Breast Flashcards
Describe the mammogram breast density scoring
A - almost entirely fatty
B - scattered fibroglandular density
C - heterogeneously dense
D - extremely dense.
A mammogram easier to interpret, more sensitive for diagnosing abnormalities, D hardest to find abnormalities, consider other imaging modality e.g. USS and MRI
Describe what features would be concerning on a mammogram
solid mass,
spiculated mass
architectural distortion
microcalcifications (<0.5mm), pleomoprphic calcifications, clustered in one area
What is mammary fistula and how would you treat it?
Definition: Connection Between Mammary Duct & Skin Surface
Most Common After Fine Needle Aspiration (FNA), Biopsy or Surgical Intervention While Breast Feeding
Higher Risk in Central Lesions than Peripheral Lesions
Presentation
Spontaneous Drainage of Milk from the Skin
Diagnosis
Clinical Diagnosis (Based on History & Physical)
US May Assist
Treatment
Stop Breast Feeding
What is granulomatous mastitis? How do you manage it?
Definition: Rare Benign Inflammatory Disease of the Breast Causing Granulomas
Causes:
Idiopathic – May Be Associated with Corynebacterium kroppenstedtii
Tuberculosis (TB)
Sarcoidosis
Presentation
Peripheral Inflammatory Breast Mass
May Have Abscess or Overlying Skin Inflammation/Ulceration
Diagnosis
Initial Imaging: US
Diagnosis: Core Needle Biopsy (CNB)
Pathology: Non-Necrotizing Granulomatous Lesions Centered on a Breast Lobule
Send for Acid-Fast Stains & Culture (Rule Out TB)
Treatment
Primary Treatment: Conservative Management
Treat Mastitis or Abscess as Indicated by sensitivities empiric for corynebacterium with doxycycline
For Tuberculosis: Typical TB “RIPE” Antibiotic Regimen (Rifampin, Isoniazid, Pyrazinamide & Ethambutol)
What is the TNM for breast cancer
Tis - DCIS
T1 < 2cm
T2 2-5cm
T3 >5cm
T4 invading into chest wall excl pecs (a) or skin (b), both (c), inflammatory (d)
N0 - no involved lymph nodes or isolated tumour cells only <0.2mm
N1 - 1-3 involved
N2 - 4-9 involved
N3 - 10+ involved
M0 no spread
M1 spread
(pN1mi means micrometastases. They are > 0.2 mm but < 2 mm.
pN1a means that there are cancer cells in 1 to 3 lymph nodes in the axilla and at least one is larger than 2 mm. A for axilla
pN1b means there are cancer cells in the sentinel lymph nodes behind the sternum (the internal mammary sentinel nodes). B for breastbone
pN1c means there are cancer cells in 1 to 3 lymph nodes in the armpit and in the sentinel lymph nodes behind the breastbone. C for
Combo
pN2a means there are cancer cells in 4 to 9 lymph nodes in the armpit, and at least one is larger than 2 mm.
pN2b means there are cancer cells in the lymph nodes behind the breastbone (the internal mammary nodes), which have been seen on a scan or felt by the doctor. There is no evidence of cancer in the lymph nodes in the armpit.
pN3a means there are cancer cells in 10 or more lymph nodes in the armpit and at least one is larger than 2 mm, or there are cancer cells in the nodes below the collarbone.
pN3b means there are cancer cells in lymph nodes in the armpit and lymph nodes behind the breastbone.
pN3c means there are cancer cells in lymph nodes above the collarbone.
What are the stages for breast cancer
Stage 1A = T1N0M0
Stage 1B = T0 or 1, N1mi M0
Stage 2A = T0 or 1, N1 M0 or T2N0M0
Stage 2B = T2, N1mi M0 or T2N1M0 or T3N0M0
Stage 3A = T0-3 N2, T3N1
Stage 3B = T4N0-2
Stage 3C = T0-4, N3
Stage 4 = M1
What are the risk factors for breast cancer
Modifiable:
- EtOH
- smoking
- obesity
- radiation exposure
Unmodifiable:
- Female
- >50yo
- Genetic predisposition (BRCA1&2, Tp53, PTEN, CDH-1, PALB-2,
- Increased oestorgen exposure
- early age menarche
- late age menopause
- nulliparity
- didn’t breastfeed
- HRT/OCP
- delayed age of first pregnancy
What is the BiRADS scoring?
