Miriam E Tucker

June 01, 2015

NASHVILLE, Tennessee — Thyroid-cancer survivors are at increased risk for developing breast cancer compared with the general population, the findings from a large database analysis suggest.

The data, from the Surveillance, Epidemiology, and End Results Database-9 (SEER-9) 1973–2011, were presented here at the American Association of Endocrine Surgeons (AAES) 2015 Annual Meeting by Jennifer H Kuo, MD, of Columbia University Medical Center, New York.

Earlier this year at the Endocrine Society meeting, Dr Kuo presented the reverse finding from the same database: Patients with breast cancer were at increased risk for the later development of thyroid cancer. But the current findings are stronger for a few reasons, she told Medscape Medical News.

"This, I think, is a little more interesting, because in terms of incidence rates there is an age-time interaction, which you don't see with thyroid [cancer] after breast [cancer]. It's the over-50-year-olds diagnosed in the past 2 decades who have the highest incidence ratios," she noted.

The current findings suggest biological differences in both the primary thyroid cancers and the subsequent breast tumors compared with those of patients who only had one of the two cancers. "With thyroid [cancer] after breast [cancer], surveillance bias may play a larger role. But with this story…there's much more meat that needs to be investigated," she said.

Asked to comment on the findings, session comoderator Alexander Shifrin, MD, surgical director of the Meridian Thyroid, Parathyroid, and Adrenal Program at Jersey Shore University Medical Center, Neptune, told Medscape Medical News that this association has been reported previously in single-institution studies and that these findings from a large national database lend important support.

"I think these data are quite valuable," he said.

Surviving One Cancer, Getting Another

In her presentation, Dr Kuo noted that while the overall incidence of thyroid-cancer diagnoses have skyrocketed over the past 3 decades, especially in women, mortality has remained low, with 5- to 10-year survival rates of 95% to 97%.

It is estimated that there will be about one million thyroid cancer survivors in the United States in the next decade, she said.

According to SEER, the cumulative incidence of developing any second cancer after thyroid cancer is 16% at 25 years. The majority of those are breast cancers, accounting for 36%. The etiology for this relationship has not been elucidated.

A total of 707,678 primary breast cancer and 52,939 primary thyroid cancer cases were identified for the current study. Of those, 704,402 had breast cancer only, 49,663 had thyroid cancer only, and 1750 developed primary breast cancer after primary thyroid cancer. (For this analysis, those who developed thyroid cancer after breast cancer were excluded.)

The median time to development of the second primary breast cancer was 5 years. The 10-year risk for developing breast cancer at age 40 years was 5.6% for those with a primary thyroid cancer, vs 1.5% for the general population.

At age 50, the risk jumped to 12.8% for those with primary thyroid cancer compared with just 2.4% of the general population. At age 60, the proportions were 7.4% vs 3.6%, and at age 70, 11.1% vs 3.8%, respectively.

"Patients diagnosed with thyroid cancer after age 50 over the past 2 decades have a much greater risk for developing a second primary breast cancer. Regression analysis confirms this significant age-time interaction," Dr Kuo noted.

While the incidence of thyroid cancer is increasing in all ages, the incidence of primary thyroid cancer among those who went on to develop breast cancer has remained stable for all ages. "This suggests that the biology of these thyroid cancers may be different from the biology of the thyroid cancer that develops in the general population," she said.

Biological Differences

Comparing 954 of the patients with breast cancer after thyroid cancer with 38,158 who had thyroid cancer only, those with both cancers tended to be older at the time of thyroid-cancer diagnosis (52 vs 46 years, P < .001), were less likely to be Hispanic (4.3% vs 6.7%, P = .002), had smaller tumors (12.0 vs 13.0 mm, P = .002), were less likely to have received radioactive iodine ablation (42% vs 45%, P = .49), and, although the majority of tumors in both groups were papillary, those with both cancers had higher rates of follicular thyroid tumors (11% vs 9%, P = .030).

On multivariate analysis, age, tumor size, and follicular tumor histology remained significant.

Comparing the same 954 with breast cancer following thyroid cancer with the 498,253 patients who had breast cancer only, this time the group with both cancers was younger (58 vs 61 years, P < .001) but also had smaller tumor size (15.0 vs 18.0 mm, P = .001).

The breast tumors in the thyroid-cancer survivors were more often estrogen-receptor/progesterone-receptor positive (72% vs 62%, P < .001), and, although the majority of tumors in both groups were ductal carcinomas, those with breast cancer following thyroid cancer had a higher percentage with mixed invasive tumor histology (14% vs 10.5%, P = .001)

On multivariate analysis, all four characteristics remained significant.

Dr Shifrin pointed out that there are estrogen and progesterone receptors in the thyroid also and that thyroid cancers can grow during pregnancy from the stimulation. Based on this new information and prior data, he said, "If I have a patient with thyroid nodules, I'm looking more carefully for breast cancer."

Dr Kuo and Dr Shifrin have no relevant financial relationships.

American Association of Endocrine Surgeons. May 19, 2015; Nashville, Tennessee. Abstract 32.

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