Association between Benign Thyroid Disorders and Breast Cancer Risk in Korean Women

Boyoung Park; Thi Xuan Mai Tran

doi:10.4143/crt.2024.787

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Original Article Breast cancer Association between Benign Thyroid Disorders and Breast Cancer Risk in Korean Women: Boyoung Park^1,2, Thi Xuan Mai Tran^1,3; Cancer Research and Treatment : Official Journal of Korean Cancer Association 2026;58(1):141-150.
DOI: https://doi.org/10.4143/crt.2024.787
Published online: February 26, 2025

¹Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, Korea

²Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea

³Institute for Health and Society, Hanyang University, Seoul, Korea

Correspondence: Thi Xuan Mai Tran, Department of Preventive Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea
Tel: 82-2-2220-0682 E-mail: maitran@hanyang.ac.kr

• Received: August 16, 2024 • Accepted: February 25, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract

Purpose
This study aimed to investigate the potential association between thyroid disorders and breast cancer (BC) risk in a cohort of Korean women.
Materials and Methods
Data for this retrospective cohort study were obtained from the Korean National Health Insurance database, including all women aged ≥ 40 who underwent BC screening from 2009 to 2010 in Korea. Thyroid disorders were identified using medical records from 2009 to 2010 and extracted using the International Classification of Diseases, 10th revision (ICD-10) codes for thyroid nodules, hypothyroidism, and hyperthyroidism. BC cases were defined using the ICD-10 codes and tracked until December 2021. A Cox regression model was used to evaluate the association between thyroid disorders and the risk of BC. Additionally, we evaluated the association between well-known risk factors of BC and thyroid disorders using logistic regression analysis.
Results
Among 5,051,633 women, the mean±standard deviation age was 55.2±10.7 years, and the median follow-up was 11.6 years, with 87,784 BC cases recorded. The proportions of patients with thyroid nodules, hypothyroidism, and hyperthyroidism were 2.5%, 1.8%, and 0.9%, respectively. The hazard ratio for BC risk associated with thyroid nodules was 1.16 (95% confidence interval [CI], 1.11 to 1.20), for hypothyroidism was 0.98 (95% CI, 0.93 to 1.03), and for hyperthyroidism was 1.13 (95% CI, 1.06 to 1.21). In both premenopausal and postmenopausal women, an increased risk of BC was significantly associated with thyroid nodules (adjusted hazard ratio [aHR], 1.16 and 1.13) and hyperthyroidism (aHR, 1.11 and 1.16). History of benign breast disease, oral contraceptive use, breastfeeding, menopausal status, and hormone replacement therapy were associated with thyroid nodules and hyperthyroidism.
Conclusion
Our findings suggest an increased risk of BC in women with a history of thyroid nodules and hyperthyroidism, whereas no such association was found in women with hypothyroidism.
Key words: Thyroid nodule, Hyperthyroidism, Hypothyroidism, Breast neoplasms, Cancer prevention

Introduction

Most breast cancer (BC) cases are related to estrogen, and high levels of thyroid hormones have been found to have estrogen-like effects on breast carcinoma cells in vitro [1,2]. This suggests a potential link between thyroid hormones and BC development via binding to estrogen receptors [1,2]. Despite substantial evidence linking thyroid cancer and BC, not only for associations between the two diseases [3] but also for shared reproductive or hormonal risk factors [4], evidence from previous studies on the associations between thyroid disorders and BC risk has been inconsistent. For instance, Chen et al. [5] found that hyperthyroidism was significantly associated with an increased risk of BC, whereas hypothyroidism was associated with a reduced risk. Conversely, an updated meta-analysis by Han et al. [6] reported no significant association among hyperthyroidism, hypothyroidism, and BC risk. However, an increased risk of BC was observed in women with autoimmune thyroiditis, goiter, and Graves’ disease.

Overall, previous studies have provided mixed evidence on the association between thyroid disorders and the risk of BC. Therefore, this study aimed to estimate the association between thyroid disorders, including thyroid nodules, hypothyroidism, and hyperthyroidism, which are the most prevalent thyroid disorders in Korea [7], and the risk of BC in a large population-based cohort of Korean women. We further assessed the association between conventional BC risk factors, particularly reproductive factors, and thyroid disorders.

Materials and Methods

1. Study design and population

This study used data from the Korean National Cancer Screening Program, which is part of the National Health Insurance Service (NHIS) database [8]. In Korea, the NHIS provides free biennial mammography BC screening for women over 40. The dataset included women who underwent mammography screening between January 1, 2009, and December 31, 2010.

Of the 5,104,109 women who were screened for BC during this period, we excluded those with a history of cancer and those who underwent screening before the age of 40 years. Additionally, participants diagnosed with any cancer and those who died within 180 days of the BC screening date were excluded to prevent the inclusion of prevalent cancer cases at screening. The final analysis included 5,051,633 women (Fig. 1). This study was approved by the Institutional Review Board of Hanyang University College of Medicine (approval No. HYUIRB-202307-023-1). Permission to use the NHIS database was granted by the National Health Insurance Sharing Service system, and de-identified data were provided to the researchers.

2. Measurement of thyroid disorders

The NHIS database includes disease diagnoses based on the International Classification of Diseases 10th version (ICD-10) codes reported by healthcare providers. Three main types of thyroid disorders were included in this study, defined as having at least two hospital visits with the relevant ICD-10 codes as the primary diagnosis within one year from 2009 to 2010, as described in previous studies [7]. Thyroid nodules were identified using ICD-10 codes E04 and D34; hypothyroidism with ICD-10 codes E02, E03, or E06.3; and hyperthyroidism with ICD-10 code E05. Based on these definitions, participants without thyroid disease were considered the control group. Although several previous Korean studies have defined thyroid diseases using diagnostic codes combined with prescriptions for thyroid hormones or antithyroid drugs [7], we could not apply prescription records due to a lack of information. However, our operational definitions showed prevalence rates comparable to those reported by Kwon et al. [7].

