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breast cancer Flashcards

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1
Q

breast cancer subtypes

A

hormone receptors: estrogen, progesterone
human epidermal growth factor 2 (HER2)
makes 4 subtypes:
HR+/HER2+
HR+/HER2-
HR-/HER2+
HR-/HER2- (TNBC)

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2
Q

TNBC

A

triple negative breast cancer
ER-, PR-, HER2-

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3
Q

genetic mutations in breast cancer

A

familial breast cancer
p53 mutation– tumor suppressor gene
BRCA1, BRCA2 mutations

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4
Q

non-modifiable risk factors

A

female
age>50
genetic mutation
family history of breast cancer (first and second degree relatives, early onset of breast cancer in a family member)

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5
Q

modifiable risk factors

A

physical inactivity
alcohol consumption
obesity/high BMI

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6
Q

highest risk of breast cancer is in ____ women

A

postmenopausal

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7
Q

endogenous vs exogenous estrogen exposure

A

endogenous: early menarche (by age 14), late menopause (at least 55 years or older), age at birth of first child (>30 years)

exogenous: oral contraceptives, estrogen replacement therapy

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8
Q

factors associated with lower risk of breast cancer

A

breastfeeding
moderate or vigorous physical activity
maintaining a healthy body weight

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9
Q

breast cancer screening

A

breast self examination (BSE), clinical breast examination (CBE)
mammography detects 80-90% of breast cancers in women without symptoms, can detect at early stage
NCI guidelines: mammography every 1-2 years starting at age 40
separate guidelines for individuals at high risk

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10
Q

breast cancer prevention?

A

prophylactic mastectomies, bilateral oophorectomies, lifestyle changes, pharmacologic prevention w/ SERMs (tamoxifen for 5 years) in pre/post menopause, raloxifene for postmenopause

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11
Q

signs and symptoms of breast cancer

A

local: painless lump (hard, irregular, immobile), stabbing/aching pain, nipple tenderness, change in breast size/shape, erythema/scaling/swelling, peau d’orange

metastatic: SOB, arthralgia, fractures, abdominal pain/jaundice, confusion, rash/nodule

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12
Q

what info is necessary to know to determine treatment options for breast cancer

A

HR (ER, PR) predicts response to endocrine therapy– if either one is +. generally less aggressive

HER2+– poorer prognosis, predicts benefit with HER2 targeted therapy

germline BRCA mutation: predicts benefit w/ adjuvant PARP inhibitor

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13
Q

quick refresh: neoadjuvant vs adjuvant

A

neoadjuvant is chemo given before surgery
adjuvant is when you get chemo after the surgery

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14
Q

pathologic types of breast cancer

A

most: adenocarcinomas
ductal carcinoma in situ: premalignant
lobular carcinoma: not premalignant
invasive ductal carcinoma most common, worst prognosis

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15
Q

describe what is the preferred endocrine therapy for pre and post menopausal women

A

premenopausal: tamoxifen x 5-10 years

postmenopausal: AI x 5-10 years

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16
Q

treatment notes for early stage HR+/HER2-

A

-goal is cure
-surgical resection is standard (+ adjuvant therapy)
-endocrine therapies are recommended in all HR+ disease regardless of menopausal status, age, HER2
-chemo is never combined with endocrine therapy. chemo is indicated for high risk of recurrence (tumor >0.5 cm, high growth rate, positive lymph nodes)

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17
Q

common adjuvant chemo regimens for HER2- breast cancer

A

AC followed by paclitaxel
TC (kind, gentle, anthracycline sparing)

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18
Q

targeted therapy options for early stage HR+/HER2-

A

Olaparib (PARP inhibitor) if germline BRCA1/2 mutation and high risk features

abemaciclib (CDK4/6 inhibitor) if lymph node positive disease with endocrine therapy

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19
Q

SERMS

A

tamoxifen
toremifene

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20
Q

SERM mechanism

A

competes with estradiol binding to estrogen receptors
making it antiestrogen in breast cancer cells and mimics estrogen at other tissues

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21
Q

SERMs are the choice for ____ women

Study These Flashcards
A

premenopausal

22
Q

SERMs drug interactions

Study These Flashcards
A

CYP2D6: fluoxetine, paroxetine, bupropion

23
Q

SERMs side effects

Study These Flashcards
A

mimics estrogen: hot flashes, vaginal dryness/discharge, IRREGULAR MENSES, endometrial thickening
serious: thromboembolism, endometrial/uterine cancer (postmenopausal)

