Breast Cancer + Benign Pathologies - Treatment, Investigation (Cytology & Biopsy) Flashcards
risk factors for breast cancer (9)
- increasing age (MAIN)
- previous breast cancer
- genetics: BRCA 1/2 (5%)
- HRT use > 10 yrs
- early menarche and late menopause
- late pregnancy
- alcohol > 14 units per week
- high weight (more adipose = more estrogen storage)
- post RT for hodgkin’s lymphoma
presentation of breast cancer (5)
- lump (MAIN) - usually painless
- mastalgia - persistent unilateral pain
- nipple changes/discharge
- change in breast size, shape, contour
- DVT, lymphedema
what is peau d’orange and what is it a sign of?
redness of pitting of the skin over the breast - like orange
sign of inflammatory breast cancer, the worst kind
3 stages of diagnosing breast cancer
- history and examination
- radiological: mammogram, USS, MRI
- cytopathological: a. FNA, b. core biopsy
what is the main difference between FNA and core biopsy?
- FNA - cell sample, cytology
2. core biopsy - tissue sample, histopathology (ER/PR, HER2 receptor status)
when is MRI used in breast imaging?
- risk of lobular cancer
- dense breast (younger)
- benign disease
which breast imaging is the most sensitive in older women?
mammogram
what is the difference between invasive and in situ disease and what investigation is needed to find out?
core biopsy needed
- in situ: within the basement membrane
- invasive: breached basement membrane
what are some of the further investigations you will do after core biopsy? (3)
- ER positivity
- PR positivity
- HER2 receptor status –> gives prognostic indication
neo-adjuvant vs adjuvant
neo-adjuvant: before surgery
adjuvant: after surgery
what are some of the adverse prognostic factors (that worsens prognosis and increases the chance of recurrence) (6)
- node involvement +
- tumor grade 3
- tumor type
- ER/PR -
- HER 2 +
- lymphovascular invasion
what prognostic factors are included int he nottingham prognostic index (NPI)? (3)
- node involvement
- tumor grade
- tumor type
what are the different types of breast cancer? divide it into invasive and non-invasive cancer, which is the most common?
- invasive - most common type:
- ductal carcinoma (75-80%)
- lobular carcinoma (10%)
- others (10%)
- non invasive:
- ductal carcinoma in situ
- lobular carcinoma in situ
what are the different methods of staging breast cancer?
- bloods: FBC, U&Es, LFTs (check liver spread), Ca2+/PCO2 (check bone spread)
- imaging: mammogram, USS, MRI
are tumor markers useful in breast cancer?
no, there is no tumor marker in breast cancer
what are the common locations of local and distant mets (for distant list them in order)
local - chest wall, nipples, skin, underlying muscle
distant:
1. bone
2. lung
3. liver
4. brain (esp HER2+)
5. bone marrow
what are some of the treatments for breast cancer?
- surgery:
- breast conservative surgery
- mastectomy
- axilla surgery
- RT
- chemo
- hormone therapy
- targeted therapy (HER2) - trastuzumab/herceptin, pertuzumab
what should you do after a routine or pre-operative USS axilla? (what happens when it is or isn’t normal)
- normal –> sentinel node biopsy
2. abnormal –> FNA
what should you do if an FNA result of axilla is negative or positive?
- negative –> sentinel node biopsy
2. positive –> axillary clearance or RT
what are the 2 dyes use in the duo technique for sentinel node biopsy?
- tachnetium 99
2. evans blue
what are some of the complications of axillary clearance? (5)
- lymphedema (10-17%)
- nerve damage and altered sensations
- reduced shoulder joint ROM
- vascular damage
- radiation induced sarcoma
when are patients given RT and what are the exceptions?
ALL patients after wide local excision need RT unless:
- > 60 yrs
- T1, N0
- low Ki67 < 25 (stained tumor cells in the total number of malignant cels)
what is the recommended regimen for RT?
3 weeks
- boosts effective in preventing local recurrence in young ppl
what are some of the complications of RT?
- skin telangiectasia
- radiation pneumonitis
- cutaneous radionecrosis, osteonecrosis
- angiosarcoma
what type of breast cancer patient is chemo most effective in? What is oncotype testing and how is this related to chemo?
