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PHAR 211 > Personalized Cancer Therapy: Breast Cancer > Flashcards

Personalized Cancer Therapy: Breast Cancer Flashcards

1
Q

What must be taken into account when making a breast cancer treatment plan? (7)

A
  1. Stage
  2. Menopausal status
  3. Hormone receptor status
  4. HER2 status
  5. Risk factors of recurrence
  6. Overall health condition
  7. Other breast cancer biomarkers
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2
Q

Breast cancer stage I: What are the steps of treatment? (5)

A
  1. Surgery (primary)
  2. Radiation therapy
  3. Hormonal therapy
  4. Chemotherapy (usually not offered)
  5. Targeted therapy (HER2+ and high risk of recurrence)
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3
Q

Breast cancer stage II: What are the steps of treatment? (5)

A
  1. Surgery (standard)
  2. Radiation therapy (including lymph nodes)
  3. Chemotherapy (adjuvant and neoadjuvant)
  4. Hormonal therapy
  5. Targeted therapy (HER2+ and high risk of recurrence)
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4
Q

Breast cancer stage III: What are the steps of treatment? (5)

A
  1. Chemotherapy (adjuvant and neoadjuvant)
  2. Targeted therapy (HER2+, ER+, or BRCA mutations)
  3. Surgery (before or after chemotherapy)
  4. Radiation therapy (after breast-conserving surgery)
  5. Hormonal therapy
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5
Q

Breast cancer IV: What are the steps of treatment? (3)

A
  1. Hormonal therapy
  2. Chemotherapy (reducing cancer growth within patient’s tolerance level of side effects)
    - Monotherapy
    - Combination therapy
  3. Targeted therapy
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6
Q

What are the 3 surface receptors seen in breast cancer?

A
  1. Estrogen receptor (ER)
  2. Progesterone receptor (PR)
  3. Human epidermal growth factor receptor 2 (HER2)
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7
Q

ER and PR are _______ receptors
HER2 is a ______ ______ receptor

A

hormone; growth factor

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8
Q

What is the Luminal A classification of breast cancer?

A

ER+ and/or PR+, HER2-

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9
Q

What is the Luminal B classification of breast cancer?

A

ER+ and/or PR+, HER2+

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10
Q

What is the HER2 classification of breast cancer?

A

ER-, PR-, HER2+

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11
Q

What is the triple negative classification of breast cancer?

A

ER-, PR-, HER2-

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12
Q

What is the normal-like classification of breast cancer?

A

Similar to luminal A (ER+ and/or PR+, HER2-)

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13
Q

Palbociclib is the first…

A

CDK4/6 inhibitor

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14
Q

What is the MOA of palbociclib? (4)

A

Inhibit cyclin-dependent kinases CDK4 and CDK6
- Block the ppylation of Rb
- Prevent cancer cells to pass the R point
- Arrest cancer cells in G1 phase

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15
Q

How are the CDK4/6 inhibitors given?

A

In combination with an aromatase inhibitor or fulvestrant to treat HR+, HER2- advanced or metastatic breast cancer
(Also, give with food)

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16
Q

The main pathway of HER2 signaling is?

A

PI3K pathway
PI3K –> AKT –> mTOR –> transcription

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17
Q

Trastuzumab is approved for which subtype of breast cancer?

A

HER2

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18
Q

What is the MOA of trastuzumab? (2)

A
  1. Monoclonal antibody targeting HER2/neu/Erbb2 protein
  2. Bind to subdomain IV of HER2 protein
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19
Q

What are some ADRs associated with trastuzumab? (4)

A
  1. Chills
  2. Fever
  3. Body pain
  4. Weakness
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20
Q

What is the MOA of pertuzumab? (3)

A
  1. Monoclonal antibody binds to subdomain II of HER2 protein
  2. Block homodimerization of HER2 and heterodimerization of HER2-HER3
  3. Inhibit HER2-signaling pathway and decrease cell growth
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21
Q

What combination of medications is given for metastatic and recurrent HER2+ breast cancer (3)?

A

Trastuzumab + pertuzumab + docetaxel

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22
Q

What does emtansine do (when in combo in T-DM1 - ado-trastuzumab emtansine)?

A

Emtansine, which is a potent cytotoxic agent, is cleaved from T-DM1 and released inside breast cancer cells

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23
Q

When is T-DM1 used?

A

Treat HER2+ metastatic breast cancer and early-stage HER2+ breast cancer after surgery

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24
Q

What is the MOA of lapatinib?

A

Dual tyrosine kinase inhibitor that can reversibly bind to the ATP-binding pockets of both EGFR and HER2

25
Q

When is lapatinib used? (2)

A
  1. In combination with capecitabine for treatment of advanced and metastatic HER2+ breast cancer
  2. In combination with letrozole for treatment of hormone receptor-positive metastatic breast cancer that overexpresses HER2
26
Q

What is the MOA of gefitinib and cetuximab?

