Professor Wang Shusen: HER2 redefines a new chapter in breast cancer targeted therapy

The HER family consists of four members, named HER1 (EGFR), HER2 (encoded by ERBB2, formerly known as neu), HER3 and HER4. Among them, human epidermal growth factor receptor 2 (HER2) is an orphan tyrosine kinase receptor belonging to the human epidermal receptor famil.

With the progress of research at home and abroad, HER2 has been redefine.

How was HER2 positivity initially defined?

In 1987, Professor Slamon published in "Science" that the amplification of erb-B2, the gene encoding HER2, is closely related to the prognosis of breast cance.

Based on this discovery, it is believed that the HER2 gene plays an important role in the occurrence and development of breast cancer, so a series of targeted drugs for this pathway have been studie.

The great achievement of targeted therapy for HER2-positive breast cancer

It is precisely based on the binary division of HER2 that the development of anti-HER2-targeted drugs has achieved great succes.

In the early years, many studies found that trastuzumab + chemotherapy in advanced first-line treatment can significantly improve progression-free survival (PFS) and overall survival (OS), establishing the once standard status of first-line trastuzuma.

The EMILIA study found that the efficacy of T-DM1 in patients with HER2-positive advanced breast cancer was significantly better than that of lapatinib + capecitabine, setting the international standard for T-DM1 in the second lin.

Multiple studies in adjuvant therapy have confirmed the therapeutic value of trastuzumab in HER2-positive early breast cance.

HER2 redefinition-proposition of the concept of HER2 low expression

In recent years, the emergence of some new drugs has also updated the treatment of low HER2 expressio.

The low expression of HER2 breaks the traditional "HER2 binary system" and forms a tripartite confrontatio.

A new chapter of ADC drugs-HER2 low expression targeted therapy

Several previous studies have used traditional drugs to treat patients with low HER2 expressio.

DESTINY-Breasto4, the first randomized phase I study of T-DXd in HER2-low mBC breast cancer, found significant improvements in PFS and OS regardless of HR+ or population-wide T-DXd for HER2-L, T-DXd A higher ORR of rapid remission can be achieved > 50%, so DESTINY-Breast04 established T-DXd as a new standard treatment for HER2 low-expressing HR+HR-mB.

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HER2-positive (HER2IHC3+ or FISH+) breast cancer has a unique law of occurrence and development, and is an independent molecular subtype of breast cancer;

In the past two decades, the research and development of targeted drugs for HER2-positive breast cancer has achieved great success, which has greatly improved the treatment landscape of HER2-positive breast cancer;

With the successful development of drugs for breast cancer with low HER2 expression, a situation in which HER2 is divided into three pillars has been forme.