3. Ascertainment of incident BC cases

BC cases up to December 2021 were identified using ICD-10 codes for invasive BC (C50.0-C50.9) and ductal carcinoma in situ (DCIS) (D05.0-D05.9). The definition of BC includes both the diagnosis code for invasive BC or DCIS and rare-incurable disease codes used for special insurance reimbursement in Korea [9]. The NHIS implemented this rare-incurable disease system as a special co-payment reduction program to enhance health coverage and alleviate the financial burden on patients with severe and rare diseases.

4. Measurement of other covariates

Information on other covariates was collected using standardized questionnaires distributed during BC screening. The questionnaires completed by the participants gathered data on health behaviors (drinking, smoking, and physical activity), family history of cancer, and reproductive factors. The covariates considered in the analysis included participants’ age at screening, history of benign breast disease, age at menarche, oral contraceptive use, number of children, history of breastfeeding, family history of BC among first-degree relatives, menopausal status, age at menopause, history of hormone replacement therapy, body mass index (BMI), and breast density. Height and weight were measured by trained medical staff, and BMI was calculated as weight (kg) divided by height (m²) and categorized according to the Asia-Pacific classification [10]. BMI groups were underweight (< 18.5 kg/m²), normal weight (18.5-23 kg/m²), overweight (23-27.5 kg/m²), and obese (≥ 27.5 kg/m²). Mammographic breast density was evaluated by trained radiologists using the Breast Imaging Reporting and Data System classification from the American College of Radiology [11], with four categories: (1) almost entirely fat, (2) scattered fibroglandular densities, (3) heterogeneously dense, and (4) extremely dense.

5. Statistical analysis

Descriptive statistics were performed for the total population and stratified according to BC development status. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between thyroid disorders and BC risk, with and without adjustment for the aforementioned covariates. Time-to-event was calculated from the BC screening date to the BC development date. The risk of BC was analyzed separately for each thyroid disorder. Additional analyses stratified by premenopausal and postmenopausal status at BC screening were performed (excluding women with a history of hysterectomy from the stratified analysis).

Using logistic regression, we also assessed the association between conventional BC risk factors and thyroid disorders associated with BC risk. The analysis was conducted separately for each thyroid disorder. Two-sided p-values < 0.05 were considered statistically significant. All the analyses were performed using SAS ver. 9.4 (SAS Institute Inc.). This study adhered to Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

Results

The mean±standard deviation age at the screening of the study population was 55.2±10.7 years (Table 1). The proportion of women diagnosed with thyroid nodules, hypothyroidism, and hyperthyroidism was 2.5%, 1.8%, and 0.9%, respectively. The median follow-up period for the total study population was 11.9 years (interquartile range, 11.3 to 12.4 years). In the total population, 39.4% had a normal BMI (18.5 to < 23), and 6.2% reported a history of benign breast disease.

Thyroid nodules were associated with an increased BC risk, with an adjusted HR (aHR) of 1.16 (95% CI, 1.11 to 1.20) overall, an aHR of 1.13 (95% CI, 1.08 to 1.17) for invasive BC, and 1.38 (95% CI, 1.28 to 1.48) for DCIS cases (Table 2). No significant association was observed between hypothyroidism and BC risk, with an overall aHR of 0.98 (95% CI, 0.93 to 1.03). A significantly increased risk of BC was observed in women with a history of hyperthyroidism, with an aHR of 1.13 (95% CI, 1.06 to 1.21). Similarly, a higher HR was observed for DCIS with an aHR of 1.23 (95% CI, 1.09 to 1.40), while the aHR for invasive BC was 1.12 (95% CI, 1.05 to 1.20).

In the stratified analysis by menopausal status (Table 3), thyroid nodules were associated with increased BC risk in premenopausal and postmenopausal women, with aHRs of 1.16 (95% CI, 1.08 to 1.23) and 1.13 (95% CI, 1.06 to 1.20), respectively. Hyperthyroidism was associated with increased BC risk in postmenopausal women with an aHR of 1.16 (95% CI, 1.05 to 1.29) and in premenopausal women with an aHR of 1.11 (95% CI, 1.002 to 1.23). No association was found between hypothyroidism and the risk of BC in either menopausal group.

Several BC risk factors were significantly associated with thyroid nodules, hyperthyroidism, and an increased risk of BC (Table 4). Women with a history of benign breast disease were more likely to have thyroid nodules and hyperthyroidism, with adjusted odds ratios (aORs) of 1.58 (95% CI, 1.55 to 1.61) and 1.16 (95% CI, 1.12 to 1.21). Oral contraceptive use was associated with thyroid nodules (aOR, 1.02; 95% CI, 1.003 to 1.04) and hyperthyroidism (aOR, 1.06; 95% CI, 1.03 to 1.08). Additionally, there was an increased prevalence of thyroid nodules and hyperthyroidism in women with later menopausal age or longer hormone replacement therapy use after menopause. Breastfeeding (aOR of breastfeeding ≥ one year vs. none: 0.96 [95% CI, 0.94 to 0.98] and 0.92 [95% CI, 0.89 to 0.96]) and premenopausal status (aOR, 0.83 [95% CI, 0.81 to 0.85] and 0.85 [95% CI, 0.82 to 0.89]) were associated with a decreased risk of thyroid nodules and hyperthyroidism.

