Breast Flashcards
Classification of benign breast lumps
o Non proliferative breast lesions
▪ Simple cysts
▪ Papillary apocrine change
▪ Mild usual type hyperplasia
o Proliferative breast lesions
▪ Intraductal papilloma
▪ Usual type hyperplasia
▪ Sclerosing adenosis
▪ Radial scar
▪ Fibroadenoma
o Atypical hyperplasia
▪ ADH
▪ ALH
Indications of breast MRI
• Breast implants
• Recurrent disease where conventional imaging inadequate
• Risk of multifocality in lobular cancer or occult cancer on mammography
• Assess response after neoadjuvant chemotherapy
- high risk breast screening (<50)
Fibroadenoma
• Pathology
o Aberration of normal development
o Formed by a combination of connective tissue and proliferative epithelium
o Arises from hormone-dependent terminal duct lobular unit
o Influenced by hormones
• Classification
o Depends on stromal element
▪ Simple fibroadenoma – low cellularity stroma with regular cytology
▪ Phyllodes tumour
• Thought to arise from fibroadenoma • Marked cellularity and atypica with stroma
• Simple fibroadenoma
o Features
▪ Benign, mobile, discrete
▪ Rubbery masses
o Clinical
▪ Usually seen in late teens and early 20s
▪ Incidental finding on imaging or palpable lump
▪ Single or multiple
o Aetiology
▪ Unknown
▪ Links to OCP
▪ Links to EBV following immunosuppression
o Workup
▪ US guided core biopsy (patients >23)
o Pathology
▪ Rapid growth can occur in juvenile fibroadenoma or in perimenopausal group
▪ Tumours >5cm are considered ‘giant fibroadenoma’
▪ Macro
• Discrete, bosselated, white tumours that bulge when cut
• Management
o Core biopsy to confirm diagnosis
▪ If multiple, biopsy largest lesion
o <4cm with histological confirmation
▪ Reassurance and discharge
o Symptomatic, significant increase in size, distortion of breast
▪ Excision
o >4cm
▪ Excision
o Histological concern about stroma activity
▪ Excision
Phyllodes tumour
o Definition
o Fibroepithelial tumour with a diverse range of biologic behaviours
▪ From phyllodes – leaf-like
▪ Papillary projections on pathology
o Epidemiology
▪ Rare, 4% of all breast neoplasms
▪ Women 42-45y
▪ older more likely to be malignant
▪ Present 15-20 years later than fibroadenoma
o Can be related to P53 gene mutation
o Clinical
▪ Breast mass
▪ Smooth, multinodular, mobile, painless
▪ 1-41cm
▪ Mass effect rare but can change breast contour
▪ Can have rapid growth
▪ Can produce marked distension and cutaneous venous engorgement
▪ Can have ulceration
▪ Incidental finding on biopsy for fibroadenoma
▪ LN mets very rare (usually haematogenous spread)
• Workup
o Mammogram/ ultrasound / biopsy
▪ Core → stromal overgrowth, mitoses, stromal cellularity
o Pathology
▪ Cauliflower-like appearance
▪ Pseudocapsule with stromal tongues protruding into breast tissue
▪ Brownish colour with areas of necrosis
▪ Not fixed to skin or muscle
o Classify (SAMSOM)
benign vs borderline vs malignant
▪ Stromal cellularity and atypia
▪ Mitotic activity • <4, 4-9, >9/10hpf
▪ Infiltration or circumscribed margins
▪ Stromal overgrowth – most important
o Management
▪ Excision with 1cm surgical margin, clear macroscopic margin
▪ RTX for borderline or malignant
▪ CTX for high risk malignant
▪ No role for hormonal treatment
▪ Metastatic disease
• poor response to radiation, hormone, chemotherapy
• Follow up
o 6 monthly for 2 years
o Prognosis
▪ Local recurrence in 20%
▪ Lymph node metastases are rare (5%)
• Metastasis usually haematogenous like sarcomas → lung most common
▪ Metastasis • <5% phylloides tumours metastasise
o 25% if malignant
o 5YS for malignant phyllodes → 60-80%
Nipple discharge
• Epidemiology
o 5% of referrals of breast clinic
o 20% due to in situ or malignant disease
• Clinical assessment
o Single or multiple ducts
o Coloured or bloodstained
o Induced or spontaneous
o Unilateral or bilateral
o Frequency, colour, consistency of discharge
o Increased risk of cancer
▪ Blood stained (but sensitivity/specificity not high)
▪ Persistent discharge >2x/week
▪ Age
• 3% <40, 10% 40-60, 32% >60
▪ No blood, no mass, <1% cancer
• Aetiology
o Physiological discharge
▪ Coloured opalescent discharge from multiple ducts
o Galactorrhoea
▪ Bilateral, copious, pale milky discharge from multiple ducts
▪ Usually develops after ceasing breast feeding
▪ Causes
• Prolactin secreting pituitary adenoma
• Medications that influence esotrogen/progesterone/prolactin pathway
• Hypothyroidism
• Marijuana
▪ Workup
• Check prolactin level (if >1000mIU/L = elevated)
o Cause – pituitary tumour secondary to medication
o Duct ectasia
▪ Older women with thick yellow discharge
▪ Tortuous and dilated ducts predispose to fluid accumulation
• Results in multiduct discharge
o Benign breast changes (ANDI)
o Papilloma (80% of bloody discharge), cancer, epithelial hyperplasia, DCIS
▪ Serosanguineous, bloody discharge from a single duct
o Inflammatory cause
▪ Periductal mastitis/ abscess
• Examination
o Breast examination for mass
o Pressure around areola to identify any dilated duct (will produce discharge)
o Testing of discharge
▪ Haemoglobin
Investigations
o Ductoscopy
▪ Microendoscope passed into offending duct to directly visualize lumen
▪ Can assist in directing duct excision at surgery and detecting deeper lesions missed by blint centlra excision
o Ductal lavage
▪ Cannulation of duct then irrigation and cytology on subsequent discharge
▪ Role has been questioned due to low sensitivity/specificity
o Ductography
▪ Can identify intraductal lesions
• Filling defect or duct cut off has high PPV for papilloma or carcinoma
▪ Painful therefore limited use
▪ Not widely practiced
o Cytology
▪ Poor sensitivity, limited use
o Mammogram
▪ If patient >35
o Ultrasound
▪ Can occasionally identify papillomas and malignant lesions in ducts close to nipple
• Next steps
o Single duct spontaneous discharge
▪ → surgery to determine cause if
• Blood stained discharge
• Persistent >2x/week
• Associated with a mass
• New serosanguineous discharge in postmenopausal women
Mastalgia
• Symptoms
o Main consideration is referred pain vs breast pain
▪ Referred pain is unilateral, associated with activity, reproduced with pressure on chest wall
