Sickness absence and disability pension among women with breast cancer: a population-based cohort study from Sweden

Background Women’s return to work after diagnosis of breast cancer (BC) is becoming more prevalent. However, register-based national investigation on sickness absence (SA) and disability pension (DP) in BC women is lacking. The aim of the study was to explore SA and DP before and after a first BC diagnosis and the possibility to predict new cancer-related SA by using disease-related and sociodemographic factors. Methods A longitudinal register study of the 3536 women in Sweden aged 19–64 with a first BC diagnosis in 2010 was conducted by linkage of five nationwide registers. Particularly, detailed information on SA and DP was obtained from the National Social Insurance Agency. Descriptive statistics on SA and DP 2 years before through 3 years after the BC diagnosis were performed. The risk of having a new SA spell due to BC or BC-related diagnoses was modeled using logistic regression. Results The proportion of women with SA increased during the year following the BC diagnosis date and declined over the next 2 years to proportions before diagnosis. At the time of BC diagnosis, half of the women began a new SA spell > 14 days with cancer, cancer-related, or mental diagnosis. Disease-related and sociodemographic factors including occupational sector, living area, age, cancer stage, educational level, and number of previous SA days showed statistical significance (p < 0.05) in predicting a new SA around BC diagnosis. By using these factors, it was possible to correctly predict 67% of the new SA spell. Conclusions SA among women with BC was elevated mainly in the first year after diagnosis. New SA following BC diagnosis can accurately be predicted.


Introduction
Breast cancer (BC) is a major health problem with 1.67 million new cases worldwide annually [1]. Due to early detection and better treatments, mortality has decreased, hence more knowledge is needed on potential adverse long-term social consequences of BC for the growing number of survivors [2][3][4]. About half of the women diagnosed with BC are of working age, [5,6] thus, BC might imply sickness absence (SA) or even disability pension (DP) for many of them due to effects of BC and/or BC treatments. Studies indicate that many women with BC value paid work highly and want to continue working after diagnosis or return to work (RTW) as soon as possible [7][8][9][10], and more knowledge is needed on patterns of SA and DP in order to get the knowledge base for interventions to facilitate part-or full-time (return to) work.
Studies of SA, DP, and RTW among women with BC indicate that the majority of RTW happens within 2 years [5,11,12]. Nevertheless, studies from Sweden and the Netherlands show that BC is associated with higher SA as long as 5 years after diagnosis [13][14][15] and that some are granted DP up to 10 years after diagnosis [13,15,16]. Advanced cancer stage, [11][12][13]17] chemotherapy, [15,18] pre-diagnosis SA, [13][14][15]19] comorbidity, [20] and several sociodemographic factors [12-15, 17, 19-30] were negatively associated with RTW, alternatively positively with SA/DP, depending on the outcome used. Thus, such variables need to be included in this type of studies. However, studies of SA, DP, and RTW vary greatly in terms of study design, outcomes, selection of included women, national health insurance systems, and female employment frequency, [5,11,16,[20][21][22][31][32][33] the latter implying different healthselection effects on outcomes. Sweden has a high female employment rate, also in higher ages (> 50 years old) [34]. Thus, the healthy-selection effects on outcomes in Sweden are smaller which is an advantage when aiming at gaining knowledge on associations of BC with future SA/DP.
Most of the previous studies were based on short follow-ups, selected study populations, high drop-out, or only self-reported SA/DP, and lacked information on DP and pre-diagnosis SA/DP [20]. Although elevated levels of post-diagnostic anxiety and depression have been reported, [35,36] detailed analyses of SA and DP due to mental diagnoses have seldom been conducted. Thus, knowledge is limited on pre-and post-diagnosis diagnosis-specific SA and DP in women with BC, in nationwide population-based studies; knowledge that is needed to better understand the situation for women diagnosed with BC, as a basis to identify potential risk factors for SA/DP as a basis for preventive measures. Moreover, in healthcare, among employers, insurance organizations, and patients, information regarding possible future SA following a BC diagnosis is asked for in order to take prevention measures and facilitate work accommodations [37]. Using information on disease-related and sociodemographic factors is one way to gain more such basic knowledge [38]. To the best of our knowledge, this is the first study to test a model for prediction of SA following a first BC diagnosis.
The aims were: (a) to explore the annual prevalence of SA and DP due to cancer, other somatic, and/or mental diagnoses during the 2 years before and the 3 years following a BC diagnosis, and (b) to predict risk of a new SA spell following a BC diagnosis.

