And Nancy, can you tell us a little more about this study?

Sure.

So this study was a phase three randomized non-inferiority trial that was looking at test-directed chemotherapy versus no chemotherapy in patients with high clinical risk, ER positive, HER2 negative, early breast cancer.

So here's the study design.

So this is quite distinct from the Taylor-RX or R-Exponder trials where patients were randomized to chemo or no chemo.

Instead, here are patients who were over the 40 years or older who had ER positive, and this was defined as at least 10% by IHC.

either node-negative or node-positive disease, this went up to nine positive nodes, were randomized to either receive chemotherapy followed by endocrine therapy in the control arm or test-directed therapy where a proscina test was performed.

Does this study resolve that issue? Do we still need to accrue to the offset trial? Or is this still an open question in your mind?

Nancy?

Yeah, thank you.

So we're going to switch gears a little bit and talk about the issue of brain metastasis.

So first of all, why were we talking about this in HER2-positive disease? These are data from a very large U.S.

database, and essentially by third line of therapy, 20% of hormone receptor positive HER2-positive, 36% of hormone receptor negative HER2-positive patients have developed brain metastases.

And we know if we follow these patients until death, about 50% will develop brain metastases.

Those were data from unscreened populations, but there's increasing interest in doing clinical trials of screening brain MRIs in patients.

You don't see this with chemo?