Incidence of hypothyroidism after treatment for breast cancer—a Danish matched cohort study

Abstract

Background 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. Methods Using 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. Results We 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]. Conclusions BCS 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.

Incidence of hypothyroidism after treatment for breast cancer: A Korean population-based study

“…In the subgroup analysis of patients who underwent mastectomy, the adjusted HR was 1.267 (95% CI, 0.991–1.620; p = 0.059). We confirmed that the cumulative incidence and relative effect estimates in Korean patients with breast cancer were similar to those observed in previous studies [ 9 , 12 – 14 ].…”

“…Among the cancer treatments, RT to regional lymph nodes and chemotherapy showed the highest risks, with an HR of 1.74 (95% CI 1.50–2.02). In analyses restricted to the breast cancer cohort alone, nodal RT with or without chemotherapy was associated with an elevated risk of hypothyroidism compared to not receiving these therapies [ 12 ]. In a Canadian database study, changes in comorbidities before and after treatment were investigated in patients who received breast cancer treatment between 2005 and 2009, and this was compared with the matched cohort.…”

“…However, the contributions of other treatment modalities remain unclear. A few studies have evaluated the synergistic effects of chemotherapy, with conflicting results [ 12 , 17 , 18 ]. The possibility of an earlier diagnosis owing to frequent regular contact with healthcare services or symptoms of hormone therapies cannot be eliminated.…”

The effect of the polycystic ovary syndrome and hypothyroidism on the risk of fibrocystic breast changes: a meta-analysis

“…After a mean period of 3.4 years, 859 patients (2%) out of 34,191 ones with healthy thyroid developed hypothyroidism. Nevertheless, no significant relationship was reported between hypothyroidism and the fibrocystic breast disease (either at the time of diagnosis or during follow-up of patients) [ 39 ]. Anil et al designed a case–control study to evaluate the prevalence of benign breast diseases in patients with thyroid disorders.…”

An Underestimated Toxicity Radiation-Induced Hypothyroidism in Patients Multimodally Treated for Breast Cancer

“…The 5-year cumulative incidence of hypothyroidism in breast cancer patients was significantly higher than that reported in the control group (1.8% vs. 1.6%). The study also shows an increased rate of hypothyroidism in patients receiving radiotherapy and chemotherapy compared to those who received surgery alone, mentioning the combination of chemotherapy and radiation therapy on the lymph nodes as factors that need to be known as risk factors for hypothyroidism [ 60 ]. The Dutch Society of Radiation Oncology breast cancer platform proposed establishing a consensus for the delimitation of target volumes and OARs based on cases proposed for planning in 19 main radiotherapy centers.…”