Cardiovascular Mortality and Morbidity Burden in Successive and Age Pre-Stratified Case-Control Cohorts of Breast Cancer Women. A Population-Based Study

Background: The existence, the components and the clinical relevance of treatment related cardiotoxicity in breast cancer patients are still the subject of controversial findings and recommendations. Two of the possible main determinants of uncertainty were taken as the focus of the present analysis of cardiovascular (CV) mortality and morbidity: the overtime changing risk profile of breast cancer protocols; the age-dependence of the role of background CV risk. Methods: Prospective comparative assessment of two cohorts of breast cancer women, cases, and their closely matched controls followed for three (36 330) and five years (23 906), covering the period Jan 1, 2007 to Dec 31, 2013. The pertinent NHS administrative databases were analyzed with Cox proportional hazards regression models to assess the differences in the incidence of fatal and not fatal CV events between pre-stratified cohorts of cases and controls representing three successive generations of breast cancer care and three age groups: <50, 50-69, ≥70 years. Findings: The hypothesis of important improvements in the benefit /risk profile in successive cohorts of exposed women is documented by the decreases in directly breast cancer related deaths (7*7, 7*0, 6*5%), in the presence of stable rates of cardiac causes of death. What matters more is the very low and decreasing incidence (from 1*3 to 0*5%) of the expectedly most significant indicator of cardiac toxicity, heart failure (HF), whose hazard ratio (HR) reaches a reasonable level of significance only in the first period studied (HR:1*71 95%CI: 1*19-2*46). Morbidity and longer follow-up confirm the above data on HF incidence and risk (HR:1*52 95%CI: 1*13-2*04). Incidence and HR for hospitalization for thromboembolic events, recognized CV events associated with the systemic toxicity of oncological conditions, more than to its treatments, are an indirect but strong indicator of the informative validity of the database analyzed. Interpretation: In agreement with most recent experimental and epidemiological data, our report documents a low, decreasing incidence and clinical relevance of treatment-related cardiotoxicity. Awareness of its potential occurrence must be accompanied by the expected directly related CV risk of a cancer and age-dependent condition. Besides the routine assessments, personalized monitoring, on the basis of concomitant CV risks or morbidity, could be needed especially in older patients. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interest: No competing interests. Ethical Approval: 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). No informed consent is required when using anonymous aggregated data.