in situ
Non invasive
Cancer of epithelial cells of breast ducts
Lobular carcinoma in situ
Non invasive
Cancer of epithelial cells of breast ducts
Invasive carcinoma
Has spread beyond the basement membrane
Infiltrating ductal carcinoma
Infiltrating lobular carcinoma
Infiltrating ductal carcinoma
Most common type- 80% of invasive
Arise from epithelial layer of ducts within the breast + has shown invasion through the basement membrane
Hard, irregular, well defined lump
Infiltrating lobular carcinoma
15-20% invasive carcinomas
Arises from epithelial tissue within lobules
Presents as diffuse thickening (rather than distinct lump)
Hard to see on mammogram and not as distinct on clinical exam, so delay in diagnosis compared to ductal
Paget’s disease of breast
Adenocarcinoma that mainly affects nipple
Associated with underlying parenchymal cancer (usually IDC or more uncommonly DCIS)
Lymphoma
Large number of lymph nodes within breast so lymphoma can occur
Inflammatory carcinoma
Uncommon
Malignant Breast cancer presentation- Mass
Often non-tender
Often hard, fixed to skin/muscle, irregular texture, poorly defined margins
Doesn’t change with menstrual cycle
Malignant Breast cancer presentation- Skin changes
Thickening of skin
Oedema–> peau d’orange
Erythema + other discolouration
Malignant Breast cancer presentation- lymph nodes
Enlarged in axilla
Malignant Breast cancer presentation- Nipple changes
Inversion Discharge (often bloody, spontaneous and one duct only)
Malignant BC imaging
First line if above 40- mammogram (can localise lesion + show micro-calcification)
Second line- ultrasound (good for differentiating cysts from solid masses)
MRI may be indicated in high risk patient due to increased sensitivity
Malignant BC Biopsy
FNA- can obtain rapid diagnosis of cancerous cells but can’t differentiate between malignancies
Core biopsy- preferred modality of diagnosis as enable differentiation between pre-invasive and invasive, less likely to be associated with inadequate sampling + also enables assessment of receptor status
Grading BC
1= well differentiated 2= moderately differentiated 3= poorly differentiated
Staging BC
T= tumour (X-4d) N= nodal involvement (X-3) M= metastasis (X-1)
Staging BC- T
Tis= carcinoma in situ T1= tumour <2cm in greatest dimension T2= 2-5cm T3= >5cm T4= any size with extension to chest wall (4a), oedema (4b), both (4c), or inflammation (4d)
Staging BC- N
N0- no nodal involvement
N1-3= metastasis to increasing number of nodes
Staging BC- M
M0- no evidence
M1= distant metastasis >0.2m
Oestrogen + progesterone receptors in BC
Determined using immunohistochemistry on samples obtained from core biopsy
Scoring system 0-5 used to show proportion of cells that stain positive
Scoring system 0-3 used to show staining intensity
Combined score 0-2 negative, score 3-8 positive
HER2 in BC
Initial test performed using immunohistochemistry
If IHC score 2+ –> fluorescent in situ hybridisation (FISH) can be used to see if HER2 being overexpressed and therefore poses as potential treatment target 9e.g. Herceptin)
Tumour size- stage
Larger size increases risk of nodal involvement + recurrent risk
Lymphatic + vascular invasion- stage
Increases risk of local + distant invasion –> worse prognosis
Nodal involvement- stage
Any nodal involvement suggests local advancement of disease–> worse prognosis
Distant metastasis- stage
Decreases change of recovery and remission
Grade
Higher grade tumours have worse prognosis compared to lower grade as tend to grow slower + less likely to spread
Receptor status- HER2
HER2+ is a negative prognostic factor –> increased tumour aggressiveness and rate of recurrence
Receptor status- ER and PR
ER- and PR- is a negative prognostic factor (HR+ status usually means tumour is of a lower grade and less aggressive
Receptor status- triple negative
Poor prognosis
Proliferation markers
Can be used to asses speed of growth
Age of diagnosis
Women diagnosed under 35 tend to have more aggressive, high-grade tumours
Wide local excision
Tumours <2-4cm in diameter or a low tumour to breast volume ratio
Therapeutic mammoplasty can be used to reshape the breast using woman’s own tissue to prevent large defects
All cases of WLE for invasive cancer require post-op radiotherapy
May need repeat surgery if surgical margins not clear
Mastectomy
