Sept12 M1,2-Breast Cancer Flashcards
RFs for breast ca
- > 50
- FHx breast or ovarian ca
- PHx BRCA1 or 2 mut or bx with breast lesion
- estrogen: early menarche, late menopause, late age at first term pregnancy, nulliparity, HRT
- lifestyle (weight, sedentary life, alcohol consumption)
3 screening methods
- mammography (every 2 years for 50-75)
- self breast exam
- clinical PE
most common breast ca presentation + others
- mammogram
- painless mass
- skin changes
- nipple abnormalities
(IMP) most common site of dev for breast cancer
upper outer quadrant
(IMP) where beast cancer arises
terminal duct lobular unit
possible breast pathologies
- fibrocystic changes (non atypical OR atypica hyperplasia either ductal, lobular of flat epithelial)
- in-situ CA (ductal and lobular)
- invasive CA
- fibroepithelial lesions (fibroadenoma and phyllodes tumor)
- papilloma
(IMP) tx of non atypical fibrocystic disease
no tx
tx of atypical fibrocystic disease (hyperplasia) like ADH (atypical ductal hyperplasia) or ALH (atypical lobular hyperplasia)
consider surgical excision
fibrocystic changes on histo
- cells of cystic spaces have apocrine metaplasia
- sweat gland like
- eosinophilic
3 types of in situ CAs of the breast
- DCIS (ductal carcinoma in situ): precursor to invasive CA. HAS CADHERIN.
- LCIS (lobular): precusor lesion + marker of increased risk for invasive CA. NO CADHERIN
- Paget disease (DCIS extendign in skin by travelling in duct)
- NOT invasive
two main subtypes of LCIS
- classic
- pleiomorphic
classical LCIS tx
follow up
DCIS and pleiomorphic LCIS tx
excise
DCIS vs invasive CA
DCIS didn’t invade the stroma
DCIS most common detection
CALCIFICATIONS on mammography
-DCIS doesn’t form a mass
DCIS subtypes
- low grade (less likely ca)
- high grade (higher risk of invasive ca)
high grade DCIS on histo
- atypia
- mitosis
- necrosis
- calcifications
Paget disease symptoms
- eczematous (red) nipple
- red bc inflammatory reaction to cancer cells
LCIS vs DCIS on histo
- LCIS more detached cells bc no cadherin
* cadherin positive = DCIS
3 types of classification of invasive CA
- histological classif (ductal, lobular, mucinous, medullary, tubular)
- based on R expression (ER+ or ER-, HER2+ or HER2-, triple negative)
- molecular classif (luminal A, luminal B, HER2 enriched, basal type)
link between molecular classif and R classif
- luminal A and B = ER+, HER2-
- basal type = triple negative
most common type of breast ca
ductal CA NOS (histo classif) NOS = not otherwise specified. that’s the name and that’s it
(IMP) lobular CA: what Rs and markers
- ER+
- PR+
- HER2-
- cadherin negative (like LCIS counterpart)
(IMP) medullary CA charact, Rs, etc.
- triple negative (ER-, PR-, HER2-).
- circumscribed
- differs from all other breast cas in that it is circumscribed
(IMP) tubular CA markers
- ER+
- PR+
- HER2-
- like lobular and tubular*
(IMP) ductal CA markers
can be postive or negative for all, it’s variable
mucinous CA markers
- ER+
- PR+
- HER-
- like lobular and tubular*
3 breast cancers that are ER+, PR+, HER2-
- tubular
- lobular
- mucinous
breast invasive CA with good prognosis
- medullary CA (best prognosis)
- ductal
- tubular
receptor/molecular classification of breast invasive CA
- ER+, HER2-
- HER2+ (ER+ or ER-)
- triple negative (ER-, PR-, HER2-)
how to remember if a cancer responds well to chemo
higher grade = responds well to chemo. not low grade bc chemo kills cells dividing very fast
ER+ HER2- invasive CA: grade, complete response to chemo, relapse time
- grade 1 or 2
- weak resp to chemo (bc low grade)
- time to relapse >10 yrs (so never considered cured)
HER2+ (ER+ or ER-) invasive CA: grade, complete resp to chemo, time to relapse
- grade 2 or 3. more aggressive
- ER- = good resp to chemo. ER+ = weak resp to chemo
- <10 years to relapse
triple negative invasive CA: grade, complete resp to chemo, time to relapse
- grade 3
- 30% resp to chemo
- <8 years relapse
drug for HER+ tumors
herceptin (given on side of the chemo)
herceptin MOA
- paralyzes the HER2 Rs so its prolif function stops
- cells don’t prolif but don’t die so it’s not chemo
trick to remember what’s a good prognosis for breast invasive CA
more negatives = worse prognosis. EXCEPT MEDULLARY.