• NSAIDs relieve symptoms
o True mastalgia is associated with swelling and nodularity of breasts
▪ Resolves spontaneously in 20-40%, but can recur
▪ Worse before and relieved after menstruation
▪ Exacerbated by perimenopausal state, exogenous hormones (HRT, OCP)
• Aetiology
o Cyclical mastalgia thought to be related to excess prolactin, excess estrogen or lack of progesterone, or increased sensitivity of receptors in breast tissue
• Workup
o History as above
o Examine chest wall
▪ Roll patient and palpate chest wall
o Mammography if patient >40 years
▪ 5% of women with breast cancer complain of pain
▪ 2.7% women complaining of pain are diagnosed with cancer
• Management
o Exclude worrisome diagnoses
o Reassurance
o Analgesia
o Firm bra 24h/day
o Gentle stretching exercises, swimming
o Evening primrose oil not shown to be of benefit in RCA
o Phytoestrogens (soy milk, agnus castus – a fruit extract) – have been shown to have a mild benefit
o Reducing dietary fat intake (<15% dietary calories) – some benefit
o Severe symptoms
▪ Tamoxifen 10mg daily or danazol during luteal phase
Sclerosing adenosis
o Present with palpable mass and breast pain
o Mammogram
▪ Microcalcifications
o Histology
▪ Fibrosis with excessive myoepithelial proliferation
Management
Excisional biopsy
Radial scar and complex sclerosing lesions
o Radial scar <1cm, CSL>1cm
o Usually asymptomatic, found on mammogram
▪ Occasionally present as palpable mass
o Pathology
▪ Can serve as background for formation of ADH, CIS
o Can appear like malignancy mammographically, macro/histo
• Management
o High volume core biopsy or excision biopsy to exclude malignancy
Pseudoangiomatous stromal hyperplasia of the breast
• Benign myofibroblastic proliferation of non-specialised mammary stroma
o Often incidental finding on biopsies
o Can be confused histologically with mammary angiosarcoma – needs IHC to distinguish
• Management
o Excision biopsy
Fibromatosis
• Aka desmoid tumour of breast
• Features
o Infiltrative fibroblastic and myofibroblastic proliferation
o Risk of local recurrence but not metastases
o Rare, <0.2% all primary breast lesions
o Most likely arises from chest wall muscles
• Workup
o Biopsy – often core or vacuum assisted needle biopsies required
▪ If this insufficient, open excision biopsy required
• Management
o Observation only if confirmed diagnosis
o If becomes symptomatic (by invading chest wall and intercostal nerves) → pain → excision
o If recurs after excision, consider excision with 1cm margins
Periductal mastitis
▪ Young women
▪ associated with smoking – toxic metabolites (lipid peroxidase, epoxides, nicotine, cotinine) accumulate
• Gram negative bacteria (smoking inhibits gram positive bacteria) or anaerobes/mixed
• Local ischaemia contributes due to microvascular changes from smoking
▪ May present with mass or abscess
• Often anaerobes
• High rate of recurrence
Treatment
o As for other abscesses (aspiration)
30% get mammary duct fistula after incision & drainage
o Aim for excision 6 weeks after resolution of infection
Mammary duct fistula
• Fistula between damaged / infected duct and skin
• Occurs in 1/3 patients after I+D periareolar abscess
• Management
o Fistulotomy – cut onto a probe into fistula and allow healing by secondary intention
▪ Painful, scarring is worse
o OR Fistula excision and primary closure
▪ Use circumareolar incision if possible for best cosmetic outcome
▪ Need to completely excise granulation tissue-lined tract and affected ducts under nipple
Granulomatous mastitis
o Noncaseating granulomas and microabscesses within a breast lobule
o Epidemiology
▪ Rare
▪ Usually young women, not associated with smoking
o Presentation
▪ Firm irregular mass (may be suspicious for cancer)
▪ Multiple recurrent abscesses
o Aetiology
▪ Thought to be related to Corynebacterium but treatment of these infections does not seem to resolve infection
o Management
▪ Confirm diagnosis on biopsy
▪ Avoid excision of mass
• Usually has persistent wound discharge and failure of wound healing
▪ Steroids and immunosuppressants have variable efficacy
• Does improve symptoms but does not alter course of condition
• Controversial whether useful
▪ Treat superimposed infections as they appear and supportive therapy only
• Usually resolves spontaneously after 6-18 months
Mondor’s disease
o Spontaneous superficial thrombophlebitis of a breast vein
▪ Thoracoepigastric vein
▪ Lateral thoracic vein
▪ Superior epigastric vein
o Thickened palpable cord with surrounding erythema
▪ Never involves upper inner part of breast
o Resolves spontaneously with NSAIDs and massage
Gynaecomastia
• Definitions and epidemiology
o Hyperplasia of stromal and ductal tissue of male breast
▪ Pseudogynaecomastia → similar appearance but is related to excess adipose tissue not hyperplasia or stromal or ductal tissue
o Any age
o Common – 35% men
o Painful concentric swelling
o Benign and reversible
o Differential diagnosis is primary breast cancer
▪ Usually painless eccentric masses
• Aetiology
o Associated with Klinefelter syndrome
▪ Increased risk of male breast cancer
o Relative hyperestrogenism
▪ Decreased androgen production, increased estrogen production
▪ increased peripheral aromatization, reduced androgen receptors
o cause
▪ physiological
• neonatal, puberty, elderly
o usually self-limiting
▪ pathological
• → Klinfelter’s syndrome, hyperprolactinaemia, bilateral cryptochidism, testicular tumour, lung Ca, chronic liver disease, thyrotoxicosis, adrenal disease
▪ pharmacological
• increased beer or cannabis intake – phytoestrogens present in beer
• antiandrogens (spironolactone), gonadotrophin disturbance (H2 antagonists (cimetidine), antipsychotics, methyldopa), estrogen receptor competitors (digoxin, cannabis, griseofulvin), anabolic steroids
• antiretrovirals for HIV
▪ idiopathic
Clinical
o History to identify cause as above
o Examination of breast, axilla, testis, abdomen
o Investigations – aim to identify pathological cause or and exclude primary breast cancer
