Breast Cancer Flashcards
each breast has _____ lobes
15-20
breast cancer is most common in the ___ > ____ > _____
ducts > lobes > other
list 3 RF for breast cancer
increasing age, female, personal and family hx, estrogen exposure (endogenous and exogenous), radiation exposure to chest at a young age, alcohol, obesity, dense breast tissue
genetic RF for breast cancer
BRCA1 and 2
BRCA genes are
tumor suppressor genes
what ancestry is more prone to breast cancer
ashkenazi jew
what is the recommended age range for breast cancer screening
1. 40-49
2. 50-74
3. 40-74
4. >75
2
should those who have had top surgery still get a mammogram?
yes
should trans women with feminizing surgery get a mammogram?
yes if >5yrs of hormone therapy
stage 0 breast cancer is
in situ
stage 1 breast cancer is
<2cm and no spread to lymph nodes
stage 2 breast cancer is
2-5cm or <2cm and spread to lymph nodes
stage 3 breast cancer is
> 5cm or lots of lymph node involvement
stage 4 breast cancer is
metastasis present in other areas
which has a worse prognosis?
1. ductal carcinoma
2. lobular carcinoma
ductal
pathology of BC conosiders
subtypes (lobular or ductal)
lymphovascular invasion
grade
Ki67
HR
HER2
hormone receptors are
transcriptional factors that activate signal transduction upon hormone binding
HER2 is an ____
oncogene encoding protein
what is oncotype Dx
assigns recurrence score to predict which pts are most likely to benefit from chemo
oncotype Dx is only for
stage 0 or 1, HR+, HER2-
prosigna classifies
tumors into 4 intrinsic subtypes based on expression measures of 50 genes
removes breast tumor without removal of remaining surrounding tissue
lumpectomy
removes entire breast
simple/ total mastectomy
removes entire breast + axillary lymph nodes
modified radical mastectomy
removes entire breast tissue along with some muscles of chest + more extensive axillary node dissection
radical mastectomy
Sentinel nodes are
first lymph nodes reached by metastasizing cancer cells from tumor
what is a sentinel lymph node biopsy
Inject radioactive material into breast - trace lymph drainage to first lymph node- if sentinel node free of cancer = unlikely to have spread = don’t need to remove additional lymph nodes
when should radiation therapy be done in stage 1-3
pts with breast conserving surgery, close or + margins, high risk features (large tumor, high grade, LVI, younger, metastasis)
how to sequence radiation therapy in a pt who will have adjuvant chemo
chemo, then radiation
when should radiation be done in a post op pt who will not undergo adjuvant chemo
after post op healing done
T or F: radiation can not be concurrent with trastuzumab and endocrine therapies
F- can be concurrent, just not with chemo
most breast cancer chemos combos
anthracycline + taxanes
-rubicin are
anthracyclines
-taxel are
taxanes
anthracyclines MOA
binds to DNA via intercalation and inhibits DNA repair by inhibiting TP2
also chelates with iron and binds to DNA and cell membrane, producing free radicals that cleave the DNA and cell mem
list 3 AEs for anthracyclines
myelosuppression
N/V
mucositis
alopecia
secondary malignancies
cardiotoxicity- cumulative
vesicant- causes necrosis of surrounding tissues
what are the 2 major issues with anthracyclines
cumulative cardiotoxicity = reduced LVEF or CHF
is a vesicant
cyclophosphamide MOA
alkylating agent that binds to DNA = breakage and repair inhibition
T or F: cyclophosphamide is a prodrug
T- requires activation by liver
cyclophosphamide AEs
hemorrhagic cystitis
N/V
myelosuppression
alopecia
fertility suppression
taxanes MOAs
disrupts MT network essential for mitotic and interphase cellular functions
hypersensitivity reactions to taxanes are due to _____ and most commonly seen in _______
diluent
first 2 cycles within first minutes of infusion
when can a taxane induced hypersensitivity not be rechallenged
if it is severe- bronchospasm, HPTN, rash/erythema, anaphylaxis
what are some issues with taxane diluents
cause hypersensitivity reactions
has enough ethanol to cause intoxication
AEs from taxanes
fluid retention (more with docetaxel) = pleural and pericardial effusion, ascites, dyspnea
myelosuppression
hypersensitivity
alopecia
nail changes
lacrimation
severe fatigue
peripheral neuropathy
acute intoxication
why might dex be given before docetaxel
to reduce freq of hypersensitivity rxn and fluid retention
+ antiemetic
dexamethasone dosing pre docetaxel
8mg PO BID starting day before docetaxel
must have at least 3 doses before infusion, or can give by IV right before
carboplatin MOA
covalently binds to DNA and disrupts DNA dunction
carboplatin dosing is based on the
calvert formula
what is the calvert formula and what is it used for?
