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oncology > breast cancer > Flashcards

breast cancer Flashcards

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

A

premenopausal

22
Q

SERMs drug interactions

A

CYP2D6: fluoxetine, paroxetine, bupropion

23
Q

SERMs side effects

A

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

24
Q

AIs

A

anastrazole
letrozole
exemestane

25
Q

aromatase inhibitor mechanism

A

inhibit aromatase– the enzyme which catalyzes the conversion of androgens to estrogens. inhibition leads to a significant decrease estrogen

26
Q

aromatase inhibitors: when are they the choice and WHY

A

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
Q

aromatase inhibitor side effects

A

hot flashes, arthralgias/myalgias, bone loss (long term), vaginal dryness, headaches, diarrhea, mild nausea, alopecia, hair thinning

28
Q

early stage HR+/HER2+ or HR-/HER2+ disease

A

HER2 targeted therapy for a total of one year
can consider neratinib for an additional 1 year (total 2 years)

29
Q

anti-HER therapies for early stage

(will get to metastatic later)

A

trastuzumab, pertuzumab, neratinib

30
Q

major adverse effects of trastuzumab, pertuzumab

A

cardiac (CHF, MI, decrease LVEF)
do not administer concurrently with an anthracycline

31
Q

pertuzumab pearls

A

used in combo with trastuzumab
is not effective as a monotherapy

32
Q

neratinib pearls

A

causes diarrhea: use prophylactic loperamide for 8 weeks

33
Q

what is the preferred adjuvant chemotherapy with HER2 targeted therapy?

A

AC: taxane + trastuzumab +/- pertuzumab
TCH: docetaxel, carboplatin, trastuzumab +/- pertuzumab
paclitaxel + trastuzumab

34
Q

what are the options with early stage HR-/HER2- (TNBC) disease

A

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
Q

treatment considerations for invasive ductal carcinoma locally advanced

A

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
Q

what is the goal for metastatic breast cancers

A

palliation, cure is very unlikely; want to just prolong and maximize quality of life. continue treatment until disease progression or unacceptable toxicity

37
Q

bone vs symptomatic visceral (soft tissue) metastases implications for treatment

A

Bone: better prognosis; likely to respond to endocrine therapy if ER/PR+

Visceral: require chemotherapy due to need for rapid response

38
Q

preferred treatment regimens for extensive or symptomatic visceral metastases

A

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
Q

preferred treatment regimens for NO extensive or symptomatic visceral metastases

A

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
Q

_____ or _____ can be used for germline BRCA1/2 mutation in metastatic disease

A

olaparib, talazoparib

(PARP inhibitors)

41
Q

1st line treatment regimen for HR+ HER2- metastatic disease

A

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
Q

which drugs are CDK4/6 inhibitors

A

palbociclib
ribociclib
abemaciclib
side effects are neutropenia

43
Q

which drugs are P13K/AKT/mTOR pathway inhibitors
&
when are these agents used?

A

alpelisib
capivasertib
everolimus

indicated in combo with endocrine therapy or fulvestrant for HR+, HER2- cancer

44
Q

1st line regimen for TNBC (ER-, PR-, HER2-)

A

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
Q

what are the oral anti-HER tyrosine kinase inhibitors for HER2+ metastatic breast cancer

A

lapatinib, neratinib, tucatinib

44
Q

overview of all HER2 targeted therapy agents

A

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
Q

complications of breast cancer

A

bone complications (IV bisphosphonate, RANK-L inhibitor, calcium & vitamin D supplementation)
menopausal symptoms
pain syndromes

46
Q

LHRH agonists

A

goserelin, leuprolide, triptorelin

47
Q

SERDs

A

fulvestrant, elacestrant

48
Q

SERDs mechanism

A

binds to and degrades estrogen receptor: used in postmenopausal (if premenopausal, must add ovarian suppression)

oncology (19 decks)

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