Methods
A population-based longitudinal cohort study was performed.
We included all the 3536 women in Sweden, aged 19-64 who were diagnosed with a first malignant neoplasm of breast (International Classification of Diseases 10th version (ICD-10) [39]  -National Social Insurance Agency's Micro-data for Analyses of Social Insurance (MiDAS) (SA and DP benefits 2008-2013: dates, full-or part-time, main diagnosis).Data were linked at individual level using the ten-digit personal identity numbers assigned to all residents in Sweden [41].

SA and DP public benefit schemes in Sweden
All people in Sweden ≥16 years, with an income from work or unemployment benefits, with reduced work capacity due to disease or injury can be granted SA benefit from the Social Insurance Agency [42]. The employers usually provide reimbursement for the first 14 days of a SA spell, which is why we do not have information on SA spells ≤14 days. From day 8, a medical certificate issued by the treating physician is required. SA spells can go on for long periods, even years. All residents aged 19-64, irrespective of labour market status, can be granted DP if having long-term or permanent work incapacity due to disease or injury. People aged 19-29 can be granted temporary DP. In those ages DP can also be granted if, due to disease or injury, needing more time to complete elementary or secondary school. SA and DP can be granted for full-time (100%) or part-time (25, 50, or 75%) of ordinary working hours, that is, people can be on partial SA and DP at the same time. SA benefits cover 80% and DP 64% of lost income, up to a certain level.

Measures
We investigated two types of outcomes; DP and SA (for spells > 14 days). SA and DP days were transformed into net days; e.g., 2 days on half-time SA or DP were counted as one net day. SA and DP diagnoses were coded by the certifying physician who assessed the patient's condition and work capacity. Diagnoses were for some of the analyses classified into four categories: 1): BC (ICD-10: C50), BC-related diagnoses (Z80, Z85, N61-N63), and other cancer (C00-D48), 2): mental diagnoses (F00-F99, Z73), 3): other diagnoses (all remaining ICD codes), and 4): missing information. The outcome in the predictive model was defined as starting a new SA spell > 14 days due to one of the following SA diagnoses (C00-D48, Z80, Z85, N61-N63, F00-F99, or Z73) during the time-window of 14 days before to 29 days after the BC diagnosis. This time window was based on the frequencies of start of new SA spells in the full cohort, in relation to diagnosis date (T 0 ). For some women there was a delay before the diagnosis was included in the Cancer Register (even if the women were informed) and for others, treatment did not start until weeks later. The reason for including "diagnoses related to BC" and "other cancer diagnoses" in the predictive model was that sometimes a broader category of cancer diagnoses is given in the medical certificate [43]. Mental diagnoses were also included in the predictive model as a cancer diagnosis might lead to anxiety or depression [44,45].
The included sociodemographic, disease-related, and comorbidity covariates (listed in Table 1) were selected for the predictive model based on previous findings regarding factors influencing SA and RTW [13,14,17,20,23,25,26,29]. Missing information on educational level was coded as elementary school. Cancer-stage groups were assigned using the TNM Classification of Malignant Tumours [40] and categorized as: T0N0M0 + stage 0 + I, stage II, stage III + IV, and missing all TNM (with no T, N, or M information), respectively. When T, N, or M information was missing in one or two of the categories or classified as 'X' (assessment not possible), the value was set to 0. If more than one tumour was registered, with different diagnosis dates in 2010, the most advanced tumour was selected. The main ICD-10 diagnoses for healthcare were coded by the treating physicians. Healthcare due to uncomplicated delivery (O80) or not related to morbidity (e.g., screening) was excluded.

