Risk of type 2 diabetes after breast cancer treatment: a population-based cohort study in Denmark

Abstract

Purpose: Data on type 2 diabetes (T2D) risk after breast cancer (BC) could guide preventive strategies. Yet, studies had limitations regarding sample size, follow-up, and contemporary treatments. We evaluated the risk of T2D after BC overall, by cancer treatment, and compared with a matched cohort of cancer-free women.

Methods: We assembled a population-based cohort of early-stage BC patients aged 30 years or more diagnosed during 1996-2021 in Denmark. We created a comparison cohort of 5 cancer- and T2D-free women for each BC patient, matched 6 months after BC diagnosis date on age and region. We followed both cohorts until T2D diagnosis, emigration, death, or December 31, 2022. We computed 5-year cumulative incidences and used Cox models to calculate time-varying adjusted hazard ratios (aHR) of T2D.

Results: Among 74 526 BC survivors and 372 630 matched cancer-free women, 5-year cumulative incidences of T2D were 3.8% (95% confidence interval [CI] = 3.7 to 3.9) and 3.3% (95% CI = 3.3 to 3.4), respectively. The aHR of T2D was elevated but attenuated over follow-up (aHR5-years = 1.20, 95% CI = 1.15 to 1.25, and aHR15-years = 1.09, 95% CI = 1.05 to 1.12). Adjuvant endocrine therapy (aHR = 1.14; 95% CI = 1.10 to 1.19), aromatase inhibitors (aHR = 1.25; 95% CI = 1.18 to 1.32), and less so tamoxifen (aHR = 1.05; 95% CI = 0.99 to 1.11), were associated with elevated risk of T2D in women with BC vs cancer-free women. Among BC patients, chemotherapy (aHR = 1.10, 95% CI = 1.03 to 1.17) and radiation therapy (right-sided aHR = 1.18, 95% CI = 1.09 to 1.27 and left-sided aHR = 1.24, 95CI = 1.15 to 1.33) were associated with increased T2D risk.

Conclusion: BC was associated with excess risk of T2D, although of lower magnitude than previously reported. The excess risk was temporary and related to BC treatment but could also be influenced by obesity and heightened T2D diagnostic activity.

Figure 1.

Cumulative incidence for type 2 diabetes in Danish women diagnosed with early-stage breast cancer during 1996-2021 and a matched comparison cohort of cancer-free women. Time zero defined as 6 months after the breast cancer diagnosis.

Figure 2.

Time trends of hazard ratios for type 2 diabetes among women diagnosed with early-stage breast cancer during 1996-2021 vs matched cancer-free women. *Adjusted for age, region of residence, comorbidity, and marital status. Abbreviations: HR = hazard ratio; CI = confidence interval; T2D = type 2 diabetes.

Figure 3.

Incidence rates and hazard ratios for type 2 diabetes among women diagnosed with early-stage breast cancer during 1996-2021 vs matched cancer-free women, according to intention-to-treat cancer-directed treatments. ^aAdjusted for age, region of residence, comorbidity, and marital status. ^bSystematic recording of HER2 status was available only after 2005. Abbreviations: CI = confidence interval; HER2 = human epidermal growth factor receptor 2; HR = hazard ratio; IR = incidence rate; PY = person-years; T2D = type 2 diabetes.

Figure 4.

Incidence rates and hazard ratios for type 2 diabetes among women diagnosed with early-stage breast cancer during 1996-2021, according to intention-to-treat cancer-directed treatments (among women with breast cancer only). ^aAdjusted for age, region of residence, comorbidity, and marital status. ^bSystematic recording of HER2 status was available only after 2005. Abbreviations: CI = confidence interval; HER2 = human epidermal growth factor receptor 2; HR = hazard ratio; IR = incidence rate; PY = person-years; T2D = type 2 diabetes.