Other factors associated with an increased likelihood of having thyroid nodules included higher levels of dense breast tissue (category b: 1.15, category c: 1.14, and category d: 1.04, respectively), having two or more children compared to no children (aOR, 1.08 [95% CI, 1.04 to 1.12]), family history of BC (aOR, 1.18 [95% CI, 1.13 to 1.24]), and a history of hysterectomy surgery compared to premenopausal status (aOR, 1.27 [95% CI, 1.14 to 1.41]). Regarding factors associated with hyperthyroidism, women with a higher BMI were less likely to have the disease, with aORs for BMI 23 to < 25 and BMI ≥ 25 of 0.79 (95% CI, 0.78 to 0.81) and 0.91 (95% CI, 0.89 to 0.93), respectively.

Discussion

In this retrospective cohort study, women with a history of thyroid nodules or hyperthyroidism had a significantly higher risk of developing BC. No significant association was observed between hypothyroidism and the risk of BC. The results remained consistent in the stratified analysis of pre- and postmenopausal women, showing an elevated risk of BC associated with thyroid nodules and hyperthyroidism. Considering these significant findings, we investigated the relationship between thyroid disorders and known BC risk factors. Several factors, including a history of benign breast disease, oral contraceptive use, menopausal status, later age at menopause, and longer duration of hormone replacement therapy, were associated with both thyroid nodules and hyperthyroidism, which increased the risk of BC. Women with a longer breastfeeding duration were less likely to have thyroid nodules and hyperthyroidism, suggesting a potential link between reproductive features and the studied thyroid disorders. Additionally, increased breast density, more childbirths, and a family history of BC were only associated with thyroid nodules. In contrast, a higher BMI was associated with a lower likelihood of hyperthyroidism.

Our findings reveal a significantly increased risk of BC in women with thyroid nodules. Non-malignant thyroid nodules have been reported to be more prevalent in women with BC than in those without BC [12]. Some studies found an increased BC risk in individuals with thyroid cancer [13,14]. While most thyroid nodules are benign, a portion of thyroid nodules is malignant. Thyroid cancer occurs in approximately 5%-10% of patients with thyroid nodules [15,16], and the increased BC risk associated with thyroid cancer [13,14] might explain the increased risk of BC in patients with thyroid nodules.

Consistent with our findings, several studies have shown that an increased risk of developing BC is associated with hyperthyroidism [17,18]. A population-based cohort study in Denmark, including 80,343 women diagnosed with hyperthyroidism, reported a slightly increased BC risk compared with the general population, with a standardized incidence rate of 1.11 (95% CI, 1.07 to 1.16) [19], which is similar to our findings. In another small-scale cohort study of Korean women, abnormally high serum FT4 levels were associated with an increased risk of BC incidents [20]. This study further reported that the association between high serum FT4 levels and BC tended to be stronger in postmenopausal women than in premenopausal women [20], which is consistent with the higher risk observed in our study. Similarly, an increased risk of BC associated with hyperthyroidism was further supported by studies showing an increased BC risk among women with high serum thyroxine levels [21,22]. Several biological mechanisms have been described to explain the association between hyperthyroidism and the risk of BC. One study found that serum triiodothyronine (T3) regulates actin remodeling and cell movement in BC T-47D cells through FAK recruitment and plays a significant role in cell migration [23]. Another potential link is the use of I-131 (radioactive iodine, RAI) treatment for hyperthyroidism and its association with BC risk, although the results on this mechanism remain conflicting [24]. Although RAI is commonly used as a first-line therapy in patients with hyperthyroidism [25], most hyperthyroid patients in Korea are prescribed antithyroid drugs as first-line treatment rather than RAI [26]. Concerns have been raised about the potentially increased risk of BC following RAI treatment in patients with hyperthyroidism because an elevated risk of BC has been observed among people with thyroid cancer who received high RAI doses [25]. Additionally, patients with hyperthyroidism treated with RAI had higher organ-absorbed doses, which were modestly associated with an increased risk of death due to BC [27]. However, we were unable to assess the impact of RAI treatment on the association between hyperthyroidism and the risk of BC due to the unavailability of relevant data, which is a limitation of this study. Future studies with detailed RAI treatment data are needed to clarify the potential role of RAI in the risk of BC in patients with hyperthyroidism.

Our findings support the lack of association between hypothyroidism and BC. The HRs showed a negative association; however, not all the results were statistically significant. These findings were previously observed in a large-scale cohort study [19] and meta-analysis [5]. Even though Sogaard et al. [19] reported from their cohort in Denmark that hypothyroidism was associated with a slightly lower risk of BC, the effect size marginally reached the statistically significant level (0.94; 95% CI, 0.88 to 1.00). A similar issue was observed in a meta-analysis by Chen et al. [5], who reported a significantly reduced risk of BC associated with hypothyroidism; however, the overall effect size and CI suggested a marginal association (OR, 0.95; 95% CI, 0.91 to 1.00). Moreover, none of the studies included in this meta-analysis found an association between hypothyroidism and the risk [5]. Thus, our findings add more evidence to support the null association between hypothyroidism and future BC risk.

Our findings indicate that thyroid nodules and hyperthyroidism are associated with several risk factors of BC. We found a negative association between BMI and hyperthyroidism, which is consistent with previous findings showing that reduced weight is associated with hyperthyroidism [28]. Similarly, the KARMA cohort study found that women with a longer breastfeeding duration were less likely to have hyperthyroidism [24]. The association between breastfeeding duration and hyperthyroidism could be explained by the impact of pregnancy on Graves’ disease and toxic nodular goiter, which are the most common causes of hyperthyroidism [28]. These conditions are strongly affected by pregnancy, often leading to early cessation of breastfeeding [24], thus explaining the negative association between breastfeeding duration and BC risk.

Our results also indicated that women with a history of benign breast disease were more likely to have thyroid nodules and hyperthyroidism. This is consistent with previous studies that reported an elevated risk of thyroid cancer in women with benign breast disease [29,30]. Women with a family history of BC were more likely to have thyroid nodules. The KARMA cohort, which focused on hyperthyroidism, reported a significant association between the BC polygenic risk scores and hyperthyroidism [24]. One SNP in DIO1 has been associated with both free T4 and BC [31], suggesting that deiodinase activity affected the association between thyroid function and BC. According to the KARMA cohort, the genetic association between hyperthyroidism and BC was significant only for estrogen receptor (ER)–positive BC but not ER-negative cases, suggesting that the genetic mechanism involved shared hormonal pathways in both diseases [24].