Statistical analyses
Different measures of SA and DP days were calculated.
Per year, using the BC diagnosis date (T 0 ) as reference: having had 0, > 0-30, > 30-90, > 90-180, or > 180 SA net days; in general, and by three SA diagnoses groups; having had any DP days/year, in general and by three DP diagnoses groups.
Moreover, the mean number of SA and of DP net days/year, respectively, were calculated for all women, using the BC diagnosis date (T 0 ) as reference, for the 2 years before T 0 and 3 years after T 0 (Y − 2 to Y + 3 ). This was done for all SA and DP as well as for the four SA/ DP diagnostic categories mentioned above. The annual numbers and proportions of women with SA/DP due to the different diagnoses were also calculated. The denominator used in these calculations varied somewhat over the years due to the exclusion of women (due to turning 65 years, emigration, or death).
In the predictive model regarding risk of new SA related to time of diagnosis, 2954 women were included. For those analyses we excluded the 521 women (14.7%) already on SA or on DP for full-time or nearly full-time (75-100%) at T 0 . Additionally, 61 women were excluded due to lack of covariate information, or because of extreme values on some of the continuous variables, e.g., number of healthcare visits or inpatient days.
The risk of a new SA spell due to BC or related diagnoses, other cancer diagnoses, or mental diagnoses was modelled using multivariable logistic regression [46,47] with a logistic model formulated as follows: log [P(Y i = 1)/P(Y i = 0)] = x i 'β where Y i denotes the SA status of individual i, and x i is a vector of observed covariates. Natural cubic splines [48][49][50] were used to model potentially nonlinear effects of continuous covariates. We used two internal knots at the empirical quantiles 1/3 and 2/3. The five variables that were modelled using splines were: age and number of previous: SA days, DP days, outpatient healthcare visits, and inpatient days, respectively, in the two pre-diagnostic years. We developed two versions of the model: one without interactions; and another one with interactions between family composition-marital status, region-city size, previous SA days-outpatient visits, previous SA days-inpatient days. An optimal threshold c was selected, such that predicting SA whenever the fitted probability was above c, minimized the sum of false positive (FP) and false negative (FN) and maximized the proportion of correctly classified observations. Also, the receiver operating characteristic (ROC) was calculated. These values were also calculated using leave-one-out cross-validations.

Results
Sociodemographic and diagnostic covariates are presented in Table 1 for the entire cohort (N = 3536) as well as for the group included in the modelling (n = 2954). About 40% of the women in both groups were ≥ 56 years. The compositions of women regarding distribution of characteristics in the two groups were fairly similar, except for percentage of women with no DP during the two pre-diagnostic years: 82% among all vs. 94% in the model, as expected due to the inclusion criteria in the modelling group. The majority had the earliest stages of BC. In the two pre-diagnosis years (Y − 1 and Y − 2 ), the majority had no SA days (81% vs. 83%), about half (56% vs. 53%) had at least one visit in specialized outpatient healthcare while few (12% vs. 8%) had at least one inpatient day. At BC diagnosis, 11.3% of the women were already on SA and 17.5% already on DP.

Proportions of women with SA and/or DP
During the year after the BC diagnosis date (Y + 1 ), 28% of the women had no SA > 14 days (  Included in the table were all women in Sweden < 65 years with a first breast cancer diagnosis in 2010 (N = 3536), during the 2 years before and 3 years after the breast cancer diagnosis date, presented for all SA/DP as well as by three categories of SA/DP diagnoses. Also, the number of women not included in the respective year are presented by reason for not being included a The first 14 days of SA spells are excluded b ICD-codes: C00-D48, Z80, Z85, N61-N63 c ICD-codes: F00-F99, Z73 d In the group" Other diagnoses", also SA/DP with missing information on diagnosis were included e Women who turned 65, died, or emigrated were included up to and including the year of the event

Mean SA and DP days/year
During Y + 1 , the mean number of SA days irrespective of SA diagnosis, among all the women in the cohort was 121.3. This was significantly higher than the numbers before diagnosis; (6.7 in Y − 1 and 9.0 in Y − 2 ) (Fig. 1). During Y + 1 , 108.8 of these SA days were due to cancer. That number was lower already in Y + 2 , i.e., 26.6 days. In Y + 3 , it was 14.0 days. Mean number of DP days/year was about 50 before BC diagnosis. Due to that some of the older women who already had DP in the year before T 0 became 65 years of age, that number of DP days decreased to about 40 days/year in Y + 2 and Y + 3 . Even in Y + 1 , the mean numbers of SA/DP days for the whole cohort was below less than half of the year.

New SA spell
For the 3015 women who did not have an ongoing SA nor DP of the extent of 75-100% at the time of BC diagnoses (T 0 ), Table 3 shows the numbers and percentages of women who had a first new SA spell in relation to T 0 . The same is shown for three specific SA diagnostic groups, i.e., cancer, mental diagnoses, and the other diagnoses (including missing), respectively. Of these women, 51% had a first new SA spell in relation to T 0 , that is, the period that was studied in the predictive modelling. Of these SA spells, 95% were due to cancer. In the following 30-day period, i.e., from 30 to 59 days after T 0 , another 20% had a first SA spell, of which 96% were with cancer. In the period from T 0 until end of follow-up 3 years later, a little less than one fifth of the women (18%) had no new SA spells. Nine women were granted DP during that period. That is, about 80% of those at risk of a new SA spell following BC diagnosis, had such a spell in the first year (Y + 1 ), and the majority of them (70%) in the first 3 months.