PR- invasive CA charact
- more aggressive
- generally ER+
- tend to give chemo
why the medullary invasive CA is an exception and prognosis is good
is well contained by the associated inflammation and the lymphocytes that contain the tumor
invasive ductal CA detected how
irregular mass on radiology
what can also cause irregular mass on radiology (ddx of that)
radial scarrs (are benign)
invasive ductal CA on macro
- firm
- irregular border
- whitish
normal ductal anatomy
- myoepithelial cells on periphery
- luminal cells inside producing milk in lobules and forming the ducts
- fat and fibrous stroma around the whole thing
DCIS charact (is NOT ductal invasive CA) on histo
tumor cells are still inside the duct and myoepithelial cells are present
how to recognize that a carcinoma of the breast is still in situ
myoepithelial cells surround it (periphery) and the tumor cells didn’t reach the BM
invasive ductal CA charact
- no assoc myoepith cells
- monoclonal prolif
inflammatory ductal CA sx and dx
- sx: breast red and inflamed. (reason = lymphovascular invasion and the tumor cells block the lymphatics)
- dx: bx
ddx to inflammatory ductal CA (red inflamed breast)
- nursing
- pregnant
tx of inflammatory ductal CA
- neoadjuvant chemo (meaning before surgery)
- total mastectomy 6 months later
Nottingham grading for breast CA (ductal especially bc most common)
- well diff, low grade = 1 (lot of grands, more tubules)
- interm grade = 2
- poorly diff = high grade = 3 (sheets of cells)
- based on atypia, mitotic count and tubule formation*
charact of invasive LOBULAR Ca
- doesn’t form a mass
- E cadherin neg
- invades stroma
E cadherin + vs -
+ is ductal
- is lobular
mucinous CA charact
- elderly
- ER+ (better prognosis)
- rarely metastasizes
mucinous CA on histo
neoplastic cells floating in a lake of mucin
possible region of metastasis for breast cancers
- lung
- bone
- brain (usually ER+ (bc herceptin doesn’t cross the BBB) or triple negative)
(imp?) most common mets for breast cancer
bone
charact of ER and PR staining
- are nuclear Rs so nuclear stain
- nucleus round = positive
- all white, blue = negative
charact of HER2/Neu staining
- cytoplasmic memb R
- honeycomb pattern = positive
other test for HER2 Neu testing
FISH (fluorescent in situ hybridization)
- red probe for her2 neu
- green probe for chromosome 17
- if over 2 red probes per cell (one cell has 2 green probes) = amplified = positive
goal of HER 2 Neu testing
if positive, can tx with herceptin (lapatinib)
how does tamoxifen work (for ER+ tumors)
- partial agonist
- in the breast, acts as an antagonist and suppresses breast ca dev
- not cytotoxic
- can cause uterine ca*
aromatase inhibitors do what
inhibit conversion of estrogen in fatty tissue, only good to give in post menopausal women
aromatase inhibitors vs tamoxifen for ER+ tumors: when to use
- pre menopausal woman: tamoxifen
- post menopausal woman: can use both
2 types of fibroepith lesions in the breast
- fibroadenoma
- Phyllodes tumor
(imp) most common tumor of the breast
fibroadenoma. can regress. can become huge in pregnancy
charact of fibroadenomas
- biphasic (2 components): stromal + epithelial components
- before age 30
- bigger in late menstrual cycle and pregnancy
- regresses after menopause
spectrum of lesions of fibroadenomas
like any tumor
- benign
- borderline
- malignant
- fibroepith has 2 benign kinds and 1 borderline kind
phyllodes tumor charact
- malignant
- hematogenous spread (no lymph node dissection)
- old tumor with a tumor increasing in size (can’t be fibroadenoma bc would be regressing)
- benign (usually), borderline or malignant
2 components of fibroadenomas
- stroma
- glandular (epith)
- both benign*
phyllodes tumor on macro
- larger than fibroadenoma
- leafy nodular
- cystic spaces
components of phyllodes tumor
also biphasic
- epithelial comp benign
- stromal comp more on the malignant, atypical side. stromal comp is exaggerated, more prominent. if becomes malignant = sarcoma. (sarcomas spread in blood first)
ddx of nipple serous or bloody discharge
#1 papilloma #2 cancer
2 types of papillomas
- peripheral. small and multiple = papillomatosis. (more likely to be malignant. same risk as atypical hyperplasia)
- central (big and single)
intraductal papilloma charact
- lactiferous duct for ex
- papillary structures look like normal breast tissue
- benign lesion
how to stop bloody discharge in papillomas
take it out
