Long term follow-up (F/U) report of symptomatic cardiac events (SCEs) in 2,809 breast cancer (BC) patients (pts) treated with adjuvant trastuzumab...

Date 28 September 2019
Event ESMO 2019 Congress
Session Proffered Paper – Supportive and palliative care
Topics Supportive Measures
Biological Therapy
Breast Cancer
Supportive and Palliative Care
Presenter Serena Di Cosimo
Citation Annals of Oncology (2019) 30 (suppl_5): v718-v746. 10.1093/annonc/mdz265
Authors S. Di Cosimo1, A. Trama2, I. Merlo3, P. Minicozzi4, L. Tarantini5, G. Apolone6, G. Corrao3, M. Franchi3
  • 1Department Of Applied Research And Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 2Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3Laboratory Of Healthcare Research And Pharmacoepidemiology Department Of Statistics And Quantitative Methods, University of Milano-Bicocca, Milan/IT
  • 4Analytical Epidemiology And Health Impact Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 5Department Of Cardiology, Azienda Ospedale San Martino, ASL n. 1, Belluno/IT
  • 6Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT



Clinical trials, focusing on selected pts, may have underestimated toxicities in cases with advanced age and co-morbidities, that are common in RW practice. Furthermore, clinical trials do not provide extended F/U. Thus, we assessed acute and long-term SCEs after adjuvant T in a large/unselected BC pt population.


Using healthcare administrative database, ie clinical discharge records and drug prescriptions of the Lombardy region (Italy), we selected pts newly diagnosed with early BC between 01/2008 and 12/2011 and monitored until 12/2016. Pts treated with T were 1:2 matched with pts treated with chemotherapy only for age, date of treatment, and cardiovascular risk factors. SCEs included heart failure and cardiomyopathy based on ICD9-CM codes. The cumulative risk of SCEs was estimated using the Kaplan-Meier method; independent predictors were assessed by the Cox regression model.


Of a cohort of 34,218 pts with incident BC, 2,809 pts treated with T were matched to 5,618 pts treated with chemotherapy only. One SCE during F/U was experienced in 52 (1.8%) of T-users and 88 (0.26%) of non-T users. No cardiac death occurred. The 1-year cumulative risk of SCEs was 0.96%, with 1/4 of SCEs occurring within the first 6 months, in T-users, and 0.16% in non T-users. However, the T-user excess risk disappeared after 1 year of T. Thus, the hazard ratio [HR] was 9.96 (95%CI 3-78-26.2) during the first year, and 1.41 (95%CI 0.99-2.02) during the entire F/U period. HR was higher in the elderly, age>70 years, 8.77 (95%CI 5.25-14.64), and in pts with at least one pre-existing CRFs 2.32 (95%CI 1.68-3.22).


In RW practice, SCEs during/after T are infrequent, early and self-limiting. Based on the timeline of SCEs, it might be unnecessary to monitor cardiac toxicity beyond the period of T treatment. Besides, to reduce the excess of cardiac risk of the first year, strategies including shortening T exposure or increasing the number of check-ups in asymptomatic pts should be accompanied by the development of biomarker(s) able to identify pts at risk before/immediately after T initiation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Serena Di Cosimo.


Associazione Italiana per la Ricerca sul Cancro (AIRC).


S. Di Cosimo: Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Teva; Advisory / Consultancy: EpiOnpharma; Advisory / Consultancy: Bayer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: GSK; Travel / Accommodation / Expenses: Celgene. All other authors have declared no conflicts of interest.