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Therapeutics > Exam 2 lecture 3 > Flashcards

Exam 2 lecture 3 Flashcards

1
Q

Epidemiology of breast cancer

A

Most common malignancy in women
2nd most common cancer death
1 in 8 life time risk

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2
Q

Incidence and mortality of breast cancer over time? why?

A

incidence and mortality has decreased. Decrease in hormone replacement therapy could contribute to this.

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3
Q

Risk factors for breast cancer

A

More than 60% of pts will NOT have any risk factors
Risk increases with age
FH
personal history
Radiation
estrogen exposure (early menarche and late menopause)
exogenous estrogen (OC/HRT)
alcohol
elevated BMI
diet

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4
Q

What percent of breast cancers are familial

A

5-10%

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5
Q

What are the two tumor suppresor genes? Difference between them?

A

BRCA-1
-increased risk of ovarian cancer (40% life time risk) and breast cancer (60%)
-high prevalence of variants in jews

BRCA-2
-greater risk of breast cancer (50%) lower risk for ovarian (20%)
-greater incidence in male breast cancer

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6
Q

What are the different types of breast cancer?

A

Invasive carcinoma
non-invasive carcinoma
Inflammatory carcinoma

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7
Q

Define invasive carcinoma (what are the different types)

A

Invasive carcinoma- has invaded beyond the basement membrane of the duct or lobule
1. invasive ductal carcinoma (IDC)- most common accounting for 70% of all breast cancer
2. Invasive lobular carcinoma (ILC)- second most common type (15%)

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8
Q

What are the different types of non invasive breast cancer

A

Ductal carcinoma in situ (DCIS)- normal cells have undergone pre-malignant genetic transformation
typically see as microcalcifications on mammogra

lobular carcinoma in situ (LCIS)- has not invaded beyond the lobule basement membrane

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9
Q

Define inflammatory breast cancer

A

Looks like an orange.
Aggressive breast cancer with poor prognosis and rapid onset (days - weeks)
Edema, rendess, warmth

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10
Q

How does breast cancer usually present?

A

> 90% of patients present with a painless lump in breast.
<10% of patients have stabbing or aching pain as 1st symptom

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11
Q

What is FISH testing

A

Tests for HER2 by detecting gene amplification

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12
Q

prognostic tools that are used in cancer? What is it a predictor of?

A

Oncotype DX

Multigene assay validated for use in newly diagnosed breast cancer, stage I or II, lymph node negative and positive, ER positive, HER2 negative

good predictor of distant recurrence and classifies a patients risk as high, medium and low risk

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13
Q

What number is low risk and high risk for oncotype DX? What is the treatment you would use for each?

A

Low risk <26= hormonal therapy only

High risk>26 or += chemo and hormonal therapy

for ER and/or PR (+), HER2-, LN(-)

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14
Q

did medium score group benefit from chemo? (16-25)
Did women<50 y/o and score of 16-25 benefit from chemo?

A

Medium score group did not benefit from chemo
women<50 and score of 16-25 did incur benefit from chemi

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15
Q

Low risk and high risk oncotype and treatment for LN(+) disease

A

Low risk- <26, hormonal therapy alone
high risk- > or = 26, chemotherapy and hormonal therapy

for both pre and post menopausal patients with LN+ disease

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16
Q

Sites of metastasis of breast cancer?

A

Bone, liver, lungs, brain, distant lymph nodes and/or skin

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17
Q

What are the general treatment strategies of stage I, II, IIIA breast cancer

A

goal is cure.
-breast conserving surgery
-modified radical mastectomy
-some II and IIIA pts may have neoadjuvant chemo
-Most women will receive adjuvant therapy after surgery

Adjuvant=after surgery

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18
Q

General treatment strategies for stage IIIB and IIIC

A

Most women will have neoadjuvant chemotherapy (before surgery) followed by MRM or lumpectomy and XRT
- adjuvant therapy as appropriate

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19
Q

General tx strategies of stage IV

A

Treatment is palliative and consists of chemo, hormonal therapy, +/- biologics and immunotherapy

