Breast cancer and cardiovascular disease risk

Abstract

Breast cancer is the most frequently diagnosed cancer in women worldwide. There were over three million five-year breast cancer survivors worldwide in 2012. Cardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Breast cancer therapies such as radiation therapy, certain types of chemotherapy, and targeted treatment increase the risk of CVD, especially in patients with pre-existing CVD risk factors including higher age, hypertension, diabetes mellitus, and a history of CVD. Coronary artery calcification (CAC) and thoracic aortic calcification (TAC) are (subclinical) markers of atherosclerosis and are associated with a higher risk of coronary heart disease. CAC and TAC are measured on computed tomography (CT) scans. Breast cancer patients treated with radiation therapy routinely undergo a CT scan of the breasts for radiotherapy planning, on which the coronary arteries and aorta are visible. Calcifications in these areas can be quantified without exposing patients to additional radiation and without additional costs. Currently, presence of CAC and TAC is not routinely assessed in breast cancer patients on RT planning CT scans. However, systematic incorporation of CAC and TAC scores in breast cancer treatment decision potentially reduces cardiovascular mortality and morbidity. In this thesis, the first steps towards a more systematic approach of cardiovascular risk assessment in breast cancer patients are taken. We first estimated the risk and determinants of CVD in breast cancer patients. Secondly, we investigated the prevalence of CAC and TAC on radiotherapy planning CT scans in Western (i.e. the Netherlands) and Asian (i.e. Singapore) breast cancer patients. For this, we used a new developed software, based on the state-of-the-art deep learning technique, that automatically measures CAC and TAC on radiotherapy planning CT scans. In the Netherlands, the absolute ten-year risk of death from CVD after breast cancer decreased from 56 per 1,000 women in 1996 to 41 in 2005 (relative decrease of 23.9%). The relative risk of death from CVD is 77% higher in Dutch breast cancer patients compared to Dutch women without breast cancer, when pre-existing CVD risk factors are taken into account. Prevalence of coronary artery calcification (CAC) and thoracic aorta calcification (TAC) is considerable and increases with age. CAC occurred in up to one third of patients aged under 70 years. Comparing patients from the Netherlands with patients from Singapore, CAC was more prevalent in patients aged over 70 years from Singapore (70%) than in patients aged over 70 years from the Netherlands (55%). TAC was prevalent in two third of patients from the Netherlands and Singapore. The performance of automatic CAC and TAC scoring was good compared to manual scoring in planning CT scans from the Netherlands and Singapore. The new developed automatic software is a promising fast technique (less than one minute per scan) to systematically detect calcifications on planning CT scans of patients treated with radiotherapy. In the future, calcification status may be used to screen patients for CVD risk, and to indicate who could benefit from cardiac monitoring, cancer therapy with reduced risk of cardiotoxicity and/or cardioprotective medication.