(Vienna, 07-12-2018) In the case of HER2-positive early breast cancer, which had already been treated with antibody therapy prior to surgery (neoadjuvant therapy) and in which a residual tumor remained, it is possible for standard therapy to change fundamentally. This is borne out by the results of an international study carried out with the significant participation of the Comprehensive Cancer Center (CCC) of MedUni Vienna and AKH Vienna. The scientists were able to show that in this disease, a well-known antibody-drug conjugate (trastuzumab emtansine) reduces the risk of relapse by 50 percent compared to standard therapy.
The work has now been presented at the world's leading breast cancer congress, the San Antonio Breast Cancer Symposium in the USA.
Breast cancer is a disease that breaks down into many subgroups. In one of these subgroups, tumor cells form a receptor to an excessive extent: the human epidermal growth factor receptor 2 (HER2). As a result of this, the cell receives too many signals for division and multiplication, which causes the tumor to spread very rapidly and uncontrollably. Around 15 to 20 percent of breast cancer patients suffer from this type of breast cancer. Depending on the progression of the disease, HER2-positive tumors are treated differently.
The standard therapy for HER2-positive early breast cancer (with and without a residual tumor after neoadjuvant treatment) is the administration of the antibody trastuzumab to prevent or delay relapse and eventual metastasis. The mechanism of action: Trastuzumab blocks HER2 and the growth signals can no longer get inside the cell.
Regarding relapses and life expectancy however, only those persons who have a complete remission after the neoadjuvant therapy, i.e. no residual tumor, benefit significantly. Therefore, a treatment option was tested for those with residual tumors.
Groundbreaking study results
As Günther Steger, Department of Internal Medicine I at MedUni Vienna and AKH Vienna, member of the CCC and director of the study in Austria explains: "The substance is the innovative antibody-cytostatic conjugate trastuzumab emtansine, which is already fully established in metastasis therapy. This substance is almost selectively absorbed by the antibody component only in tumour cells and the cytostatic component is then only released in this. