Lecture 3-4 Flashcards
Breast Cancer
Breast Cancer can happen in :
Ducts ***
Lobules
Other areas
What action has proven to be reducing the risk of cancer ?
Breastfeeding
What are the risks factors for breast cancer ?
Age
Sex
History
Estrogen exposure
Radiation at a young age
Alcohol
Obesity
Dense breast tissue
Can contraceptives have a high risk of cancer ?
No currently low
What age has a high risk of breast cancer ?
45 - 65 yo
What type of estrogen exposure can increase the risk ok breast cancer ?
Endogenous : early puberty, late menopause, first pregnancy > 30 yo
Exogenous: HRT after menopause , HRT > 5 yo
What is BRCA gene and relation to breast cancer ?
Breast cancer susceptibility genes
Tumour suppressor gene that increases the risk of breast cancer
Most common in Ashkenazi Jewish
What is Li Fraumeni Syndrome ?
Rare germ line mutation to TP53 gene , tumor suppressor gene that increases the risk of breast cancer .
How does radiation works as oncology Tx ?
Rays cause DNA damage … which accumulates and causes the cells to no longer divide —> DEATH
Only cancer cells cannot repair DNA but normal cells can effectively repair it
What is the main difference between **external beam RT ** and Brachytherapy ?
External is the most common , the higher the energy beam and the deeper the radiation
Brachytherapy requires an implant directly to the tumor and body cavity . This limits the absorption of other healthy cells
How often is RT usually given ?
Daily
Which of the cancer is palliative when RT is involved ?
Lung
Head/ Neck Cancer
What are radiosensitizers ?
Chemicals that increase the biological effects of RT
Some chemo agents are radiosensitizers
Which of the chemotherapy agents or radio sensitizers?
5FU and cisplatin
What percentage of RT is given with palliative intent?
About 50%
What are indications for palliative RT?
Bone metastases, spinal cord compression brain metastases, advance lung cancer, superior vena cava syndrome
Give an example of RT emergencies
Spinal cord compression
What are one of the generalized side effects of radiation therapy?
fatigue
What is Gene TP 53? What happens when it’s mutated?
TP 53 is it true or surface one mutated it increases the risk of breast cancer
At what age would you recommend screening for breast cancer through mammograms?
Asymptomatic women, transgender, gender, diverse, and non-binary people excluded risk 45 to 74 years old is recommended for screening mammograms
From the LGBTQ community , who can we screen ?
breast tissue
>5 years of feminizing hormone
maybe top surgery ( decided by the doctor)
What are the predictive markers of breast cancer ?
Hormone receptors, HER2
What are the prognostic markers for bresat cancer ?
Ki67
BAsed on the breast type, which has the worsr prognosis ?
Invasive Ductal carcinoma
what is stage IV breast cancer ?
metastatic
What is stage 1 breast cnacer ?
early stage disease ( resectable)
<2 and no nodes
What is stage 0 breast cancer ?
insitu only
What is stage 2 breast cancer ?
Stage 3 : > 5 and lots of nodes
early stage - resectable
What is HIGH grade ?
less differiential cells
poor prognosis and better response to therapy
What is Ki67 ?
marker of proliferation
What is an oncogene in breast cnacer ?
hER2/neu
What are the genomic test for cancer ?
OncotypeDx
Prosigna
Which genomic test will provide onformation about which tx would work for breast cancer ( chemo, endocrine, HER ) ?
OncotypeDx
What is the goal of tx at stage 0 ?
prevention of the invasice cancer
When would you consider adding endocrine tx in cancer breast ?
Stage 0 and down
When would you consider adding chemo adjuvant in breast cancer ?
Stage 1 and down
When would you consider adding HER2 target for breast cancer ?
stage 2 and down
What is the main diff in modified and radical masectomy ?
modified : entire breast and some auxillary nodes
radical : entire breast and more axillary nodes
What is the use of sentinnel nodes in breast cancer ?
hypothetical first affected nodes
free of cancer, don’t spread the infected radioactive agent
what is a possible consequence of blocked or removed axillary nodes ?
lymphedema
What does it mean grade 1 breast cancer ?
Low grae, well differentiate and growing slow and well organized
What is the suffix of anthracycline ?
“rubicin”
What are the drug combination for stage 1-3 breast cancer ?
“3 aunties can talk feeding”
3 : carboplatin, cyclophosphamide , ALONE - capecitabine
AC, TC , FECD, CT
What is the difference in chemo tx for stage 1-3 to 4 ?
4 : now includes vinca alkoid or NAB-Pacitaxel
What are the MOA of doxorubicin ?
Intercalated base pairs
inhibits topoisomerase 2
Chelates with iron → radicals
Which of the anthracyclines stays longer in the body ?
Doxorubicin is longer because fastter metabolism of epirubicin
What are your f/u measures for anthracyclines ?
Rubicin
red urine
cardio ( ECG , LVEF)
blister
N/V
What is the MOA of cyclophosphamide ?
alkylatin agent –> nitrohen mustard
breaks DNA
What is the ADR or cyclophosphamide ?
Hemorrhagic cystitis ( acrolein)
nausea ( ** if with the anthracyclines)
fertility suppression
a patient is taking cyclophosphamide , what can you counsel them ?
Drink lots of water and pee often * help with cystitis
Fertility is suppressed
What is the MOA or taxanes ?
“tangles vines “
disrupts the microtbules
What are the main ADR of taxanes?
hypersensitivity rxn
Acute intoxications
fluid retention
fatigue
neuropathy and nail changes
What is the role of dexamethasone with taxanes and with which agent ?
Dexa + doctaxel ( double D’s)
helps with fluid retention, hypersensitivity and ??? antiemetic
How is carboplatin vs cisplatin ?
Less oto/nephrotoxic
N/V ( <cisplatin)
More myelosuppression
What is HER receptors ?
Transmembrane protein that stimulates intracellular signaling to proliferate .
HER2 is activated by COUPLING
Name the breast cancer HER2 tx ?
Trastuzumab :
Trastuzumab + DM1: emtansine
Trastuzumab + Dxd : Deruxetecan
Pertuzumab
Tucutinib
Lapatinib
What is the MOA of trastuzumab ?
mABs of HER2 –> ligand dependent
leading to NK cells to kill it
What is MOA of pertuzumab ?
inhibits the dimerization of HER2 - HER1/3/4
Which hormonal Tx for breast cancer is best after menopause ?
Tamoxifen
aromatase inhibitors ( anastrozole/letrozole/exemestane)
Fulvestrant
CDK4/6 ( palbociclib,ribociclib,abemaciclib)
Where does tamoxifen bind ?
agonist on the endometrium/bone/lipids
antagonist on the breast / breast cancer cells
What is the DDI between tamoxifen and Fluoxetine vs venlafaxine ?
Fluoxtine –> CYP2D6 inhibitors ( not activation of tamoxifen)
venlafaxine –> not a CYP2D6 inhibitors
What is exemestane ?
Aromatase inhibitors used in the breast cancer ER+/PR+
What are tamoxifen side effects ?
Side effects :
Menopause like
Flare-ups
Myalgias
?! DVT/PE
What are the MOA of anstrozole ?
Aromatase inhibitors for breast cancer
Stops the production of estrogen from the adipose tissue
What are the Side effects of letrozole ?
Aromatase inhibitors :
Myalgia
Edema
Vaginal dry
Bone loss
Hypercholesterol
What is the fulvestrant ?
FULL estrogen antagonist
Which of the CDK4 /6 inhibitors is used in early disease ?
abemaciclib
What is palociclib ?
CDK 4/6 inhibitors - breast cancer : metastatic
What should we monitor for pt on ribociclib ?
CDK4/6 inhibitors –> metastatic
CYP3A4 –> not grapefruit
fatigue
bone marrow suppression
Watch for Qtc
what are the side effects for fulvestrant ?
Injection site rxn
Hypersensitivity
Hepatoxic
Hot flashes
What is Olaparib ?
PARP inhibitors in BRCA mutations
What are the immune checkpoint therapies for breast cancer ?
Pembrolizumab
Olaparib
Natural health ( vitamib D)