Breast imaging reporting and data system.
Standardises reports, risk assessment and quality assurance tool that applies to mammograms and USS.
0 = incomplete - need repeat/further imaging
1 = normal, symmetrical, no masses or distortion.
2 = benign
3 = probably benign (<2% chance of malignancy)
4 = suspicious (2-95% chance of malignancy) recommend core biopsy
5 = malignant (>95% chance). recommend biopsy.
6 = already biopsy proven malignant lesion
What is ‘early’ breast cancer?
<5cm (T1-2)
Stage 1, 2a,2b,3a
no local invasion or mets
What are concerning features on breast USS?
- taller than wide
- posterior acoustic shadowing
- hypoechoic
- architectural distortion
- irregular margins
- lobulated
- internal vascularity
What are concerning features on axillary USS?
- calcifications in lymph nodes
- enlarged
- loss of fatty hilum
- thickened cortex
- round instead of oval
- hypervascular
- loss of corticomedullary differentiation
What are indications for an MRI breast?
Screening:
- high risk, young women, dense breasts for screening
Diagnostic:
- to assess extent +/- multifocality/centrality of lobular cancer and contralateral breast
- pagets disease of nipple to assess for multi centrality
- implant associated concerns e.g rupture or BIA-ALCL
Treatment response
- to assess response to neoadjuvant chemo
Why don’t we use MRI for all breast cancer patients?
Although it has a high sensitivity it also has a high false positive rate which can lead to more interventions than should be required and anxiety. Can also upgrade to multifocal/multicentric disease which can be of debatable clinical significance in case of small ductal breast cancers that would otherwise undergo a BCS and adj rx to that whole breast. Debatable whether detection of these leads to overall survival benefit.
What is meant by ER and PR positive?
Estrogen receptor and progesterone receptors are nuclear hormone receptors.
ER is a ligand dependent transcription factor and PR is activated in response to ER activation.
55% of cancers are ER/PR+
75% will respond to hormone therapy.
What is HER2 expression and its relevance?
Stands for human epidermal growth factor receptor 2.
It is a tyrosine kinase receptor protooncogene on ch 17. Upregulates cell growth. Only 1 mutation is required to turn into oncogene.
Assessed on immunohistochemical staining.
<10% of cells expressing it or >10% but only faintly expressing it = negative.
weak to moderate staining = equivocal and should be sent for FISH to confirm.
>10% strongly staining = 3+ positive.
Poorer prognosis but can treat with trastusumab (Herceptin)
What are the molecular subtypes of breast cancer?
Luminal A - ER/PR+, HER2-, good prog, lower grade, low ki67 (<14%), poor response to chemo
Luminal B - ER and/or PR +, HER2 -/+, poorer prog, high grade, high ki67 , poor response to chemo
Her 2 enriched - ER/PR-, HER2+, poorer prog, high grade, high ki67, good response to chemo
Basal type (Triple neg) - ER/PR/HER2 -. poorer prog, high grade, high ki67, good response to chemo
What is the breast cancer grading system?
Modified Bloom-Richardson system looks at 3 areas each scored out of 3.
Tubule formation:
1 = >75% normal
2 = 10-75% normal
3 = <10% normal
Nuclear pleomorphism:
1 = small, uniform
2 = enlarged, uniform
3 = pleomorphic, nonuniform, lots of nucleoli
Mitotic rate per 10hpf:
1 = 0-9
2 = 10-19
3 = 20+
Overall score:
3-5 = grade 1 low grade, well differentiated
6-7 = grade 2, intermediate
8-9 = grade 3, high grade, poorly differentiated
What are some of the histological subtypes of breast cancer?
- Invasive carcinoma of no special type (70-80%)
- lobular (10-15%)
- medullary (10%)
- mucinous
- tubular
- papillary and micropapillary
- metaplastic (v poor prog)
- apocrine
- NETs
What is invasive carcinoma of no special type?
- It is the most common histological subtype of breast cancer.
