Breast carcinoma In situ Flashcards
Etiology of breast cancer
1 in 8 women, nearlth 20% cancer deaths (2nd to lung) average age is mid 50s
Risk factors for breast carcinoma
75% are over 50
more in north america and northern europe
Highest in non-hispanic
early period adn late menopause = higher risk
first birth >35 higher risk
Family Hx and breast cancer
1st degree relative: 13% adn 87% wont get cancer
prior atypical breast biopsy or prior estrogen exposure, radtiation or carcinoma of other breast
Three main factors for breast pathogenesis
Genetics (proto-onco mutatio in Her2/Neu) (Tumor suppressor genes of BRCA1 or 2)
Hormonal
Environmental
Major risk = hormone exposure, seen in POST mentopauseal women with OVERexpression of estrogen receptor ER
Sporadic Breast Carcinoma
____ breast cancers are Hereditary
_____ are Familial
______ are Sporadic
5-10% Hereditary
15-20% Familial
70-80% are sporadic
Dx after menopause, low incidence of cancer in the family, influcenced by environmental factors, increases with age (hormones) and lifestyle (alcohol/obese)
Sporadic Breast cancer
Caused by a combination of factors: MULTI- FACTORIAL, Multiple low-penetrance genes may play a role and interact with Environmental triggers and see family ‘clustering’
Familial Breast Cancer
Main cause is a single germline gene mutation in the family, Multiple generations often affected Typically young age of breast cancer onset (<50 yrs)
Hereditary Breast Cancer
Hereditary Breast and Ovarian Cancer (HBOC)
Ashkenazi Jewish
Triple negative tumors (BRCA1)
Cowden syndrome (PTEN gene): Breast, thyroid, uterine
Li Fraumeni syndrome (TP53 gene) Breast, brain, leukemia, sarcoma
Examples of Hereditary Breast cancer with clustering
What is the 3-2-1 rule
3 family members with breast cancer REGARDLESS of age
2 family members with breast cancer, 1 dx <50 yrs
1 family member with Ovarian cancer
______is more relevant than the number of women with the disease
Age of onset of breast cancer
Ovarian cancer is an important indicator of
hereditary risk, although it is not always present.
BRCA1 and BRCA2 are associated with what cancers?
Breast, ovarian, pancreatic, prostate
What kind of genes are BRCA1 and BRCA2
they repaire ds DNA breaks; tumor suppresor gene
damage here in germline is bad news!
Pattern of inhericance for BRCA1 and BRCA2
lifetime risk of breast cancer:
associated cancer
Auto Dominant
45-85% risk of breast cancer
15-45% ovarian cancer risk
incrase prostate, male breast, pancreatic and melanoma
Key for Dx of neoplasm
is it benign or malignant, what tissue is it from, why type of cancer, did it met?
is it invasive,
Grade: how simuar to normal cells or differentiated
Stage: extent of spread
What is progression of breast disease to carcinoma
NOrmal–> Hyperplasia–> Atypical hyperplasia–> Carcinoma in situ
–> invasive cancer
Normal duct cells will have this intact and you can see it on staining, means cancer is still IN situ
intact myoepithelila layer of duct
What happens in INvasive ductal carcinoma in situ
normal duct, ductal cancer cells break through basement membrane
Ductal CArcinoma in situ (DCIS)
Mean age:
bilateral:
palpabel?
HOw do we find them?
ductal carcinoma in situ: mean age is 50-59, not often bilateral nor palpable
represents 30-40% cacrinomas found on mammograpy
See this on mammogram of 55 year old pt. No mass was noted. What is the likely dx?
Ductal carcinoma in situ
<20% palpable and found incidentally
Types of Ductal carsinoma in situ
Comedo, cribiform, micropapillary, papillary, solid, flat
Whats going on in this histology?
Comedo carcinoma in situ: ducts expanded by purple which is cellular, pink stuff is necrosis and looked like zits and purple shit is calcificaion
What are these nasty things?
Cribiform and Solid CDIS one of left is cribiform and other is solid type
What kind of lesion is this?
Form of DCIS extends into skin, ulcertates and looks excematous. See carcinoma cells in epidermis
often high grade or comedo type
Pagets
Pathophysiology of Pagets
Pagets is type of DCIS
Describe Pagets histology
Pale cytoplasm are neoplastic cells and are pagets cells, lots of inflammation
Tx for DCIS
surgery, radiaiton, hormonal:
if untreated will progress to invasive carsinoma
Average age for LObular carcinioma in situ
are they bilateral or multicentric?
are there calcifications?
LCIS age 44-54
70% multicentric
50-70%
rarely have calcification with no mass
What is this?
LObular carcinoma in situ; marker for carcinoma and direct precursor in some cases
Marker of risk for carcinoma with direct precursor of some cancers,
In 20 years 30% devo cancer; BOTH breasts at equal risk
LCIS
What tx do we give pts with LCIS?
