title: Hypothyroidism might be related to breast cancer in post-menopausal women.
abstract: An association between breast cancer and thyroid (autoimmune) diseases or the presence of thyroid peroxidase antibodies (TPOAb; a marker of thyroid autoimmune disease) has been suggested. However, little is known about whether women with thyroid (autoimmune) diseases are at increased risk for developing breast cancer. This cross-sectional and prospective cohort study investigated whether the presence of TPOAb or thyroid dysfunction is related to the presence or development of breast cancer. An unselected cohort of 2,775 women around menopause was screened for the thyroid parameters thyrotropin (TSH), free thyroxine (FT(4)), and TPOAb during 1994. Detailed information on previous or actual thyroid disorders and breast cancer, and on putative factors related to breast cancer and thyroid disorders, was obtained. Clinical thyroid dysfunction was defined by both abnormal FT4 and TSH, and subclinical thyroid dysfunction by abnormal TSH (with normal FT4). A TPOAb concentration >or= 100 U/ml was defined as positive (TPOAb(+)). The study group was linked with the Eindhoven Cancer Registry to detect all women with (in situ) breast cancer (ICD-O code 174) diagnosed between 1958 and 1994. Subsequently, in the prospective study, all women who did not have breast cancer in 1994 (n = 2,738) were followed up to July, 2003, and all new cases of (in situ) breast cancer and all cancer-related deaths were registered. Of the 2,775 women, 278 (10.0%) were TPOAb(+). At the 1994 screening, 37 women (1.3%) had breast cancer. TPOAbs were (independently) related to a current diagnosis of breast cancer (OR = 3.3; 95% CI 1.3-8.5). Of the remaining women, 61 (2.2%) developed breast cancer. New breast cancer was related to: (1) an earlier diagnosis of hypothyroidism (OR = 3.8; 95% CI 1.3-10.9); (2) the use of thyroid medication (OR = 3.2; 95% CI 1.0-10.7); and (3) low FT4 (lowest tenth percentile: OR = 2.3; 95% CI 1.2-4.6). In the first 3 years follow up, the relationship between FT4 and log-TSH was disturbed in women with a new breast cancer diagnosis. The presence of TPOAb was not related to breast cancer during follow-up. A direct relationship between thyroid autoimmunity and breast cancer is unlikely. Hypothyroidism and low-normal FT4 are related with an increased risk of breast cancer in post-menopausal women. Studies are needed to clarify the origins of this possible association.
authors.affiliation: Comprehensive Cancer Center South, IKZ, Eindhoven, The Netherlands.
authors.forename: Johannes L P
authors.initials: JL
authors.lastname: Kuijpens
authors.forename: Ivan
authors.initials: I
authors.lastname: Nyklíctek
authors.forename: Marieke W J
authors.initials: MW
authors.lastname: Louwman
authors.forename: Tony A P
authors.initials: TA
authors.lastname: Weetman
authors.forename: Victor J M
authors.initials: VJ
authors.lastname: Pop
authors.forename: Jan-Willem W
authors.initials: JW
authors.lastname: Coebergh
mesh_terms: D001943:Breast Neoplasms / Q000150:complications*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000150:complications*; D007453:Iodide Peroxidase / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D011446:Prospective Studies; D012307:Risk Factors; D013960:Thyroid Function Tests; D013974:Thyroxine / Q000097:blood
chemical_list: D007453:Iodide Peroxidase; D013974:Thyroxine