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Oncology > Breast Cancer 🎀 > Flashcards

Breast Cancer 🎀 Flashcards

1
Q

Risk Factors of Breast Cancer

A
  1. Age
  2. Inherited gene mutation BRCA1/2
  3. Overweight
  4. Alcohol
  5. Combined hormonal contraception
  6. Radiotherapy
  7. Smoking
  8. Food
  9. Race
  10. Age at first birth of first child
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2
Q

What does BRCA stand for?

A

BReast CANCER gene

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3
Q

BRCA1 and BRCA2 normal role…

A

Tumour suppressor genes
Ie. Encode proteins involved in DNA repair

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4
Q

Genetic mutations in BRCA1 or 2 cause…

A
  1. Germ-line mutations
  2. A lack of functional DNA repair protiens
  3. Breast cancer predisposing mutations
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5
Q

Luminal A …

A

HER2- / HR+

= Most favourable prognosis due to response of hormone therapy.

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6
Q

Luminal B…

A

HER+ / HR+

= Poorer prognosis than Luminal A.

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7
Q

HER2- enriched …

A

HER2+ / HR-

= Poorer prognosis than HR+ but improving after development of targeted therapies

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8
Q

Triple negative BC (TNBC) and
Basal Like BC (BLBC) ….

A

HER2- / HR-
=poorest prognosis, most aggressive

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9
Q

Cytotoxic Drugs for BC…

A
  1. Anthracyclines (doxorubicin, epirubicin)
  2. Alkylating agents (cyclophosphamide)
  3. Taxane (dovetail, paclitaxel)
  4. Platinums (carboplatin)
  5. Antimetabolites (flurouracil, methotrexate, capecitabine)
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10
Q

SERMS
Selective Estrogen Receptor Modulators… selectivity for?

A

Tissues

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11
Q

Objectives of SERMS (selective estrogen receptor modulators) … ×2

A
  1. Anti-estrogenic at breast &/or endometrium = inhibit tumour growth
  2. Estrogenic at other tissues (ie. Bone, liver, lipid, endrometriun)
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12
Q

Name SERMS drugs (×2) ….

A
  1. Tamoxifen
  2. Endoxifen
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13
Q

SERMS… Tamoxifen and endoxifen,
which drug has more affinity for ER?

A

Endoxifen

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14
Q

MOA of Aromatase inhibitors

A

Inhibit estrogen production,
By stopping conversion of androgens to estrogen.

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15
Q

Who are Aromatase Inhibitors indicated for?

A

Mainly POST- menopausal woman.

In PRE- menopausal, use WITH ovarian suppression (ie. GOSERELIN - Gonadotrophin- releasing hormone agonist).

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16
Q

Name AROMATASE INHIBITOR drugs…

A
  1. Anastrozole
  2. Letrozole
  3. Exemestane (steroidal AI)
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17
Q

Estrogen Receptor Antagonists MOA:

A

Competitively binds to ERs on cancer cells inhibiting Receptor dimerization = ER down-regulate.

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18
Q

Estrogen Receptor Antagonists, indicated for?

A

POST menopausal
… if disease progresses following use of SERMS

+ for ER+ advanced/metastatic.

19
Q

Name Estrogen Receptor Antagonists…

A

Fulvestrant
(Fulvestrol)

20
Q

ER Antagonist
Fulvestrant used in combo with?

A

Targeted therapies
CDK 4/6 Inhibitors

21
Q

Why do we NOT dose Tamoxifen (SERM) based on CYP2D6?

A

No CYP2D6 guided dosing as…
Only 20-40% of variability in Endoxifen level is explained by CYP2D6 phenotype.

22
Q

Drug switch in POST menopausal?

A

Use of AI’s in post-menopausal is favoured over Tamoxifen monotherapy.

*extended adjuvant endocrine therapy with AIs beyond 5 years =
Reduced secondary breast cancer occurrence
BUT MORE toxicity.