Predictive model
The model without interactions had similar crossvalidated ROC-AUC as the model with interactions (results not shown). We, therefore, choose to report results for the simpler model without interactions for the sake of parsimony. Out of the variables (see Table 1 Table 4 where the area under the curve (AUC) [51,52] is also reported.

Discussion
In this longitudinal population-based cohort study of all women in Sweden aged 19-64 years with a first BC diagnosis in 2010, the proportion with SA > 14 days increased substantially in the post-diagnostic 12 months. Nevertheless, most women were not on SA for extensive times during the first year after diagnosis date (e.g., > 180 net days) and about 17% were already on SA/DP due to other diagnoses when diagnosed with BC. In the third year after BC diagnosis date (Y + 3 ), the mean number of SA and DP days was low and 25% of the women had no SA at all. The variation in proportion of women with DP was minor during the 5 years being studied. The elevated proportion of women on SA and the higher number of SA days after BC diagnosis, compared to the years before BC diagnosis, was in SA due to cancer throughout follow-up, e.g., not due to mental diagnoses. Of the 3015 women not already on SA/DP at time of BC diagnosis, 51% had a new SA spell and for 98% of them the SA was due to a cancer diagnosis, cancer-related diagnosis, or mental diagnosis. Using a predictive model including disease-related and socio-demographic factors, 67% of the women could be correctly classified into having or not having a new SA spell, indicating that it ≥730 days after T 0 27 (0.9) 18 15 67 The included individuals were 3015 women < 65 years related to date of a first breast cancer diagnosis in 2010 (T0), during the following 3 years; all SA and diagnosis-specific SA (cancer, mental, or others) a Women already (nearly) full-time (75-100%) SA or disability pension (DP) at T 0 were not included b ICD-codes: C00-D48, Z80, Z85, N61-N63 c Nine of these women were granted DP during follow-up

Strengths and limitations
The data from the entire population of Sweden provided us with a rare opportunity to study SA and DP in connection with BC diagnosis in all women of working age. Other strengths are the longitudinal cohort design, that all women fulfilling the inclusion criteria of a first BC diagnosis in a whole country could be included, not a sample; also that extensive microdata on morbidity and sociodemographic variables from several high-quality registers could be linked at individual level [41,53,54]; and that data were not self-reported, avoiding recall bias. The large cohort also allowed sub-group analyses of specific SA/DP diagnoses, not only the BC diagnosis. The latter circumstance makes the results and model more useful in practice. High female employment frequency, complete coverage of the public SA/DP insurances, and no dropouts make the internal validity of the study very strong. A further strength is that we were able to exclude women when they during follow-up, due to death, turning 65, or emigration no longer were at risk of the outcome SA/DP. Findings can be generalized to women with BC in countries with comparable employment frequencies and coverage of SA/DP benefits. Another strength was the use of several different measures of SA and DP, which provided a wide picture of the complex data that SA and DP data provide, e.g., regarding skewed distribution, regarding occurrence of spells and durations of spells and time between spells, different diagnoses and seriousness [55][56][57]. Regarding the predictive model, we found that the specified interactions did not improve the predictive performance of the model. While it is possible that other interactions between included variables exists, we expect limited gains in terms of predictive power from the inclusion of more interactions, as well as a risk for overfitting. The aim here was to explore if predictions could be possible, which we found. Future studies need to further develop such analyses, both regarding this outcome and others, e.g., durations of SA spells.
The validity of SA and DP diagnoses is sometimes discussed but seldom investigated. To the best of our knowledge, there is only one such study, regarding SA diagnoses, [43] and that study found the validity to be acceptable. The validity of DP diagnoses is likely to be even higher, since DP is only granted after a long process of medical evaluation [42]. However, the stigma associated with mental diagnoses [58] might imply an underestimation of SA/DP due to such diagnoses. Other limitations of our study are that we had no information on SA spells ≤14 days and only information about the first and main SA diagnosis of a SA spell. Further, we did not have information on cancer treatment, which is a factor that might attenuate the association between cancer stage and SA [14,15]. Previous studies have, e.g., shown that chemotherapy is associated with higher levels of SA/DP [15,18].