Tamoxifen; have risk for carcinoma
How do invasive carcinomas present
Palpable mass, dimple of skin, retraction of nipple
On mammography: see mass/density and calcification
Palpable mass, dimpling, retraction of nipple
mass and calcifications
Invasive carcinoma
Most common area of breast carcinoma
second location
50% in UPper OUter quad
20% in subaerolar central area
Microaarray see 4 molecular subtypes of breast carcinoma
Luminal A
Luminal B
HER2
Basal-like
firm white masses with INDISTINCT borders, associated with DCIS and rarely LCIS
Invasive ductal carcinomas
INvasive ductal carcinoma-NOS
____express ER/PR and ____express Her2/Neu
firm white masses
2/3 express ER/PR
1/3 expresses Her2/Neu
MOre common in postmenopausal women and are more multicentric then other carcinomas, sometimtes have prior or concrrent contralateral carcinoma
Invasive Lobular Carcinoma
E-cadherin negative
Mets to: CSF, Ovaries, uterus, BM,
Invasive lobular carcinoma
Gross tumor: Very hard, with irregular borders, lacks margins and blends with surrounding tissue
see a spiculated mass/density
Invasive lobular carcinoma (ILC)
small cells, SINGLE file pattern with targetoid growth pattern
no glands with signet rings
Invasive lobular carcinoma
targetoid growth pattern, single file cells, seen in which age group, what type of mass?
invasive lobular carcinoma
hard tumor with irregular border
What age group affected by Medullary cardcinoma, and what genetic defect incraes its incicence
MEdullary carcinoma seen in YOUNGER age with BRCA1 mutaion
PRognosis of medullary carcinoma
better then invasive ductal carcinoma NOS, metastases
No Her2/New expression, Negative for ER/PR
increased in BRCA1
MEdullary carcinoma
What do we see on mammography of medullary carcinoma
oval circumscribed mass can be mistaken for fibroadenoma
soft fleshy tumor, lobulated and bulging cut surface with circumscribed border
Gross findings of Medullary carcinoma
Syncytial growth pattern in 75% of tumor cells with high grade nuclear
lymphoplastic infiltrate with a PUSHING border but non-infiltrative
MEdullary carcinoma
Sheets of ugly tumors cells
NEG for ER/PR and HER2neu negative
lymphocytic infiltrate
MEdullary carcinoma
Common in mid to late 40s
seen in PERIPHERY of breast
with excellent prognosis and
mets to axillary10%
Tubular carcinoma
On mammograhpy see a small stellate lesion.. the woman had no symptoms
Tubular carcinoma
biopsy shows a ill defined STELLATE mass: its gray-white and firm
less then 1 cm
Tubular carcinoma
See single layer of epithelial cells lining glands with NO MYOMETRIAL layer
glands are scattered with desmoplastic stroma
tubular carcinoma
Seen in postmenopausal women
very SLOOW growing mass
mets to axiallary <20% time
Colloid Mucinous carcinoma
Colloid mucinous carcinoma see more in
women with BRCA1 mutation
goog prognosis
Gross mass is circumstribed and soft
pale blue and gelatinous surface
YOu see this microscopically
tumor cells and nests in pools of mucin
whats prognosis
Colloid carcinoma
good prognosis (BRCA1 association) seen postmenopausal
skin erythema, peau d’orange
Inflammatory carcinoma
see pt with Peau d’orange, THICK skin adn induration of breast parenchyma
what is the differential dx
INflitrative carcinoma
(could be acute mastitis)
What do we look for microscopically in infiltrative breast disease?
Look for lymphhatic tumor emboli
BAD pronosis of only 10 year survival of 30%
Staging of cancer involves:
Tumor sixe
Node staus
Mets
Tumor grade involves
architectual type
nuclear grade
mitosis
Prognostitc factors in breast CA
Stage (TNM), Grade, HIstology, HOrmoen receptors, overexpreeion of Her2/Neu
histological grade of invasive breast carcinoma correlates with
prognosis
for tumor grading
most important prognostic factor in INVASIVE carcinoma in the absence of distant mets
axillary lymph node status
applicable only for pts with early carcinoma, small node negative and ER+
expression of set of genes predicts pts response to chemo
oncotype
breast enlargement, uni or bilateral, may present as subaerolar mass
periductal hyaline and collagenous tissue
epitheilual hyperplasia of ducts with NO bresat lobules present
male gynecomastia
When do we see male gynecomastia
Klinefeleter XX, cirhosis, drugs (alchol and weed) or funciton testitiucarl tumor
risk factor for male breast carcinoma
BRCA2, 1st degree relative w/ breast cancer, decreaed testicuarl fucntino, exposure to estrogen, increaes age, INFERTIlty and obestity
Presentation of male breast carcinoma
nipple discharge
palpable subaerolar mass
axillary lymph node involved
distant met to: liver, lung, brain
same tx for women