23
Q

Targeted therapy

Name
Cyclin-dependant Kinase 4 & 6 (CDK4/6) Inhibitors ….

A
  1. Palbociclib
  2. Ribociclib
  3. Abemaciclib
24
Q

TT:
Name
mTOR kinase …

A

Everolimus

25
Q

TT: HER signalling pathway
Name
HER2 monoclonal antibody …

A

Trastuzumab
Pertuzumab

26
Q

TT: HER signalling pathway

Name COMBO:
HER2 Receptor targeting with antibody-drug conjugate (ADC)…

A
  • Trastuzumab - emtansine or T-DM1 (Kadcyla)
  • Trastuzumab - deruxtecan (Enhertu)
27
Q

Name Tyrosine kinase (TK) ….

A

Lapatinib (tykerb)
Neratinib (nerlynx)

28
Q

MTOR kinase Inhibitors
Indicated for?

A

HR+ and HER2- adv. Breast cancer in POST menopausal after failure of treatment with letrozole abd anastrozole.

BOLERO-2 trial: everolimus + exemestane

29
Q

HER signalling pathway and Tyrosine kinases - Receptor family?

A

ErbB family of Receptor Tyrosine kinases (RTKs) > ErbB2/HER2

30
Q

HER2 activation results in cancer cell proliferation via… (×2)

A
  1. MAPK ( RAS, RAF, MEK, ERK) pathway
  2. PI3K / AKT / MORE pathways
31
Q

HER2 monoclonal antibody: Trastuzumab MOA

A

Binds to HER2 extracellular domain, and inhibits kigand- independent HER2 signalling.

32
Q

HER2 monoclonal antibody
Pertuzumab MOA?

A

HER2 Receptor dimerisation inhibitor.
Binds to the dimerisation site in the HER2 domain abd orients ligand- mediated pairing of HER2 with other HER2 Receptors (HER3) by steric hindrance.

33
Q

Which drug has complementary action to trastuzumab? (Favourable combo)

A

Trastuzumab- taxane + PERTUZUMAB

34
Q

Trastuzumab-emtasine (aka. T-DM1 or kadycla)
Indicated for?

A

2nd line for HER2+
And
1st line for HER2+ metastatic patients unsuitable for taxane based therapy

35
Q

Trastuzumab deruxtecan (enhertu)
Indicated for?

A

Metastatic BC.
Who have recieved 2+ prior anti-HER2 based regimes.

**deruxtecan is 10× more potent thN SN-38

36
Q

Targeted therapy:
Tyrosine Kinases (TKs) for HER2+
Name ×2

A
  1. Lapatinib (tykerb)
  2. Naratinib (nerlynx)
37
Q

Tyrosine kinase
LAPATINIB
MOA

A

Dual tyrosine kinase inhibitor of HER2

Binds thr intracellular adenosine triphosphate binding domain of HER1 and HER2 and results in cell signalling inhibition.

38
Q

Tyrosine kinase
Neratinib
MOA

A

Irreversible tyrosine kinase inhibitor that targets the human
HER1 (EGFR)
HER2
HER4

39
Q

Targeted therapy
Trop2. Receptor
(Trophoblast Cell Surface Antigen 2 (Trop2) targeting with an ADC

NAME

A

Sacituzumab govitecan
(Trodelvy)

40
Q

Trop2 Receptor
Sacituzumab govitecan

Indicated for?

A

Patients with unrepeatable locally advanced or metastatic triple-negative BC.

41
Q

PARP proteins
(DNA damage repair)
Moa

A

Tumour collaboration with a mutated BRCA gene have trouble repairing damaged DNA -> blocking PARP proteins cancer cell death

42
Q

TT with BRCA gene mutations
What is BRCA?

A

BRCA1 and BRCA2 genes protect against BC.

43
Q

Name meds (2) for BRCA gene mutations patients

A

Olaparib
Tazoparib

44
Q

Immune checkpoint Inhibitors PD-L1 blocked by

A

Atezolizumab + nab- paclitaxel

Oncology (15 decks)

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