300P - Data-driven timing of optimal LVEF assessment in breast cancer patients exposed to trastuzumab

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Complications/Toxicities of Treatment
Breast Cancer
Biological Therapy
Presenter Jeffrey Sulpher
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors J.A. Sulpher1, P. Andrew1, H. Majeed2, C. Johnson3, N. Graham1, S. Dent1
  • 1Medical Oncology, The Ottawa Hospital Cancer Centre, K1H 8L6 - Ottawa/CA
  • 2Internal Medicine, The Ottawa Hospital, K1H 8L6 - Ottawa/CA
  • 3Cardiology, The Ottawa Hospital, K1H 8L6 - Ottawa/CA



While adjuvant trastuzumab has improved outcomes in patients with HER2/neu positive breast cancer, this treatment has also been associated with decreased left ventricular ejection fraction (LVEF). No data-driven schedule exists to inform clinicians of the optimal timing for serial measurements of LVEF following initiation of trastuzumab therapy. We conducted a hypothesis-generating pooled trend analysis to identify a timeline for monitoring LVEF changes secondary to trastuzumab therapy in patients with breast cancer.


An English language search of Medline, Cochrane, ASCO Library, and an extensive bibliography search from January 1999 to April 2014 were performed. Inclusion and exclusion criteria were met by 35 clinical trials (n = 9,936). Primary outcome was interval reduction in percent LVEF following trastuzumab versus baseline (post-anthracycline).


A quadratic trend was identified between LVEF and trastuzumab across time. Decline in LVEF with trastuzumab occurred significantly early (2 months), peaked (7 to 15 months), and recovered (post 30 months) (Friedman ANOVA; F = 19.9, p<0.05). Sensitivity analyses revealed robustness of analysis to concurrent non-anthracycline chemotherapy (p>0.05).


This pooled trend analysis reveals that LVEF assessment and potential cardiac intervention should be concentrated within the early months of trastuzumab therapy, consistent with current clinical and research protocols. Further research is required to define an optimal LVEF monitoring schedule once trastuzumab therapy is complete.


All authors have declared no conflicts of interest.