XRT may be used to palliate symptoms
surgery only used for symptomatic relief

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20
Q

When do we use neoadjuvant therapy in stage I, IIA, III disease? What are benefits of neoadjuvant chemo

A

For patients with larger tumors (>1cm)
Benefits
1. allows less extensive surgery
2. allows you to see response to chemo while tumor is still intact

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21
Q

What to do if we have a tumor <0.5 cm which is hormone positive, lymph node negative and positive, HER2 negative

A

Consider adjuvant endocrine therapy

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22
Q

What do we do if tumor >0.5cm or 1-3 positive nodes exist for a hormone positive, lymphnode negative an dpositive, HER2 NEGATIVE drug

A

strongly consider 21 genes RT-PCR assay

  1. If 21 gene RT-PCR assay isnt done, Do adjuvant endocrine therapy or adjuvant chemo followed by endocrine therapy
  2. If RS<26, do adjuvant endocrine therapy
  3. RS>or=26, do adjuvant chemo therapy followed by adjuvant endocrine therapy
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23
Q

What to do with hormone positive, lymph node - and +, HER2 negative premenopausal women based on RS score

A

<15= adjuvant endocrine therapy +/- OS
16-25= adjuvant therapy +/- OS or adjuvant chemo followed by endocrine therapy
>25= Adjuvant chemo followed by endocrine therapy

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24
Q

What to do with hormone positive, lymph node - and +, HER2 POSITIVE patient based on tumor size

A

tumor<0.5- COnsider adjuvant endocrine therapy +/- chemo with HER2 TARGETTED THERAPY

Tumor>0.6- Adjuvant chemo with HER2 targetted therapy followed by endocrine therapy

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25
Q

What are adjuvant hormonal therapies

A

Surgical ablation (oopherectomy)
LHRH analogs (goserelin, leuprolide)
SERMs (tamoxifen)

26
Q

What is adjuvant hormonal therapy with regard to surgical ablation, how does it work?

A

Oopherectomy- removes largest source of estrogen (ovaries)

27
Q

What is a SERM used as adjuvant hormonal therapy?

A

tamoxifen

28
Q

How does tamoxifen act as an adjuvant hormonal therapy? Toxicity?

A

Anti estogenic effects in breast but estrogenic properties in other tissues
Reduces risk of contracting breast cancer

Major toxicity- hot flashes, endometrial cancer, DVT

29
Q

What are LHRH analogs that act as adjuvant hormonal therapies? short term and long term effects in body

A

leuprolide, goserelin

Initially causes increased release of FSH and LH. Long term sustained exposure inhibits LH and FSH. Inhibits estrogen production by ovaries

30
Q

What are aromatase inhibitors used in? When is the exception? adverse effects? What are the drugs?

A

USED ONLY IN POSTMENOPAUSAL PATIENTS
(WILL need ovarian suppression if in pre menoapusal women)

fewer adverse effects, no DVT/endometrial cancer, but has no bone protective effect (like tamoxifen)
Leads to osteoporosis, hot flashes, muscle aches and pains

non-steroidal- anastrazole, letrozole
steoroidal- exemestane

31
Q

Adjuvant hormone therapy for premenopausal at diagnosis? What if the patient is still premenopausal after first round of treatment? What if they are post menopausal after first round of treatment

A

If pre menopausal at diagnosis either
1. Tamoxifen for 5 years with or without ovarian suppression (OS)
2. aromatase inhibitor for 5 years WITH OVARIAN SUPPRESSION

if premenopausal afetr these
1. Tamoxifen for 5 more years to complete a totl of 10 years or no further endocrine therapy

If post menopausal after these
1. could consider an additional 5 years to AI to total 10 years or
2. could consider tamoxifen for 5 more years

32
Q

Adjuvant hormonal therapy if post menopausal at diagnosis

A

Aromatase Inhibitor x 5 years then consider AI for additional 5 more years (treatment of choice)

or

Tamoxifen for 2-3 years followed by AI to complete 5 years

33
Q

most common adjuvant chemotherapeutic agents? What duration is ideal for adjuvant chemotherapy

A

Doxorubicin, epirubicin, cyclophosphamide, methotrexate, fluorouracil, carboplatin, paclitaxel, docetaxel

durations longe rthan 3 to 6 months of adjuvant chemotherapy do not appear to improve survival

34
Q

standard chemo consists of how many cycles? How often are they given?
How many cycles do neoadjuvants have?

