Triple-negative breast cancer means that the tumor doesn't express estrogen and progesterone receptors. It is also HER2/neu-negative tumor. And this breast cancer historically has been difficult to treat with the worst prognosis. What new therapies for triple-negative breast cancer today?

Immunotherapy, for sure. If you have triple-negative breast cancer and you are expressing PD-L1 on the tumor, you can combine chemotherapy with the immune checkpoint inhibitor. There is a clear overall survival benefit. Another approach is with Sacituzumab Govitecan. It is an antibody-drug conjugate that demonstrated an improvement in overall survival in triple-negative breast cancer. Finally, we have the opportunity to use the PARP inhibitors for patients with BRCA-mutant triple-negative breast cancer. And in the metastatic triple-negative breast cancer setting, you have a progression-free survival benefits.

What level of PD-L1 expression is considered positive on the histology for breast cancer tumors?

This is a very good question. Suppose you use atezolizumab on more than 1% PD-L1 expression. If you use pembrolizumab, you have a major benefit on a CPS score of more than 10%.

Well, it's very important because the PD-L1 scores would be different for different types of tumors. Yes. What are the challenges in the targeted therapy for triple-negative breast cancer?

Up to now, of course, you have limited overall survival benefits. So you know, we have to do NGS. But it's quite uncommon in breast cancer, beyond NTRK, RET, and BRCA mutations, to find other targeted therapies. I hope in the future. We will have a more sensitive technology to do deep genomic sequencing. I am quite sure that also for this triple-negative breast cancer patient population, maybe you can better stratify the risk, and you can better personalize treatment. We know very well that in the early triple-negative breast cancer if a patient's tumor is enriched with tumor-infiltrating lymphocytes, you have a better prognosis. So maybe in the future, with a better stratification of the risk, it may be possible to avoid chemotherapy in some patients. We may use personalized treatment in other breast cancer patients.

New diagnosis of triple-negative breast cancer. How do you weigh doing the neoadjuvant chemotherapy versus proceeding with the surgery and doing the adjuvant chemotherapy?

Any patient with stage two and three triple-negative breast cancer should receive neoadjuvant chemotherapy. But I am quite sure that in some stage one triple-negative breast cancer patients, we may also avoid chemotherapy. We can go directly for surgery and radiation therapy.

So is the indication for neoadjuvant therapy in triple-negative breast cancer historically was for the ability to downgrade the surgical stage. What is the indication for neoadjuvant chemotherapy right now in triple-negative breast cancer and maybe in other breast cancer types? Is it purely based on the advantages for the long-term survival of patients?

Of course, the aim of neoadjuvant chemotherapy is not only related to a downstaging of the tumor. But potentially also neoadjuvant therapy can improve overall survival. We have many more data demonstrating that if you achieve a pathological complete response after neoadjuvant chemotherapy, there is an improved outcome also in terms of overall survival,

Some breast cancer tumors that I think have an overall better prognosis nevertheless achieve complete pathological response in the fewer percentage of the cases. How does it work?

In triple-negative disease, the potential of pathological complete response (PCR) is close to 70%. If you combine chemotherapy and immune checkpoint inhibitors, other subtypes of triple-negative breast cancer like adenoid cystic or mucinous carcinoma or lobular triple-negative breast cancer usually do not derive benefit from chemotherapy. But they may also have an excellent outcome with surgery and radiotherapy.