Kuijpens Johannes L P, Nyklíctek Ivan, Louwman Marieke W J, Weetman Tony A P, Pop Victor J M, Coebergh Jan-Willem W
Comprehensive Cancer Center South, IKZ, Eindhoven, The Netherlands.
Thyroid. 2005 Nov;15(11):1253-9. doi: 10.1089/thy.2005.15.1253.
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.
乳腺癌与甲状腺（自身免疫性）疾病或甲状腺过氧化物酶抗体（TPOAb；甲状腺自身免疫性疾病的标志物）之间的关联已被提出。然而，对于患有甲状腺（自身免疫性）疾病的女性患乳腺癌风险是否增加知之甚少。这项横断面和前瞻性队列研究调查了TPOAb的存在或甲状腺功能障碍是否与乳腺癌的存在或发展有关。1994年，对2775名处于围绝经期的未经过筛选的女性队列进行了促甲状腺激素（TSH）、游离甲状腺素（FT4）和TPOAb等甲状腺参数的筛查。获取了关于既往或当前甲状腺疾病和乳腺癌以及与乳腺癌和甲状腺疾病相关的假定因素的详细信息。临床甲状腺功能障碍定义为FT4和TSH均异常，亚临床甲状腺功能障碍定义为TSH异常（FT4正常）。TPOAb浓度≥100 U/ml定义为阳性（TPOAb(+)）。该研究组与埃因霍温癌症登记处建立联系，以检测1958年至1994年间诊断出的所有（原位）乳腺癌女性（ICD - O编码174）。随后，在前瞻性研究中，对1994年未患乳腺癌的所有女性（n = 2738）进行随访至2003年7月，记录所有新的（原位）乳腺癌病例和所有癌症相关死亡情况。在2775名女性中，278名（10.0%）为TPOAb(+)。在1994年的筛查中，37名女性（1.3%）患有乳腺癌。TPOAb与当前乳腺癌诊断（独立）相关（OR = 3.3；95% CI 1.3 - 8.5）。在其余女性中，61名（2.2%）患了乳腺癌。新发乳腺癌与以下因素有关：（1）较早诊断为甲状腺功能减退（OR = 3.8；95% CI 1.3 - 10.9）；（2）使用甲状腺药物（OR = 3.2；95% CI 1.0 - 10.7）；（3）低FT4（最低十分位数：OR = 2.3；95% CI 1.2 - 4.6）。在随访的前3年中，新诊断为乳腺癌的女性中FT4与log - TSH之间的关系受到干扰。随访期间TPOAb的存在与乳腺癌无关。甲状腺自身免疫与乳腺癌之间不太可能存在直接关联。甲状腺功能减退和FT4略低于正常水平与绝经后女性患乳腺癌风险增加有关。需要开展研究以阐明这种可能关联的根源。
