Thyroid Diseases and Breast Cancer

Abstract

Epidemiological studies aimed at defining the association of thyroid diseases with extra-thyroidal malignancies (EM) have aroused considerable interest in the possibility of revealing common genetic and environmental factors underlying disease etiology and progression. Over the years, multiple lines of evidence indicated a significant relationship between thyroid carcinomas and other primary EM, especially breast cancer. For the latter, a prominent association was also found with benign thyroid diseases. In particular, a meta-analysis revealed an increased risk of breast cancer in patients with autoimmune thyroiditis, and our recent work demonstrated that the odds ratio (OR) for breast cancer was raised in both thyroid autoantibody-positive and -negative patients. However, the OR was significantly lower for thyroid autoantibody-positive patients compared to the negative ones. This is in agreement with findings showing that the development of thyroid autoimmunity in cancer patients receiving immunotherapy is associated with better outcome and supports clinical evidence that breast cancer patients with thyroid autoimmunity have longer disease-free interval and overall survival. These results seem to suggest that factors other than oncologic treatments may play a role in the initiation and progression of a second primary malignancy. The molecular links between thyroid autoimmunity and breast cancer remain, however, unidentified, and different hypotheses have been proposed. Here, we will review the epidemiological, clinical, and experimental data relating thyroid diseases and breast cancer, as well as the possible hormonal and molecular mechanisms underlying such associations.

Keywords: breast cancer; epidemiology; etiology; extra-thyroidal malignancies; thyroid disease.

Figure 1

Histological (A) and molecular (B) classification of breast cancer. * Infiltrating ductal carcinomas evaluated on the basis of nuclear morphology, glandular/tubule formation, and mitotic index are further sub-classified in well-differentiated, moderately differentiated, and poorly differentiated carcinomas.

Figure 2

Influence of the hypothalamic–pituitary–thyroid axis on breast cancer progression. Thyrotropin-releasing hormone (TRH); thyrotropin (TSH); prolactin (PRL); thyroid hormone (TH).