A

Standard chemo consists of 4-6 cycles given every 3 to 4 weeks.

neoadjuvant consists of 4-6 cycles

35
Q

adjuvant chemotherapy regimen for HER2 negative disease

A

Dose dense anthracycline–>paclitaxel
Doxorubicin IV
cyclophosphamide IV
repeat every 14 days x 4 (MUST GIVE GROWTH FACTORS)
followed by paclitaxel every 14 days x 4 (must give growth factor)

or

TC
Docetaxel
cyclophosphamide
repeat every 21 days x 4

36
Q

From the CALBG trial, which group got the best outcome

A

Group 4 receiving concurrent doxorubicin and cyclophosphamide every 2 weeks X 4 followed by paclitaxel X 4

That is why it is called dose dense anthracycline

37
Q

when should you avoid anthracycline based regimen and switch to non anthracycline based regimen

A

Cardiac risk
If cardiac problems, can consider docetaxel and cyclophosphamide (TC) chemotherapy regimen to avoid anthracyclines.

38
Q

a patient has a 1.8 cm tumor and positive lymph nodes. Patient received positive lymph nodes, they received chemo consisting of dose dense doxorubicin and cyclophosphamide x 4 cycles followed by paclitaxel x 12 weeks. WHat should patient receive as pre medication with paclitaxel and why?

A
  1. Steroid (dexamethasone)
  2. Diphenhydramine (H1 antagonist)
  3. H2 antagonist

why?
to prevent hypersensitivity reactions seen with paclitaxel solubilizer

39
Q

Is HER2 positive disease better treated when HER2 targeting drugs like trastuzumab are included

A

Yes

40
Q

Drugs to use in ER/PR negative HER2+ patient

A

1= APT
Paclitaxel x 12 doses
trastuzumab with 1st dose of paclitaxel
followed by trastuzumab x 11 weeks
followed by 6 mg/kg every 3 weeks to complete 1 year.

2= TCH
Docetaxel day 1
Carboplatin day 1
Trastuzumab week 1
repeat every 21 days x 6
followed by 6 mg/kg every 21 days to complete 1 year of trastuzumab

3= TCH+pertuzumab (TCHP)
Docetaxel day 1
caroplatin day 1
trastuzumab week 1
pertuzumab day 1
Followed by both trastuzumab and pertuzumab to complete 1 year

41
Q

What is triple negative breast cancer and how do we treat it

A

Triple breast cancer negative ER (-), PR (-), HER2 (-)

Treated by pembrolizumab+chemotherapy
Paclitaxel days 1, 8 and 15
Carboplatin on days 1, 8, 15
Pembrolizumab day 1, repeat every 21 days x 4
followed by doxorubicin day 1
cyclophosphamide day 1
pembrolizumab every 3 weeks, repeat every 21 days x 4 followed by pembrolizumab to complete 1 year of therapy

42
Q

Goal of therapy for metastatic disease? Median survival time? WHich metastases respond better to hormonal therapy?

A

goal- palliation
median survival is 3 years
Bone and soft tissue metastases tend to have better prognosis and respond to hormone therapy

43
Q

How t treat ER/PR+, bone mets, asymptomatic, visceral disease

A

Hormone therapy (bone disease add bisphosphonates or denosumab). Endocrine therapy +/- bisphosphonates or denosumab

44
Q

ER-/PR- symptomaic visceral disease or hormone refractory question

A

If her2+ add anti HER2 therapy +/-chemo

if HER2-, do chemotherapy

45
Q

How to decide when to give hormonal therapy vs chemotherapy

A

Hormonal therapy- ER and/or PR positive disease
Long disease free survival
Prior reponse to therapy
Bone only disease

Chemotherapy- ER/OR negative
Short disease free interval
rapidly progressing disease
Disease refractive to hormonal
therapy

46
Q

Link between disease free length and whether we should use hormonal or chemo therapy

A

Long DFS (disease free state)= likely to respond to another hormonal agent
If shorter disease free interval, hormone therapy will not work, switch to chemo

47
Q

single aent vs combination in chemo

A

COmbination offers a higher response rate but has more toxicities.

rapid response needed due to toxicities from disease, then combination chemo can be given

48
Q

What is the recommended 1st line option for HER2+ metastatic disease?