24
Q

AIs

Study These Flashcards
A

anastrazole
letrozole
exemestane

25
aromatase inhibitor mechanism
inhibit aromatase-- the enzyme which catalyzes the conversion of androgens to estrogens. inhibition leads to a significant decrease estrogen
26
aromatase inhibitors: when are they the choice and WHY
postmenopausal they should not be used as a single agent therapy for premenopausal women-- the main source of estrogen comes from ovaries in premenopausal women, instead of the periphery
27
aromatase inhibitor side effects
hot flashes, arthralgias/myalgias, bone loss (long term), vaginal dryness, headaches, diarrhea, mild nausea, alopecia, hair thinning
28
early stage HR+/HER2+ or HR-/HER2+ disease
HER2 targeted therapy for a total of one year can consider neratinib for an additional 1 year (total 2 years)
29
anti-HER therapies for early stage (will get to metastatic later)
trastuzumab, pertuzumab, neratinib
30
major adverse effects of trastuzumab, pertuzumab
cardiac (CHF, MI, decrease LVEF) do not administer concurrently with an anthracycline
31
pertuzumab pearls
used in combo with trastuzumab is not effective as a monotherapy
32
neratinib pearls
causes diarrhea: use prophylactic loperamide for 8 weeks
33
what is the preferred adjuvant chemotherapy with HER2 targeted therapy?
AC: taxane + trastuzumab +/- pertuzumab TCH: docetaxel, carboplatin, trastuzumab +/- pertuzumab paclitaxel + trastuzumab
34
what are the options with early stage HR-/HER2- (TNBC) disease
think: now you can't do endocrine therapies or HER2 targeted therapies. but you can use olaparib (PARP inhibitor) x 1 year in adjuvant setting for patients who are high risk with germline BRCA1/2 mutation can use immunotherapy pembrolizumab combined with chemotherapy before surgery and continued as single agent after surgery
35
treatment considerations for invasive ductal carcinoma locally advanced
considered curative treatment: neoadjuvant chemotherapy (decrease tumor size before surgery, can't do surgery right away bc too much disease) +/- anti-HER2 agents x 1 year surgery--> adjuvant chemo--> +/- endocrine therapy +/- abemaciclib for select patients or olaparib x 1 year for select patients
36
what is the goal for metastatic breast cancers
palliation, cure is very unlikely; want to just prolong and maximize quality of life. continue treatment until disease progression or unacceptable toxicity
37
bone vs symptomatic visceral (soft tissue) metastases implications for treatment
Bone: better prognosis; likely to respond to endocrine therapy if ER/PR+ Visceral: require chemotherapy due to need for rapid response
38
preferred treatment regimens for extensive or symptomatic visceral metastases
HR+/-: -HER2- chemotherapy (+/- pembrolizumab if HR-, HER2-, PDL1 CPS>10) -HER2+: chemotherapy + HER2 targeted therapy (if HR+ it is acceptable to switch to endocrine based therapy after disease is stabilized)
39
preferred treatment regimens for NO extensive or symptomatic visceral metastases
HR+: -HER2-: endocrine therapy +/- targeted therapy -HER2+: chemo + HER2 targeted therapy OR endocrine therapy +/- HER2 targeted therapy HR-: -HER2-: chemo (+/- pembrolizumab if PDL1 CPS>10) -HER2+: chemo + HER2 targeted therapy
40
_____ or _____ can be used for germline BRCA1/2 mutation in metastatic disease
olaparib, talazoparib (PARP inhibitors)
41
1st line treatment regimen for HR+ HER2- metastatic disease
Endocrine +/- targeted therapy.... 1st line CDK4/6 inhibitor + AI or CDK4/6 inhibitor + fulvestrant if premenopausal, options include the above + ovarian suppression (LHRH agonist or oophorectomy)
42
which drugs are CDK4/6 inhibitors
palbociclib ribociclib abemaciclib side effects are neutropenia
43
which drugs are P13K/AKT/mTOR pathway inhibitors & when are these agents used?
alpelisib capivasertib everolimus indicated in combo with endocrine therapy or fulvestrant for HR+, HER2- cancer
44
1st line regimen for TNBC (ER-, PR-, HER2-)
depends on PD-L1, BRCA mutation status: -if PD-L1 CPS>10: pembrolizumab + chemo -if PDL1 CPS<10 and no germline BRCA1/2 mutation: systemic chemo -if PDL1 CPS<10 and germline BRCA1/2 mutation: PARP inhibitor or platinum chemotherapy
44
what are the oral anti-HER tyrosine kinase inhibitors for HER2+ metastatic breast cancer
lapatinib, neratinib, tucatinib
44
overview of all HER2 targeted therapy agents
all settings: trastuzumab, pertuzumab extended adjuvant therapy and metastatic disease: neratinib (select early stage, metastatic) adjuvant therapy and metastatic disease: ado-trastuzumab emtansine (select early stage, mets) metastatic disease: fam-trastuzumab deruxtecan-nxki, lapatinib, tucatinib, margetuximab
45
complications of breast cancer
bone complications (IV bisphosphonate, RANK-L inhibitor, calcium & vitamin D supplementation) menopausal symptoms pain syndromes
46
LHRH agonists
goserelin, leuprolide, triptorelin
47
SERDs
fulvestrant, elacestrant
48
SERDs mechanism
binds to and degrades estrogen receptor: used in postmenopausal (if premenopausal, must add ovarian suppression)

oncology (19 decks)

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