Associations between breast cancer survivorship and adverse mental health outcomes: A matched population-based cohort study in the United Kingdom

Abstract

Background: Breast cancer is the most common cancer diagnosed in women globally, and 5-year net survival probabilities in high-income countries are generally >80%. A cancer diagnosis and treatment are often traumatic events, and many women struggle to cope during this period. Less is known, however, about the long-term mental health impact of the disease, despite many women living several years beyond their breast cancer and mental health being a major source of disability in modern societies. The objective of this study was to quantify the risk of several adverse mental health-related outcomes in women with a history of breast cancer followed in primary care in the United Kingdom National Health Service, compared to similar women who never had cancer.

Methods and findings: We conducted a matched cohort study using data routinely collected in primary care across the UK to quantify associations between breast cancer history and depression, anxiety, and other mental health-related outcomes. All women with incident breast cancer in the Clinical Practice Research Datalink (CPRD) GOLD primary care database between 1988 and 2018 (N = 57,571, mean = 62 ± 14 years) were matched 1:4 to women with no prior cancer (N = 230,067) based on age, primary care practice, and eligibility of the data for linkage to hospital data sources. Cox models were used to estimate associations between breast cancer survivorship and each mental health-related outcome, further adjusting for diabetes, body mass index (BMI), and smoking and drinking status at baseline. Breast cancer survivorship was positively associated with anxiety (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI): 1.29-1.36; p < 0.001), depression (1.35; 1.32-1.38; p < 0.001), sexual dysfunction (1.27; 1.17-1.38; p < 0.001), and sleep disorder (1.68; 1.63-1.73; p < 0.001), but not with cognitive dysfunction (1.00; 0.97-1.04; p = 0.88). Positive associations were also found for fatigue (HR = 1.28; 1.25-1.31; p < 0.001), pain (1.22; 1.20-1.24; p < 0.001), receipt of opioid analgesics (1.86; 1.83-1.90; p < 0.001), and fatal and nonfatal self-harm (1.15; 0.97-1.36; p = 0.11), but CI was wide, and the relationship was not statistically significant for the latter. HRs for anxiety and depression decreased over time (p-interaction <0.001), but increased risks persisted for 2 and 4 years, respectively, after cancer diagnosis. Increased levels of pain and sleep disorder persisted for 10 years. Younger age was associated with larger HRs for depression, cognitive dysfunction, pain, opioid analgesics use, and sleep disorders (p-interaction <0.001 in each case). Limitations of the study include the potential for residual confounding by lifestyle factors and detection bias due to cancer survivors having greater healthcare contact.

Conclusions: In this study, we observed that compared to women with no prior cancer, breast cancer survivors had higher risk of anxiety, depression, sleep problems, sexual dysfunction, fatigue, receipt of opioid analgesics, and pain. Relative risks estimates tended to decrease over time, but anxiety and depression were significantly increased for 2 and 4 years after breast cancer diagnosis, respectively, while associations for fatigue, pain, and sleep disorders were elevated for at least 5-10 years after diagnosis. Early diagnosis and increased awareness among patients, healthcare professionals, and policy makers are likely to be important to mitigate the impacts of these raised risks.

Fig 1. Flowchart of the selection of the cohorts used in analyses.

CPRD, Clinical Practice Research Datalink; EHR, electronic health record. *Women with research quality follow-up, as defined by CPRD based on systematic checks for data quality at both patient and practice level. ^†Almost all had a first record of breast cancer a few days after the recorded date of death.

Fig 2. Incidence of adverse mental health outcomes, fatigue, and pain in breast cancer survivors and in women who did not have cancer.

Full red line: breast cancer survivors; dashed blue line: women who never had cancer. *Please note the different scale used in this graph.

Fig 3. Forest plots of the association between breast cancer survivorship and adverse mental health outcomes, fatigue, and pain, stratified by potential effect modifiers.

95% CI, 95% confidence interval; HR, hazard ratio; IMD, Index of Multiple Deprivation.

Fig 4. Results of sensitivity analyses.

Note: Read codes for very specific diagnoses are provided in S1 Codelists. For anxiety, these included, for example, generalised anxiety disorder and panic, and for depression, major depressive disorder. 95% CI, 95% confidence interval; CPRD, Clinical Practice Research Datalink; HES, Hospital Episodes Statistics; HR, hazard ratio; IMD, Index of Multiple Deprivation.