Abstract
BackgroundThe survival rates of women with breast cancer have improved significantly over the last four decades due to advances in breast cancer early diagnosis and therapy. However, breast cancer survivors have an increased risk of cardiovascular complications following chemotherapy. While this increased risk of later occurring structural cardiac remodeling and/or dysfunction has largely been attributed to the cardiotoxic effects of breast cancer therapies, the effect of the breast tumor itself on the heart prior to cancer treatment has been largely overlooked. Thus, the objectives of this study were to assess the cardiac phenotype in breast cancer patients prior to cancer chemotherapy and to determine the effects of human breast cancer cells on cardiomyocytes.MethodsWe investigated left ventricular (LV) function and structure using cardiac magnetic resonance imaging in women with breast cancer prior to systemic therapy and a control cohort of women with comparable baseline factors. In addition, we explored how breast cancer cells communicate with the cardiomyocytes using cultured human cardiac and breast cancer cells.ResultsOur results indicate that even prior to full cancer treatment, breast cancer patients already exhibit relative LV hypertrophy (LVH). We further demonstrate that breast cancer cells likely contribute to cardiomyocyte hypertrophy through the secretion of soluble factors and that at least one of these factors is endothelin-1.ConclusionOverall, the findings of this study suggest that breast cancer cells play a greater role in inducing structural cardiac remodeling than previously appreciated and that tumor-derived endothelin-1 may play a pivotal role in this process.
Highlights
The survival rates of women with breast cancer have improved significantly over the last four decades due to advances in breast cancer early diagnosis and therapy
There were no differences in left ventricular (LV) ejection fraction (LVEF) or LV stroke volume (Fig. 1d, e) between the observed groups suggesting that patients with breast cancer can be characterized by a relative LV hypertrophy (LVH) with normal systolic function
Our findings indicate that breast tumors may directly induce cardiomyocyte hypertrophy and suggest a breast cancer cell-released soluble factor may be responsible for this effect
Summary
The survival rates of women with breast cancer have improved significantly over the last four decades due to advances in breast cancer early diagnosis and therapy. Breast cancer survivors have an increased risk of cardiovascular complications following chemotherapy While this increased risk of later occurring structural cardiac remodeling and/or dysfunction has largely been attributed to the cardiotoxic effects of breast cancer therapies, the effect of the breast tumor itself on the heart prior to cancer treatment has been largely overlooked. Based on the well-established cardiotoxic effects of many chemotherapies used in breast cancer treatment, the prevailing theory is that the drugs trigger a dose-dependent left ventricular (LV) remodeling that can, in the worst cases, progress to heart failure and death [3,4,5]. Given that monitoring of cardiac structure/function in women diagnosed with breast cancer is often not initiated until after the initiation of chemotherapy, it is currently unknown if the breast tumor itself contributes to cardiac remodeling independently from the chemotherapy
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