< 50 yrs and have the adverse prognostic factors
oncotype testing done for those who are ER+/HER2- and have no nodal involvement to see whether chemo would still be effective for them despite not having the adverse prognostic factors
what are the 3 types of hormone and therapy used (drug names) - tell their mechanism of action, dosage, differences in benefits and side effects
- tamoxifen
- 20 mg once daily for 5-10 yrs
- blocks ER receptor directly
- effective in all age groups
- effective after chemo
- side effects: thromboembolism, avoid in PE/DVT
- AI (letrozole, arimidex) - inhibits ER synthesis
- 2.5 and 1 mg respectively, once daily for 5 yrs
- inhibits ER synthesis
- used in postmenopausal women
- improves disease survival if switching drugs
- side effects: osteoporosis
- zoladex - blocks FSH/LH
what receptor does hormone therapy target?
ER, FSH and LH (hormones), enzymes used in the synthesis of ER
what are the 2nd and 3rd generation drugs in chemo?
3rd gen: docetaxel - MOST potent
2nd gen: doxorubicin, epirubicin
what is the most effective treatment for HER2+ breast cancer?
trastuzumab (herceptin), pertuzumab
what is the follow up like after diagnosis of breast cancer?
0-5 yrs after diag: annual clinical examination check
5-10 yrs after diag: annual mammo
what is included in the triple assessment in symptomatic clinic for breast cancer?
- surgeon (examination)
- radiologist (scans)
- cytopathologists (FNA/biopsy)
what is the difference in cell arrangement between lobular and tubular carcinoma?
- lobular carcinoma - cytoplasmic vacuole arrangement
2. tubular carcinoma - cells arranged in tubes
what are some of the findings of benign vs malignancy cytology? (4 points)
- cellularity
- B: low/moderate cellularity
- M: high cellularity
- cell groups
- B: cohesive group of cells, flat sheet, uniform in size
- M: crowding/overlapping of cells, loss of cohesion
- appearance of nucleus
- B: oval (bare) nuclei
- M: nuclear pleomorphism, loss of bipolar nuclei
- chromosome pattern
- B: uniform
- M: hyperchromasia
can aspiration cure cysts?
yes, aspiration is curative for cysts, unless there is blood or residual mass in the aspirated fluid.
what would cytology find in ductus ectasia?
macrophages only
what will nipple scrape find in Paget’s disease?
squamous cells + malignant cells
what are some of the things that can be confirmed with core biopsy but not with FNA?
- grading
- confirm invasion (staging)
list some of the benign conditions of the breast - which of these is the most common? (6)
- fibrocystic change
- fibroadenoma (MOST COMMON)
- intraductal papilloma
- fat necrosis
- phyllodes tunmor
- dut ectasia
fibrocystic change presentation
- can be typical or atypical
- painful lump area
- fluctuate with menstrual cycle
what are the different types of fibrocystic change? (5)
- fibrosis
- adenosis: increased gland formation
- cysts: dilated ducts
- apocrine metaplasia: special epithelium with pink cytoplast and brown nuclei
- ductal epithelial hyperplasia
presentation of firboadenoma (4) - what is the peak age of onset?
most common in adolescents or young adult - peak age 3rd decade
- painless
- freely mobile
- well circumscribed
- may naturally regress with age even if left untreated
what are the 2 different types of fibroadenoma and how are they different?
- intracanalicular growth pattern: elongated ducts into slits due to surrounding fibrous tissue
- pericanalicular growth pattern: ducts not compresed by fibrous tissue
presentation of intraductal papilloma - what is the age for this?
- middle aged women
- lactiferous duct and nipple discharge
- papillary structure
- can show typical or atypical hyperplasia –> malignancy
what is the most common cause of fat necrosis? (expected to see this in their history) - explain the process of how this leads to fat necrosis
trauma - RT, surgery
trauma –> dead breast tissue –> healing and calcification of fibrous tissue –> mass
presentation of fat necrosis
- mimics radiological and clinical symptoms of carcinoma
- lipid filled cysts
- histiocytes with foamy cytoplasm
- fibrosis and calcifications –> characteristic egg shell appearance on mammo
phyllodes tumor - what are its 2 components?