Second line

A

Trastuzumab
pertuzumab
docetaxel

given every 3 weeks

second line- fam-trastuzumab, deruxecan NXKI

49
Q

Other than 2nd line, what else is Fa-trastuzumab used for

A

HER2 low patients

50
Q

what is 1st line for HER2(-) women that are postmenopausal. (or premenopausal receiving ovarian suppressin.

A

1st line- aromatase inhibitor +CDK 4/6 inhibitor (abemaciclib, palbociclib or ribocyclib)

51
Q

2nd line of treatement for HER2 (-) and postmenopausal (or premenopausal receiving ovarian suppression)

A

fluvestrant + CDK 4/6 inhibitor (palbociclib, tibociclib) f not used before
Everolimus +endocrine therapy (exemestance, fluvestrant)

52
Q

What are some CDK 4/6 inhibitors and what to monitor with each?

A

Abemaciclib- Monitor CBC, gives patent diarrhes
palbociclib- CBC
ribiciclib- CBC and QT prolongation

53
Q

What are some pharmacologic and non pharmacologic modalities to prevent breast cancer

A

Non pcol- Prophylactic mastectomy (reduces risk by 90%)
Bilateral oophorectomy (reduced estrogen exposure)

pcol- tamoxifen, raloxifen, exemestance

54
Q

Pros and cons of tamoxifen

A

Reduces risk of invasive and non invasive breast cancer in all women, reduced skeletal events

did increase endometrial cancer
did increase risk of stroke, PE and DVT

55
Q

compare prevention of raloxifen and tamoxifen

A

Raloxifen had fewer uterin cancers and fewer blood clots, but did not reduce risk of LCIS or DCIS like tamoxifen

56
Q

Women with early stage triple negative breast cancer chemo course

A

Paclitaxel days 1, 8 and 15
Carboplatin on days 1, 8, 15
Pembrolizumab day 1, repeat every 21 days x 4
followed by doxorubicin day 1
cyclophosphamide day 1
pembrolizumab every 3 weeks, repeat every 21 days x 4 followed by pembrolizumab to complete 1 year of therapy

57
Q

Woman with early stage ER/PR negative, HER2 positive disease chemo course

A

3= TCH+pertuzumab (TCHP)
Docetaxel day 1
caroplatin day 1
trastuzumab week 1
pertuzumab day 1
Followed by both trastuzumab and pertuzumab to complete 1 year

58
Q

WOman with early stage ER/PR positive, HER2 negative disease chemo treatment course

A

. If RS<26, do adjuvant endocrine therapy

  1. RS>or=26, do adjuvant chemo therapy followed by adjuvant endocrine therapy

If we do need to give chemo, we can use

Dose dense anthracycline–>paclitaxel
Doxorubicin IV
cyclophosphamide IV
repeat every 14 days x 4 (MUST GIVE GROWTH FACTORS)
followed by paclitaxel every 14 days x 4 (must give growth factor)

or

TC
Docetaxel
cyclophosphamide
repeat every 21 days x 4

59
Q

Treatment course of ER/PR positive, HER2 negative metastatic disease

A

hormone therapy
(aromatase inhibitor with CDK4/6 inhibitor)

60
Q

What would tx option for a patient with HER2 positive, ER/PR negative metastatic disease

A

TCH+pertuzumab (TCHP)
Docetaxel day 1
caroplatin day 1
trastuzumab week 1
pertuzumab day 1
Followed by both trastuzumab and pertuzumab to complete 1 year

Therapeutics (36 decks)

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