- Makes up 70-80% of breast cancer
- Often associated with DCIS
- Heterogenous, nests, cords, diffuse sheets of cells. Variable duct differentiation.
- Spreads via lymph to liver and lung
What is lobular carcinoma?
- It accounts for 10-15% of breast cancers.
- Characterised by negative staining for e-cadherin and discohesive cells and indian file tumour cells.
- Subtypes include:
- classic
- pleomorphic (need to reexcise this one if pos margins)
- signet ring
- tubulolobular
- histiocytoid
- Spreads to peritoneum, GIT and ovaries.
- Assoc with CDH-1 mutations
What is mucinous or colloid carcinoma of the breast?
A breast cancer that is most common in 7th decade of life.
Has good prognosis
Characterised by mucin production
What is medullary breast cancer?
- Accounts for <10%
- tends to be in younger women
- associated with BRCA 1 mutation
- better prognosis than ductal ca
- characterised by diffuse sheets of tumour cells, pushing border, stromal lymphoid infiltration
What is tubular carcinoma of the breast?
Rare cancer
Good prognosis
Single layer of epithelial cells with low grade nuclei and atypical cytoplasmic snoutings arranged in tubules or glands.
- low chance of lymph node involvement
What is papillary cancer of the breast?
Very rare
Invasive papillary and invasive micropapillary.
Associated with papillomas.
Therefore centrally located.
Good prognosis (except for micropapillary which has poor prog)
ER/PR+
What is apocrine breast cancer?
Rare high grade poor prog cancer
What is adenoid cystic cancer of the breast?
low grade, rare tumour similar to salivary tumours in appearance. Tends to be in post menopausal women
What is metaplastic breast cancer?
Rare (<1%), highly aggresive cancer. Spreads haematogenously.
Grow very large very rapidly.
Subtypes spindle cell, carcinosarcoma, SCC of ductal origin, adenoSCC, pseudoadenomatous metaplasia
What is Mondors disease?
Superficial thrombophlebitis of the lateral thoracic vein or tributary.
Presents usually after recent trauma or surgery as a tender palpable subcutaneous cord.
Treat with NSAIDS and compresses
Describe breast pain eitiology and treatment.
Usually benign eitiology. Can be divided into cyclical or non-cyclical.
Cyclical usually late luteal phase and recedes with menstruation.
Non-cyclical; Ill fitting bra, v large breasts, cysts, fibroadenomas, fibrocystic change
Extramammary: costochondritis, cardiac, referred.
Treat with reassurance good bra fitting, dietary modification (cut out caffeine), NSAIDs, compresses, evening primrose oil to alter FAs 3months.
Refractory breast pain can consider tamoxifen, danazol (androgen) or bromocryptine. OCP if cyclical.
What is fibrocystic change and its clinical relevance?
Changes to the breast with involution most commonly in perimenopausal women.
Results in fibrous tissue and/or cyst formation.
Clinically relevant as can be a cause of breast pain or lumpiness or nipple discharge.
Very common.
How do you manage breast cysts?
Usually reassurance however if associated with any concerning features then biopsy and complete triple assessment.
If these are symptomatic and large these can be aspirated. If bloody or recurrent discharge send for cytology and excise. If thickened wall post aspiration then excise.
What is a complex breast cyst?
A cyst with a solid component or internal vascularity on imaging. Would need core needle biopsy.
What is a fibroadenoma?
A dominant mass in the breast clinically. Non-Proliferative lesion with solid lobulated margins appearance on USS.
Biphasic growth of both epidermal cells and stromal cells.
How do you manage fibroadenoma?
Triple assessment.
Can reassure most of the time.
Excise if:
- risk factors,
- disconcordance or diagnostic uncertainty
- symptomatic
- >3cm
- rapidly enlarging
What is a giant fibroadenoma?
> 6cm
can be difficult to distinguish from phyllodes
What is a complex fibroadenoma?
Fibroadenoma with sclerosing adenosis, papillary apocrine metaplasia or epithelial cell calcs or cysts
Increased risk of cancer
What is a tubular fibroadenoma?
Benign, epithelial cell proliferation.
