Director Zhang Jian: The latest clinical progress of HER2-positive breast cancer

Mays Medicine: The incidence of HER2-positive breast cancer in the whole breast cancer, what are the pathological characteristics?

Director Zhang:

According to molecular classification, breast cancer is divided into four categories, two of which are related to HER2-positive breast cancer, one is ER-negative HER2-positive, that is, pure HER2-positive breast cancer; the second is ER-positive HER2-positive double-positive or triple-positive breast cancer.

Characteristics of HER2-positive breast cancer: In the absence of previous anti-HER2 target therapy, patients have a higher risk of recurrence; after anti-HER2 target therapy (including trastuzumab, pertuzumab, high-risk adjuvant enhanced T -DM1) After treatment, the risk of relapse decreased significantly

Thus, HER2 is a powerful breast cancer driver gene

Mays Medicine: How to determine HER2 positive, what if the pathological results do not match the clinical manifestations?

Director Zhang:

National industry standards for HER2 determination:

HER2 positive mainly refers to two cases, one is HER2 immunohistochemistry (3+), the other is HER2 immunohistochemistry (2+), and ISH (in situ hybridization) is positive at the same time

Therefore, in the new ASCO/CAP specification, there is no mention of how HER2(1+) or HER2(0) but FISH-positive patients are classified

Corresponding changes have also occurred in the evaluation criteria of FISH.

Whether this criterion will change in the future with novel ADC drugs is unknown

Mays Medicine: Recently, there has been a saying that the low expression of HER2 needs to "stand on its own".

Director Zhang:

In fact, this issue has been discussed at many conferences, and everyone has formed a certain consensus, but there are still some disputes

There is no need for HER2 low expression as an independent prognostic subtype

For therapeutic subtypes, low HER2 expression has some value

Thanks to the excellent results of the DB04 clinical study, low HER2 expression has attracted more and more attention.

Therefore, low HER2 expression has been recognized by everyone as a therapeutic subtype.

Mays Medicine: What is the current clinically recommended standard treatment for HER2-positive breast cancer?

The standard treatment regimen for HER2-positive breast cancer needs to be discussed separately according to the two categories of early breast cancer and advanced breast cancer:

1.

There are different recommended regimens based on the risk of HER2-positive breast cancer recurrence, such as:

2.

It is recommended to adopt "dual target first", which mainly refers to trastuzumab, pertuzumab and taxanes

The commonly used second-line treatment regimens are capecitabine + pyrotinib or T-DM1
.
With the advent of DS-8201, especially in the results of DB03-related clinical studies, where the investigator-assessed PFS exceeds 25 months, the pattern of second-line therapy may change (shaking T-DM1's status as a standard second-line therapy)
.
In addition, independently assessed PFS values ​​in the DB03 clinical study have not yet been published, and we expect it to be longer
.

3.
Third-line or above treatment is a matter of opinion
.

Overall, the treatment landscape of anti-HER2-positive breast cancer has undergone important changes.
More and more new drugs and drugs with excellent efficacy are advancing.
We expect that some anti-HER2 ADC drugs can be used in neoadjuvant/adjuvant intensive therapy.
There have been breakthroughs in the treatment, so that patients have an increasing chance of recurrence-free survival
.

Mays Medicine: Where are the current research hotspots in HER2-positive breast cancer?

Director Zhang:

Drug resistance in HER2-positive breast cancer
.

First, for macromolecular monoclonal antibodies, small molecule inhibitors and even ADC resistance mechanisms are still immature, especially ADCs are poorly understood.
Therefore, ADC resistance mechanisms are one of the current research hotspots.
It will open up new space for new drug design and treatment of HER2-positive breast cancer
.

The back line goes to the front line, and the front line advances to neo-auxiliary/auxiliary research
.

When new anti-HER2 therapeutic drugs are available, the basic strategy of conducting relevant clinical research from the back-line to the front-line is usually adopted, but sometimes it is also carried out simultaneously to speed up the acquisition of research results and the benefit of patients
.

The deployment of anti-HER2 therapeutics
.

For example, anti-HER2 antibodies, TKIs and ADCs may become first-, second-, and third-line treatments for each other in the future
.
Which one is better or worse, it remains to be seen
.