▪ Bloods – if rapidly growing gynaecomastia
• LFTs, renal function
• Prolactin, AFP, bHCG, total testosterone, TFTs
▪ Imaging – if indeterminate cause, suspicious for cancer or considering surgery
• Mammography / US +/- FNA or core needle biopsy
• US testis/abdo
• Treatment
o Reassurance
▪ 80% resolve in 2 years without treatment
o Stop drug if drug related
o Address underlying cause if pathological
o Medical management
▪ Tamoxifen 10mg daily or danazol 100mg BD for 1 week, TDS for 5 weeks
o Surgical management
▪ If medical failure or if large (class IIa/III)
▪ Technical aspects
• Periareolar incision
• Leave disc of breast tissue behind nipple with intact pectoral fascia and overlying fat to prevent retraction and fixation to muscle (saucer deformity)
• Keep thick skin flaps thick to reduce risk of skin necrosis
• If large consider free nipple grafts , excision of excess skin
▪ Risks
• Nipple necrosis, sensory changes, cosmesis
FNA vs core biopsy
• FNA previous standard of care
o Easy to perform, rapid diagnosis
o No architectural information
o ER but no PR/HER2
• Core biopsy
o Improved sens and spec
o Architectural information
o ER/PR/HER2 receptor status
• FNA still useful for assessment of suspicious lymph nodes
ADH
• Indicator of risk rather than a precursor lesion
• Diagnosis
o Found on core needle biopsy of mammographic microcalcifications
• Histology
o Proliferation of uniform epithelial cells with monomorphic round nuclei
▪ Fill part but not all of duct
o Similar to low grade DCIS but only involves <2mm
• Management
o Wire-localised excision biopsy to exclude associated malignant lesion
▪ 10-20% get upgraded to DCIS or cancer
o No need for re-excision if positive margins
▪ Unless positive only at margins which suggests missed lesion
ALH
• Diagnosis
o Incidental finding on breast biopsy
• Histology
o Proliferation of monomorphic, evenly spaced dyshesive cells that fill but don’t expand a lobule
▪ Can also involve ducts
o Has same cytological and architectural features of LCIS, but is less quantitatively
• Management
o Concordant lesion, incidental ALH → no further treatment
▪ Upgrade to DCIS or cancer is <3% after biopsy
DCIS
• Definition
o Clonal proliferation of malignant epithelial cells confined within basement membrane of mammary ducts, precursor lesion for invasive Ca
• Classification
o Subtype
▪ Comedo
• Central necrosis, multiple mitotic figures, large pleomorphic nuclei
▪ Non-comedo
• Absence of necrosis, no mitotic figures
• Solid, papillary, micropapillary or cibriform, flat (clinging) architecture
o Grade
▪ Low/intermediate/high
• Nuclear morphology
• Mitotic index
▪ High grade
• Necrosis, aggressive biologic characteristics
• High local recurrence rates
▪ I: irregular nuclei, small, no necrosis
▪ II: some necrosis, small nuclei
▪ III: pleomorphic nuclei, commedo necrosis
• Scoring system Van Nuys (Size, Margin, Age, Pathology) – for risk of local recurrence
o Lumpectomy alone for scores 4, 5, 6, lumpectomy and radiation for scores 7, 8, 9. Mastectomy for 10, 11, 12
• Clinical
o 90% asymptomatic
▪ Detected as pleomorphic or linear microcalcifications on mammogram
• Indeterminant calcifications can be examined using magnification views
▪ Incidental calcifications on mammogram that end up being malignant → • 65% pure DCIS • 32% DCIS with cancer • 4% breast cancer
▪ Sterotactic core needle biopsy shows diagnosis
o 10%
▪ Palpable mass
▪ Pagets
▪ Nipple discharge
Indication of mastectomy in DCIS
• Preferred if:
o Multicentric DCIs
o Large lesions
o Centrally located disease
o Inadequate margins after re-excision after BCS
o Patient preference
o Adjuvant radiotherapy contraindicated
• Should have immediate breast reconstruction
Margins for DCIS
2mm margin
SLNB in DCIS
• Nodal metastasis in DCIS <3%
• Consider SLNB if
o Large DCIS >4cm
o Palpable breast lesion, ie mass forming DCIS
o High grade disease
o Microinvasive disease
o Suspicious nodes on examination of ultrasound o → these high risk features increase risk of invasive cancer to 20%)
o Mastectomy
Indication of adjuvant radiotherapy for DCIS
• Indicated after BCS – reduces local recurrence (50%) but does not improve survival
• To chest wall if re-excision for local recurrence or positive margins
• 45-50G over 5 weeks
Indication of hormonal therapy after DCIS surgery
Hormonal therapy (tamoxifen – NSABP-B24 trial)
• Recommended in patients with high risk of developing breast cancer, especially ER+ DCIS
• ER neg – no role
LCIS
• Epidemiology
o Usually presents in 40s
▪ Median age 44-46 (10 years younger than DCIS)
▪ 10% post menopausal
o Increased risk of IBC (7-18x)
▪ 0.5-1% / year
▪ Cumulative risk 7.1% at 10 years = lifetime risk 30-40%
▪ 3x more likely in ipsilateral breast than contralateral breast
• Pathology
o LCIS subtypes
▪ Classic
• Monomorphic population of small, round, polygonal/cuboidal cells
• Thin rim of cytoplasm
• High N:C ratio
• Regular spaced, loosely cohesive
• Fill and distend acini
• Small nucleoli and a few mitotic figures
• Pagetoid spread – neoplastic cells spread along adjacent ducts
▪ Pleomorphic (treat like DCIS as high risk)
• Larger nuclei with prominent nucleoli and mitotic figures
• Central necrosis, calcification within lobules
o Diagnosis pathologically
▪ LCIS → 50% of acini in an involved lobular unit is filled and distended by LCIS cells
• Therefore no central lumina
▪ ALH → cells fill <50% acini or no distension of lobule
• Lumina visible 0.5-3.8% of otherwise benign breast biopsies
• Clinical
o Usually incidental finding after breast biopsy
▪ No specific symptoms, incidence in population therefore unknown
o Often multifocal and bilateral
▪ 50% have multiple foci in same breast
▪ 30% have LCIS in contralateral breast
• Management
o Treat as risk factor for invasive breast cancer
o Excision biopsy recommended to rule out malignancy
▪ Further resection required if pathology/imaging are discordant
o Risk reduction
▪ BRCA1/2 – bilateral mastectomy
▪ Tamoxifen in high risk patients
o Surveillance
▪ 6-12 monthly breast examination
▪ Annual mammogram
Genes involved in breast cancer.
