New Paradigms Emerging in Diagnosis, Management of Thyroid Cancer

BRAF has been identified as the most prevalent of the mutations identified in papillary thyroid cancer.

This kind of worries me, because if BRAF is a marker of aggressive behavior, then you would expect that a large majority of our patients from whom samples were obtained, are likely to go on to have bad aggressive disease clinically, and I’m not sure this is necessarily true, Dr. Ezzat said. I would emphasize that on the aspirates, you can do RET/PTC rearrangements and you can do BRAF point mutations. And if you do these two and combine it with morphology, at least as of 2006, you’ve got it pretty much nailed in terms of combining molecular diagnosis with morphology.

Dr. Ezzat said there are drugs available now that specifically inhibit BRAF and they have been shown in recent studies to actually inhibit tumor growth, indicating that if it is possible to target this pathway, it’s not just of diagnostic value, but potentially of therapeutic value.

What I’m worried about, however, is not so much the diagnosis of papillary cancer, but I’m worried about papillary cancer that is going to invade, potentially metastasize, and potentially have impact on morbidity and mortality in that patient, he said. I think that’s where our efforts really need to lie.

And it’s not just the thyroid cancer that researchers and clinicians need to be thinking about, Dr. Ezzat emphasized, but also the thyroid neighbors-the so-called stromal elements and the matrix outside.

It’s this neighborhood interaction between the cancer cell, the host, and its cellular environment that’s going to be absolutely crucial in teaching us how we’re going to stop cancer from being a small indolent malignancy to one that has the ability to invade and metastasize and cause a lot more clinically aggressive disease, he said.

Risk Stratification

Approximately 25,000 cases of thyroid cancer were diagnosed in the United States last year, with an expected 30,000 this year. Fortunately, most of the patients with thyroid cancer are going to do very well. But how do you identify those few patients who are going to do poorly?

We used to say thyroid cancer was a rare disease, but if you look at the actual number of thyroid cancer cases diagnosed, it’s really not much different than the number of Hodgkin’s disease, myeloma patients, and kidney cancers that are diagnosed throughout the United States, said R. Michael Tuttle, MD, an endocrinologist at Memorial Sloan-Kettering Cancer Center in New York. The numbers have actually more than doubled in women since the 1970s, from six per 100,000 women to 13 per 100,000, and those numbers are going to go up.