![Page 1: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/1.jpg)
Tallal Younis, MBBCh. FRCP (UK). FACP.
Professor of Medicine, Dalhousie University
Medical Oncologist, QE II Health Sciences Centre
Breast Cancer: A Focus on HER2 Targeted Therapy
Canadian Cardiac Oncology Network Meeting
Montreal April 26th, 2019
![Page 2: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/2.jpg)
Disclosures
Dr Younis has participated in various advisory boards,
and acted as consultant and expert witness,
for Roche Canada (Trastuzumab, Pertuzumab, and TDM1)
![Page 3: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/3.jpg)
Talk Objectives
Clinical Applications in Cardio-Oncology
✓ To highlight the role of anti-HER2 therapy
in the management of HER2 positive breast cancers.
✓ To review the cardio-toxicity risks associated with
anti-HER2 therapy in breast cancers.
✓ To illustrate the current management approach
for anti-HER2 therapy associated cardiotoxicity.
![Page 4: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/4.jpg)
Basal
like
LuminalLow Risk
HER2
Enriched
LuminalHigh Risk
Breast Cancer Subtypes HER2 positive
ER / PR positive
4
![Page 5: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/5.jpg)
HER2 Testing
(IHC & FISH)
⚫ Her-2/neu (red signals)
⚫ CEB 17 (green signals)
Breast Series, Clinical Practice. Australian Family Physician, 2005
“High-level Her-2/neu protein expression”
![Page 6: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/6.jpg)
Metastatic
Palliative Intent
Systemic Therapy for Breast Cancer
Curative Intent
I II III IV0
Locally
AdvancedEarly Stage
Pre
Invasive
Local (Surgery +/- XRT) +/- Systemic Systemic +/- Local
Survivorship (& Relapse) End of Life Care
Adjuvant & (NeoAdjuvant) Palliative
![Page 7: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/7.jpg)
Slamon et al, N Engl J Med. 2001
Taxol 1%
AC 8%
Taxol + TZ 13%
AC + TZ 27%
Trastuzumab
Cardiotoxicity
Retrospective Review
Asymptomatic & Symptomatic
Cardiac Dysfunction
![Page 8: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/8.jpg)
Yin et al, PLoS One 2011
Disease Free Survival
Adjuvant Trastuzumab in Breast Cancer
![Page 9: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/9.jpg)
Cochrane Meta-Analysis ↓ LVEF HF
Trastuzumab (n= 5471) 11.2% 2.5%
Control (n=4810) 5.6% 0.4%
Relative Risk (95%CI)1.83
(1.36 -2.47)
5.11
(3.00-8.72)
Adjuvant Trastuzumab Cardiotoxicity
Moja et al. Cochrane Database Syst Rev. 2012
![Page 10: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/10.jpg)
Risk
Anti HER2 based Therapy for Breast Cancer
Benefit
Cardio-ToxicityEarly Stages: ↓ Relapse & ↑ OS
Metastatic: ↑ QOL & ↑ OS
![Page 11: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/11.jpg)
• Older Age
• Lower Baseline LVEF% (or CHF)
• Underlying CVS Risks (HTN, CAD,
AF, DM, Obesity, Dyslipidemia, Renal Failure)
Trastuzumab Cardiotoxicity
(Risk Factors)
• Longer vs Shorter Anti HER2 therapy
• Concurrent vs Sequential Therapy
• Anthracycline Use (current or past)
Treatment
Patient
![Page 12: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/12.jpg)
Goldhirsch et al, SABCS 2012
Trastuzumab Cardiac Toxicity(Duration of Trastuzumab Therapy)
HERA Trial
![Page 13: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/13.jpg)
Outcome Longer (1-Year) vs shorter (6 or 3 Months)
DFS HR = 1.13; 95% CI 1.03–1.25; p=0.01
OS HR = 1.16; 95% CI 1.01–1.32; p=0.03
Cardiac OR = 0.52; 95% CI 0.43–0.62; p < 0.00001
Chen et al, Cancer Treat Rev 2019Meta-Analysis Six studies (11,496 Patients)
Trastuzumab Cardiac Toxicity(Duration of Trastuzumab Therapy)
![Page 14: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/14.jpg)
N 9831 Control Sequential Concurrent
Incidence 0.0% 2.2% 3.3%
95% CI (0.0-0.7%) (1.1-3.8%) (2.0-5.1%)
Perez et al. Proc ASCO 2005
At 9 months analysis (500 patients per arm) for normal or ≤ 15 % decrease in
LVEF after AC. Concurrent received 3 additional months of Trastuzumab.
