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  • br To our knowledge our study is the


    To our knowledge, our study is the first to find evidence of an increased risk of sick leave and disability pension because of mental disorders in women with breast cancer. This is not surprising, given that earlier studies have reported increased rates of depression, anxiety, and stress-related disorders following a breast cancer diagnosis [24e28]. The risk of psychological problems has been reported to be highest in the first two years [26], which is likely to reflect immediate reactions to the cancer diagnosis. Our study provides evidence that women with breast cancer of all disease stages are at an increased risk of mental health problems affecting working life for several years after diagnosis.
    Previous studies have found an increased risk of cardiovascular events in women with breast cancer [24,29e32]. We found that it BYL-719 was more common for women with breast cancer than for control women to leave the labor market because of cardiovascular disease. The cardiotoxic effects of certain breast cancer treatments are well-known; anthracycline-based chemotherapy, trastuzumab, and radiotherapy are associated with an increased risk of cardiovascular events [33]. Breast cancer and cardiovascular disease also share common risk factors such as tobacco use, physical inactivity, and diabetes, which may also explain the coincidence of the diseases [33].
    We also observed an increased risk of disability pension due to inflammatory diseases. It has been suggested that treatment for breast cancer can induce autoimmune or inflammatory diseases, 
    such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis [34,35]. Rheumatoid symptoms of joint pain and joint swelling are common following breast cancer treatment, but do not necessarily involve systemic inflammation [36]. It cannot be excluded that the association may be the opposite; many chronic inflammatory diseases (and their treatments) are associated with increased cancer risks [37], although current literature point to-wards no increased risk of breast cancer in some of the most common inflammatory diseases [38,39].
    The major strength of this study was the use of data from Swedish population-based registers with high completeness, minimizing selection and information bias. Through linkage be-tween different registers we were able to study the underlying causes of absence from work, taking several important factors such as for example disease progression into account. Another important strength included the use of multi-state models, which captures the complexity of the data with multiple, closely related and possibly also recurrent outcomes. Our finding that treatment-related adverse events can cause permanent work loss in women with breast cancer is generalizable also to other countries with high female labor force participation rates, although the observed impact on working life might differ according to legislation and generosity of sickness benefits.
    One limitation of the study was uncertainty of the precision of registered diagnoses. Sickness benefits are granted based on the assigned diagnoses, but coding practices may have varied by local routines, between certifying physicians, and calendar periods. So-cial insurance legislation has changed during the study period, which led to a more strict assessment of the entitlement for long-term sick leave and disability pension. It cannot be excluded that these changes also influenced which diagnoses were recorded and accepted on the medical certificate. Additionally, information on the diagnosis was only available for the start of a period with sick leave or disability pension; changes of the original diagnosis were