Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk

Abstract

Thyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross-sectional studies have measured thyroid hormones/autoantibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause-effect direction in these studies. Only three prospective studies have reported on the subject so far. The aim of our study was to investigate prediagnostically measured levels of thyroid hormones, thyrotropin (TSH) and thyroid autoantibodies in relation to subsequent risk of breast cancer. The Malmoe Diet and Cancer study examined 17,035 women between 1991 and 1996. Blood samples were collected at baseline and free triiodothyronine (T3), free thyroxin (T4), TSH and thyroid peroxidase autoantibodies (TPO-Ab) levels were measured in 676 cases and 680 controls. Relative risks with 95% confidence intervals were assessed using a logistic regression analysis adjusted for potential confounders. Free T4 levels were positively associated with a high risk of breast cancer, and the OR for women with free T4 levels above vs. below the median was 1.40 (1.10-1.77). This association was most pronounced in overweight women (1.51:1.07-2.12). Women with high levels of TPO-Ab had a lower risk of breast cancer, but only the analysis of TPO-Ab as a continuous variable reached statistical significance. Free T4 was in our study positively associated with a high risk of breast cancer. This association was most pronounced in overweight/obese women. Women with a high level of TPO-Ab had a relatively low risk of breast cancer.Experimental, clinical and epidemiological studies suggest that there is an association between thyroid disorders and breast cancer risk. There have been several record-linkage studies using cohorts of patients with thyroid disorders that have investigated the risk of subsequent breast cancer, but the results are not conclusive. [1][2][3][4][5][6][7][8] Another category of studies have investigated the association between thyroid hormone levels/autoantibodies and breast cancer risk, the majority of these studies were cross-sectional measuring hormone levels in cases following diagnosis, as compared to controls, and they may suggest a cause-effect relationship, but it is difficult to draw conclusions from cross-sectional studies. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] To date, there are only three prospective studies that have reported on the association between thyroid hormone/thyrotropin (TSH) levels and subsequent risk of breast cancer. The smallest found that low levels of free thyroxin (T4), and high levels of TSH, were associated with an increased risk of breast cancer. 24 Another, investigating only TSH, found no association with breast cancer risk. 25 We have in a previous study found that triiodothyronine (T3) levels were positively associated with breast cancer risk in postmenopausal women. 26 Autoimmune thyroiditis has also been positively associated with breast cancer ris...

Hypothyroidism and hyperthyroidism and breast cancer risk: a nationwide cohort study

“…Most of the previous studies examined the effect of thyroid hormone levels on breast cancer risk in a case-control setting (14,16,17,29), in which reverse causation may be difficult to rule out. Our findings are in line with three of the earlier cohort studies that found an association between higher premorbid levels of thyroid hormone and breast cancer risk (11,12,15), while the fourth cohort study found an association between low levels of free thyroxine and an increased risk of breast cancer (9). The lack of increase in the risk of breast cancer in women with hypothyroidism, observed in this study, is also in agreement with the results of a recent meta-analysis of 12 observational studies showing no association between hypothyroidism and breast cancer risk (18).…”

“…Some epidemiological studies have reported increased risks associated with hypothyroidism (8,9), hyperthyroidism (10,11,12), goiter (13) and thyroid autoimmune diseases (14,15), while others have found no association (9,16,17,18). Only four studies employed a cohort design (9,11,12,15); in case-control studies, reverse causation is a plausible competing explanation since breast cancer or its treatment may affect thyroid hormone levels (19).…”

Risk of Breast Cancer in Patients with Thyroid Cancer Receiving or Not Receiving 131I Treatment: A Nationwide Population-Based Cohort Study

“…It has been reported that there is an association between breast cancer and thyroid cancer; this association may be attributable to common etiologic features, pathologic processes, or treatment-related factors (27,28) that these 2 cancers share. Previous studies suggested the relationship between serum levels of thyroid hormones or thyroid peroxidase autoantibodies and the risk or prognosis of breast cancer (29)(30)(31)(32). Radioiodine therapy is the main postoperative treatment for patients with differentiated thyroid cancer.…”

The prevalence of benign breast diseases in patients with nodular goiter and Hashimoto’s thyroiditis

“…This issue needs clarification with further research both pathophysiologically and clinically. Most of these studies have commonly emphasized the necessity of screening for breast cancer in patients with thyroid disorders [13][14][15][16][17][18].…”