Evidence suggests that estrogen may directly impact human thyroid cells by mediating the effects of estrogen receptors on the thyroid tissue [32]. This might explain the increased likelihood of both thyroid nodules and hyperthyroidism in women at a later age during menopause found in this study. Similarly, in a cohort of Korean women, the prevalence of overt and subclinical hypothyroidism was significantly elevated during late menopausal transition [33]. Hormone replacement therapy raises the circulating levels of thyroxine-binding globulin, increases the bound fraction, and decreases the circulating thyroxine fraction [34]. This mechanism may explain the association between hormone replacement therapy use and thyroid disorders in our study. The association between oral contraceptive use, thyroid nodules, and hyperthyroidism supports the role of estrogen.

The strengths of our study include the cohort design with consideration of potential confounders of BC risk, a large sample size with a population-based design, and long-term follow-up of BC development. However, this study had some limitations. Thyroid disorders were defined based solely on medical records. The use of medical claims data, which lacks information on thyroid status as measured by thyroid function tests or medication use, could lead to the potential misclassification of thyroid diseases. This may explain the slight discrepancies in the disease prevalence rates observed in our study compared to the prevalence study by Kwon et al. [7], where our cohort showed a lower prevalence of thyroid nodules (2.5% vs. 3.6%, data not shown) and hypothyroidism (1.8% vs. 4.0%). Although additional medication and treatment information was used in the study by Kwon et al. [7], our results showed a lower prevalence. In addition, it is worth mentioning that there might also be differences between actual diagnoses and claims data, as the NHIS database relies on diagnostic codes and prescriptions submitted by physicians for insurance claims. In this study, any misclassification of thyroid diseases, if present, was likely to be non-differential, which could lead to the observed null association between thyroid disease and BC risk. As a result, this misclassification may bias the association between thyroid diseases and BC risk might be biased towards the null, potentially underestimating the true association [35]. In our study, the mammography screening rate after thyroid disorder diagnosis was slightly higher in individuals with thyroid disorders than in the control group (people without thyroid diseases) (data not shown). This increase in screening could lead to earlier BC detection because of earlier access to mammography. However, the median follow-up time for a diagnosis of BC was slightly longer in individuals with thyroid nodules, hypothyroidism, and hyperthyroidism than in the control group despite the higher screening rate in the groups with thyroid diseases than in the controls (data not shown). If increased screening leads to earlier detection, we would expect a shorter time interval in groups with thyroid disorders. Therefore, a key limitation of our study is the inability to directly assess whether a higher mammography screening rate among individuals with thyroid disease contributed to earlier BC detection. However, although the screening rate in people with hypothyroidism was higher than that in the controls, they did not show an increased risk of BC according to our findings. Thus, the effect of an increased screening rate in people with thyroid diseases on earlier BC detection would be minimal.

In conclusion, our large cohort study observed that women with thyroid nodules or hyperthyroidism had an increased risk for BC compared with women without thyroid disorders. The increased risk of BC associated with thyroid nodules or hyperthyroidism may be attributed to shared known BC risk factors and independent estrogen-like mechanisms of thyroid diseases. Our findings suggest that women with thyroid nodules or hyperthyroidism should be aware of and assessed for the possible risk of BC in addition to the risk of thyroid cancer.

NOTES

Ethical Statement

The Institutional Review Board of Hanyang University College of Medicine (approval no. HYUIRB-202307-023-1) approved this study.

Author Contributions

Conceived and designed the analysis: Park B, Tran TXM.

Collected the data: Park B, Tran TXM.

Contributed data or analysis tools: Park B, Tran TXM.

Performed the analysis: Park B, Tran TXM.

Wrote the paper: Park B, Tran TXM.

Project administration: Park B.

Supervision: Tran TXM.

Conflicts of Interest

Conflict of interest relevant to this article was not reported.

Funding

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and was funded by the Ministry of Education (grant no. RS-2023-00241942), a National Research Foundation of Korea (grant no. 2021R1A2C1011958, RS-2024-00462658), and by Korea Basic Science Institute (National research Facilities and Equipment Center) grant funded by the Ministry of Education. (grant no. 2023R1A6C101A009).

Fig. 1.

Flow diagram of the selection of eligible population.

Table 1.

