Abstract

BackgroundHypothyroidism may occur as a late effect of breast cancer-directed treatment, particularly after radiotherapy, but little is known whether hypothyroidism affects the prognosis after breast cancer. We investigated the association between hypothyroidism and breast cancer recurrence, and all-cause mortality.MethodsIn this population-based cohort study, we used national medical registries to identify all Danish women 35 years or older diagnosed with stage I–III, operable breast cancer between 1996 and 2009. Hypothyroidism was defined as hospital diagnoses ascertained via diagnostic codes, or as prescriptions for levothyroxine. Two analytic models were used: (i) hypothyroidism present at the time of the breast cancer diagnosis (prevalent) and (ii) hypothyroidism diagnosed during follow-up as a time-varying exposure lagged by 1 year (incident). Breast cancer recurrence was defined as any local, regional, or distant recurrence or contralateral breast cancer. All-cause mortality included death from any cause in any setting. We used Cox regression models accounting for competing risks to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer recurrence and all-cause mortality.ResultsThe study cohort included 35,463 women with breast cancer with 212,641 person-years of follow-up. At diagnosis, 1272 women had hypothyroidism and 859 women developed hypothyroidism during follow-up. In total, 5810 patients developed recurrent breast cancer. Neither prevalent nor incident hypothyroidism was associated with breast cancer recurrence (adjusted HRprevalent 1.01, 95% CI 0.87–1.19; adjusted HRincident 0.93, 95% CI 0.75–1.16, respectively). Furthermore, no differences were seen for all-cause mortality for prevalent or incident hypothyroidism (adjusted HRprevalent 1.02, 95% CI 0.92–1.14, and HRincident 1.08, 95% CI 0.95–1.23, respectively). Stratification by menopausal status, oestrogen receptor status, chemotherapy, or radiotherapy did not alter the estimates.ConclusionsHypothyroidism present at diagnosis or during follow-up was not associated with breast cancer recurrence or all-cause mortality in women with breast cancer. Our findings provide reassurance to patients and their physicians that hypothyroidism is unlikely to impact on the clinical course of breast cancer or survival.

Highlights

  • Hypothyroidism may occur as a late effect of breast cancer-directed treatment, after radiotherapy, but little is known whether hypothyroidism affects the prognosis after breast cancer

  • We investigated potential effect measure modification stratifying by menopausal status, chemotherapy, and endocrine therapy (ET)/Oestrogen receptor (ER) use and for the incident model stratifying by radiotherapy

  • In the Danish Breast Cancer Group (DBCG) registry, 38,442 Danish women ≥ 35 years were diagnosed with non-metastatic breast cancer between 1996 and 2009

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Summary

Introduction

Hypothyroidism may occur as a late effect of breast cancer-directed treatment, after radiotherapy, but little is known whether hypothyroidism affects the prognosis after breast cancer. Over the last 25 years, mortality has decreased by 36% leading to an increased number of breast cancer survivors [1]. This considerable decline is likely attributable to advances in mammographic screening and improved surgical, radiation, and adjuvant therapies [2]. Hypothyroidism is diagnosed in about 3% of the population, more frequently in women, and risk increases with age; some breast cancer patients develop hypothyroidism long before their breast cancer is diagnosed [4]

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