Breast cancer

Question 1

HER2 path

Answer 1

HER2-PI3K-AKT-mTOR-ER

Question 2

ER-positive mutations

Answer 2

PI3K (36%), AKT, HER2, ESR1, FGFR1 (11%)

Question 3

PI3K

Answer 3

36% of Breast ca (65% have one of the classic aberrations PI3K, AKT, ESR1, etc.)

Question 4

Pertuzumab mechanism

Answer 4

Binds to HER2 preventing dimerization of HER3

Question 5

CLEOPATRA study

Answer 5

first line pertuz/tras/doce v. tras/doce –> 6.1mo improvement in PFS, 15.7mo improvement in OS (median 56.5mo). If you remove PI3K mutants, survival doubles

Question 6

T-DM1 mechanism

Answer 6

binding, internalization, release of emtansine, block microtubules

Question 7

EMILIA study

Answer 7

T-DM1 v. lapatinib/cape, n=991, OS 30.9 v. 25 mo

Question 8

TH3RESA study

Answer 8

3rd line T-DM1 v. Tras+chemo–>, PFS 6.2 v 3.2 mo

Question 9

MARIANNE study

Answer 9

T-DM1 v +pertuz v. tras/taxane for first line–> NONINFERIOR

Question 10

Mechanisms of ER-resistance

Answer 10

ERa mutations–>increased to 22%, make receptors ligand-independent

Question 11

Fulvestrant mechanism

Answer 11

ER binding and degradation. however residual receptor found in 38% of patients

Question 12

SERD

Answer 12

selective estrogen receptor degrader (ARN-810/GDC-0810) with complete receptor silencing.

Question 13

mTOR signaling

Answer 13

cross-talk with ER.

Question 14

everolimus

Answer 14

not very active in PI3Ka mutants (36% of pts)

Question 15

PI3K subtypes

Answer 15

alpha-specific-breast (BYL719, GDC-0032); delta/gamma-important for lymphoid

Question 16

PI3Ka blocking

Answer 16

when you block, ERa signaling is reactivated, therefore you may have to combine with fulvestrant

Question 17

ERBB2 mutations

Answer 17

neratinib,

Question 18

CDK4 signaling

Answer 18

regulates cells into S-phase, important for ER-positive; pablociclib + letrozole v. letrozole–> 20 v. 10 month PFS (randomized non-blinded phase 2)

Question 19

luminal A

Answer 19

50%, bone/soft tissue, indolent, endocine

Question 20

luminal B

Answer 20

HER+ER+’s, or high Ki67, visceral

Question 21

visceral crisis

Answer 21

a lot of liver, rapid tempo, bulky pulmonary disease, then consider foregoing endocrine.

Question 22

incremental benefit of AI v tam

Answer 22

4 month incremental benefit

Question 23

fulvestrant v. anastrazole first line

Answer 23

FIRST trial: endpoint SD+>24wks, no difference, however TTP favored fulvestrant over anastrozole. consider as a first line option.

Question 24

FALCON

Answer 24

fulvestrant500 v. anastrazole in naive to see if front line

Question 25

EFECT trial: fulvestrant 250 v. exemestane following AI

Answer 25

same TTP. suboptimal fulvestrant dose

Question 26

CONFIRM study, fulvestrant 250 v. 500

Answer 26

fulvestrant 500 has OS advantage

Question 27

fulvestrant+AI v. AI?

Answer 27

SWOGS0226- mod OS improvement, FACT trial: no improvement. but fulvestrant 250. (SWOG pts were tam naive, more with de novo-->most significant gain) THEREFORE IF DE NOVO, consider combination

Question 28

SoFEA- after AI progression, what about fulvestrant/anastrazole

Answer 28

no difference between fulv/anastrazole, fulv, or exemestane

Question 29

BOLERO-2

Answer 29

everolimus/exemestane v. exe--> improved PFS, no improved survival

Question 30

everolimus

Answer 30

pneumonitis 15%, 3% grade III/IV, fatigue, hyperglycemia,

Question 31

palbociclib

Answer 31

Paloma 1 trial: phase II letrozole v. letro+palbo ER+HER2-, , improved PFS 20 v. 10mo,

Question 32

HER2+ER+ disease

Answer 32

letrozole/lapatinib is approved based on PFS benefit

Question 33

AI + tras +/- pertuz?

Answer 33

PERTAIN trial, allows discretionary induction chemotherapy,

Question 34

pertuz tox

Answer 34

more diarrhea 8%, more febrile neutropenia 14% (w doce), not more LVEF, (weekly taxol is better 0% febrile neutropenia)

Question 35

lapatinib in BC

Answer 35

lapatinib+tras better than lapatinib alone

Question 36

T-DM-1 in BC

Answer 36

EMILIA study: improved OS 6 months over cape/lapit, less diarrhea, hand foot

Question 37

TDM-1 tox

Answer 37

occasional thrombocytopenia, LFT elevations

Question 38

T-DM-1 v T-DM1+pertuz, v. taxane/H

Answer 38

negative study (MARIANNE- not fully reported)

Question 39

chemo for TNBC

Answer 39

weekly taxane (Seidman JCO 2008), better than q3wk

Question 40

ixabepilone + cape

Answer 40

approved, based on improved response rate (1.6mo), but no OS, you have more peripheral neuropathy/fatigue

Question 41

Hope Rugo trial CALGB 40502 taxmen comparison

Answer 41

no taxane better

Question 42

eribulin

Answer 42

2-5 prior therapy EMBRACE--> improved OS against TPC

Question 43

tam for adjuvant

Answer 43

ATLAS and atom--> 10yr>5yr, improved OS.

Question 44

AI for adjuvant

Answer 44

AI>Tam, Tam2-3+AI>Tam

Question 45

stage I ER+ adjuvant therapy

Answer 45

NSABP B20: 4% absolute improvement in DFS (89 v. 85) with CMF, versus tam alone

Question 46

oncotype Dx

Answer 46

low31, based on B20 (CMF chemo),

Question 47

adjuvant chemo

Answer 47

CMF: Bonnadanna BMJ 2005; 30 years FU, improved OS for CMF

Question 48

GeparSixto carbo TNBC

Answer 48

carbo+taxol+dox v. taxol/dox--> pCR 38%-58%, significant, no long-term outcome

Question 49

CALGB40603- taxol/ddac, +bev, +carbo, +carbo/bev

Answer 49

pCR- 46-->60% for adding carbo, but no OS data. for TNBC, if goal is to improve response.

Question 50

tras function

Answer 50

binds domain 4 (at surface),