Hypothyroidism and the risk of breast cancer recurrence and all-cause mortality - a Danish population-based study

Anne Mette Falstie-JensenEmail author View ORCID ID profile,
Anders Kjærsgaard,
Ebbe Laugaard Lorenzen,
Jeanette Dupont Jensen,
Kristin Valborg Reinertsen,
Olaf M. Dekkers,
Marianne Ewertz and
Deirdre P. Cronin-Fenton

Breast Cancer Research201921:44

https://doi.org/10.1186/s13058-019-1122-3

Received: 25 June 2018
Accepted: 14 February 2019
Published: 22 March 2019

Abstract

Background

Hypothyroidism 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.

Methods

In 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.

Results

The 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.

Conclusions

Hypothyroidism 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.