Characteristics of the study population

Characteristic	Total	Breast cancer development
Characteristic	Total	No	Yes
Age at screening (yr), mean±SD	55.2±10.7	55.3±10.7	51.8±9.0
Thyroid nodule (yes)	128,022 (2.5)	125,340 (2.5)	2,682 (3.1)
Hypothyroidism (yes)	92,493 (1.8)	90,841 (1.8)	1,652 (1.9)
Hyperthyroidism (yes)	45,431 (0.9)	44,506 (0.9)	925 (1.1)
Age at screening (yr)
40-49	1,705,306 (33.8)	1,665,710 (33.6)	39,596 (45.1)
50-59	1,625,439 (32.2)	1,595,851 (32.2)	29,588 (33.7)
60-69	1,103,521 (21.8)	1,088,860 (21.9)	14,661 (16.7)
≥ 70	617,367 (12.2)	613,428 (12.4)	3,939 (4.5)
BMI group (kg/m²)
< 18.5	116,165 (2.3)	114,375 (2.3)	1,790 (2.0)
18.5 to < 23	1,990,149 (39.4)	1,954,584 (39.4)	35,565 (40.5)
23 to < 25	1,271,594 (25.2)	1,250,227 (25.2)	21,367 (24.3)
≥ 25	1,672,620 (33.1)	1,643,582 (33.1)	29,038 (33.1)
Missing	1,105	1,081	24
Benign breast disease history
No	3,747,834 (74.2)	3,687,130 (74.3)	60,704 (69.2)
Yes	314,296 (6.2)	305,035 (6.2)	9,261 (10.6)
Missing	989,503 (19.6)	971,684 (19.6)	17,819 (20.3)
BI-RADS breast density
Category a	1,452,472 (28.8)	1,438,873 (29.0)	13,599 (15.5)
Category b	1,329,157 (26.3)	1,308,767 (26.4)	20,390 (23.2)
Category c	1,411,914 (28.0)	1,380,016 (27.8)	31,898 (36.3)
Category d	708,168 (14.0)	688,416 (13.9)	19,752 (22.5)
Missing	149,922 (3.0)	147,777 (3.0)	2,145 (2.4)
Age at menarche (yr)
< 15	977,105 (19.3)	954,855 (19.2)	22,250 (25.4)
16-17	1,780,445 (35.2)	1,748,399 (35.2)	32,046 (36.5)
≥ 18	1,558,473 (30.9)	1,538,599 (31.0)	19,874 (22.6)
Missing	735,610 (14.6)	721,996 (14.6)	13,614 (15.5)
Oral contraceptive use
No	3,555,256 (70.4)	3,494,194 (70.4)	61,062 (69.6)
Yes	833,110 (16.5)	818,799 (16.5)	14,311 (16.3)
Missing	663,267 (13.1)	650,856 (13.1)	12,411 (14.1)
No. of pregnancies
None	159,634 (3.2)	155,507 (3.1)	4,127 (4.7)
One	408,453 (8.1)	398,736 (8.0)	9,717 (11.1)
Two or more	3,828,598 (75.8)	3,766,938 (75.9)	61,660 (70.2)
Missing	654,948 (13.0)	642,668 (13.0)	12,280 (14.0)
Breastfeeding
None	502,000 (9.9)	489,349 (9.9)	12,651 (14.4)
< 1 year	1,476,932 (29.2)	1,446,837 (29.2)	30,095 (34.3)
≥ 1 year	2,399,677 (47.5)	2,367,290 (47.7)	32,387 (36.9)
Missing	673,024 (13.3)	660,373 (13.3)	12,651 (14.4)
Family history of breast cancer
No	4,986,011 (98.7)	4,900,524 (98.7)	85,487 (97.4)
Yes	65,622 (1.3)	63,325 (1.3)	2,297 (2.6)
Menopausal status
Premenopausal	1,564,310 (31.0)	1,527,694 (30.8)	36,616 (41.7)
Postmenopausal	2,541,477 (50.3)	2,508,125 (50.5)	33,352 (38.0)
Hysterectomy surgery	289,068 (5.7)	283,567 (5.7)	5,501 (6.3)
Missing	656,778 (13.0)	644,463 (13.0)	12,315 (14.0)
Age at menopause
Premenopausal/Hysterectomy surgery	1,853,378 (36.7)	1,811,261 (36.5)	42,117 (48.0)
< 49 years	639,805 (12.7)	633,098 (12.8)	6,707 (7.6)
49 or 50 years	729,203 (14.4)	720,337 (14.5)	8,866 (10.1)
≥ 51 years	1,014,421 (20.1)	999,130 (20.1)	15,291 (17.4)
Missing	814,826 (16.1)	800,023 (16.1)	14,803 (16.9)
Hormone replacement therapy
No	2,149,374 (42.6)	2,123,176 (42.8)	26,198 (29.8)
Yes, < 5 years	310,821 (6.2)	305,498 (6.2)	5,323 (6.1)
Yes, ≥ 5 years	67,271 (1.3)	65,643 (1.3)	1,628 (1.9)
Premenopausal	1,564,310 (31.0)	1,527,694 (30.8)	36,616 (41.7)
Missing	959,857 (19.0)	941,838 (19.0)	18,019 (20.5)

Values are presented as number (%). BI-RADS, Breast Imaging Reporting and Data System; BMI, body mass index (weight in kilograms divided by height in meters squared); SD, standard deviation.

Table 2.

Association between thyroid disorders and breast cancer development

	No. of cases	HR (95% CI)
	No. of cases	Model 1	Model 2
Thyroid nodule
Breast cancer (any)	2,682	1.21 (1.16-1.25)	1.16 (1.11-1.20)
Invasive breast cancer	2,362	1.17 (1.13-1.22)	1.13 (1.08-1.17)
DCIS	756	1.46 (1.36-1.57)	1.38 (1.28-1.48)
Hypothyroidism
Breast cancer (any)	1,652	1.02 (0.97-1.07)	0.98 (0.93-1.03)
Invasive breast cancer	1,482	1.01 (0.96-1.06)	0.97 (0.92-1.02)
DCIS	409	1.08 (0.98-1.19)	1.02 (0.92-1.12)
Hyperthyroidism
Breast cancer (any)	925	1.14 (1.07-1.22)	1.13 (1.06-1.21)
Invasive breast cancer	830	1.13 (1.06-1.21)	1.12 (1.05-1.20)
DCIS	241	1.26 (1.11-1.43)	1.23 (1.09 -1.40)

Model 1 was adjusted for age at screening. Model 2 was adjusted for age at screening, body mass index, history of benign breast cancer, Breast Imaging Reporting, and Data System breast density, age at menarche, use of oral contraceptives, number of pregnancies, breastfeeding, family history of breast cancer among first-degree relatives, menopausal status, age at menopause, and history of hormone replacement therapy. CI, confidence interval; DCIS, ductal carcinoma in situ; HR, hazard ratio.

Table 3.

