Breast Cancer - Cardiotoxicity Flashcards
ASCO Risk Factors for Cardiotoxicity
- High-dose anthracycline (i.e., cumulative doxorubicin dose ≥ 250 mg/m2, epirubicin ≥ 600 mg/m2
- High-dose radiotherapy (RT; ≥ 30 Gy) where the heart is in the treatment field
- Lower-dose anthracycline (i.e., doxorubicin < 250 mg/m2, epirubicin < 600 mg/m2) in combination
with lower-dose RT (< 30 Gy) where the heart is in the treatment field - Treatment with lower-dose anthracycline or trastuzumab alone, and presence of any of the following risk factors:
– Multiple CV risk factors (≥ two risk factors), including smoking, hypertension, diabetes, dyslipidemia, and obesity, during or after completion of therapy
– Older age (≥ 60 years) at cancer treatment
– Compromised cardiac function (i.e., borderline low LVEF (50 – 55%), history of myocardial infarction (MI), ≥ moderate valvular heart disease) at any time before or during treatment - Treatment with lower-dose anthracycline followed by trastuzumab (sequential therapy)
CARDIOTOXICITY
Anthracyclines
Risk Factors
- HTN
- Dyslipidemia
- DM
- Age >65
- Fx hx of cardiomyopathy
- High cumulative anthracycline dose
- low normal LVEF (50-54%)
- Hx of CV comorbiditites
CARDIOTOXICITY
Anthracyclines
Acute
- Occurs immediately after a single dose or course of therapy with an anthracycline
- Uncommon and transient
- May involve abnormal ECG findings, including QT-interval prolongation, ST-T wave changes, and arrhythmias
- Rarely, CHF and/or pericarditis are observed
- May be caused by an inflammatory response
- Not related to cumulative dose
CARDIOTOXICITY
Anthracyclines
CHRONIC
- Usually w/i a year of receiving anthracycline
- Rapid onset and progression
- more common and life threatening
- Relative to cumulative dose
- Can be resistant to treatment
CARDIOTOXICITY
Anthracyclines
Dexrazoxane
Approved for use in metastatic breast cancer patients who have received cumulative dose >300mg/m2 of doxorubicin
NOT recommended for use in adjuvant setting
- Dosed in 10:1 ratio (dexrazoxane to doxorubicin)
- Doxorubicin must be administered w/i 15-30 minutes of dexrazoxane
CARDIOTOXICITY
Anthracyclines
Recommendations
Any Patient w/ risk factor for cardiotoxicity should have a baseline evaluation of cardiac function ECHO/MUGA
For patients w/ LVEF >50%
Consider repeating after reaching 250-300mg/m2 or equivalent:
- Repeat after reaching 400mg/m2 in patients w/ known risk factors
OR
- Repeat after reaching 450mg/m2 in absence of risk factors
If receiving anthracyclines and dexrazoxane, ASCO guideline on the use of chemo protectants recommend cardiac monitoring for patients who have received cumulative doses of 500mg/m2 and then repeat monitoring after every 50mg/m2 thereafter
CARDIOTOXICITY
Anthracyclines
When to discontinue
Functional signs of cardiotoxicity and/or
Absolute Decrease in LVEF ≥ 10% associated with a decline to a level of <50%
CARDIOTOXICITY
Trastuzumab (all types)
Cardio toxicity is NOT dose related (~5% overall risk)
- appears to be reversible and short lived once discontinued
Cardiomyopathy leading to CHF; clinically similar to anthracycline-induced CHF but reversible with medication despite continuing trastuzumab therapy.
BLACK BOX -> Left ventricular dysfunction
Appears to be responsive to to HF medication therapy however few patients recover to baseline (may recover to LVEF >50% but some damage remains)
CARDIOTOXICITY
Trastuzumab (all types)
Monitoring
Assess LVEF prior to initiation, every 3 months during and upon completion of trastuzumab
Repeat LVEF measurement at 4 week intervals if trastuzumab is held
LVEF measurement every 6 months for at least 2 years following completion of adjuvant trastuzumab
Routine ECHO survellance in patients w/ MBC continuing to receive trastuzumab indefinitely
CARDIOTOXICITY
Trastuzumab (all types)
Management
WITHHOLD trastuzumab for at least 4 weeks for any of the following:
- ≥ 16% absolute decrease in LVEF from baseline
- LVEF below institutional limit of normal and ≥ 10% absolute decrease from baseline
RESUME if LVEF returns to normal limits and absolute decrease from baseline is <= 15% (within 4-8 weeks)
Permanently DISCONTINUE if persistent (>8 weeks) LVEF decline or if suspended ≥ 3 occasions for cardiomyopathy
CARDIOTOXICITY
Pertuzumab
BLACK BOX for Left Ventricular Dysfunction
Asymptomatic LV systolic dysfunction was 3.4% and 6.5% and symptomatic HF was 1.1% pertuzumab/non-anthracycline based chemotherapy and pertuzumab/trastuzumab respectively
CARDIOTOXICITY
Pertuzumab
Management
WITHHOLD Pertuzumab (and trastuzumab) for at least 3 weeks for:
- MBC: LVEF <40% or 40-50% with a fall of ≥ 10% below baseline
- Neoadjuvant/adjuvant: LVEF <50% with a fall of≥ 10% baseline
RESUME if LVEF recovers to:
- MBC: >45% or 40-45% with a fall of <10% baseline
- Neoadjuvant/adjuvant: ≥ 50% or <10% baseline
- Repeat LVEF assessment within approximately 3 weeks.
DISCONTINUE if LVEF has not improved or declined at repeat assessment
CARDITOXICITY
Ado-trastuzumab emtansine (T-DM1)
BLACK BOX for Left Ventricular Dysfunction
CARDITOXICITY
Ado-trastuzumab emtansine (T-DM1)
MONITORING
LVEF should be monitored at baseline and regular intervals (every 3 months) during therapy
CARDITOXICITY
Ado-trastuzumab emtansine (T-DM1)
Management
METASTATIC BREAST CANCER
Metastatic Breast Cancer
- LVEF >45% then continue treatment
T-DM1 should be WITHHELD for at least 3 weeks and LVEF repeated within 3 weeks if:
- LVEF decreases <40% OR
- LVEF decreases to 40-45% with at least 10% decrease from baseline
Treatment can be RESUME if LVEF recovers to >45% or to 40-45% w/ <10% decrease from baseline value within 3 weeks
DISCONTINUE for symptomatic Heart Failure
