Hormone-positive, 
HER2-negative breast cancer. Antibody-drug conjugates. 3

Hormone-positive, 
HER2-negative breast cancer. Antibody-drug conjugates. 3

Hormone-positive, 
HER2-negative breast cancer. Antibody-drug conjugates. 3

Can we help?

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You lead the Early Drug Discovery Program at the European Institute of Oncology. You focus specifically on breast cancer treatment and other solid tumors. Could we discuss the advances in breast cancer treatment in three major situations? The hormone receptor-positive breast cancer, the HER2-neu positive breast cancer. And triple-negative breast cancer, which historically has had a very challenging prognosis. So perhaps we could start with the estrogen and progesterone receptor-positive breast cancer, but HER2/neu-negative breast cancer. What is new on the horizon in treatment for those breast cancer patients?

What we can mention about those patients is the opportunity to use PI3 Kinase alpha-selective inhibitors. We know that 41% of those patients are PI3K kinase-mutant. In this patient population, you can combine Alpelisib, which is an alpha-selective PI3 kinase inhibitor, with fulvestrant. This leads to the improvement of progression-free survival. I must confess that in the future, also in ER-positive breast cancer, you may have the opportunity to use antibody-drug conjugates. Actually, there is a prospective randomized clinical trial ongoing (DESTINY-Breast06) for those patients who progress to CDK4/6 inhibitors. They are randomized to trastuzumab deruxtecan if they have too low expression of HER2/neu antigen. Another clinical trial arm is chemotherapy at the investigator's choice. So these are breast cancer treatments on the horizon that we may have in a short time. We may have these breast cancer therapies in five years, maybe are the new oral SERDs (Oral Selective Estrogen Receptor Degraders). Specifically, these are estrogen receptor degraders that can be taken orally with a better quality of life and measured compliance for patients.

So this is very interesting. You mention a completely new sort of drug-conjugates, antibody-drug conjugate medications. What are antibody-drug conjugates?

Specifically, antibody-drug conjugates are sacituzumab govitecan and trastuzumab deruxtecan, and ladiratuzumab vedotin.

And what is the principle behind this new class of breast cancer medications?

It is like a Trojan horse. You target a specific signal on the breast cancer cell. The antibody is conjugated with a very high payload of chemotherapeutic agents that will go directly into the cancer cells, sparing the normal tissue. So you will have a higher therapeutic index and lower toxicity of breast cancer chemotherapy.

So that seems like a very revolutionary paradigm. There are also antibody conjugates with the locally-acting radiopharmaceuticals. They have already been used in medicine.

This is a new approach to cancer treatment. We can call it the agnostic approach. And I am quite sure that in the future, we will have a similar approach also in breast cancer.

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