Discussion of results
We were able to replicate previous findings that the prevalence of SA was considerably higher in the year post-BC diagnosis than before diagnosis, using a population-based nationwide cohort [13,14]. In a previous Swedish population-based study of all women aged 20-65 with a first BC diagnosis in 2005, [13] almost the same proportion of women as here presented (71% vs. 72%) had some SA during the first 12 months following BC diagnosis. In the cohort from 2005, however, a larger proportion of women, i.e., 19%, had SA already in the year before BC diagnosis, compared to 11% in our 2010 cohort. Also, proportions on DP were slightly higher in the pre-diagnostic year (Y − 1 ) in the 2005 cohort compared to the current cohort, 20.6% vs. 17.5%. In the following 2 years, the decline in SA was somewhat faster in our 2010 cohort. This difference might imply an impact of the stricter Swedish SA/DP regulations implemented in 2008 [59,60]. However, the hypothesis should be studied further using other study designs.
The higher prevalence of SA after BC diagnosis, compared to the pre-diagnostic period, was due to cancer only, not due to mental nor to other somatic diagnoses in neither our cohort nor the 2005 cohort used in the previous Swedish study from our group, [13] i.e., SA due to mental diagnoses did not increase after the BC diagnosis. This is noteworthy, as studies have reported higher risks of anxiety and depression after BC diagnosis [35,36]. One possible explanation is that mental disorders in women with BC are not recognized by sickness certifying physicians [61]. Another explanation is that such mental disorders did not reduce work capacity to such a high level that SA was required or that the women, if needed, soon had adequate treatment for mental disordersmore knowledge is needed on this. It is also possible that mental diagnoses was stated as a secondary SA diagnosis or becoming a main SA diagnosis later during the SA spell [62] and thus not captured by our data. Regarding the predictive model, our ROC.AUC of 0.71 is considered below recommended levels for clinical use [38,63]. Nevertheless, the results from the model are promising regarding the possibility to further develop a predictive model. It also can be used to inform patients, healthcare staff, and other stakeholders that all women diagnosed with BC do not require SA very soon.
Our results highlight the importance of communicating to women with BC as well as to employers of the fact that most women with BC return to work rather quickly, in order to promote optimal work adjustments as soon as possible, especially for groups with an elevated risk of SA/DP.

Conclusions
In this population-based prospective cohort study we found that although BC and BC treatment can have large impacts on work capacity, not all women diagnosed with BC had extensive SA/DP even in the first 12 months after diagnosis. Moreover, it is possible to give a good prediction of which women with BC who are at high risk of new SA. Our predictive model should be further developed to assist the RTW measures for people with cancer diagnosis in the future.

Data permission
The data used in this study is administered by the Division of Insurance Medicine, Karolinska Institutet. These data cannot be made available publically due to privacy regulations. Specifically, according to the General Data Protection Regulation, the Swedish law SFS 2018:218, the Swedish Data Protection Act, the Swedish Ethical Review Act, and the Public Access to Information and Secrecy Act, these type of sensitive data can only be made available for specific purposes, including research that meets the criteria as determined by a legal review. The Ethical Review Board and the datakeeping authorities have made these sensitive personal microdata available for the project with the strict notion that only researchers of the project can work with them. Readers may contact Professor Kristina Alexanderson (kristina.alexanderson@ki.se) regarding the data administrated by the Division of Insurance Medicine, Karolinska Institutet, included analyses conducted for this study.

Authors' contributions
Contribution statement: KA, PK, EM-R, and EF were responsible for the study concept and design. KA obtained the research funding and the database. PF conducted the data management and analysis, aided by MB. GA conducted the reanalyses, e.g., regarding the prediction model, informed by PF and MB. PK outlined the first versions of the results and manuscript, thereafter, LC finalized the results and manuscript, and was responsible for manuscript submission. All authors (KA, PK, LC, EM-R, MB, PF, GA, and EF) were involved in result interpretation and manuscript revisions. All authors had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. The authors read and approved the final manuscript.

Funding
This work was financially supported by the Swedish Research Council for Health, Working Life and Welfare and the Swedish Social Insurance Agency. The funders had no role in the study design, obtaining data, analyses, interpretation of data nor in writing the manuscript. Open Access funding provided by Karolinska Institutet.