BRCA 1, BRCA 2, p53, STK 11, CDH1, PALB2, PTEN, ATM
Pathophysiology of breast cancer.
o 95% sporadic, 5% hereditary
o Sporadic tumours are related to estrogen exposure
- early menarche
- late menopause
- nulliparity
- COCP/HRT
o Cyclical proliferation of glandular cells within breast related to oestrogen result in increased risk of DNA damage
Morphology of breast cancer.
- ductal carcinoma - 80%
- lobular carcinoma - 10%
- tubular/cribriform - 5%
- mucinous, medullary, micropapillary, metaplastic (5%)
Features of invasive lobular cancer
- 5-10%
Presentation
o often presents as an ill-defined thickening.
o Calcification uncommon, mammogram may be normal or show asymmetry
o FNA error-prone - ~50% false -ve
o Tend to be larger at Dx, but biochemical/genetic features more favourable
o If multicentric in 1 breast, 24% have +ve contralateral biopsy
Pathology
o small cells, “Indian filing”, multicentric. May have co-existing ductal component o Other pathological types - solid, alveolar, mixed
o Cells are monotonous, -> grading is difficult
o Pleomorphic type has nuclear pleomorphism and has poorer prognosis
o Most show loss of expression of CDH1 which encodes E-cadherin
- ER/PR positive, HER 2 negative
Prognosis
o As larger and can be multicentric, more often need mastectomy compared with IDC
o patients with ILC tended to be older and have lower grade tumours, hormone-receptor positive, of larger size and with absence of vascular invasion.
ILC showed indolent but progressive characteristics with nearly linear survival curves that crossed those of IDC after approximately 10 years of follow-up, thus eventually exhibiting a worse long-term outcome.
Secondaries to meninges, serosa, GIT, genital tract, adrenal, other unusual sites
Grading of breast cancer.
- Bloom-Richardson grade (TNM).
- Tubule formation (majority, moderate, little or none)
- Nuclear size/pleomorphism (small, moderate, marked variation)
- Mitotic rate ( 0-5, 6-10, >11)
Grade 1 - 3-5
Grade 2 - 6-7
Grade 3 - 8-9
ER/PR
- Both ER & PR are steroid receptors located in the cell nucleus
Measured using IHC (immunohistochemistry) - recognition of receptor by Ab
Only nuclear (not cytoplasmic) staining indicates a +ve result
Include in report:
o an estimate of the % of nuclei stained
o the predominant intensity of staining (low, intermediate or high)
o a conclusion as to whether the assay is positive or negative
e.g. ≥1% nuclei staining at any intensity (low, intermediate or high)
What percentage of patients respond to hormonal treatment?
o 30% of all comers
o 50-60% of oestrogen receptor positive tumours
o up to 80% of oestrogen/ progesterone receptor positive tumours
HER 2
Human Epidermal Growth Factor Receptor 2
Encoded by ERBB2, a proto-oncogene on chromosome 17
Can heterodimerise with any of the other 3 receptors
o Results in autophosphorylation of tyrosine residues -> signalling pathways -> increased cell proliferation -> decreased apoptosis
HER-2 is over-expressed in 25-30% of breast cancers (gene amplification & up-regulation, not mutation)
HER2 status predicts the response to specific antibody therapy, and several other systemic therapies (e.g. good response to anthracycline chemo, poor response to endocrine Rx), as well as being a general prognostic marker
HER2 assays - currently available techniques for routinely evaluating HER2 status include
o immunohistochemistry for detecting protein overexpression and
A positive HER2 result is 3+, uniform, intense membrane staining of > 30% of invasive carcinoma cells.
A negative result is 0 or 1+ staining.
An equivocal result is 2+. (In this case, in situ hybridisation testing is required.)
o in situ hybridisation for detecting gene amplification.
E.g. chromogenic in situ hybridization (CISH), fluorescence in situ hybridisation (FISH)
FISH measures number of copies of HER2 gene on CH17 (>2 = +ve)
Ki6
▪ Marker of proliferation
-MIB-1 monoclonal antibody staining
Mollecular profiling/subtypes
Luminal A: 50%. Low grade. ER+, PR+, HER2 – [Ki67<14%]
Luminal B: 10%. Higher grade. ER+, PR+/-, HER2 +/- [Ki67>14%]
HER2 enriched: 5-10%. High grade. P53 mutation, ER-, PR-, HER2+
Basal: 30%. Mostly “triple negative”, high grade. ER-, PR-, HER2-
Oncotyping for breast cancer
-Clinical gene expression assays: eg Oncotype DX.
-21 gene reverse transcription PCR assay on tissue provides indepedent prognostic information (individualised risk estimate/recurrence score (0-100) -low<18, inter 18-30, high >30
Breast screening.
o 2 yearly mammogram (sensitivity 80%, specificity 90%) for patients aged 50-74 years
▪ Women 40-49 or >75 can also access screening program
- asymptomatic
- ADH, LCIS, ALH -> annual screening
- hx of breast cancer >5 years since diagnosis -> annual screening
- 200 women, 100 screened, 5 women recalled (4 further imaging, 1 biopsied), 1 cancer.