Trastuzumab Cardiac ToxicityConcurrent vs Sequential
![Page 15: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/15.jpg)
BCIRG 006 Trial
Arm CHF
AC → T 7 (0.7%)
AC → TH 21 (2.0%)
TCH 4 (0.4%)
No Cardiac Deaths. CHF NYHA G3-4 Slamon et al, NEJM 2011
Disease-Free Survival
Overall Survival
SS
![Page 16: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/16.jpg)
Real-World Trastuzumab CardioToxicity
“OHERA Observational Study”
CHF NYHA II-IV : 2.8%
Cardiac Deaths : 0.2%*
CHF Resolution : 73%*All with cardiac disease history
Lidbrink et al, Breast Cancer Research Treatment 2019
• Age ≥ 65
• Cardiac History
• Hypertension
• CVS Medications
• Baseline LVEF ≤ 55%
3733 Patients (Stages I-IIIB)
CHF Risk Factors
![Page 17: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/17.jpg)
Baselga et al, Crit Rev Oncol Hematol. 2017
Anti HER2 Systemic Therapy for Breast Cancer
![Page 18: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/18.jpg)
Anti HER2 Systemic Therapy Cardio-Toxicity
Verma et al, NEJM 2012
![Page 19: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/19.jpg)
Anti HER2 Systemic Therapy for Breast Cancer
Trastuzumab + Chemo
Trastuzumab + Chemo +/- Pertuzumab
Trastuzumab + Chemo +/- Neratinib
Adjuvant
Palliative
NeoAdjuvantTrastuzumab + Chemo +/- Pertuzumab
Trastuzumab + Chemo +/- TDM1
Trastuzumab + Chemo +/- Pertuzumab
TDM1
Capecitabine + Lapatinib
![Page 20: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/20.jpg)
Florido et al,
J Am Heart Assoc 2017
Cardio-Toxicity Management
Cardio-Oncology Clinics
![Page 21: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/21.jpg)
Risk
Trastuzumab-based Therapy for Breast Cancer
Benefit
Cardio-ToxicityEarly Stages: ↓ Relapse & ↑ OS
Metastatic: ↑ QOL & ↑ OS
Patient Selection & ManagementPrognostic & Predictive
![Page 22: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/22.jpg)
Conclusions
⚫ Anti-HER2 therapy is a pivotal component
of the current treatment of HER2 positive breast cancer.
⚫ The predominant concerning adverse event during anti-
HER2 based therapy is cardiotoxicity.
⚫ Anti HER2 therapy decisions depend on predicted
benefits and anticipated / encountered cardiotoxicities.
⚫ The role of preventive measures for cardio-toxicity
within treatment paradigms require further research.
![Page 23: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/23.jpg)
Take Home Message
In the era of improved breast cancer outcomes
achieved with refined anti HER2 therapy,
the management (& prevention) of associated
cardio-toxicities is critical.
![Page 24: Breast Cancer: A Focus on HER2 Targeted Therapycardiaconcology.ca/wp-content/uploads/19.-HER2... · Conclusions ⚫Anti-HER2 therapy is a pivotal component of the current treatment](https://reader035.vdocuments.us/reader035/viewer/2022070800/5f0250307e708231d403a698/html5/thumbnails/24.jpg)