How do you think about selecting patients for this escalation strategy? And what factors influence whether you might consider adjuvant TDXD for a patient who did not

achieve a PCR? It's a great question, Sarah, and I think really exciting data from the DESTINY Breast O5 trial.

I was glad to see it added so rapidly, actually, into the NCCN guidelines.

So just to refresh everybody's memory about the design of the DESTINY Breast O5 trial, this was a trial that took patients who had residual disease after receiving chemo plus HER2-directed therapy for early-stage HER2-positive breast cancer and randomized them to either 14 cycles of trastuzumab, druxtecan, or TDXD versus the historical standard 14 cycles of the alternative antibody drug conjugate TDM1, which was initially established about 10 years ago based on the Catherine trial.

And I think it's important to point out, and it's important when we think about which patients are we going to go to the adjuvant TDXD for, that the patients who are eligible for Destiny Breast 205 were really a particularly high-risk population.

This was a trial whose eligibility criteria selected for higher risk patients than even the Catherine trial had.

So in order to get on to Destiny Breast 05, you had to either have not just residual disease but residual disease in your lymph nodes, so a particularly high risk situation, or if you had residual disease just in the breast, you had to have had very high risk clinically staged disease at the outset prior to receiving your neoadjuvant chemo and HER2 directed therapy.

How are you thinking about the role of ADCs, particularly TDXD, in metastatic HER2-positive breast cancer? And how are you sequencing, let's say, TDXD and TDM1 in the metastatic setting?