br Analyses were performed using
Analyses were performed using R (version 3.4.1) and STATA (version 15.0/IC; Stata Corporation, College Station, TX). We considered p values of 0.05 or less to be statistically significant; all tests were two-sided.
The proportion of women on sick leave, disability pension, and death by reported cause and time since diagnosis is presented in Fig. 1. At year five post-diagnosis, 15% of women with breast cancer were on all-cause sick leave, disability pension, or were deceased, compared with 5% among control women. Causes other than can-cer accounted for around half of all sick leave (3.5% out of 6.8% of women) and disability pension (1.4% out of 2.6%) but only a few deaths (0.5% out of 5.6%) in women with breast cancer. In control women, diseases other than cancer was the recorded cause for nearly all sick leave (3.2% out of 3.5%) and disability pension (1.1% out of 1.1%), and around half of all deaths (0.3% out of 0.7%). During the five-year period following diagnosis, women with breast cancer spent on average 341 days on sick leave, of which the majority (281 days) were attributed to cancer, compared with a total sick-leave period of 56 days in control women (Table 2). In addition to sick leave due to cancer, women with breast cancer had an increased risk of sick leave due to mental disorders (HR 1.24, 95% CI 1.15e1.33) and other diseases (HR 1.63, 95% CI 1.56e1.70).
Women with breast cancer were also at increased risk of disability pension due to mental disorders (HR 1.54, 95% CI 1.29e1.85) and inflammatory diseases (HR 1.46, 95% CI 1.05e2.03) (Table 3). The risk of disability pension due to cardiovascular dis-ease was also elevated, although only statistically significant in women diagnosed after 2005 (HR 2.24, 95% CI 1.22e4.13). In ana-lyses stratified by stage of disease, women with stage III breast cancer had the highest risk of disability pension due to cancer, mental disorders, and cardiovascular disease. Several clinical fac-tors were independently associated with a higher risk of disability pension attributed to cancer, including axillary 5 Azacytidine node dissection, chemotherapy, and mastectomy. Few factors were associated with disability pension attributed to the other causes under study, among them mastectomy which was associated with a higher risk of disability pension due to mental disorders.
When allowing for non-proportional hazards, we found that women with breast cancer eight years after diagnosis remained at a ten-fold increased risk of disability pension attributed to cancer (Fig. 2). While the risk of disability pension due to mental disorders was highest two years after diagnosis (HR 1.96, 95% CI 1.41e2.74), and declined to equal that of control women after eight years; the risk due to cardiovascular disease increased steadily over the whole follow-up period (HR 2.22, 95% CI 0.94e5.23 at year eight).
Since cancer was the most commonly recorded cause of disability pension, we further investigated the possible contribu-tion of post-diagnostic intermediate events (Table 4). Metastatic disease was the strongest contributing factor, but mental disorders, fatigue, pain or insomnia, and infections were also significant contributors in models both excluding (Model 1) and including treatment and tumor characteristics (Models 2 and 3).
In this large population-based cohort study, women with breast cancer were at increased risk of sick leave and disability pension because of a wide range of medical conditions. Disease progression
Fig. 1. Proportion of women on sick leave, disability pension, or death by reported cause and years since diagnosis. The figure includes women of working age diagnosed with breast cancer 2005e2012.
was a strong contributing factor, but also mental disorders, car-diovascular and inflammatory diseases, lymphedema, and fatigue and pain-related conditions were more commonly reported causes of sick leave and disability pension in women with breast cancer compared with control women. Women with stage III breast cancer generally had the highest risk of the studied causes of disability pension, but the risk of disability pension due to mental disorders and inflammatory disease was also increased in women with stage I disease. Although the absolute risk increase of sick leave and disability pension was small for causes other than cancer, the relative risk estimates indicate that breast cancer represents an important risk factor also for these less common causes.
Corroborating results of a previous study , we found that nearly half of all women on sick leave or disability pension at year five post-diagnosis were reported as absent from work because of cancer. Metastatic disease was the strongest, but not the only, contributing factor for cancer-specific disability pension, indicating that when cancer was assigned as a cause, a number of conditions directly or indirectly related to the cancer diagnosis could be involved. Whether or not coded as cancer, side effects of treatment have been suggested to increase the risk of absence from work in previous studies [5e8,20,21]. For example, Paalman et al. found that receipt of chemotherapy increased the risk of disability pension, also after controlling for new cancer events . Axillary