Breast Cancer Flashcards
What is the most common type of cancer in women?
breast cancer
-1 in 8 Canadian females are expected to be diagnosed in their lifetime
How do we screen for breast cancer?
mammogram
What are some considerations when determining breast cancer treatment plan?
stage
menopausal status
hormone receptor status
HER2 status
risk factors of recurrence
overall health condition
other breast cancer biomarkers
What is the treatment for stage I breast cancer?
surgery (primary)
radiation therapy
hormonal therapy
chemotherapy (usually not offered)
targeted therapy (HER2+ and high risk of recurrence)
What is the treatment for stage II breast cancer?
surgery (standard)
radiation therapy (including lymph nodes)
chemotherapy (adjuvant and neoadjuvant)
hormonal therapy
targeted therapy (HER2+ and high risk of recurrence)
What is the treatment for stage III breast cancer?
chemotherapy (adjuvant and neoadjuvant)
targeted therapy (HER2+, ER+, or BRCA mutations)
surgery (before or after chemotherapy)
radiation therapy (after breast-conserving surgery)
hormonal therapy
What is breast-conserving surgery?
removing cancer while leaving as much normal breast as possible
What is the treatment for stage IV breast cancer?
hormonal therapy
chemotherapy (reducing cancer growth within patients tolerance level of side effects)
-monotherapy: common, fewer side effects
-combo: can be used if tolerable
targeted therapy
What are the surface receptors used to classify breast cancer?
estrogen receptor (ER)
progesterone receptor (PR)
human epidermal growth factor receptor 2 (HER2)
Differentiate the following:
-luminal A
-luminal B
-HER2
-triple negative
-normal like
luminal A: ER+ and/or PR+, HER2-
luminal B: ER+ and/or PR+, HER2+
triple negative: ER-, PR-, HER2+
normal like: similar to luminal A
What are some antibodies used to treat cancer?
trastuzumab
pertuzumab
margetuximab
What are some antibody-drug conjugates used to treat cancer?
ado-trastuzumab emtansine (T-DM1)
fam-trastuzumab deruxtecan
What is the MOA of trastuzumab?
monoclonal antibody binds to subdomain IV of HER2 protein
What is the MOA of pertuzumab?
monoclonal antibody binds to subdomain II of HER2 protein
block homodimerization of HER2 and heterodimerization of HER2-HER3
inhibit HER2-signaling pathway and decrease cell growth
What is a combination therapy for metastatic and recurrent HER2+ breast cancer?
trastuzumab + pertuzumab + docetaxel
What is the MOA of margetuximab?
chimeric IgG monoclonal antibody binds to the extracellular domain of HER2 receptor
-trastuzumab and margetuximab bind to the same epitope on HER2 receptor
What is the use of margetuximab?
adults with metastatic HER2+ breast cancer who have received two or more prior anti-HER2 regimens
Describe T-DM1.
conjugate of trastuzumab and emtansine
emtansine:
-cytotoxic agent cleaved from T-DM1 and released inside breast cancer cells
What is the use of T-DM1?
HER2+ metastatic breast cancer and early-stage HER2+ breast cancer after surgery
Describe fam-trasutuzumab deruxtecan.
conjugate of trastuzumab and deruxtecan
deruxtecan:
-topoisomerase I inhibitor
-cleaved from antibody-drug conjugate by lysosomal enzymes and released inside breast cancer cells
What is the use of fam-trasutuzumab deruxtecan?
unresectable or metastatic HER2+ breast cancer who have received two or more prior anti-HER2 regimens
What are examples of tyrosine kinase inhibitors?
lapatinib
neratinib
tucatinib
What is the MOA of lapatinib?
dual tyrosine kinase inhibitor that can reversibly bind to the ATP-binding pockets of both EGFR and HER2
What are some combo options with lapatinib?
with capecitabine for advanced and metastatic HER2+ breast cancer
with letrozole for hormone receptor + metastatic breast cancer that overexpress HER2
What is the MOA of neratinib?
irreversible pan-HER tyrosine kinase inhibitor
What is the use of neratinib?
early stage HER2+ breast cancer for an extended period after surgery
What is the MOA of tucatinib?
reversible tyrosine kinase inhibitor with exception selectivity to HER2 receptor
What is the use of tucatinib?
in combo with trastuzumab and capecitabine for advanced unresectable or metastatic HER2+ breast cancer who have one or more prior anti-HER2 regimens
What are examples of CDK4/6 inhibitors?
palbociclib
ribociclib
abemaciclib
What is an example of an mTOR inhibitor?
everolimus
What is an example of a PI3K inhibitor?
alpelisib
What is the first CDK4/6 inhibitor?
palbociclib
What is the MOA of palbociclib?
inhibit cyclin-dependent kinases CDK4 and CDK6
-block the phosphorylation of Rb
-prevent cancer cells to pass the R point
-arrest cancer cells in G1 phase
What is the use of palbociclib?
in combo with an aromatase inhibitor and fulvestrant to treat HR+, HER2- advanced or metastatic breast cancer
What is the MOA of ribociclib?
CDK4/6 inhibitor
inhibit cyclin-dependent kinases CDK4 and CDK6
What is the use of ribociclib?
same as palbociclib
What is the MOA of abemaciclib?
inhibit cyclin-dependent kinases CDK4 and CDK6
What is the use of abemaciclib?
same as palbociclib
can be used as monotherapy
What is the MOA of everolimus?
mTOR inibitor
-bind mTORC1
What is the use of everolimus?
combo with exemestane for advanced HR+, HER2- breast cancer
What is the MOA of alpelisib?
a-specific PI3K inhibitor
-approximately 40% of pts diagnosed with HR+, HER2- breast cancer have PIK3CA activating mutations
What are BRCA1 and BRCA2?
tumor suppressors
-mutations can cause cancer cells significantly relying on PARP for DNA repairs
-PARP inhibitors block DNA repairs in cancer cells, leading to apoptosis of cancer cells (normal cells have a backup DNA repair system)
What are examples of PARP inhibitors?
olaparib
talazoparib
What is the MOA of olaparib?
PARP inhibitor
What is the MOA of talazoparib?
PARP inhibitor
-~100 fold more efficient than olaparib
Describe sacituzumab govitecan.
conjugate of sacituzumab and govitecan
sacituzumab:
-monoclonal antibody targeting Trop-2 protein
govitecan:
-topoisomerase I inhibitor
What is Trop-2 protein?
trophoblast cell surface antigen 2, a tumor-associate antigen overexpressed in a large variety of solid tumor cells
