Recognizing the Complexity of TNBC

Joyce O’Shaughnessy, MD:Triple-negative breast cancer is one of the most challenging breast cancers that we have. Although we really do cure about 75% to 80% of women with standard chemotherapy, we simply do not have the tools for the other 20% at this moment. We don’t have any specific targeted therapies because what is actually driving that resistant triple-negative breast cancer is not well understood. So for metastatic triple-negative breast cancer, the lifespan is very short. It’s in the 12-month to 18-month range. This is because it’s very genomically unstable and we don’t have a clear way to kill off that perfuse heterogeneity that we have within the tumor cells.

Metastatic triple-negative breast cancer occurs in about 20% to 25% of women who were originally diagnosed with triple-negative breast cancer. This is in spite of our best therapies, which are chemotherapy at this point. The problem with metastatic triple-negative disease is that we’ve not had a specific target to go after and the cancer’s very genetically unstable. There are all different sorts of subclones and there is a great deal of heterogeneity. And so, any one treatment doesn’t work very well against it. Unfortunately, the median survival is in the 12-month to 18-month range. We have a lot of unmet medical need there. Of course, our most important unmet need is to prevent the metastatic breast cancer in the first place. But the discoveries are made in the metastatic setting, and then are moved up into the curative setting.

There’s a tremendous amount of research and a growing understanding of some important targets in triple-negative breast cancer. These are usually evaluated in the metastatic setting first. The immunotherapies are the leading contenders. They’re the furthest along. The challenge is to find the correct subset of patients who may benefit. Other important targets include the AKT pathway, for example. This is a key driver in triple-negative breast cancer and we’ve seen some early proof-of-concept trials in the triple-negative breast cancer setting. In metastatic disease, there is a phase III trial going on now with ipatasertib.

We know that the androgen receptor is important in triple-negative breast cancer, but it is still very much of a work in progress to find out which patients may benefit from an androgen receptor inhibitor alone or in combination.

And then there are new antibody drug conjugates in triple-negative breast cancer. Sacituzumab is pending before the FDA right now, with regard to an accelerated approval. The preliminary data looked very good in triple-negative breast cancer. There are a number of new agents coming, thankfully, and there is no do doubt that we will soon be able to break triple-negative breast cancer down into subtypes that can be specifically targeted.

Transcript edited for clarity.