Mohammad Jahanzeb, MD: When we think of factors that go into decision making, we are assessing the risk of relapse in the patient, basically. And historically, we have thought of tumor size, nodal status, grade of the tumor, and obviously receptor status, and we have known for more than 30 years—actually going on 40 years—that HER2-positive disease has a worse prognosis than HER2-negative disease. They tend to be more aggressive. And anti-HER2 therapy has changed all of that because these are very effective, well-tolerated therapies, and they have come into the adjuvant setting and cut the risk of relapse by at least one-third or sometimes even in half.

And then when therapies are so effective, you have to calculate the risk of relapse to calculate the absolute benefit in a given patient. And now we know that even some-centimeter tumors have up to a 23% risk of relapse. So, we consider and offer trastuzumab-based therapy even to those patients. The only difference is we don’t give them full-scale chemotherapy. We may give them just 12 weekly doses of paclitaxel. Now we have more than 4 years’ follow-up on that cohort presented by Dr. Tolaney from Dana-Farber Cancer Institute, and the results are phenomenal. We are still seeing disease-free status at that follow-up of more than 4 years at 98% or so.

If you then go into patients with larger tumors, greater than 1 cm, with or without node positivity, the standard of care has been 1 year of trastuzumab.

Transcript Edited for Clarity