Breast Cancer Survivors at Increased Risk for Thyroid Cancer

Miriam E Tucker

March 08, 2015

SAN DIEGO, California — Breast cancer survivors are at increased risk of developing primary thyroid cancer compared with the general population, a new database analysis suggests.

The findings were presented March 7 here at the annual meeting of the Endocrine Society, ENDO 2015, by Jennifer Hong Kuo, MD, assistant professor of surgery at Columbia University, in New York City.

The figures, obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 (SEER 9) database, also suggested that breast cancer survivors who develop thyroid cancer are younger and have smaller and more aggressive breast cancers. Moreover, the heightened risk is not fully explained by either increased exposure to radiation or by greater surveillance in women with breast cancer, although both most certainly play a role, Dr Kuo said at a press briefing held during the meeting.

Clinically, the implication is that thyroid cancer screening should be considered for breast cancer survivors, she told Medscape Medical News.

"I'm not taking a hard stance that every breast cancer patient should have surveillance ultrasound every year afterward, but I think that...if you see a breast cancer survivor who has a nodule, you want to be aware that there's a higher risk of cancer in that nodule than in the general population, even though they may not have a family history of thyroid cancer or have been a Chernobyl survivor....Just having an awareness that we're dealing with a patient population that is slightly higher at risk can change your clinical approach to that patient just enough to manage them appropriately."

Asked to comment on the findings, briefing moderator Jason A Wexler, MD, an endocrinologist and thyroid specialist at Washington Hospital Center, in Washington, DC, said: "I think it...highlights that for many of our cancer patients, there are important considerations for secondary cancers that occur over time, and this study highlights the thyroid cancer risk."

However, he added, "As a practicing endocrinologist, I don't know how I would approach a breast cancer patient differently if a medical oncologist sent them to me and asked for screening for thyroid cancer. I don't think we're quite there yet, based on the data from [this new] study, but I think it identifies these patients as requiring careful follow-up, even beyond the treatment and resolution of their primary malignancy."

Younger Patients, Smaller and More Aggressive Cancers

Between 1973 and 2011, a total of 707,678 women with breast cancer and 52,939 women with thyroid cancer were identified in the SEER database, which covers about 9% of the US population. Of those, 1526 had been diagnosed with thyroid cancer after breast cancer, 704,405 had breast cancer only, and 49,663 had thyroid cancer only. (The 1750 patients who developed breast cancer after thyroid cancer were excluded from the current analysis.)

The 10-year risk of developing thyroid cancer was 16.0% for the breast cancer survivors who were diagnosed at age 40 years compared with just 0.33% in the general population of that age and 12.0% vs 0.35% at age 50. Women diagnosed with breast cancer in their 60s and 70s did not have an increased risk for thyroid cancer.

Compared with the breast cancer survivors who did not develop thyroid cancer, those who did were younger (54 vs 61 years, P < .001), had larger breast tumors (18 mm vs 15 mm, P = .001), and were more likely to have invasive ductal carcinoma (7.6% vs 5.5%, P = .002).

Compared with the thyroid cancer patients who did not have a preceding breast cancer, those who did had smaller tumors (11.0 mm vs 13.0 mm, P = .004) and were less likely to have received radioactive iodine treatment (37% vs 45.5%, P < .001).

In the thyroid cancers that developed in women with prior breast cancer, there were also higher percentages of tall-cell variant of papillary-thyroid carcinoma, oxyphilic follicular thyroid cancer, and anaplastic cancers.

Among the breast cancer survivors who developed thyroid cancer, more received adjuvant radiation therapy ― 48% of those with dual cancers vs 44% of the group with only breast cancer (P = .021) ― but this was not an independent predictor of the second primary cancer, Dr Kuo said.

What's the Connection?

In an interview with Medscape Medical News, Dr Wexler noted that the timeline was not clear from this database analysis and that "it's a critical issue to know whether they're really linked or whether the thyroid cancer may have been there all along and was simply discovered later, because these people see doctors more regularly and they're having more scans."

"They are associated, but it's unclear whether there's a causal link between breast cancer and the development of thyroid cancer. I think that's the key question that needs to be answered."

As for the histologic differences in the thyroid tumors between those who did and those who did not have breast cancer, he said, "The risk ratios were rather small. I wonder whether that's a spurious finding or real, but it is concerning if it's a reproducible finding that these patients have more aggressive variants."

"Anaplastic cancer is typically found in much older individuals, yet [these] cancer findings tended to skew younger. If there really is a link, is it possible that breast cancer therapy is inducing a more adverse profile of thyroid cancers compared with the general population of women in their 40s and 50s who get thyroid cancer?"

Second Primary Cancers: A New Paradigm

In her presentation, Dr Kuo pointed out that breast cancer survival has been improving dramatically, now reaching 89.2% at 5 years. With that comes the relatively recent phenomenon of second primary tumors rather than metastases.

Overall, the risk for a second primary cancer in breast cancer survivors has been estimated at 18% to 30%. Most of those are hormonally mediated, including ovarian and uterine cancers, but thyroid cancers are in the mix.

She told Medscape Medical News, "The focus for so long was on primary cancers. Now because we're so good at treating the primary cancers, we're realizing that these patients are developing second cancers. It's a newly recognized phenomenon, and we're trying to understand it better."

Dr Kuo and coauthors as well as Dr Wexler have disclosed no relevant financial relationships.

ENDO 2015: The Endocrine Society Annual Meeting. Abstract THR-049, presented March 7, 2015.

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