Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis

Solmunde, Elisabeth; Falstie-Jensen, Anne Mette; Lorenzen, Ebbe Laugaard; Ewertz, Marianne; Reinertsen, Kristin V.; Dekkers, Olaf M.; Cronin‐Fenton, Deirdre

doi:10.1016/j.breast.2023.02.008

Cited by 9 publications

(5 citation statements)

References 53 publications

(189 reference statements)

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“…The pathophysiological mechanism of this association, through direct thyroid cell injury or indirect due to damage in small thyroid vessels, has been described [ 20 ] and is further supported by dosimetric data showing higher mean radiation dose to the thyroid gland in patients treated with radiotherapy including regional lymph nodes compared to patients with radiotherapy only to breast / chest wall [ 19 ] and a dose-dependent association between dose to the thyroid gland and decreased thyroid volume [ 11 ]. The present study strengthens the current evidence by overcoming some of the main limitations of previous studies [ 21 ]. First, previous studies included a relatively small sample size [ 7 , 22 , 23 ], thus reducing their validity to provide reliable results on potential associations.…”

Section: Discussionsupporting

confidence: 88%

Incidence and risk factors of hypothyroidism after treatment for early breast cancer: a population-based cohort study

Digkas,

Smith,

Wennstig

et al. 2023

Breast Cancer Res Treat

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Purpose An increased incidence of hypothyroidism among breast cancer survivors has been observed in earlier studies. The impact of the postoperative treatment modalities and their potential interplay on hypothyroidism development needs to be studied. Methods We conducted a population- and registry-based study using the Breast Cancer Data Base Sweden (BCBaSe) including females diagnosed with breast cancer between 2006 and 2012. In total, 21,268 female patients diagnosed with early breast cancer between 2006 and 2012, with no previous prescription of thyroid hormones and no malignant diagnosis during the last ten years before breast cancer diagnosis, were included in the final analysis. Results During the follow-up (median follow-up time 7.9 years), 1212 patients (5.7%) developed hypothyroidism at a median time of 3.45 years from the index date. No association of the systemic oncological treatment in terms of either chemotherapy or endocrine therapy and hypothyroidism development could be identified. A higher risk (HR 1.68;95% CI 1.42–1.99) of hypothyroidism identified among patients treated with radiation treatment of the regional lymph nodes whereas no increased risk in patients treated only with radiation therapy to the breast/chest wall was found (HR 1.01; 95% CI 0.86–1.19). The risk of hypothyroidism in the cohort treated with radiotherapy of the regional lymph nodes was present irrespective of the use of adjuvant chemotherapy treatment. Conclusions Based on the results of our study, the implementation of hypothyroidism surveillance among the breast cancer survivors treated with radiotherapy of the regional lymph nodes can be considered as reasonable in the follow-up program.

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Section: Discussionsupporting

confidence: 88%

Incidence and risk factors of hypothyroidism after treatment for early breast cancer: a population-based cohort study

Digkas,

Smith,

Wennstig

et al. 2023

Breast Cancer Res Treat

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“…Most studies reported that hypothyroidism events occurred within 5 years, with a median clinical latency of 8–27 months; however, they can occur even after this period. Specifically, irradiation to the supraclavicular field was associated with an increased risk of hypothyroidism compared with radiation to the breast and chest wall only [17] , [19] , [21] , [34] , with a pooled relative risk of 69 %, according to a recent meta -analysis [35] . Additionally, radiation-induced thyroid volume reduction [36] , [37] , [38] or a smaller thyroid volume was associated with a higher incidence of radiation-induced hypothyroidism [23] .…”

Section: Discussionmentioning

confidence: 99%

Normal tissue complication probability models of hypothyroidism after radiotherapy for breast cancer

Park,

Cho,

Chang

et al. 2024

Clinical and Translational Radiation Oncology

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“…Previous studies have supported the association of cancer incidence with hypothyroidism risk. However, these results are inconsistent [41]: Breast cancer and radiation therapy to the supraclavicular lymph nodes are linked to hypothyroidism risk [42]. Elevated TSH, increased reactive oxygen species production, and mutation/polymorphisms of genes have been involved in increased cancer risk or pro-tumoral cell behavior [43].…”

Section: Discussionmentioning

confidence: 99%

Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study

Kim,

Park

2023

Nutrients

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Hypothyroidism is a prevalent endocrine disorder and is associated with a variety of metabolic disturbances. This study aimed to investigate the polygenic variants associated with hypothyroidism risk and the interaction of polygenic risk scores (PRS) with dietary patterns in influencing disease risk in 56,664 participants aged >40 in a hospital-based cohort. The participants were classified as having hypothyroidism (n = 870) diagnosed by a physician and no hypothyroidism (n = 55,794). Genetic variants associated with hypothyroidism were identified using a genome-wide association study (GWAS). Genetic variants interacting with each other were selected using a generalized multifactor dimensionality reduction analysis, and the PRS generated was evaluated for interaction with lifestyle parameters. Coffee, alcohol, meat intake, and a Korean balanced diet were inversely associated with hypothyroidism risk, as were selenium, copper, and manganese intakes. White blood cell (WBC) counts and serum alkaline phosphatase and triglyceride concentrations were positively associated with hypothyroidism risk, as were osteoporosis and thyroid cancer. The GMDR analysis generated a three-single nucleotide polymorphism (SNP) model comprising dual oxidase-1 (DUOX1)_rs1648314; thyroid-stimulating hormone receptor (TSHR)_rs75664963; and major histocompatibility complex, class-II, DQ Alpha-1 (HLA-DQA1)_rs17426593. The PRS derived from the three- and seven-SNP models were associated with a 2.11- and 2.32-fold increase in hypothyroidism risk, respectively. Furthermore, the PRS from the three-SNP model showed interactions with WBC counts, wherein the positive association with hypothyroidism risk was more pronounced in participants with low WBC counts than those with high WBC counts (≥4 × 109 /L). Dietary patterns, such as the plant-based diet (PBD) and the Western-style diet (WSD), along with smoking status, exhibited interactions with the PRS, influencing hypothyroidism risk. In participants with a high PRS, those in the high-PBD, low-WSD, and smoker groups had a higher proportion of hypothyroidism than those in the low-PBD, high-WSD, and non-smoker groups. In conclusion, genetic variants related to immunity and thyroid hormone secretion were linked to hypothyroidism risk, and their PRS interacted with PBD and WSD intake and smoking status. These results contribute to a better understanding of hypothyroidism and its prevention strategies for precision medicine intervention.

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Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis

Cited by 9 publications

References 53 publications

Incidence and risk factors of hypothyroidism after treatment for early breast cancer: a population-based cohort study

Incidence and risk factors of hypothyroidism after treatment for early breast cancer: a population-based cohort study

Normal tissue complication probability models of hypothyroidism after radiotherapy for breast cancer

Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study

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