Association between thyroid disorders and breast cancer development in pre- and postmenopausal women

	No. of cases	HR (95% CI)
	No. of cases	Model 1	Model 2
Premenopausal women
Thyroid nodule
Breast cancer (any)	943	1.19 (1.11-1.27)	1.16 (1.08-1.23)
Invasive breast cancer	817	1.14 (1.06-1.22)	1.11 (1.04-1.19)
DCIS	302	1.53 (1.37-1.72)	1.47 (1.31-1.64)
Hypothyroidism
Breast cancer (any)	591	0.97 (0.89-1.05)	0.94 (0.87-1.02)
Invasive breast cancer	536	0.97 (0.89-1.06)	0.95 (0.88-1.04)
DCIS	141	0.93 (0.78-1.09)	0.89 (0.75-1.05)
Hyperthyroidism
Breast cancer (any)	371	1.13 (1.02-1.25)	1.11 (1.00-1.23)
Invasive breast cancer	327	1.10 (0.99-1.23)	1.09 (0.98-1.21)
DCIS	102	1.24 (1.02-1.50)	1.20 (0.99-1.46)
Postmenopausal women
Thyroid nodule
Breast cancer (any)	1,098	1.20 (1.13-1.28)	1.13 (1.06-1.20)
Invasive breast cancer	979	1.17 (1.10-1.25)	1.11 (1.04-1.18)
DCIS	274	1.37 (1.22-1.55)	1.27 (1.12-1.43)
Hypothyroidism
Breast cancer (any)	677	1.05 (0.97-1.13)	0.98 (0.91-1.06)
Invasive breast cancer	595	1.01 (0.93-1.09)	0.95 (0.87-1.03)
DCIS	176	1.24 (1.07-1.44)	1.15 (0.99-1.33)
Hyperthyroidism
Breast cancer (any)	363	1.18 (1.06-1.30)	1.16 (1.05-1.29)
Invasive breast cancer	335	1.19 (1.07-1.32)	1.18 (1.06-1.31)
DCIS	83	1.23 (0.99-1.53)	1.20 (0.97-1.50)

Women with a history of hysterectomy were excluded from this analysis. Model 1 was adjusted for age at screening. Model 2 was adjusted for age at screening, BMI, history of benign breast cancer, Breast Imaging Reporting, and Data System breast density, age at menarche, use of oral contraceptives, number of pregnancies, breastfeeding status, and family history of breast cancer among first-degree relatives. For postmenopausal women, the model was additionally adjusted for age at menopause and history of hormone replacement therapy. CI, confidence interval; DCIS, ductal carcinoma in situ; HR, hazard ratio.

Table 4.

Association between conventional breast cancer risk factors with thyroid nodules and hyperthyroidism (reference group: women without thyroid diseases)

Characteristic	OR (95% CI)
Characteristic	Thyroid nodule	Hyperthyroidism
Age at screening (yr)	0.989 (0.988-0.990)	0.983 (0.982-0.985)
BMI group (kg/m²)
< 18.5	0.78 (0.75-0.81)	1.12 (1.06-1.19)
18.5 to < 23	Reference	Reference
23 to < 25	1.07 (1.06-1.09)	0.91 (0.89-0.93)
≥ 25	0.99 (0.97-1.00)	0.79 (0.78-0.81)
Benign breast disease history
No	Reference	Reference
Yes	1.58 (1.55-1.61)	1.16 (1.12-1.21)
BI-RADS breast density
Category a	Reference	Reference
Category b	1.15 (1.13-1.16)	1.03 (1.01-1.06)
Category c	1.14 (1.12-1.16)	0.99 (0.96-1.01)
Category d	1.04 (1.02-1.07)	0.96 (0.92-0.99)
Age at menarche (yr)
< 15	Reference	Reference
16-17	1.04 (1.02-1.06)	1.00 (0.97-1.03)
≥ 18	0.98 (0.96-1.00)	0.99 (0.96-1.02)
Oral contraceptive use
No	Reference	Reference
Yes	1.02 (1.00-1.04)	1.06 (1.03-1.08)
No. of pregnancies
None	Reference	Reference
One	1.00 (0.96-1.04)	1.09 (1.03-1.16)
Two or more	1.08 (1.04-1.12)	1.00 (0.95-1.06)
Breastfeeding
None	Reference	Reference
< 1 year	1.03 (1.01-1.05)	0.95 (0.92-0.99)
≥ 1 year	0.96 (0.94-0.98)	0.92 (0.89-0.96)
Family history of breast cancer
No	Reference	Reference
Yes	1.18 (1.13-1.24)	0.96 (0.88-1.04)
Menopausal status
Postmenopausal	Reference	Reference
Premenopausal	0.83 (0.81-0.85)	0.85 (0.82-0.89)
Hysterectomy surgery	1.27 (1.14-1.41)	1.09 (0.90-1.31)
Age at menopause (among postmenopausal)
< 49 years	Reference	Reference
49 or 50 years	1.13 (1.10-1.15)	1.11 (1.07-1.15)
≥ 51 years	1.27 (1.24-1.30)	1.17 (1.13-1.21)
Hormone replacement therapy (among postmenopausal)
No	Reference	Reference
Yes, < 5 years	1.39 (1.36-1.42)	1.24 (1.19-1.28)
Yes, ≥ 5 years	1.54 (1.48-1.61)	1.22 (1.13-1.32)

BI-RADS, Breast Imaging Reporting and Data System; BMI, body mass index; CI, confidence interval; OR, odds ratio.

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Association between Benign Thyroid Disorders and Breast Cancer Risk in Korean Women

Cancer Res Treat. 2026;58(1):141-150. Published online February 26, 2025

DOI: https://doi.org/10.4143/crt.2024.787

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Abstract
Introduction
Materials and Methods
Results
Discussion
NOTES
REFERENCES

Association between Benign Thyroid Disorders and Breast Cancer Risk in Korean Women

Fig. 1. Flow diagram of the selection of eligible population.