What is Phyllodes tumour and how do you differentiate it from fibroadenoma. How do you manage Phyllodes tumours?
Increased growth of epithelial and stromal cells in leaf life projections with proportionally more cellularity of the stroma compared to fibroadenomas.
Needs 1cm margins’
Can be benign, borderline or malignant (10%).
>5mitoses/hpf incr malignant potential
Stain positive for vimentin and actin
Rare to metastasise but if does its haematogenous therefore no role for SNB. Many (Up to 20%) Have palpable Axillary Lymphadenopathy although most are reactive, metastatic lymph node involvement is rare.
Note if found to be phyllodes post excision with enucleation thinking it was a fibroadeanoma then benign or borderline would accept clear margins but if malignant then do need to return to gain 1cm margins. High rate of local recurrence.
Note there is no known treatment for metastatic disease.
What are concerning features of nipple discharge?
- Older women
- Unilateral
- Bloody
- Spontaneous
- Persistent or recurrent
- Assoc skin changes or mass
What is duct ectasia?
Dilatation of the subareolar duct in peri or post- menopausal women.
Can give viscous discharge
Assymptomatic reassure, symptomatic duct excision
What is the pathogenesis of lactational mastitis? How is it treated?
Due to blocked lactiferous sinus and trapped bacteria usually s.aureus.
Treat with NSAIDs, cold compresses, abx
if abscess treat with aspirations preferred over I&D to avoid milk fistula but I&D may still be required in those >5cm, reccurent despite asps, skin compromise
What is the pathogenesis of non-lactational mastitis and breast abscess’? How do you treat them?
Usually related to smoking, piercings and duct ectasia with most common organism being s.aureus.
Treat with abx +/- I&D of abscess.
Biopsy skin to r/o inflammatory breast ca.
What is radial scar?
Benign proliferative sclerosing lesion of the breast with a stellate shaped centre of collagen/elastin entrapped with epithelial elements.
<1cm
(>1cm = complex sclerosing lesion)
Excise due to concerning appearance on mammogram.
It is not a premalignant lesion but is associated with 1.7-2.2x increased risk of breast cancer in life time and often on excision may be upgraded to DCIS or invasive cancer.
What is atypical lobular hyperplasia?
Increased number of cells that line the lobules with atypical features e.g. nuclear pleomorphism etc.
Not a premalignant lesion but a marker of 8-12x increased lifetime risk of developing breast cancer.
Treat with excisional biopsy then tamoxifen or aromatase inhibitor and annual breast MRI
What is tamoxifen?
It is a selective estrogen receptor modulator. Binds to and blocks the receptor. This blocks the cells from being stimulated by estrogen to multiply.
Administered usually as a tablet once a day. (can come in liquid preparation too)
What are some indications for tamoxifen?
Malignant and benign indications:
It is used in premenopausal women in chemoprophylaxis post resection of ER+ DCIS, atypical ductal hyperplasia, atypical lobular hyperplasia or invasive carcinomas to reduce recurrence rate and overall survival.
It can be used as sole treatment for ER+ advanced stage or comorbid patients in palliative setting to slow rate of growth.
It can be used in women with high risk of developing breast cancer to reduce chances of ever developing one.
It can be used in refractory severe mastalgia
It can be used in men with refractory gynaecomastia.
It can be used for desmoid tumours.
What is Cowdens syndrome?
Mutation in tumour suppressor gene PTEN (Phosphatase Tensin). Responsible for regulating cell growth, apoptosis, angiogenesis, cell adhesion and cell movement. Other name is multiple Hamartoma syndrome. Autosomal dominant inheritance on ch10.
30-85% risk of breast cancer over their lifetime, 35% risk of thyroid predominantly follicular, CNS and endometrial, colorectal and melanoma.
Benign features includes mucocutaneous lesions like papillomatous papules on tongue and in mouth. Hamartomatous polyps in small or large bowel. Lipomas. Fibrocystic changes in breast. Adenomas or MNG thyroid.
Neurodevelopmental Associations 1
Neurodevelopmental associations:
Macrocephaly (Large Head Size) – 94%
Dolichocephaly (Head Longer than Wide)
Autism
Intellectual Disability
Developmental Delays