- early detection benefits -> increased survival, increased treatment options, improved quality of life.
- reduction in breast cancer mortality highest in 50-69yo (21-28%).
WHO principles of screening.
1) important health problem
2) recognisable latent or early symptomatic stage
3) disease process well understood
4) acceptable treatment for patients with disease
5) test with high level of accuracy
6) test accceptable to the population
7) facilities for diagnosis and treatment
8) agreed policy on whom to treat as patients
9) cost should be economical
10) screening should be a continuining process
Managing risk -> average or slighly higher risk (1.5x)
95% population
Criteria
- No FHx of breast cancer
- One FDR diagnosed with breast cancer ≥50yo
- One SDR diagnosed with breast cancer at any age
- 2 SDRs on the same side of the family diagnosed with breast cancer ≥50yo
- 2 FDRs or SDRs diagnosed with breast cancer ≥50yo, but on different side of the family
Management
Usual screening
(Managing risk breast cancer) Moderately increased risk 1.5-3x (<4% of the female population)
Criteria
-One FDR diagnosed with breast cancer <50yo
-2 FDRs on the same side of the family diagnosed with breast cancer
-2 SDRs on the same side of the family, at least one <50yo
Management
At least 2 yearly MMG from 50-74yo
Annual MMG from 40yo if FDR diagnosed <50yo
Consider tamoxifen for risk reduction
(Managing risk breast cancer) High risk >3x, or carrying a mutation (<1% female population)
Criteria
-Women at potentially high risk of ovarian cancer
-3 or more FDRs or SDRs on the same side of the family with breast or ovarian cancer
-2 or more FDRs or SDRs on one side of the family diagnosed with breast or ovarian cancer if any of the following applies to at least one of the relatives:
-Breast cancer <40yo
-Ovarian cancer <50yo
-Bilateral breast cancer
-Breast and ovarian cancer in the same woman
-Ashkenazi Jewish ancestry
-Male breast cancer
-One FDR or SDR diagnosed <45yo plus another FDR or SDR on the same side of the family with sarcoma <45yo
-Member of family in which presence of a high risk breast cancer gene mutation has been established
Management
-Individualised surveillance program - may include regular clinical examination and annual breast imaging with MMG, MRI or U/S
-MRI screening rebated by Medicare for screening of asymptomatic women <50yo who are high risk due to strong family hx or genetic mutation
-Referral to cancer specialist of family cancer clinic for risk assessment, possible genetic testing
Risk reduction strategies
-Bilateral mastectomies (>30yo)
-Aim to reduce risk as close to 0% as possible
-4% recurrence at 10 years
-BSO (>40yo)
-Lifetime ovarian ca risk
-BRCA1 - 40-50%
-BRCA2 - 10-20%
-96% risk reduction
Reduces breast cancer incidence 30-45%
Early BSO not recommended
Average age ovarian ca 51yo
Premature menopause -> require HRT -> increased cancer risk again
What is BIRADS classification?
- Breast imaging, reporting, and data system.
- 7 categories.
0 - incomplete (needs further imaging)
1 - negative (routine screening)
2 - benign (routine screening)
3 - probably benign (risk of Ca <2%, short interval f/up)
4 - suspicious (risk of Ca 2-95%, biopsy)
5 - highly suggestive of malignancy (risk of Ca >95%)
6 - biopsy proven Ca
Types of biopsy on a breast lesion.
o Core needle biopsy is preferred
▪ Sensitivity 95-99% vs FNA 70-90%
▪ Provides histological and architectural information rather than just cytology
o Image guided
▪ Ultrasound preferred if lesion visible on ultrasound or palpable
▪ Alternative is stereotactic using mammography-guidance o If unable to safely biopsy lesion
▪ Can place guidewire and perform surgical excision biopsy
o Discordance
▪ Imaging suggestive of malignant but biopsy is benign → excision biopsy to exclude malignancy
Staging for breast cancer
-TNM staging.
T stage
- Tis: carcinoma in situ
- T1: <2cm
- T2: 2-5cm
- T3: >5cm
- T4a: chest wall
- T4b: satellite
- T4c: a+b
- T4d: inflammatory breast cancer
N stage
- N1: 1-3 LN (axillary)
- N2: 4-9 LN or internal mammary without axillary
- N3: 10+ LN or infraclavicular, int mammary, supraclavicular with axillary
M stage
- M1: distant mets
Breast conserving: WLE + RTx.
o Survival equivalence to mastectomy. LR rates ~14% BCS + RT vs 10% Mastec. (LR 35% without RT)
o Contraindications: muticentric/multifocal, extensive DCIS or indeterminant calcs, locally advanced or inflammatory br ca, tumour to breast ratio >20%, relative contra in BRCA.
o Localisation: palpation, image guided HWL (US, stereo), radionucleotide seed implant, Bx clip, carbon
o Procedure: Incision over tumour (curvilineal skin tension lines or radial in inf/medial breast), excise with adequate margins (>2mm microscopically clear), orientate, specimen imaging
Contraindication of nipple areolar complex sparing mastectomy.
- extensive DCIS
- tumour >4cm
- <2cm from NAC
- inflammatory breast ca
Indications for axillary clearance.
- palpable lymphadenopathy
- FNA pos node
- T4/inflamm tumour
- Pos SNBx (>3 nodes, [consider in 1-2 macromets], T3 tumour, mastectomy, no breast radiation)
Indications for radiotherapy as adjuvant treatment.
o Post WLE: 6/52 whole breast external beam radiation + boost to tumour bed
o Post mastectomy: positive margins, nodal disease >3 or 2 (with 15yr life expectancy), T3/4 tumour
Locally Invasive Breast Cancer Definition
<5cm
impalpable or palpable but not fixed nodes
no mets
T1-2, N0-1, M0
Risk of breast cancer with benign breast disease.
