DR RUGO: Clearly, triple-negative or highly proliferative disease is more immunogenic. And we’ve seen in those patients more tumor infiltrating lymphocytes. And that’s kind of been an interesting window. There’s a whole lot of data that came out at ASCO looking at tumor infiltrating lymphocytes with, like, widely variable conclusions. It matters. It doesn’t matter. It matters when you’re diagnosed but not after chemo. Or it does matter after chemo more. So we’re still learning this and, I think, learning about the markers.

But we do know that if you have more tumor infiltrating lymphocytes at diagnosis with these proliferative cancers that you do tend to have a better outcome. And that’s true for ER-negative and also HER2-positive disease. And Sherene Loi from Melbourne has done a lot of this work on multitudes of studies. We also know that PD-L1 expression seems to have some impact on outcome, either in some cases a better outcome in the early-stage setting, in some cases a worse outcome depending on how you measure it. We know that there’s no standard way to measure PD-L1, no standard antibodies.

What we’ve learned, actually, is that if you respond to a checkpoint inhibitor and you have a clear RECIST response that those patients often have very durable and long-lasting responses, even if it’s a very small number of patients, which is intriguing. We’re hoping now that, by giving chemotherapy or other immune agonist together with the checkpoint inhibitors that we’ll be able to stimulate the immune response and then allow it to be unblocked by giving the checkpoint inhibitor. It’s a really clever idea. And you can make a nice cartoon about it. And now we have to see whether it works in the clinic.

The question is, if you didn’t have an immune response and you stimulate that immune response, can you then unblock the blinding by the tumor cell and make it work for your patient? And that, I think, is the question being asked by numerous trials ongoing, including our Phase III trials and Phase II combination studies.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers