Breast/Thyroid Cancer Review Article
Breast/Thyroid Cancer Review Article
The relationship between breast and thyroid cancer is one that has been widely discussed and debated in the literature. Although there is a clear association between the two cancers, the cause of this association and the subsequent risks for each cancer remain unclear. The topic is very important for practicing clinicians as the incidence of thyroid cancer continues to rise, and the survival rates for patients with thyroid and breast cancer continue to increase due to improved therapy and earlier detection, putting more women at risk to develop a second neoplasm over their lifetime.
Differentiated thyroid cancer is the most common endocrine malignancy, and while it only accounts for 1.5% of cancers diagnosed in the United States, the age-adjusted incidence continues to rise in this country and in other parts of the world (Ronckers et al. 2005; Ries, Eisner, Kosary et al. 2005). Women are more than three times more likely to develop thyroid cancer as men, illustrated by the latest data from the U.S Surveillance, Epidemiology, and End-Results (SEER) cancer registries program (2005-2009) which estimate that 5.9 per 100,000 men and 17.3 per 10,000 women are diagnosed with thyroid cancer each year (SEER website). Well-differentiated thyroid cancer, including papillary and follicular subtypes, makes up about 90% of cases, while less than 5% of cases are poorly differentiated anaplastic or medullary cancers (Correa & Chen, 1995). The 10-year survival rate for thyroid cancer is greater than 90% and the overall survival for papillary thyroid cancer is close to 99% (Gilliand, Hunt, Morris, et al. 1997). Another unique aspect of thyroid cancer is the age distribution; incidence in females increases steeply from mid-teens until age 50 and decreases thereafter. In males, the increased risk at earlier ages is less pronounced and continues through age 70 (SEER, Ronckers et al. 2005).
Though both breast and thyroid cancer occur predominately in females, breast cancer affects about seven times more women than thyroid cancer with an annual incidence of 124.3 per 100,000 females in United States (SEER website), and it is the most common malignancy in females around the world. Less than 1% of breast cancers are diagnosed in men (Spiers and Shaaban, 2009). In contrast to thyroid cancer, incidence rates of breast cancer are substantially higher for women age 50 or older compared with women younger than 50, with approximately two-thirds of breast cancer cases diagnosed over the age of 55 (SEER websites). Similar to thyroid cancer, the prognosis for breast cancer without distant metastasis is very good, with a 5-year survival rate ranging from 84-98% depending on the presence of local invasion to lymph nodes (SEER website).
To some extent, an association between breast and thyroid cancer is assumed since both are hormonally-driven cancers occurring primarily in females. As thyroid cancer tends to occur in younger women and usually has an excellent prognosis, it is expected that a proportion of these women will go on to develop breast cancer at a later age. However, there is a large body of literature on the association between breast and thyroid cancer, dating back to 1966, that suggests the risk of breast cancer following thyroid cancer and even thyroid cancer following breast cancer is higher than expected. As a whole, there are no concrete conclusions from these studies regarding the degree of risk and how it should be managed. A review of this topic is warranted because the studies conducted vary widely in their design, study populations and conclusions, making interpretation and translation to clinical practice particularly difficult. To our knowledge, this is the first review of the association between breast and thyroid cancer. We will explore the current hypotheses for the underlying association and discuss the most relevant studies on the topic. In reviewing the literature, four hypotheses surface as possible explanations for the breast and thyroid cancer link, including shared risk factors (female gender, hormones, etc.), treatment effect (radioactive iodine, radiation), detection bias, and genetic susceptibility. While it is unlikely that there is one explanation for the association between breast and thyroid cancer, ….
II. Hypotheses for breast/thyroid cancer association
The finding that breast cancer occurs more frequently than expected in thyroid cancer patients was first reported by Chalstrey and Benjamin in 1966. However, the idea that thyroid dysfunction and breast cancer could be intrinsically linked dates back to 1896 when Sir George Beatson, surgeon to Glasgow Cancer Hospital, proposed thyroid hormones as a treatment for inoperable breast cancer (Goldman, 1990; Beatson, 1896). Although Beatson ultimately concluded that the administration of thyroid hormones alone did little to delay cancer progression, the idea was revisited by Loeser 60 years later when he claimed that patients who had undergone subtotal thyroidectomy were at a greater risk for breast cancer than hyperthyroid patients (Goldman, 1990; Loeser, 1954). He hypothesized that it was the deficiency of thyroid hormone in these women that caused malignant growth of breast cells, and thyroid hormones could be used prophylactically to prevent breast cancer recurrence (Loeser, 1954). Conversely, Chalstrey and Benjamin believed pituitary dysfunction to be the root of breast cancer development in patients with thyroid disease or cancer, but did emphasize the importance of preventing a prolonged hypothyroid state following thyroidectomy in order to avoid pituitary overstimulation (Chalstrey and Benjamin, 1966). The following sections expound on the hormonal mechanisms that may link breast and thyroid cancer and explore additional hypotheses developed in later years. A full discussion of thyroid disease and breast cancer risk is out of the scope of this review.
A. How and why could they be associated? Why is it even a question?
a. Etiology/shared risk factors: female gender, hormones, etc.
b. Genetic susceptibility
c. Treatment effect (RAI, radiation)
d. Detection bias
A. Current state of knowledge of BC/TC association
B. Summarize studies
a. Organize by category of association
b. Clinical/Histological associations: No studies on histologic type, size and estrogen-receptor status of BCs that develop after TC?