- no proliferative aspect - no increased risk
o proliferative - <double
o atypical hyperplasia - 4 x increase,
o atypical + FHx - 10 x increase
o LCIS - 10x increase (bilateral), DCIS - 10x (unilateral)
Staging in breast cancer
clinical stage III disease further investigation is warranted (staging).
o CA 15.3
o Bone scan
o CT CAP
ITC vs micro vs macromets
ITC -> <0.2mm
micrometastases - 0.2mm - 2mm
macrometastases - >2mm
Synoptic report for breast cancer
Site
o E.g location in mastectomy, distance from margins
Tumour type
Invasive carcinoma size & lesion size
o E.g. 3mm invasive in 10mm DCIS
Grading (Bloom & Richardson -> Tubular formation, Nuclear size/score, Mitotic rate; grade 1 3-5, grade 2 6-7, grade 3 8-9)
- LVI
- resection margins (invasive Ca -> no tumour on ink, DCIS -> 2mm)
- receptors (ER/PR/HER 2)
- DCIS
- other findings (ALH/ADH)
- axillary findings (SLNBx vs ALND; no of pos nodes; no of nodes harvested; ITC vs micro vs macromets; extranodal extension)
Trastuzumab (Herceptin)
Humanised monoclonal Ab to EC domain of HER2 protein
Patients with early breast cancer are eligible for immunotherapy with trastuzumab only if HER2 gene amplification has been demonstrated by in situ hybridization (41% of FISH +ve respond to herceptin, 5% of FISH -ve)
Patients with metastatic disease are eligible for trastuzumab therapy if a 3+ positive result has been demonstrated by immunohistochemistry or HER2 gene amplification has been demonstrated by in situ hybridisation.
Contraindications of WLE
o T4, N2 or M1
o Patient choice
o Clinically/radiologically evident multifocal/multicentric disease
o Large/central tumours in small breasts
o High risk women (FHx, BRCA)
o Contraindication to XRT
Pregnancy
Previous XRT
Collagen vascular diseases
Types of breast reconstruction
Immediate vs delayed
Autologous vs implant
Immediate breast reconstruction
Advantages
o No loss of ‘breast’
o Single operation & hospital stay
o Preservation of skin & inframammary fold
o Skin-sparing & subcutaneous mastectomy techniques can lead to better cosmetic result
Disadvantages
o Limited time for decision-making
o increased operating time
o difficulties of co-ordinating two surgical teams
does not compromise adjuvant treatment
o although complications could result in delay in starting adjuvant treatment
Adjuvant radiotherapy
o Can have detrimental effects on breast reconstructions
o These can be decreased by choosing autologous over implant
o Consider delayed-immediate reconstruction
Delayed breast reconstruction
Advantages
o Unlimited time for decision-making -> Full pathology available
o Avoids any potential delay of adjuvant treatment
o Avoids detrimental effects of adjuvant therapy on reconstruction
Disadvantages
o Skin-sparing mastectomy techniques can’t be used (poor aesthetic outcomes of contracted skin envelope)
larger skin paddle required
o needs 2nd operation/hospitalisation
Implant based reconstruction
Tissue expansion
o Serial expansion of chest-wall to replace skin lost with mastectomy
o ± replacement with silicon implant
o difficult to create ptosis
best result with bilateral procedures
Indications
o Small, non-ptotic breasts
o Bilateral reconstruction
o Unwilling/unfit to undergo autologous
Contraindications
o Very thin chest-wall tissues
o Mastectomy skin flaps threatened
o Absent pec major
o Radiotherapy significantly increases risk of complications & decreases aesthetic result
Surgical techniques
o Tissue expander under pec major
o Weekly serial expansion after 2-4 weeks
o 1-3 months after maximal expansion – expander removed, capsulectomy & definitive implant
o 30% will need further surgery within 1st 5yrs to optimise aesthetic appearance
o long-term aesthetic results decrease with time (ptosis of contralateral breast -> asymmetry)
Complications
o Early: haematoma, infection, skin flap necrosis, wound dehiscence
o Late: implant rupture, malposition, extrusion, capsular contracture (increased after XRT), breast implant associated - anaplastic large cell lymphoma)
Autologous breast reconstruction
Indications
o Immediate reconstruction when adjuvant radiotherapy planned
o Delayed reconstruction following adjuvant XRT
o Large ptotic breasts
o Failure of previous implant reconstruction
Pedicled Latissimus dorsi flap
o Usually combined with an implant
o Lowest flap failure rate
o Indications
High risk for autologous reconstruction
Abdomen unsuitable as donor site
o Disadvantages
Scar on back
Shoulder stiffness & impairment of upper limb function
o Complications
Early: haematoma, infection, breast skin necrosis, partial/complete flap failure
Late: seroma, implant Cx
- Lower abdominal flaps
o Contraindications
Absolute
Previous ligation of flap pedicle
Previous abdominoplasty
Relative
Multiple abdominal scars
Previous abdominal liposuction
o Surgical techniques
Transverse rectus abdominus myocutaneous (TRAM) flap -> Pedicled or free
Deep inferior epigastric perforator (DIEP) flap
o Complications
Early: Thrombosis of arterial or venous anastomosis, Haematoma, Partial or total flap loss, Fat necrosis, Wound breakdown
Late: Donor-site bulge or hernia, decreased abdominal strength
SNAC (SN bx vs AC)
o Multicentre randomised controlled trial
o SNAC 1
Is SNB associated with less morbidity and equivalent cancer-related outcomes than AC in early breast cancer?
Yes (decreased arm swelling & functional problems)
o SNAC 2
Extended eligibility
1o tumours >3cm, multiple tumours in same breast
endpoints: local axillary recurrence, diagnostic accuracy of SNB
Management of breast cancer in pregnancy.
Local
o Risk of spontaneous abortion highest in 1st trimester
o Mastectomy is procedure of choice, especially if 1st trimester (delay to XRT)
o Breast conserving surgery is feasible in 2nd & 3rd trimesters
Axilla
o SLNB
can be performed with lymphoscintigraphy, effect of blue dye (& risk anaphylacxis)
Systemic
o Chemo contraindicated in 1st trimester but can be given safely in 2nd & 3rd
Recommended in node +ve disease (within 6 weeks of surgery)
- If using trastuzumab – monitor for oligohydramnios
Should be stopped 3 weeks before delivery to avoid myelosuppression & septic complications in mother & baby
o Endocrine Rx not recommended
Locally advanced & inflammatory cancer
o 3 strategies
termination of pregnancy
chemo with acceptance of foetal risks
delay cancer Rx with acceptance of cancer risks
Future pregnancy
o Counselling re effect of chemo
o Should wait at least 6 months after completion of treatment
Prognosis
o Tends to be Dx at more advanced stage
o More likely to have large tumours, LVI & mets
Indications for neoadjuvant chemotherapy in breast cancer.