dose (mg) = AUC x (CrCL +25)
for carboplatin
___% of breast cancer has HER2 overexpression
20%
HER2 is a
oncogene- transmembrane protein that stimulates growth
trastuzumab is a __MAb that blocks ___ by targeting _____
humanized MAb
blocks HER2
targets extracellular domain
trastuzumab is used in ____ and ____ breast cancer
early (adjuvant)-stage+
metastatic
pertuzumab is given with ___ and ____ in metastatic breast cancer
trastuzumab and taxane chemo
lapatinib is a
oral small molecule dual kinase inhibitor
lapatinib is given with ______ in ___ breast cancer
capecitabine
in metastatic breast cancer
trastuzumab emtansine MOA
attached to cytotoxic drug DM1 that inhibits tubulin polymerization and MT dynamics
trastuzumab deruxtecan MOA
HER2 MAb and TP1 inhibitor
which 2 HER2i are commonly given together
pertuzumab and trastuzumab (synergistic)
why are pertuzumab and trastuzumab given together
tras = inhibits ligand independent HER2 signaling and activates ADCC
pertuz = inhibits ligand dependent HER2 dimerization and signalling + activates ADCC
trastuzumab AEs
cardiotoxicity - decreased LVEF and CHF, arrhthmias
not dose related and mostly reversible
are trastuzumab cardiotoxicities reversible
yes
T or F: trastuzumab cardiotoxicities are dose dependent
F
lapatinib AE
diarrhea
what is the rationale behind hormone/ endocrine therapies
to deprive estrogen for cancer cells that rely on it for growth/ prolfieration
tamoxifen is most commonly seen as ___ therapy of ____ disease
adjuvant
early
what are the 4 endocrine therapies for BC
tamoxifen
aromatase inhibitors
fulvestrant
CDK 4/6 inhibitors
MOA of tamoxifen
SERM mixed agonist (E) and antagonist (antiE) activity depending on tissue. Competitively binds to E receptors for (ER+/PR+) = produces nuclear complex that reduces DNA synthesis = antiE effect
tamoxifen is an estrogen antagonist on
breast and breast cancer cells
tamoxifen is an estrogen receptor agonist on
endometrium, bone, lipids
why is tamoxifen kind of a prodrug
it is metabolized to NDM-TAM and 4-OH-TAM, then NDM-TAM is metabolzied to CYP2D6 to endoxifen which is 30-100x more potent
which CYP enzyme is important for endoxifen’s antiE potency
CYP2D6
how much tamoxifen is given daily
20mg po daily
tamoxifen AEs
hot flashes, menopausal sx (80%), depression, amenorrhea if premenopausal, decreased libido, vaginal dryness, arthralgia/ myalgia, tumor pain/ flare (if metastatic setting)
serious risks of tamoxifen
DVT/PE
uterine cancers
tamoxifen interacts with
strong 2D6 inhibitors (fluoxetine, paroxetine, bupropion), warfarin
aromatase inhibitors are for _____ pts
post menopausal pts or those with induced menopause
what medications can induce ovarian suppression
goserelin or leuprolide
aromatase inhibitors used in the adjuvant setting are adminstered ________ yrs or up to ___ yrs after ____
5 yrs, 5 yrs
after tamoxifen therapy
aromatase inhibitors AEs
arthralgias/ myalgia, hot flashes, peripheral edema, vaginal dryness
what to monior for with aromatase inhibiors
bone loss, hypercholestrolemia
aromatase inhibitors used in metastatic/ palliative settings have durations based on
pt tolerance or disease
how can aromatase inhibitors be used if the cancer is HER2-
give with CDK4/6 inhibitors
what is an estrogen receptor antagonist with no partial agonist effects?
fulvestrant
fulvestrant MOA
competitive binding with estrogen receptors with affinity comparable to estradiol
fulvestrant place in therapy
HR+, HER2-
post menopausal or induced
metastatic disease
fulvestrant AEs
injection site reaction, hypersensitivity reaction, headache, hepatotoxicity, bleeding/ hematoma at injection site if on anticoagulants or severe thrombocytopenia
CDK is ___ from estrogen receptor signaling
downstreak
CDK4/6 facilitates __________ allowing progression from G1 to S
phosphorylation of retinoblastomas
what is overactive in cancer cells so there is uncontrolled cell cycle progression + is targeted by an endocrine therapy
CDK4/6 - use inhibitors
palbociclib is a
CDK4/6 inhibitor
what blocks signal process that is downstream from estrogen receptor?
CDK4/6 inhibitors
CDK4/6 inhibitors has synergism with
antiestrogen therapies
what are CDK 4/6i first line for?
metastatic breast cancer that is ER/PR+ and hER2- in combination with an aromatse inhibitor
what is a ribociclib combo that is second line for HR+, HER2- BC
ribociclob with fulvestrant
CDK4/6i AEs
bone marrow suppression, fatigue, infections ,pulmonary embolism, QTc prolongation
T or F: NHPs for menopausal sx from chemo is recommended
why or why not?
F- generally not recommended as products containing phytoestrogens can encourage growth of HR+ breast cancers
CDK4/6i is a CYP ___ substrate
3A4
what NHPs may be recommended for breast cancer and chemo
multivitamin
vit D 1000U for bone health (if serum calcium lvl not elevated)
T or F: antioxidants are generally recommended during chemo
F
exemestane is a
aromatase inhibitor
anastrozole is an
aromatase inhibitor
letrozole is an
aromatase inhibitor