For larger tumours or a large tumour to breast vol. ratio
Also used commonly for tumours involving nipple
Indicated for locally advanced tumours including inflammatory cancers
Breast reconstruction
Sentinel node biopsy
Done if preoperative ultrasound + biopsy of axillary lymph nodes show no abnormality–> only done in DCIS if imaging suggests invasive disease
Blue dye and technetium 99 injected in breast to identify sentinel node which can then be removed and sent for biopsy –> if comes back with cancer cells, clearance or radio
Axillary node clearance
Done if preoperative ultrasound + biopsy of axillary lymph nodes show suggestion of migration of cancer to axillar nodes
If even one suspected, all nodes removed
Breast surgery complications- Musculoskeletal
Anaesthesia of armpit
Winged scapula
Frozen shoulder
Stiffness
Breast surgery complications- Lymphoedema
5-50% women following axillary surgery
–> manual lymphatic drainage, massage, arm elevation, compression garments
Breast surgery complications- wound problems
Skin flap necrosis
Breakdown wound edges
RFs- smoking, diabetes, obesity, CT disorders
Adjuvant therapy
Therapy given after surgery to reduce recurrence risk
Adjuvant therapy- Low Risk
Hormonal therapy only
Node negative, tumour <2cm, grade 1, no lymphovascular invasion, HER2 not overexpressed, age >35
Adjuvant therapy- Medium Risk
Hormonal therapy if responds, or chemo
Node negative
1 of: tumour >2cm, lymphovascular invation, HER2 overexpressed, age<35
Adjuvant therapy- High Risk
Hormonal therapy + chemo
Node positive + HER2 overexpressed
Neoadjuvant therapy
Given before surgery to make surgery possible or easier
Often done for tumours >2cm or nodal involvement
Common combination neoadjuvant therapy for aggressive HER2 positive breast cancer
trastuzumab
peruzumab
docetaxel
Radiotherapy
High energy x ray beams directed at cancer cells to kill them
Used to treat residual disease in breast + reduce chance local recurrence
Radiotherapy SEs
Erythema Skin desquamation Aches and pains Breast fibrosis Breast lymphoedema Rib fractures and pain Pneumonitis Brachial plexus discharge
High risk cases for Radio
Large tumours >5cm
Margins <1cm from pec major or skin
Positive lymph nodes 4+
Lymphovascular invasion
ER+ BC
Selective oestrogen receptor modulators
Aromatase inhibitors
GnRH agonists
Surgical oophorectomy
Tamoxifen
Selective oestrogen receptor modulator Act as oestrogen antagonists in breast + therefore reduce rate of proliferation of tumours that express oestrogen receptors Only in ER+ BCs Act as oestrogen agonists in bone First line in pre-menopausal Second line in postmenopausal after AIs
Tamoxifen SEs
Increased risk endometrial cancer
Increased thrombotic tendency
Hot flushes
Aromatase inhibitors examples
Anastrozole
Exemestane
Letrozole
Anastrozole
Aromatase inhibitor
Aromatase inhibitors MOA
In post-menopausal women, most of circulating oestrogen produced by peripheral aromatisation of testosterone produced by adrenal cortex
Drugs that can inhibit this can therefore reduce circulating oestrogen –> reduced proliferation of ER+ breast cancers
Can’t be used in pre-menopausal as has no activity with ovarian pathway of oestrogen synthesis
Aromatase inhibitors SEs
GI upset
High cholesterol
Bone pain
Decreased bone mineral density
GnRH agonists examples
Goserelin
Leuproprelin
GnRH agonists
Inhibit testosterone + oestrogen production
GnRH agonists SEs
Infertility
Decreased bone mineral density
Surgical oophorectomy
Ablation of ovaries
Infertility, decreased bone mineral density
Anti-HER2 monoclonal antibodies
Trastuzumab (Herceptin) - HF, fever, infection, headache, rash
Pertuzumab- diarrhoea, hair loss, neutropaenia
Lapatinib
Dual tyrosine kinase inhibitor against HER2 and EGFR- diarrhoea, nausea, fatigue, rash
Chemo duration
3 weekly for 4-6 months
Chemo anti-metabolite
Methotrexate
Inhibits folate synthesis
Chemo Alkylator
Cyclophosphamide
Direct DNA damage
Chemo Anthracycline
Doxorubicin
Topimerase 2 inhibitor
Chemo Taxane
Docetaxel
Prevents microtubule disassembly
Chemo SEs
Nausea + vom Sore mouth Fatigue Hair loss Bleeding Diarrhoea Oedema Nail disorders Weight loss
Radio main use
Bone metastasis
Can also be used for brain
Pain
Use opioids
Give laxatives as opioids can cause constipation
Bone metastasis + calcium
Can cause hypercalcaemia
Give biphosphonates