A

Inhibitor of EGFR

27
Q

The best screening method for breast cancer is?

A

Mammogram

28
Q

What is the secondary signaling pathway for HER2?

A

MAPK pathway
RAS –> Raf –> MEK –> MAPK —> transcription

29
Q

What are the main antibody drugs used in breast cancer? (3)

A
  1. Trastuzumab
  2. Pertuzumab
  3. Margetuximab
30
Q

What are the main antibody-drug conjugate drugs used in breast cancer? (2)

A
  1. Ado-trastuzumab emtansine (T-DM1)
  2. Fam-trastuzumab deruxtecan
31
Q

What is the MOA of margetuximab? (2)

A
  1. Chimeric IgG monoclonal antibody binds to the extracellular domain of HER2 receptor
  2. Trastuzumab and margetuximab bind to the same epitope on HER2 receptor
32
Q

Who is margetuximab used in?

A

Treat adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens

33
Q

What does deruxtecan do? (when in combo in fam-trastuzumab deruxtecan)? (2)

A
  1. A topoisomerase I inhibitor, is cleaved from the anti-body drug conjugate by lysosomal enzymes and released inside breast cancer cells
  2. Deruxtecan forms a ternary complex with topoisomerase I and DNA, causing cancer cell death
34
Q

Who is treated with fam-trastuzumab deruxtecan?

A

Treat patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens

35
Q

What are the 3 tyrosine kinase inhibitor drugs used in breast cancer treatment?

A
  1. Lapatinib
  2. Neratinib
  3. Tucatinib
36
Q

What is the MOA of neratinib?

A

Irreversible pan-HER tyrosine kinase inhibitor

37
Q

Who is treated using neratinib?

A

Treat early stage HER2+ breast cancer for an extended period (extended adjuvant therapy) after surgery

38
Q

What is the MOA of tucatinib?

A

Reversible tyrosine kinase inhibitor with exceptional selectivity to HER2 receptor (>1000-fold enhancement compared to EGFR)

39
Q

Who is treated with tucatinib?

A

In combination with trastuzumab and capecitabine for treatment of patients with advanced unresectable or metastatic HER2+ breast cancer who have one or more prior anti-HER regimens

40
Q

What are the 3 CDK4/6 inhibitor drugs?

A
  1. Palbociclib
  2. Ribociclib
  3. Abemaciclib
41
Q

What is the one mTOR inhibitor drug?

A

Everolimus

42
Q

What is the one PI3K inhibitor drug?

A

Alpelisib

43
Q

What is the MOA of everolimus?

A

Bind mTORC1

44
Q

How is everolimus given?

A

In combination with exemestane for treatment of advanced HR+, HER2- breast cancer

45
Q

What is the MOA of alpelisib?

A

alpha-specific PI3K inhibitor

46
Q

How is alpelisib given?

A

In combination with fulvestrant for treatment of HR+, HER2-, PIK3CA- mutated advanced or metastatic breast cancer

47
Q

What is a PIK3ACA mutation?

A

Induces hyperactivation of alpha-isoform (p110alpha) of PI3K

48
Q

Approximately __% of patients diagnosed with HR+, HER2- breast cancer have PIK3CA activating mutations

A

40%

49
Q

BRCA1 and BRCA2 are _____ ___________

A

tumor suppressors

50
Q

BRCA1/2 mutations can cause what?

A

Can cause cancer cells significantly relying on poly ADP-ribose polymerase (PARP) for DNA repairs

51
Q

How do PARP inhibitors work? (2)

A
  1. Block DNA repairs in cancer cells, leading to apoptosis of cancer cells
  2. Normal cell have backup DNA repair system, and thus are not killed by PARP inhibitors
52
Q

What are the 2 PARP inhibitor drugs?

A
  1. Olaparib
  2. Talazoparib
53
Q

Who is treated with olaparib?

A

Treat patients with deletrious or suspected deleterious germline BRCA-mutated HER2- metastatic breast cancer

54
Q

Talazoparib is ___x more efficient than olaparib

A

100x

55
Q

Who is treated with talazoparib?

A

Treat patients with deletrious or suspected deleterious germline BRCA-mutated HER2- locally advanced or metastatic breast cancer

56
Q

Sacituzumab govitecan is a conjugate drug. What does sacituzumab do?

A

A monoclonal antibody targeting Trop-2 protein

57
Q

What is Trop-2?

A

Trophoblast cell surface antigen 2, a tumor-associate antigen overxpressed in a large variety of solid tumor cells

58
Q

Sacituzumab govitecan is a conjugate drug. What does govitecan do?

A

A topoisomerase I inhibitor

59
Q

Who is treated with sacituzumab govitecan?

A

Treat patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease

PHAR 211 (10 decks)

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