Breast Cancer Flashcards
What is the most common type of cancer in women?
Breast cancer
1 in 8 Canadian women are expected to be diagnosed with breast cancer in their lifetime
What factors affect the treatment strategy for breast cancer?
- Stage
- Menopausal status
- Hormonal receptor status
- HER2 status
- Risk factors of recurrence
- Overall health condition
- Other breast cancer biomarkers (ex. triple negative)
What is the treatment strategy for stage I breast cancer?
- Surgery (primary)
- Radiation therapy
- Hormonal therapy
- Targeted therapy (HER 2+ and high risk of recurrence)
What is the treatment strategy for stage II breast cancer?
- Surgery (standard)
- Radiation therapy (inc. lymph nodes)
- Chemotherapy (adjuvant and neoadjuvant)
- Hormonal therapy
- Targeted therapy (never first line)
What is the treatment strategy for stage III breast cancer?
- 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+)
What is the treatment strategy for stage IV breast cancer?
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)
How are breast cancer types organized by surface proteins?
- 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)
What the most important signalling pathway for HER2+ breast cancer?
PI3K pathway
PI3K–>AKT–>mTOR
mTOR promotes increased proliferation
What antibodies are used in HER2+ breast cancer?
- Trastuzumab
- Pertuzumab
- Margetuximab
What antibody-drug conjugates are used in HER2+ breast cancer?
- Ado-trastuzumab emtansine (T-DM1)
- Fam-trastuzumab deruxtecan
How does Trastuzumab work in breast cancer therapy?
Monoclonal antibody binds to subdomain IV of HER2
Prevents HER2 from binding to activating ligand
How does Pertuzumab work in breast cancer therapy?
Monoclonal antibody binds to subdomain II of HER2 protein
Block dimerization of HER2 (inhibition of HER2-signalling pathway and decrease)
How does Margetuximab work in breast cancer?
- Chimeric monoclonal antibody binds to to extracellular domain of HER2 receptor
- HER2+ breast cancer who have received two or more prior anti-HER2 regimens
How does ado-trastuzumab emtansine work in breast cancer?
- Conjugate of trastuzumab (monoclonal antibody) and emtansine (cytotoxic)
How does Fam-trastuzumab deruxtecan work in breast cancer?
- Conjugate of trastuzumab (monoclonal antibody) and deruxtecan (topoisomerase inhibitor, disrupts transcription)
What tyrosine kinase inhibitors are involved in breast cancer therapy?
- Lapatinib
- Neratinib
- Tucatinib
How does Lapatinib therapy work?
- Reversibily binds to the ATP binding pockets of EGFR and HER2
- Blocks phosphorylation and subsequent proliferation
How does Neratinib therapy work in breast cancer?
- Irreversible pan-HER tyrosine kinase inhibitor
- Blocks phosphorylation and subsequent proliferation
How does Tucatinib work in breast cancer therapy?
Reversible tyrosine kinase inhibitor with exceptional selectivity to HER2 receptor
What are the different types of CDK4/6 inhibitors used in breast cancer therapy?
- Palbociclib
- Ribociclib
- Abemaciclib
What mTOR inhibitor is used in breast cancer therapy?
Everolimus
What PI3K inhibitor is used in breast cancer therapy?
Alpelisib
How does Palbociclib work in breast cancer therapy?
CDK4/6 inhibitor and blocks phosphorylation of Rb (prevent cell to pass the R point and arrests cancer cell in G1 phase)
How does Ribociclib work in breast cancer therapy?
CDK4/6 inhibitor
What is special about Abemaciclib?
It is a CDK4/6 inhibitor that has shown significant improved efficacy compared to other available therapies (expedited approval)
How does Everolimus work in breast cancer therapy?
mTOR inhibitor (prevents cells from entering S phase, upstream of CDK)
How does Alpelsib work in breast cancer therapy?
It is a specific PI3K inhibitor (also key kinase involved in cell signalling)
Alpelisib inhibits hyperactivation
What is a targeted therapy option for patients with breast cancer with BRCA gene mutations?
PARP inhibitors block DNA repairs in cancer cells, leading to apoptosis of cancer cells
ex. Olaparib and Talazoparib
How does Olaparib therapy work in patients with breast cancer?
PARP inhibitor (used in patients with BRCA mutations alone)
How does Talazoparib work in patients with breast cancer?
PARP inhibitor (used in patients with BRCA mutations alone)
100x more efficient than Olaparib
What is a targeted therapy option for patients with breast cancer (triple negative)?
- Sacituzumab govitecan
How does Sacituzumab govitecan work in patients with breast cancer?
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)
