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breast cancer > Breast cancer > Flashcards

Breast cancer Flashcards

1
Q

HER2 path

A

HER2-PI3K-AKT-mTOR-ER

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2
Q

ER-positive mutations

A

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

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3
Q

PI3K

A

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

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4
Q

Pertuzumab mechanism

A

Binds to HER2 preventing dimerization of HER3

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5
Q

CLEOPATRA study

A

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

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6
Q

T-DM1 mechanism

A

binding, internalization, release of emtansine, block microtubules

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7
Q

EMILIA study

A

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

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8
Q

TH3RESA study

A

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

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9
Q

MARIANNE study

A

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

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10
Q

Mechanisms of ER-resistance

A

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

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11
Q

Fulvestrant mechanism

A

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

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12
Q

SERD

A

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

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13
Q

mTOR signaling

A

cross-talk with ER.

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14
Q

everolimus

A

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

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15
Q

PI3K subtypes

A

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

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16
Q

PI3Ka blocking

A

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

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17
Q

ERBB2 mutations

A

neratinib,

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18
Q

CDK4 signaling

A

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

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19
Q

luminal A

A

50%, bone/soft tissue, indolent, endocine

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20
Q

luminal B

A

HER+ER+’s, or high Ki67, visceral

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21
Q

visceral crisis

A

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

22
Q

incremental benefit of AI v tam

A

4 month incremental benefit

23
Q

fulvestrant v. anastrazole first line

A

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

24
Q

FALCON

A

fulvestrant500 v. anastrazole in naive to see if front line

25
Q

EFECT trial: fulvestrant 250 v. exemestane following AI

A

same TTP. suboptimal fulvestrant dose

26
Q

CONFIRM study, fulvestrant 250 v. 500

A

fulvestrant 500 has OS advantage

27
Q

fulvestrant+AI v. AI?

A

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

28
Q

SoFEA- after AI progression, what about fulvestrant/anastrazole

A

no difference between fulv/anastrazole, fulv, or exemestane

29
Q

BOLERO-2

A

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

30
Q

everolimus

A

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

31
Q

palbociclib

A

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

32
Q

HER2+ER+ disease

A

letrozole/lapatinib is approved based on PFS benefit

33
Q

AI + tras +/- pertuz?

A

PERTAIN trial, allows discretionary induction chemotherapy,

34
Q

pertuz tox

A

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

35
Q

lapatinib in BC

A

lapatinib+tras better than lapatinib alone

36
Q

T-DM-1 in BC

A

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

37
Q

TDM-1 tox

A

occasional thrombocytopenia, LFT elevations

38
Q

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

A

negative study (MARIANNE- not fully reported)

39
Q

chemo for TNBC

A

weekly taxane (Seidman JCO 2008), better than q3wk

40
Q

ixabepilone + cape

A

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

41
Q

Hope Rugo trial CALGB 40502 taxmen comparison

A

no taxane better

42
Q

eribulin

A

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

43
Q

tam for adjuvant

A

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

44
Q

AI for adjuvant

A

AI>Tam, Tam2-3+AI>Tam

45
Q

stage I ER+ adjuvant therapy

A

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

46
Q

oncotype Dx

A

low31, based on B20 (CMF chemo),

47
Q

adjuvant chemo

A

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

48
Q

GeparSixto carbo TNBC

A

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

49
Q

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

A

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

50
Q

tras function

A

binds domain 4 (at surface),

breast cancer (1 decks)

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