Correspondence re: Simon et al., Do Thyroid Disorders Increase the Risk of Breast Cancer? 11: 1574–1578, 2002¹

In a recent report from the National Institute of Child Health and Human Development Women’s Contraceptive and Reproductive Experiences Study, which included 4575 women with breast cancer and 4682 controls, Simon et al. (1) found an excess risk for breast cancer among parous women with a history of thyroid cancer (OR,³ 3.4; 95% CI, 1.5–8.1). No association with breast cancer risk was found for benign conditions of the thyroid gland, including nodules, goiter, hyperthyroidism, or hypothyroidism.

The relationship between thyroid disorders or treatments and breast cancer risk has long been suggested by in vitro experiments and clinical observations (2, 3, 4, 5). However, a selection or diagnostic bias is plausible because women with benign thyroid disorders may undergo more frequent breast examinations. Most epidemiological investigations found no strong evidence of any association between benign conditions or treatments of the thyroid gland and breast cancer risk (3, 4, 5, 6, 7). Weak inverse associations between specific thyroid disorders and breast cancer risk have been occasionally reported, such as for thyroid nodules (OR, 0.7; 95% CI, 0.5–0.9; Ref. 8) and hypothyroidism or goiter (OR, 0.3; 95% CI, 0.1–0.7; Ref. 3); whereas a positive association has been found for hyperthyroidism (OR, 2.2; 95% CI, 1.1–4.4; Ref. 9). A moderate increase of breast cancer risk after thyroid cancer has also been reported (10, 11, 12). However, a population-based study from the Danish Cancer Registry did not confirm these results (13).

Thus, evidence regarding the relationship between thyroid disorders and breast cancer risk is not conclusive and is limited by the small sample size of the studies investigating this issue and the paucity of information on specific types of thyroid disorders (1).

We considered the relationship between history of benign thyroid disorders and breast cancer risk using data derived from two hospital-based case-control studies of breast cancer. The first study was conducted between 1983 and 1991 in the greater Milan area (7), and the second study was conducted between 1991 and 2001 in six Italian areas (8) and Switzerland (14). Cases included in the first study (7) were 3415 women, 22–86 years old (median age, 53 years), with incident, histologically confirmed breast cancer who were admitted to major teaching and general hospitals in the study areas. Corresponding controls were 2916 women, 15–80 years old (median age, 53 years), who lived in the same geographical areas and were admitted for acute conditions to the same network of hospitals. Cases included in the second study (8, 14) were 2900 women (age, 23–78 years; median age, 55 years) who were admitted to hospitals with incident, histologically confirmed breast cancer. Controls were 3122 patients (age, 19–79 years; median age, 56 years) admitted to the same network of hospitals for acute, non-neoplastic conditions. Trained interviewers collected information on history of selected medical conditions. In the first study (7), information included only a question on any thyroid disorder, and the second study (8, 14) included questions on thyroid nodules (adenomas), goiter, hyperthyroidism, hypothyroidism, and unspecified thyroid disorders. Multivariate ORs and the corresponding 95% CIs were derived from unconditional multiple logistic regression models, including terms for study center, age, education, body mass index, parity, menopausal status, and use of hormone replacement therapy.

Limiting the analysis to the most recent study (8, 14), the ORs were 0.7 for a history of thyroid nodules (adenomas), 1.0 for goiter, 1.0 for hyperthyroidism, 0.6 for hypothyroidism, and 1.5 for unspecified benign thyroid disorders (Table 1). The OR for history of any benign disorder was 0.9. None of the estimates was statistically significant. The analysis in strata of parity showed similar results in parous and nulliparous women, except for an inverse association with history of hypothyroidism among parous women (OR, 0.5; 95% CI, 0.3–0.9, based on 17 cases only). No relation of breast cancer risk with benign thyroid disorders was found in pre- and post-menopausal women considered separately, except for an inverse association with thyroid nodules in premenopausal women (OR, 0.4; 95% CI, 0.2–0.7, based on 20 cases). In the first study (7), the OR for history of any benign disorder was 1.0. In the overall dataset that combined the two studies (7, 8, 14), including a total of 6315 cases and 6038 controls, the pooled OR for history of any thyroid disorder was 1.0 (95% CI, 0.9–1.1).

In conclusion, the present reanalysis from a large dataset provides enlarged evidence that allows to exclude any appreciable relationship between benign thyroid disorders and breast cancer risk.

In the Women’s CARE² study (1), we sought to address issues regarding whether or not any associations existed between breast cancer risk and thyroid diseases and/or treatments for thyroid diseases. Overall, the results from the CARE study (1) agree with results from the two case-control studies (2, 3) discussed by Altieri et al. in that no associations were found between a history of any benign thyroid disorder and breast cancer. There are, however, a few differences to note in the study populations and methodology used. In the Women’s CARE study (1), the control group consists of population-based controls, whereas in the studies cited by Altieri et al. (2, 3), the controls were chosen from women hospitalized for acute medical conditions. In the two studies cited (2, 3), the prevalence of any thyroid disorder is lower than that seen in the Women’s CARE study sample [17.5% for Women’s CARE, 9.3% for Franceschi et al. (2), and 9.2% for Talamini et al. (3)]. In addition, we used as our reference group “never having a history of any thyroid disorder” for each analysis, whereas Talamini et al. (3) utilized, for each specific thyroid disorder, women with no given thyroid condition as the reference group. In the Women’s CARE study (1), a history of a hypoactive thyroid is not associated with risk of breast cancer among parous women [OR (adjusted for age, site, race), 0.9 (95% CI, 0.8–1.1)]; among nulliparous women, OR = 0.7 (95% CI, 0.5–0.9). However, no statistically significant interaction was observed by parity status. Our study shows no association between thyroid nodules and breast cancer among either menopausal or premenopausal women: in premenopausal women, OR = 1.1 (95% CI, 0.6–2.1); and in postmenopausal women, OR = 0.9 (95% CI, 0.6–1.4). The results of these three large case-control studies (1,2 3) provide further evidence against a relationship between thyroid disorders or their associated treatments and the risk of breast cancer.

We thank Ivana Garimoldi for editorial assistance.