Thyroid cancer and multiple primary tumors in the SEER cancer registries1

Abstract

Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End-Results (SEER) cancer registries program . In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) 5 35-50%; excess absolute risk (EAR) 5 0.38/ 10,000 person-years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/ expected (O/E) 5 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2-month thyroid cancer survivors, 2,214 second cancers occurred (O/E 5 1.11, 95% CI 5 1.06-1.15; EAR 5 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E 5 1.26). Patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment-related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking-related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2-way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects. ' 2005 Wiley-Liss, Inc.Key words: multiple primary cancers; thyroid cancer; epidemiology; radiotherapy Approximately 1.5% of new cancers diagnosed in the United States in 2001 were malignancies of the thyroid gland. While the incidence rates are low, they have been increasing over recent decades in many areas of the world. 1 In the United States, about 90% of thyroid cancers are papillary or follicular adenocarcinoma, while anaplastic and medullary cancers account for less than 5% each. 2 The 10-year relative survival rate for thyroid cancer is close to 95%, 3 although the prognosis for anaplastic thyroid cancer is dismal, with few patients surviving beyond 1 year. 4 The demographic characteristics of thyroid malignancies are different from most other cancers. There is a 1:3 male-female ratio and an unusual age distribution. 1 Unlike other malignancies, female thyroid cancer rates increase steeply from the mid-teens until age 50, i.e., around menopause, and steadily decreas...

The incidence of second primary tumors in thyroid cancer patients is increased, but not related to treatment of thyroid cancer

“…Especially, the relation between these glycoproteins and matrix metalloproteinases, critical for the development of wound healing and cancer progression, is suggestive for a common genetic base. Ronckers et al recently published a large report on thyroid cancer and multiple primary tumors (18). They studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple cancers after an earlier thyroid cancer in the US, using the cancer registry program of more than 2 million patients.…”

Multiple Metachronous Malignancies, One Patient with Three Primary Malignancies

“…Increased incidence of thyroid carcinoma following breast cancer is also known [3]. Ronckers et al say that patients of <40 years of age at diagnosis of thyroid cancer have a 39% risk of second cancer, in contrast to 6% in older patients [4]. In the same study, several other cancer sites showed significantly increased risks in both directions, including salivary glands, prostate, breast, kidney, scrotum, brain and leukemia.…”

Why radioiodine remnant ablation is right for most patients with differentiated thyroid carcinoma

“…In a series of articles in the 1950s by Seidlin, the father of radioiodine treatment for thyroid carcinoma, and coworkers [31][32][33] it was well documented that there is an excess risk of leukaemia after treatment with high cumulative activities of radioiodine [34,35], correlating with the administered total radioiodine activity [36]. In practice this means that this excess risk only materializes in patients with metastatic disease after repeated (high-activity) treatments.…”

“…An increased risk of other malignancies of organs such as the salivary glands, the breasts, the stomach or even the prostate has also been reported. It is, however, unclear how much of this risk RRA treatment is responsible for, as it has been noted in multiple studies that such carcinomas are observed in excess both before and after the diagnosis and treatment of DTC [34,37]. The latter observation suggests that aetiological similarities and possible treatment effects are responsible for this excess in secondary malignancies [34].…”

“…It is, however, unclear how much of this risk RRA treatment is responsible for, as it has been noted in multiple studies that such carcinomas are observed in excess both before and after the diagnosis and treatment of DTC [34,37]. The latter observation suggests that aetiological similarities and possible treatment effects are responsible for this excess in secondary malignancies [34]. Brown et al [35] conclude that the overall risk of second primary malignancies is increased for thyroid cancer survivors and varies in relation to radioiodine therapy, latency, and age at diagnosis.…”