▪ Downstaging to facilitate BCS rather than mastectomy
▪ Unresectable / locally advanced tumours
▪ Node positive disease
▪ Inflammatory breast cancer
▪ Delay to surgery (pregnant, recent AMI)
▪ Consider in triple negative or HER2 enriched
Work up pre neoadjuvant chemotherapy and post neoadjuvant management.
▪ Needs extensive workup before starting treatment
• Core biopsy of breast
• Mark tumour and positive axillary nodes
• Axillary imaging
• Breast MRI to assess radiological response pre and post treatment
• Formal staging
o Bloods
o CT chest abdo pelvis
o Bone scan o +/- PET CT
▪ Assess response after 2-4 cycles
• If responsive, continue for 8 cycles and then assess suitability for surgery
• If unresponsive, change chemotherapy regimen or use RTX and reassess
▪ Managing axilla
• If clinically negative, perform SLNB after neoadjuvant chemotherapy
• If clinically positive, restage axilla after neoadjuvant chemotherapy
o If remains positive → axillary dissection
o If becomes negative → targeted biopsy + SLNB in select cases or ALND
Add axilla RTX after ALND.
o ECE, perinodal fat invasion, large number of +ve nodes, <10 axillary nodes dissected
Adjuvant endocrine treatment
Treat all ER positive tumours using SERM (tamoxifen) or aromatase inhibitor (anastrozole)
▪ SERMs
- Selective oestrogen receptor modulators (SERMs) are competitive ER antagonists with partial agonist activity.
- tamoxifen 20mg/d.
• For premenopausal women
• Recommended treatment for 5 years
o Decreases risk of death by 1/3
• Small increased risk of uterine carcinoma and venous thrombosis
▪ AIs
- block conversion of adrenally synthesized androgens to oestrogen
- Exemestane, anastrazole, letrozole
• For post menopausal women
• Slightly kore efficacious
• Duration is unclear, some advocate for lifelong if high risk. Otherwise 5-10 years is a good start
• Side effects
o Osteoporosis, vaginal dryness and atrophy, dyspareunia
- Zoladex
- oophorectomy
Adjuvant chemotherapy
AC followed by T – 3-4 cycles AC x2-3 weeks then 3-4 cycles T x 2-3 weeks = 12-24 weeks
▪ Anthracycline (Doxorubicin)
• Cardiotoxicity
▪ + Cyclophosphamide,
• Haemorrhagic cystitis
▪ Followed by Taxane (Paclitaxel)
• Peripheral neuropathy
Indications for referral to genetics
1) Pathogenic variant identified in the family.
2) Tumour pathology
- TNBC <=50 years
3) Personal hx of cancer
- male breast cancer
- breast cancer and Jewish ancestry
- Two primary breast cancers in the same person (where the first <60 years)
- Two or more different but associated cancers in the same person (breast and ovarian Ca)
- breast cancer <=40years
- lobular breast cancer + family hx of lobular breast/diffuse type gastric Ca
- breast Ca Dx <50 years with limited family structure/knowledge
- breast Ca + family hx of Peutz-Jegher/Cowden/Li Fraumeni
4) For those with family hx of cancer
- Two 1st or 2nd degree relatives diagnosed with breast or ovarian cancerplusone or more of the following on the same side of the family:*
+ additional relative(s) with breast or ovarian cancer
+breast cancer diagnosed <50 years
+more than one primary breast cancer in the same woman
+breast and ovarian cancer in the same woman
+Jewish ancestry
+breast cancer in a male
+pancreatic cancer
+high grade (> Gleason 7)prostate cancer
Indication to test for BRCA 1 and 2 pathogenic variant
Manchester score >= 15 (10% probability)
The scoring system includes information of the Age Dx of cancer, breast cancer histology, grade and receptors, ovarian cancer pathology, lack of family hx
Paget’s disease of breast
- Definition
Malignant intraepithelial adenocarcinoma of the nipple-areolar complex (pagetoid cells) - Pathology
o Pagetoid cells
▪ Large round or oval cells with large pleomorphic, hyperchromatic nuclei
▪ Prominent nucleoli
▪ Clear, pale cytoplasm
o Reactive epidermis/dermis changes with lymphocytic infiltration and angiogenesis
▪ Hyperaemic, exudative appearance
• Pathogenesis – 2 theories
o 1- in situ transformation theory: pagetoid cells are keratinocytes that have undergone malignant transformation
o 2 – epidermotropic theory: cells migrate along basement membranes and enter epidermis and nipple-areola complex from ducts
- Workup
o Biopsy if not clearly contact dermatitis ▪ Punch biopsy
• If non-diagnostic → excision biopsy
▪ Histology shows • → pagetoid cells, IHC positive for CK7, CAM-5.2, AE1/AE3, S100
o Note HMB-45, keratinins are negative (melanoma)
• 90% are HER2 positive
o Bilateral mammography, and ultrasound
▪ Standard investigation of lesion if found
▪ Consider MRI if select patients – mammogram can miss many underlying cancers in pagets
• Management
o Nipple areolar complex involvement only
▪ Treat as DCIS
▪ Resection of nipple areolar complex + adjuvant radiotherapy
• OR mastectomy with SLNB
▪ Adjuvant hormonal treatment
• Recommended if ER+
o Underlying tumour
▪ Total mastectomy or central lumpectomy (if centrally located) with radiotherapy
• Mastectomy if underlying tumour is distant from nipple areolar complex
▪ SLNB
Pathogenesis of duct ectasia
Theories
o ?aberration of processes of normal duct involution
o Hormonal
Endocrine-induced relaxation of contractile, myoepithelial elements of duct wall
However Dexon et al found no relation between parity/breastfeeding & duct ectasia
o Obstruction & stagnation
Terminal portion of duct often blocked with squamous cells
o 2o inflammation
o Lymphatic blockage
Lactational mastitis
Epidemiology
