Abstract P5-21-07: Unexpected low incidence of cardiovascular related events in women with primary breast cancer; population derived retrospective cohort
Authors: Papakonstantinou Antroula , Hubbert Laila , Mikiver Rasmus , Bergh Jonas , Hedayati Elham 
Published: May 2015

Abstract
Background
Many studies and even a meta-analysis of the EBCTCG found that, compared to methotrexate containing chemotherapy (non-ACT) or no chemotherapy (no-CT), anthracycline-containing chemotherapy (ACT) decreases overall mortality after breast cancer (BC). However, increased cardiac mortality was observed but did not outweigh improvement in BC survival. The incidence of cardiotoxicity after adjuvant BC treatment is reported with varying frequencies and still remains unknown.
Methods
Women younger than 60 years and diagnosed with lymph node positive BC between 1998 and 2002 were identified through the Cancer Registry of the Regional Cancer Centre in the southeast health region of Sweden. Data on patient, tumor and treatment characteristics were registered from the Cancer Registry and medical records. Information on cardiovascular toxicity (CVT) was collected from the National Patient Registry, the Cause of Death Registry and the Prescribed Drugs Registry. ICD diagnoses for cardiac diseases and hypertension were used. A predefined Kaplan Meier and Cox regression analysis and a post hoc multivariate analysis to investigate confounders were performed. CVT was registered as event only if it occurred prior to BC relapse.
Results
Of 524 eligible women, 329 were analyzed (mean age, 50 years; range, 28 to 60 years) and 195 were excluded due to missing medical records (n=153), primary metastatic disease (n=18), trastuzumab treatment (n=6) and known heart disease at BC diagnosis (n=13). Of those analyzed, 176 received ACT, 64 non-ACT and 89 no-CT. The cumulative CVT was 16 %. CVT was observed in 12 % of those that received ACT, 14 % of those that received non-ACT and 25 % of those that received no-CT. CVT was significantly higher among women that received no-CT (p=0.024) meanwhile BC relapse and BC mortality was significantly higher among women treated with ACT compared to no-CT (p=0.02). According to Kaplan Meier curve, the risk for CVT among women treated with ACT was higher than the rest the first 5 years after diagnosis. 13 out of 85 patients that received epirubicin &lt;450mg/m2 and 5 out of 54 that received epirubicin &gt;450 mg/m2 developed CVT (p=0.302). A multivariate analysis adjusted for age, treated side, obesity, smoking and received chemotherapy showed that age between 51 and 60 year was a significant risk factor for developing CVT (p=0.035).
Conclusion
Clinically overt CVT 10-14 years after adjuvant BC treatment was diagnosed in 16% of women, but the subclinical incidence remains unclear. Women that did not receive chemotherapy showed increased incidence of CVT, probably due to lower risk for BC relapse and better overall survival. Age seems to be an independent risk factor for CVT. The incidence of clinical ACT CVT was unexpected low, however, CVT was observed already in epirubicin &lt; 450 mg/m2. BC relapse still remains the most important risk factor for mortality among women with high risk BC and nowadays high-dose chemotherapy and dose dense treatments are given, increasing the risk of CVT. It is essential to co-operate with cardiologists and investigate methods to identify patients that are at risk of developing chemotherapy-related CVT and find suitable measures to prevent CVT influencing overall survival.
Citation Format: Antroula Papakonstantinou, Laila Hubbert, Rasmus Mikiver, Jonas Bergh, Elham Hedayati. Unexpected low incidence of cardiovascular related events in women with primary breast cancer; population derived retrospective cohort [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-07.