- fibrous
2. epithelial
presentation of phyllodes tumor
- fleshy tumor with leaf like pattern and cysts on cut surface
- hard to differentiate from fibroadenoma
- 1-15 cm well-circumscribed lesion
- can be benign, borderline, malignant (mets are hematogenous)
duct ectasia presentation
- nipple discharge
- macrophages on cytology
what is the best prognostic indicator of breast cancer?
node status
what is the overall prognosis for breast cancer?
64% 5 yr survival
what is Ki67, and is a low Ki67 good?
Ki67 is a marker of proliferative activity and influences prognosis (low Ki67 = good)
what is the difference between histological and molecular classification of breast cancer?
histological: invasive/in situ, ductal/lobular
molecular: tumors with the same grade can behave differently, respond to different treatment, and have different prognosis depending on their molecular subtypes (IHC)
why does triple negative cancer have worse prognosis/
doens’t respond to receptor-targeted treatments –> high rates of recurrence and worse prognosis
which one has a worse prognosis between recurrence and new primary cancer?
recurrence - because it means that it did not respond well to the treatment the first time
histological presentation of DCIS
- cribriform architecture
- comedo necrosis, calcification
- grade based on nuclear morphology
histological presentation of LCIS
- multicentric, may be bilateral
- lobules affected and distended, ducts not affected and becomes squished
- characteristic intracytoplasmis spaces due to negative staining (DCIS would be +)
what are the chances of DCIS and LCIS becoming invasive? which one has a higher risk?
- DCIS: high risk
- 30% chance in 15 yrs if low grade
- 50% chance in 8 yrs if high grade
- LCIS:
- 19% chance in 25 yrs (but can be bilateral and not on the same side)
how come LCIS cannot be excised?
because it is multicentric and can be bilateral
how many percent of special type cells will nee to be present for the tumor to be considered no special type (ductal carcinoma), special type (lobular), or mixed?
- no special type: < 50% special type cells
- mixed: > 90%
- special type: 50-90%
list the different prognostic indicators for breast cancer (10) - which of this is the MAIN one?
hint: start with NPI
- node status (MAIN)
- tumor size (< 2cm good prognosis)
- tumor grade
- tumor type (ductal worse prognosis - NST)
- age
- lymphovascular space invasion lowers prognosis
- ER/PR, HER2 negative
- proliferative rate
- gene expression profiling (oncotyping) - determines whether it is suitable for chemo
what are the 4 molecular subtypes of breast cancer and describe the IHC findings of each
- luminal A
- ER+
- HER2 -
- low Ki67
- luminal B
- ER+
- HER+/HER2- with high Ki67
- basal/triple negative - worst prognosis
- ER/PR, HER2 -
- HER2: aggressive, but responds well to treatment
- ER/PR -
- HER2 +
what is the rate of recurrence and new primary cancer after the initial diagnosis? which of this is worse and why?
there is 10% recurrence within 10 yrs of diagnosis
- < 10 yrs after diag: true recurrences
- 10 yrs after diag: 50-50
- > 10 yrs after diag: new primary
define paget’s disease and list out its presentations (5)
intraepithelial spread of intraductal carcinoma, underlying DCIS or invasive disease
- large pale staining cells infiltrating in the epidermis of nipple
- limited to the nipple/extends to alveolar
- ulceration, crusting, redness, pain, scaling, itching - presents like eczema
- serous or bloody discharge
- peau d’orang
what is the most common male breast pathology? name percentage
gynecomastia (10-30% men)
gynecomastia presentation
- increased subareolar tissue (firm disc)
- can be bilateral
- not malignant
what is the most common molecular subtype of breast carcinoma in men?
male carcinoma < 1% breast cancer, usually luminal subtype invasive with ER positivity
what are some things that can cause gynecomastia outside of breast pathology?
- hyperthyroid
- hypogonadism
- estrogen and androgen hormone use
- liver cirrhosis
- chornic kidney failure
- COPD
what type of breast cancer is paget’s disease associated with and how does it spread to the dermis?
associated with underlying ductal or invasive carcinoma which involves the dermis by spreading along the lactiferous duct