Abstract
BackgroundBreast cancer survivors (BCS) may have increased risk of hypothyroidism, but risk according to treatment modality is unclear. We estimated the incidence of hypothyroidism in women with breast cancer, and according to cancer treatment.MethodsUsing nationwide registries, we identified all Danish women aged ≥ 35 years diagnosed with non-metastatic breast cancer (1996–2009). We matched up to five cancer-free women (controls) for each BCS. We excluded women with prevalent thyroid disease. Cancer treatment was chemotherapy with or without radiotherapy (RT) targeting the breast/chest wall only, or also the lymph nodes (RTn). We identified hypothyroidism using diagnostic codes, and/or levothyroxine prescriptions. We calculated the cumulative incidence, incidence rates (IR) per 1000 person-years, and used Cox regression to estimate hazard ratios (HR) and associated 95% confidence intervals (CIs) of hypothyroidism, adjusting for comorbidities.ResultsWe included 44,574 BCS and 203,306 matched controls with 2,631,488 person-years of follow-up. BCS had a slightly higher incidence of hypothyroidism than controls [5-year cumulative incidence, 1.8% (95%CI = 1.7–1.9) and 1.6% (95%CI = 1.5–1.6), respectively]. The overall IR was 4.45 (95%CI = 4.25–4.67) and 3.81 (95%CI = 3.73–3.90), corresponding to an adjusted HR = 1.17 (95%CI = 1.11–1.24). BCS who received RTn with chemotherapy (HR = 1.74, 95%CI = 1.50–2.02) or without chemotherapy (HR = 1.31, 95%CI = 1.14–1.51) had an elevated risk of hypothyroidism compared with matched controls and compared with BCS who underwent surgery alone [HR = 1.71, 95%CI = 1.45–2.01 and HR = 1.36, 95%CI = 1.17–1.58, respectively].ConclusionsBCS have an excess risk of hypothyroidism compared with age-matched controls. BCS and those working in cancer survivorship settings ought to be aware that this risk is highest in women treated with radiation therapy to the lymph nodes and chemotherapy.
Highlights
Breast cancer survivors (BCS) may have increased risk of hypothyroidism, but risk according to treatment modality is unclear
Our large prospective study suggests that women with breast cancer had a long-term elevated risk of hypothyroidism compared with matched cancer-free women from the general population
The risk of hypothyroidism was highest in breast cancer survivors treated with RT targeting the lymph nodes, especially among those who received chemotherapy
Summary
Breast cancer survivors (BCS) may have increased risk of hypothyroidism, but risk according to treatment modality is unclear. We estimated the incidence of hypothyroidism in women with breast cancer, and according to cancer treatment. Over the past 30 years, breast cancer survival has improved substantially due to earlier detection and improved adjuvant therapies [1]. Almost 90% of patients with early-stage breast cancer receive (neo) adjuvant treatment; 10-year life expectancy after diagnosis is about 75% [2]. It is critical to identify harmful late effects of cancer treatment, such as hypothyroidism. The prevalence of hypothyroidism is higher in women and risk increases with age [3]. Hypothyroidism has a substantial negative impact on patient wellbeing and is associated with symptoms like tiredness, weakness, weight gain, and mental changes [4].
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