Cardiovascular mortality and morbidity burden in successive and age pre-stratified case–control cohorts of breast cancer women. A population-based study



To assess the existence, components and clinical relevance of cardiac causes of death and cardiovascular (CV) hospitalizations in a population-wide database of patients with breast cancer (BC).

Methods and results

A population-wide database of the Puglia Region, Italy was analyzed, with a prospective comparative design. Three successive closely matched case/control cohorts representing current care in the period 2007–2014 were also stratified according to age to focus specifically on the potential interaction of treatment-related cardiac toxicity and the expected different baseline CV risk profiles.


At 3-year follow-up, in the successive cohorts the incidence of BC-related (7.7, 7.0, 6.5%) and cardiac causes of death, specifically attributed to heart failure (HF, 1.3, 0.5, 0.5%), decreased. Significant mortality hazard ratio (HR) for HF was found in the total population (1.47, 95% CI 1.14–1.90), in particular in the 2007–2009 cohort (1.71, 95% CI 1.19–2.46) and in the 50–69 age group (7.96, 95% CI 2.81–22.55). Results at 5 years confirm the mortality findings, and a significant HR for hospitalizations for HF, non-atrial arrhythmias and ischemic heart disease in the younger than 50 subpopulation pointed to a late expression of toxicity in the youngest BC population.


The incidence of CV causes of death 3 and 5 years after BC diagnosis was very low, even if an excess in risk of death for HF as compared with the control cohort was observed. While younger patients seems to tolerate BC and BC therapy better in the short term, HF mortality and morbidity resulted significantly increased at 5-year follow-up. As the risk for hospitalization for CV reasons increased at 5-year follow-up in particular in women aged less than 50 years, CV monitoring in this subgroup of patients seems mandatory.

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We are grateful to Jennifer Meessen for her statistical assistance and Judith Baggott for language editing. This study is part of the work covered by the 2015–2020 Collaboration between the Regional Healthcare Agency of Puglia Region (AReS Puglia), Italy and the Istituto di Ricerche Farmacologiche Mario Negri IRCCS.

Author information




LS, FR, GT, RL and VL contributed to the conception and design of the study and data interpretation; LS contributed to the literature search, AD, LB and BP to the data extraction; FR contributed to data analysis; GT and RL conducted the quality assessment. All authors contributed to writing the manuscript, and all authors approved the manuscript. FR, LS, VL, RL and GT guarantees the integrity of the work. The authors had full access to all the data in the study and the final responsibility for the decision to submit for publication. The corresponding author attests that all listed authors meet authorship criteria.

Corresponding author

Correspondence to Lidia Staszewsky.

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Conflict of interest

The authors declare that they have no competing interests.

Research involving human participants and/or animals

This article does not contain any study involving humans or animals.

Ethical approval

In this study, we use aggregated anonymous data. Data anonymization prior to any analysis and data protection procedures followed the strict criteria adopted by the Puglia Region Health Care Agency, in full compliance with national regulations, and the ethical requirements foreseen for the epidemiological utilization of administrative databases (; DL August 10, 2018 No. 101; Act of Department of Health of the Puglia Region (No. 16; May 4, 2015). The use of data in this project does not require review by a Research Ethics Board.

Informed consent

According to the Italian Personal Data Protection Code (LD 30 June 2003, No. 196 and Appendix), no informed consent from patients is required when using anonymous aggregated data.

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Staszewsky, L., Robusto, F., Lepore, V. et al. Cardiovascular mortality and morbidity burden in successive and age pre-stratified case–control cohorts of breast cancer women. A population-based study. Breast Cancer Res Treat (2020).

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  • Breast cancer
  • Women
  • Total mortality
  • Cardiovascular causes of death
  • Cardiovascular hospitalizations
  • Population-based study