Fig. 1.

Association between Benign Thyroid Disorders and Breast Cancer Risk in Korean Women

Characteristic	Total	Breast cancer development
Characteristic	Total	No	Yes
Age at screening (yr), mean±SD	55.2±10.7	55.3±10.7	51.8±9.0
Thyroid nodule (yes)	128,022 (2.5)	125,340 (2.5)	2,682 (3.1)
Hypothyroidism (yes)	92,493 (1.8)	90,841 (1.8)	1,652 (1.9)
Hyperthyroidism (yes)	45,431 (0.9)	44,506 (0.9)	925 (1.1)
Age at screening (yr)
40-49	1,705,306 (33.8)	1,665,710 (33.6)	39,596 (45.1)
50-59	1,625,439 (32.2)	1,595,851 (32.2)	29,588 (33.7)
60-69	1,103,521 (21.8)	1,088,860 (21.9)	14,661 (16.7)
≥ 70	617,367 (12.2)	613,428 (12.4)	3,939 (4.5)
BMI group (kg/m²)
< 18.5	116,165 (2.3)	114,375 (2.3)	1,790 (2.0)
18.5 to < 23	1,990,149 (39.4)	1,954,584 (39.4)	35,565 (40.5)
23 to < 25	1,271,594 (25.2)	1,250,227 (25.2)	21,367 (24.3)
≥ 25	1,672,620 (33.1)	1,643,582 (33.1)	29,038 (33.1)
Missing	1,105	1,081	24
Benign breast disease history
No	3,747,834 (74.2)	3,687,130 (74.3)	60,704 (69.2)
Yes	314,296 (6.2)	305,035 (6.2)	9,261 (10.6)
Missing	989,503 (19.6)	971,684 (19.6)	17,819 (20.3)
BI-RADS breast density
Category a	1,452,472 (28.8)	1,438,873 (29.0)	13,599 (15.5)
Category b	1,329,157 (26.3)	1,308,767 (26.4)	20,390 (23.2)
Category c	1,411,914 (28.0)	1,380,016 (27.8)	31,898 (36.3)
Category d	708,168 (14.0)	688,416 (13.9)	19,752 (22.5)
Missing	149,922 (3.0)	147,777 (3.0)	2,145 (2.4)
Age at menarche (yr)
< 15	977,105 (19.3)	954,855 (19.2)	22,250 (25.4)
16-17	1,780,445 (35.2)	1,748,399 (35.2)	32,046 (36.5)
≥ 18	1,558,473 (30.9)	1,538,599 (31.0)	19,874 (22.6)
Missing	735,610 (14.6)	721,996 (14.6)	13,614 (15.5)
Oral contraceptive use
No	3,555,256 (70.4)	3,494,194 (70.4)	61,062 (69.6)
Yes	833,110 (16.5)	818,799 (16.5)	14,311 (16.3)
Missing	663,267 (13.1)	650,856 (13.1)	12,411 (14.1)
No. of pregnancies
None	159,634 (3.2)	155,507 (3.1)	4,127 (4.7)
One	408,453 (8.1)	398,736 (8.0)	9,717 (11.1)
Two or more	3,828,598 (75.8)	3,766,938 (75.9)	61,660 (70.2)
Missing	654,948 (13.0)	642,668 (13.0)	12,280 (14.0)
Breastfeeding
None	502,000 (9.9)	489,349 (9.9)	12,651 (14.4)
< 1 year	1,476,932 (29.2)	1,446,837 (29.2)	30,095 (34.3)
≥ 1 year	2,399,677 (47.5)	2,367,290 (47.7)	32,387 (36.9)
Missing	673,024 (13.3)	660,373 (13.3)	12,651 (14.4)
Family history of breast cancer
No	4,986,011 (98.7)	4,900,524 (98.7)	85,487 (97.4)
Yes	65,622 (1.3)	63,325 (1.3)	2,297 (2.6)
Menopausal status
Premenopausal	1,564,310 (31.0)	1,527,694 (30.8)	36,616 (41.7)
Postmenopausal	2,541,477 (50.3)	2,508,125 (50.5)	33,352 (38.0)
Hysterectomy surgery	289,068 (5.7)	283,567 (5.7)	5,501 (6.3)
Missing	656,778 (13.0)	644,463 (13.0)	12,315 (14.0)
Age at menopause
Premenopausal/Hysterectomy surgery	1,853,378 (36.7)	1,811,261 (36.5)	42,117 (48.0)
< 49 years	639,805 (12.7)	633,098 (12.8)	6,707 (7.6)
49 or 50 years	729,203 (14.4)	720,337 (14.5)	8,866 (10.1)
≥ 51 years	1,014,421 (20.1)	999,130 (20.1)	15,291 (17.4)
Missing	814,826 (16.1)	800,023 (16.1)	14,803 (16.9)
Hormone replacement therapy
No	2,149,374 (42.6)	2,123,176 (42.8)	26,198 (29.8)
Yes, < 5 years	310,821 (6.2)	305,498 (6.2)	5,323 (6.1)
Yes, ≥ 5 years	67,271 (1.3)	65,643 (1.3)	1,628 (1.9)
Premenopausal	1,564,310 (31.0)	1,527,694 (30.8)	36,616 (41.7)
Missing	959,857 (19.0)	941,838 (19.0)	18,019 (20.5)

