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PHAR 211 > Breast Cancer > Flashcards

Breast Cancer Flashcards

1
Q

What is the most common type of cancer in women?

A

Breast cancer

1 in 8 Canadian women are expected to be diagnosed with breast cancer in their lifetime

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2
Q

What factors affect the treatment strategy for breast cancer?

A
  • Stage
  • Menopausal status
  • Hormonal receptor status
  • HER2 status
  • Risk factors of recurrence
  • Overall health condition
  • Other breast cancer biomarkers (ex. triple negative)
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3
Q

What is the treatment strategy for stage I breast cancer?

A
  • Surgery (primary)
  • Radiation therapy
  • Hormonal therapy
  • Targeted therapy (HER 2+ and high risk of recurrence)
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4
Q

What is the treatment strategy for stage II breast cancer?

A
  • Surgery (standard)
  • Radiation therapy (inc. lymph nodes)
  • Chemotherapy (adjuvant and neoadjuvant)
  • Hormonal therapy
  • Targeted therapy (never first line)
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5
Q

What is the treatment strategy for stage III breast cancer?

A
  • Chemotherapy (adjuvant and neoadjuvant)
  • Targeted therapy (HER2+, ER+, BRCA mutations)
  • Surgery (breast conserving surgery)
  • Radiation therapy (multibeam radiotherapy)
  • Hormonal therapy (used to slow down progress of ER+)
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6
Q

What is the treatment strategy for stage IV breast cancer?

A

Cancer has likely metastasized

  • Hormonal therapy (slow down growth)
  • Chemotherapy (balance reducing cancer growth with tolerability, can use combo or mono)
  • Target therapy (given after 2-3 rounds of other therapies)
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7
Q

How are breast cancer types organized by surface proteins?

A
  • Luminal A: ER+ and/or PR+, HER2-
  • Luminal B: ER+ and/or PR+, HER2+
  • HER2+: ER- and/or PR-, HER2+ (poorer prognosis than Luminal A or B)
  • Triple-negative: ER-, PR-, HER2-
  • Normal-like: similar to luminal A (good prognosis)
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8
Q

What the most important signalling pathway for HER2+ breast cancer?

A

PI3K pathway

PI3K–>AKT–>mTOR

mTOR promotes increased proliferation

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9
Q

What antibodies are used in HER2+ breast cancer?

A
  • Trastuzumab
  • Pertuzumab
  • Margetuximab
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10
Q

What antibody-drug conjugates are used in HER2+ breast cancer?

A
  • Ado-trastuzumab emtansine (T-DM1)
  • Fam-trastuzumab deruxtecan
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11
Q

How does Trastuzumab work in breast cancer therapy?

A

Monoclonal antibody binds to subdomain IV of HER2

Prevents HER2 from binding to activating ligand

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12
Q

How does Pertuzumab work in breast cancer therapy?

A

Monoclonal antibody binds to subdomain II of HER2 protein

Block dimerization of HER2 (inhibition of HER2-signalling pathway and decrease)

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13
Q

How does Margetuximab work in breast cancer?

A
  • Chimeric monoclonal antibody binds to to extracellular domain of HER2 receptor
  • HER2+ breast cancer who have received two or more prior anti-HER2 regimens
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14
Q

How does ado-trastuzumab emtansine work in breast cancer?

A
  • Conjugate of trastuzumab (monoclonal antibody) and emtansine (cytotoxic)
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15
Q

How does Fam-trastuzumab deruxtecan work in breast cancer?

A
  • Conjugate of trastuzumab (monoclonal antibody) and deruxtecan (topoisomerase inhibitor, disrupts transcription)
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16
Q

What tyrosine kinase inhibitors are involved in breast cancer therapy?

A
  • Lapatinib
  • Neratinib
  • Tucatinib
17
Q

How does Lapatinib therapy work?

A
  • Reversibily binds to the ATP binding pockets of EGFR and HER2
  • Blocks phosphorylation and subsequent proliferation
18
Q

How does Neratinib therapy work in breast cancer?

A
  • Irreversible pan-HER tyrosine kinase inhibitor
  • Blocks phosphorylation and subsequent proliferation
19
Q

How does Tucatinib work in breast cancer therapy?

A

Reversible tyrosine kinase inhibitor with exceptional selectivity to HER2 receptor

20
Q

What are the different types of CDK4/6 inhibitors used in breast cancer therapy?

A
  • Palbociclib
  • Ribociclib
  • Abemaciclib
21
Q

What mTOR inhibitor is used in breast cancer therapy?

A

Everolimus

22
Q

What PI3K inhibitor is used in breast cancer therapy?

A

Alpelisib

23
Q

How does Palbociclib work in breast cancer therapy?

A

CDK4/6 inhibitor and blocks phosphorylation of Rb (prevent cell to pass the R point and arrests cancer cell in G1 phase)

24
Q

How does Ribociclib work in breast cancer therapy?

A

CDK4/6 inhibitor

25
Q

What is special about Abemaciclib?

A

It is a CDK4/6 inhibitor that has shown significant improved efficacy compared to other available therapies (expedited approval)

26
Q

How does Everolimus work in breast cancer therapy?

A

mTOR inhibitor (prevents cells from entering S phase, upstream of CDK)

27
Q

How does Alpelsib work in breast cancer therapy?

A

It is a specific PI3K inhibitor (also key kinase involved in cell signalling)

Alpelisib inhibits hyperactivation

28
Q

What is a targeted therapy option for patients with breast cancer with BRCA gene mutations?

A

PARP inhibitors block DNA repairs in cancer cells, leading to apoptosis of cancer cells

ex. Olaparib and Talazoparib

29
Q

How does Olaparib therapy work in patients with breast cancer?

A

PARP inhibitor (used in patients with BRCA mutations alone)

30
Q

How does Talazoparib work in patients with breast cancer?

A

PARP inhibitor (used in patients with BRCA mutations alone)

100x more efficient than Olaparib

31
Q

What is a targeted therapy option for patients with breast cancer (triple negative)?

A
  • Sacituzumab govitecan
32
Q

How does Sacituzumab govitecan work in patients with breast cancer?

A

Used in triple negative breast cancer

Conjugate of sacituzumab (monoclonal antibody against Trop-2 protein, overexpressed in many types of solid tumours) and govitecan (topoisomerase inhibitor)

PHAR 211 (18 decks)

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