The Breast Flashcards
what are the 2 major structures of the breast?
ducts (connect lobules to nipples)
lobules
what are the 2 types of breast epithelial cells?
luminal -In center
myoepithelial- around luminal
when do the breast ducts and first development of lobules start?
puberty - ovarian estrogen and progesterone induction
What are the two types of stroma ?
- Interlobular
- Intralobular
when do breasts fully develop and what contributes?
pregnancy: progesterone, prolactin → permanent ↑ in lobule #/size
oxytocin → myoepithelial differentiation and proliferation
Following lactation total breast size decreases due to?
due to apoptosis of epithelium and lobule atrophy
what happens to breast tissue after menopause?
atrophy of lobules & ducts
↓ in fibrous connective tissue
↑ adipose tissue content
where do carcinomas and fibroadenomas happen in the breast?
carcinomas: lobules & ducts
fibroadenomas: intralobar stroma
- Stroma: is the part of a tissue or organ with a structural or connective role. It is made up of all the parts without specific functions of the organ - for example, connective tissue, blood vessels, nerves, ducts, etc. The other part, the parenchyma, consists of the cells that perform the function of the tissue or organ.
what are the 3 classes of benign breast lesions and examples of each?
- non-proliferative:
- simple breast cyst (fluid filled mass, not proliferative- no risk of malignancy) - proliferative without atypia:
- fibroadenoma
→small increased risk of developing breast cancer in certain sitauations
- atypical hyperplasia: (proliferative with atypia)
- atypical ductal & lobar hyperplasia (substantial ↑ risk of breast cancer)
Simple Breast Cyst:
Can it become malignant?
Where does the fluid filled masses come from?
- no risk of becoming malignant because its non-proliferative
- fluid filled masses derived from the terminal duct lobular unit
what kind of tissue is in a fibroadenoma?
glandular and fibrous
what kind of fibroadenomas are associated with increased cancer risk?
complex fibroadenomas slight ↑ risk with multi centric proliferative changes due to calcification
-usually only w. family hx
what are the 2 likely etiologies of fibroadenomas?
Hormonal:
-estrogen, progesterone, lactation during pregnancy
-EGF (human epidermal GF) receptors on surface: respond to EFG and GH
Genetics: MED12 gene
Simple Fibroadenoma
Composition?
is there an increase in cancer risk?
- benign, solid tumors containing glandular as well as fibrous tissue
- majority: no increased risk of dev. breast cancer
What is Estrogen and where does it come from?
steroid hormone derived from androgenic precursors androstenedione and testosterone via aromatization
what are the 3 kinds of naturally occurring estrogens?
estrone (E1): predominant form of circulating estrogen after menopause
17 ß-estradiol (E2): found primarly in premenopausal women and produced by theca and granulosa cells in the ovary
estriol (E3): Is the estrogen the placenta makes during pregnancy
ER-α
predominantly found?
sustained stimulation and activation can lead to?
Predominant ER receptor in the uterus & mammary gland
-sustained stimulation and activation of receptor leads to ↑ breast & endometrial cancer risk
ER-ß
Prodominantly expressed in ?
affect on cancer?
- ovary, prostate (b - boys have it too)
- -activates anti-proliferative and pro-apoptotic pathways in many cancer cells
G-Protein Coupled Estrogen Receptor (GPER)
mediates ?
regulates ?
G-Protein Coupled Estrogen Receptor
mediates rapid estrogen signaling, expressed in ovary
→regulates follicle maturation
HER2 Oncogene
Encodes for?
Function?
encodes HER2 receptor:
controls cell growth, differentiation, angiogenesis (activates GF pathways)–cell survival
what percent of breast cancers express overamplification of HER2?
20%
what are the 3 biologic subgroups of breast cancer?
- ER positive (80%)
- HER positive (20%)
- Triple Negative (ER-, PR-, HER2-)
what should all females <60yo with triple negative breast cancer be tested for?
BRCA mutations
what is HER2 and ER cross-talk?
-complex, bi-directional
treating only one of them if they are both positive amplifies the untreated one → resistance to therapy
“Drivers” of cell proliferation and survival in majority of human breast cancers?
Estrogen Receptors (ER) & HER2 signaling pathways
>95% of breast carcinomas are what kind of tumors?
adenocarcinomas
what are the 2 in situ breast carcinomas? (in place)
ductal (most common)
lobular
what are the 2 invasive breast carcinomas?
infiltrating ductal 76%
invasive lobular 8%
What is a Ductal Carcinoma In Situ (DCIS)?
A proliferation of abnormal cells confined within the mammary ductal system
-no invastion
what are the 3 nuclear grades of ductal carcinoma in situ (DCIS) and traits of each?
- high grade: no ERs or PRs, high proliferative rate, overexpression of HER2 oncogene, P53 mutation, angiogenesis (HER2+)
- intermediate grade
- low grade: ER and PR positive, low proliferative rate (EPR+)
all: +/- necrosis
what are the 3 grades of infiltrative ductal breast carcinoma?
- well-differentiated (G1): uniform cells, no mitosis
- moderately-differentiated (G2): some glandular differentiation, moderate mitotic activity
- poorly-differentiated (G3): no gland differentiation, significant mitotic activity
****the more poorly differentiated the INCREASE in chaotic architexture of cells
Gold standard of dx for invasive ductal breast carcinoma?
biopsy
what are most familial breast cancers?
80-90% BRCA1 & BRCA2
what do normal BRCA genes do?
produce proteins to help repair DNA
what are the major risk factors for sporadic (don’t involve BRCA genes) breast cancer?
hormone exposure and age
age (at menarche and menopause, reproductive hx - more preg. less risk, breastfeeding, and exogenous estrogen exposure)
gender
radiation exposure/chemicals with estrogen like effects
estrogen (↑ breast growth during puberty/menstrual cycles/pregnangy –> ↑ cells that can be cancerous)
what are the 2 methods of computational investigation of DNA repair deficiency in sporadic breast cancer?
BRCAness profile -based on gene expression profiles between sporadic and familial tumors, influences management and txs for sporadic breast and ovarian cancers
→very important to know to give your patient the best chance at survival
sample-specific BRCA score: (homologous recombination DNA repair pathway)
why should BRCAness and sample-specific BRCA scores be evaluated for sporadic breast cancers aka what is their clinical significance?
defects in HR DNA repair pathway are susceptible to alkylating chemo (causes DNA strand breaks)
in ovarian cancer, ↑ BRCA score more sensitive to chemo, better outcomes
