Disease trajectories and mortality among women diagnosed with breast cancer

Abstract

Purpose: Breast cancer is a common disease with a relatively good prognosis. Therefore, understanding the spectrum of diseases and mortality among breast cancer patients is important, though currently incomplete. We systematically examined the incidence and mortality of all diseases following a breast cancer diagnosis, as well as the sequential association of disease occurrences (trajectories).

Methods: In this national cohort study, 57,501 breast cancer patients (2001-2011) were compared to 564,703 matched women from the general Swedish population and followed until 2012. The matching criteria included year of birth, county of residence, and socioeconomic status. Based on information from the Swedish Patient and Cause of Death Registries, hazard ratios (HR) were estimated for disease incidence and mortality. Conditional logistic regression models were used to identify disease trajectories among breast cancer patients.

Results: Among 225 diseases, 45 had HRs > 1.5 and p < 0.0002 when comparing breast cancer patients with the general population. Diseases with highest HRs included lymphedema, radiodermatitis, and neutropenia, which are side effects of surgery, radiotherapy, and chemotherapy. Other than breast cancer, the only significantly increased cause of death was other solid cancers (HR = 1.16, 95% CI = 1.08-1.24). Two main groups of disease trajectories were identified, which suggest menopausal disorders as indicators for other solid cancers, and both neutropenia and dorsalgia as diseases and symptoms preceding death due to breast cancer.

Conclusions: While an increased incidence of other diseases was found among breast cancer patients, increased mortality was only due to other solid cancers. Preventing death due to breast cancer should be a priority to prolong life in breast cancer patients, but closer surveillance of other solid cancers is also needed.

Keywords: Breast cancer; Disease trajectory; Mortality.

Fig. 1

Significant hazard ratios (HRs) of diseases among breast cancer patients, compared to matched individuals (N = 622,204). All risk increases are statistically significant after considering the issue of multiple testing (p < 0.00022). The Y-axis shows the hazard ratio (on the log scale) of the disease in breast cancer patients, compared to healthy women who were matched on year of birth, county of residence, and socioeconomic status. The X-axis shows the disease categories according to ICD codes A-N. For example, lymphedema is classified under the disease category “circulatory system disease” (ICD-10 code I97). Breast cancer patients had a 56-fold increased risk of lymphedema, compared to matched healthy women. Details of the number of cases, hazard ratios, and confidence intervals are listed in Additional file 1: Table S1

Fig. 2

Overall trajectories of other diseases among breast cancer patients. This figure illustrates an overview of disease trajectories identified in our analysis. The combined ICD-10 codes for the diseases are shown within the circle. The color of the circle represents the hazard ratio of this disease among the breast cancer patients, compared to matched individuals. The width of the arrow connecting two circles corresponds to the number of breast cancer patients with this disease trajectory. The color of the arrows indicates the odds ratio of the sequential association between the two diseases. The strongest association in this figure is C00 → K56, suggesting a 15 times increased risk of ileus after other cancer diagnosis, with 83 patients in the cohort experiencing this trajectory. Trajectories starting with M15 and M20 were not included, given their low HR (HR ≤ 1.1) and that they were probably the result of surveillance bias

Fig. 3

Disease trajectories leading to mortality among breast cancer patients. This figure shows the identified disease trajectories leading to breast cancer and other cancer mortality in our cohort. For each pair of the trajectory, the codes in the circle are the combined ICD-10 codes for the diseases. The color in the circle represents the hazard ratio of this disease among the breast cancer patients, compared to the matched individuals. The squares of a BCM and b OCM are breast cancer mortality and other cancer mortality. The width of the arrows between two circles (or square) corresponds with the number of breast cancer patients who had been first diagnosed with one disease and thereafter another. The color of the arrows indicates the odds ratio of the sequential association between the two diseases (or disease to mortality). In this figure, other solid cancer was associated with 72 times increased risk of other cancer mortality and 63 patients in the cohort had experienced the trajectory from menopausal disorder to other cancer mortality (N95 → C00 → OCM)