Clinical Validation of the Afirma Genomic Sequencing BRAF V600E Classifier


Interview with Trevor E. Angell, M.D., Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital and Harvard Medical School

Dr. Trevor Angell is an endocrinologist at Brigham and Women’s Hospital who specializes in treating thyroid disease. Dr. Angell began using the Afirma® Gene Expression Classifier (GEC) in 2014 and the next-generation Afirma® Genomic Sequencing Classifier (GSC) in 2017. He has partnered with several other thought leading physicians over the past several years to assess the Afirma classifier’s ability in identifying various thyroid cancer subtypes. Most recently, he led an evaluation of the Afirma GSC BRAF V600E classifier. Dr. Angell presented the findings from this evaluation at the American Thyroid Association Annual Meeting on October 19, 2017.

Q: What was this evaluation of the Afirma® Genomic Sequencing BRAF V600E Classifier designed to determine? 

Dr. Angell: We assessed the Afirma GSC BRAF classifier that identifies the presence of the BRAF V600E mutation in thyroid nodule fine needle aspiration biopsies. We were particularly interested in the BRAF classifier’s sensitivity and specificity for this mutation.

Q: Topline, what did you learn? 

Dr. Angell: Most importantly, we confirmed that the BRAF V600E classifier is very accurate in determining preoperatively whether this mutation is present – or not – in a thyroid nodule specimen. Physician understanding and comfort with new technology such as the Afirma GSC and BRAF classifier is an important aspect of its application. So evaluating this classifier in a way that helps physicians feel confident in its results is also an important outcome from our research.

Q: What are the real-world implications of being able to detect BRAF V600E with this level of sensitivity and specificity? What does it mean for physicians, patients and the healthcare system? 

Dr. Angell: The presence of the BRAF V600E mutation in thyroid nodules has many clinical implications. First, it confirms the presence of thyroid cancer. It really provides proof that thyroid cancer is present, so is highly important diagnostically. Second, we know that thyroid cancers tend to be more aggressive when they have this mutation, so knowing a patient’s BRAF status can influence treatment decisions. For example, it will likely prompt a more extensive surgery, rather than a lobectomy.

Q: As a physician who treats patients with thyroid nodules and thyroid cancer, what specific challenge does the Afirma GSC BRAF classifier address for you?  

Dr. Angell: The Afirma GSC’s rich RNA-sequencing technology platform supports the detection of BRAF V600E. BRAF status is always relevant in thyroid nodule evaluation and something we really like to know. It is clinically meaningful that this classifier has both high sensitivity and specificity.


Q: What would you like your peers to take away from this evaluation and/or your findings? 

Dr. Angell: I would like them to know that the BRAF V600E is a very robust classifier. Additionally, the fact that this classifier generates very few false positives is important. Using advanced, next-generation sequencing technologies, we can find BRAF V600E mutations that would have been missed by previous techniques, such as PCR. The BRAF classifier adds to the powerful genomic testing tools available for our thyroid nodule patients.

Read the Abstract Here