o Most common type of infectious mastitis
o 2-10% of breastfeeding women
Aeitiology
o Usually associated with breastfeeding problems
o Risk factors:
Mastitis with previous child
Severe prolonged unilateral engorgement
Nipple cracking
Investigations
o Milk culture may help if hospital-acquired or not responding to Abx
o U/S to exclude abscess
o MRI if inflammatory breast cancer is suspected
DDx
o Blocked lactiferous duct – tender, palpable lump without systemic un-wellness
o Galactoceles – milk retention cysts. Not tender or systemically unwell
o Inflammatory breast cancer – peau d’orange
Microbiology
o Staphylococcus aureus
o increasing incidence of MRSA
o less frequent: S. pyogenes, E. coli, bacteroides, Corynebacterium spp, coagulase negative staphylococci
Treatment
o Symptomatic relief
o Breast emptying (improve breastfeeding techniques)
o Antibiotics (cephalexin, clindamycin if suspect MRSA)
o U/S if no improvement in 48-72hrs
Post-irradiation mastitis
o related to obstructed lymphatic flow & responds to manual lymphatic drainage
Male breast cancer
• Epidemiology
o 1% all breast cancer
o 0.1% cancer death in men
o Male breast cancer belt → Atlantic to Indian oceans in sub-Saharan Africa (Tanzania 6% of breast cancers)
• Pathology
o 90% are invasive
▪ 10% DCIS
o 80% ductal 5% papillary 1% lobular
▪ Similar proportions to breast cancer in female
o Hormone status
▪ ER+/PR+ more likely in males
▪ HER2 data inconclusive
• Clinical
o Increasing incidence with age
▪ Age of diagnosis 10 years later in men than women
o Painless mass
▪ 85% of presentations
o Usually centrally located with nipple retraction, discharge, pain, ulceration
▪ 50% of presentations
o Often delayed diagnosis
▪ 22 months average from symptoms to diagnosis
o Risk factors
▪ Hormonal misbalance
• Obesity, cirrhosis (hyperestrogenic milieu)
▪ Klinefelters – 50x increased risk
• 47XXY karyotype
• Small testes
• Gynaecomastia
▪ Family history
• 15-20% male breast cancer has family history
o Probably related to BRCA1 and BRCA2 carriage
▪ Radiation exposure
▪ Obesity
▪ Gynaecomastia is not a risk factor
- Treatment
o Early breast cancer
▪ Mastectomy
• Resect part of pectoralis major to get negative margin if required
o Locally advanced disease
▪ Neoadjuvant therapy then surgery as for female breast cancer
o Axillary staging
▪ As for female breast cancer
o Adjuvant therapy
▪ As for females
• Treatment of metastatic disease
o Hormone receptor positive
▪ Tamoxifen is drug of choice
• Aromatase inhibitors less effective because
o only partially block production (80% peripheral, 20% testis)
o decreased estrogen stimulates testicular production by feedback to hypothalamus
• aromatase inhibitors therefore should only be used in conjunction with orchidectomy (medical or surgical)
o HR negative
▪ Chemotherapy
US features of abnormal LN
Round
Loss of fatty hilum
Thickened cortex (>3mm)
US features of malignant masses
o Irregular shape
o Indistinct, microlobulated, spiculated margins
o Height > length
o Hypoechogenicity
o shadowing
Lymphoedema
Definitions and epidemiology
o Abnormal accumulation of interstitial fluid and fibroadipose tissue due to impaired lymphatic drainage
Pathophysiology
• Normal flow
o Lymphatic capillaries normally uptake interstitial fluid in low flow state
▪ Facilitated by skeletal muscle contraction
o Capillaries merge into vessels which have specialized smooth muscle providing peristaltic contraction
o Lymphatic vessels have unidirectional valves
o Vessels drain into thoracic duct which enters left subclavian vein and left IJ junction
▪ Right upper body drains into right lymphatic duct via similar IJ SC vein junction
• Lymphoedema
o Occurs when lymphatic load exceeds transport capacity of lymphatic system causing fluid accumulation in interstitium
o Imbalance occurs
▪ Congenital malformation of lymphatic system
▪ Damage to lymphatic vessels or lymph nodes
o Persistent accumulation of lymphatic fluid promotes proliferation of adipocytes and deposition of collagen in the ECM resulting in fibroadipose tissue accumulation
▪ Inflammatory response with macrophages, fibroblasts → fibrosis, adipose hypertrophy, acanthosis, hyperkeratosis
▪ Predisposes to recurrent cellulitis and lymphangitis
▪ Chronic lymphoedema can degenerate to an aggressive lymphangiosarcoma (Stewart Treves syndrome)
o NOTE
▪ Rate of capillary filtration remains normal
• In generalised oedema, intact lymphatics are overwhelmed by excessive capillary infiltrate
Causes for lymphodema
Primary
- congenital
-lymphodema precox (<35)
- lymphodema tarda (>35)
Secondary (TRIMS)
Staging of lymphodema
0 - no odema, subclinical
1 - pitting odema, resolves with elevation, no fibrosis
2 - non pitting odema, not resolves with elevation, mild fibrosis.
3- lymphagiostatic elephantiasis, non pitting odema, not resolves with elevation, severe fibrosis
Managemet of lymphoedema
• General measures
o Self-monitoring
o Limb elevation
o Diet and exercise (weight loss)
o Avoid skin infection/injury
▪ Treat cellulitis aggressively
▪ Avoid blood tests / IVCs
▪ Avoid limb constriction with blood pressure cuffs (LND but not SLNB)
• Compression therapy
o Compression bandaging
o Compression garments
o Intermittent pneumatic compression
• Physiotherapy
o Manual lymphatic drainage
o Complete decongestive therapy
o Surgery
• Lymph node transplantation
• Lymphovenous bypass
▪ Debulking procedures to remove fibrofatty tissue deposits -> Liposuction