	No. of cases	HR (95% CI)
	No. of cases	Model 1	Model 2
Thyroid nodule
Breast cancer (any)	2,682	1.21 (1.16-1.25)	1.16 (1.11-1.20)
Invasive breast cancer	2,362	1.17 (1.13-1.22)	1.13 (1.08-1.17)
DCIS	756	1.46 (1.36-1.57)	1.38 (1.28-1.48)
Hypothyroidism
Breast cancer (any)	1,652	1.02 (0.97-1.07)	0.98 (0.93-1.03)
Invasive breast cancer	1,482	1.01 (0.96-1.06)	0.97 (0.92-1.02)
DCIS	409	1.08 (0.98-1.19)	1.02 (0.92-1.12)
Hyperthyroidism
Breast cancer (any)	925	1.14 (1.07-1.22)	1.13 (1.06-1.21)
Invasive breast cancer	830	1.13 (1.06-1.21)	1.12 (1.05-1.20)
DCIS	241	1.26 (1.11-1.43)	1.23 (1.09 -1.40)

	No. of cases	HR (95% CI)
	No. of cases	Model 1	Model 2
Premenopausal women
Thyroid nodule
Breast cancer (any)	943	1.19 (1.11-1.27)	1.16 (1.08-1.23)
Invasive breast cancer	817	1.14 (1.06-1.22)	1.11 (1.04-1.19)
DCIS	302	1.53 (1.37-1.72)	1.47 (1.31-1.64)
Hypothyroidism
Breast cancer (any)	591	0.97 (0.89-1.05)	0.94 (0.87-1.02)
Invasive breast cancer	536	0.97 (0.89-1.06)	0.95 (0.88-1.04)
DCIS	141	0.93 (0.78-1.09)	0.89 (0.75-1.05)
Hyperthyroidism
Breast cancer (any)	371	1.13 (1.02-1.25)	1.11 (1.00-1.23)
Invasive breast cancer	327	1.10 (0.99-1.23)	1.09 (0.98-1.21)
DCIS	102	1.24 (1.02-1.50)	1.20 (0.99-1.46)
Postmenopausal women
Thyroid nodule
Breast cancer (any)	1,098	1.20 (1.13-1.28)	1.13 (1.06-1.20)
Invasive breast cancer	979	1.17 (1.10-1.25)	1.11 (1.04-1.18)
DCIS	274	1.37 (1.22-1.55)	1.27 (1.12-1.43)
Hypothyroidism
Breast cancer (any)	677	1.05 (0.97-1.13)	0.98 (0.91-1.06)
Invasive breast cancer	595	1.01 (0.93-1.09)	0.95 (0.87-1.03)
DCIS	176	1.24 (1.07-1.44)	1.15 (0.99-1.33)
Hyperthyroidism
Breast cancer (any)	363	1.18 (1.06-1.30)	1.16 (1.05-1.29)
Invasive breast cancer	335	1.19 (1.07-1.32)	1.18 (1.06-1.31)
DCIS	83	1.23 (0.99-1.53)	1.20 (0.97-1.50)

Characteristic	OR (95% CI)
Characteristic	Thyroid nodule	Hyperthyroidism
Age at screening (yr)	0.989 (0.988-0.990)	0.983 (0.982-0.985)
BMI group (kg/m²)
< 18.5	0.78 (0.75-0.81)	1.12 (1.06-1.19)
18.5 to < 23	Reference	Reference
23 to < 25	1.07 (1.06-1.09)	0.91 (0.89-0.93)
≥ 25	0.99 (0.97-1.00)	0.79 (0.78-0.81)
Benign breast disease history
No	Reference	Reference
Yes	1.58 (1.55-1.61)	1.16 (1.12-1.21)
BI-RADS breast density
Category a	Reference	Reference
Category b	1.15 (1.13-1.16)	1.03 (1.01-1.06)
Category c	1.14 (1.12-1.16)	0.99 (0.96-1.01)
Category d	1.04 (1.02-1.07)	0.96 (0.92-0.99)
Age at menarche (yr)
< 15	Reference	Reference
16-17	1.04 (1.02-1.06)	1.00 (0.97-1.03)
≥ 18	0.98 (0.96-1.00)	0.99 (0.96-1.02)
Oral contraceptive use
No	Reference	Reference
Yes	1.02 (1.00-1.04)	1.06 (1.03-1.08)
No. of pregnancies
None	Reference	Reference
One	1.00 (0.96-1.04)	1.09 (1.03-1.16)
Two or more	1.08 (1.04-1.12)	1.00 (0.95-1.06)
Breastfeeding
None	Reference	Reference
< 1 year	1.03 (1.01-1.05)	0.95 (0.92-0.99)
≥ 1 year	0.96 (0.94-0.98)	0.92 (0.89-0.96)
Family history of breast cancer
No	Reference	Reference
Yes	1.18 (1.13-1.24)	0.96 (0.88-1.04)
Menopausal status
Postmenopausal	Reference	Reference
Premenopausal	0.83 (0.81-0.85)	0.85 (0.82-0.89)
Hysterectomy surgery	1.27 (1.14-1.41)	1.09 (0.90-1.31)
Age at menopause (among postmenopausal)
< 49 years	Reference	Reference
49 or 50 years	1.13 (1.10-1.15)	1.11 (1.07-1.15)
≥ 51 years	1.27 (1.24-1.30)	1.17 (1.13-1.21)
Hormone replacement therapy (among postmenopausal)
No	Reference	Reference
Yes, < 5 years	1.39 (1.36-1.42)	1.24 (1.19-1.28)
Yes, ≥ 5 years	1.54 (1.48-1.61)	1.22 (1.13-1.32)

Table 1. Characteristics of the study population

Values are presented as number (%). BI-RADS, Breast Imaging Reporting and Data System; BMI, body mass index (weight in kilograms divided by height in meters squared); SD, standard deviation.

Table 2. Association between thyroid disorders and breast cancer development

Table 3. Association between thyroid disorders and breast cancer development in pre- and postmenopausal women

Table 4. Association between conventional breast cancer risk factors with thyroid nodules and hyperthyroidism (reference group: women without thyroid diseases)

BI-RADS, Breast Imaging Reporting and Data System; BMI, body mass index; CI, confidence interval; OR, odds ratio.