BRCA Genetics

Question 1

What % of breast cancers are due to germline mutations? ie familial defects

Answer 1

5-10%

90% are therefore sporatic

Question 2

Which layer luminal/myoepithelial is ER+

Answer 2

luminal

Question 3

BRCA inheritance pattern

Answer 3

autosomal dominant

Question 4

BRCA genes are necessary for repairing what type of defect

Answer 4

homologus recombination

dsDNA break repair

Question 5

dsDNA break repair is done by what genes

Answer 5

BRCA

Question 6

Defect in BRCA gene results

Answer 6

not able to repair double stranded DNA

Question 7

BRCA1 job

Answer 7

create single-stranded DNA end and recruits repair machinery

Question 8

BRCA2 job

Answer 8

recruits Rad51

complex promotes strand invasion

Question 9

Breast cancer resulting from BRCA1 mutations

Answer 9

resemble basal layers
usually triple negative
ER-, PR-, ERBB2- ERBB2 = Her2

Question 10

BRCA1 and 2 account for what % of familial breast ca

Answer 10

40%

the rest are rare and only found in small populations

Question 11

ER+ confers better/worse prognosis

Answer 11

better

Question 12

Normal ER signaling

Answer 12

steroid receptor
amphiregulin release
proliferation of adjacent epithelial cells

Question 13

Cancerous ER signaling

Answer 13

direct proliferation of ER+ cells
FOXA1 overexpression binds closed chromatin and opens it up
Cyclin D1 increased in expression
unopposed G1->S transition

Question 14

Aromatase inhibitor MOA

Answer 14

block estrogen synthesis in non-ovarian tissues

Question 15

ERBB2 =

Answer 15

Her2/Neu

Question 16

Trastuzumab
MOA
TU

Answer 16

MOA: mab against ERBB2/Her2/Neu
TU: ERBB2+ breast ca

Question 17

What is ERBB2?

Answer 17

EGFR family of receptors

when amplified, no ligand is needed to create proliferation signal

Question 18

Lapatinib
MOA
TU

Answer 18

MOA: inhibits TK of ERBB2/Her2/Neu
TU: Her2+ breast ca

Question 19

Oncotype Dx

Answer 19

assesses risk of recurrence/mets

based on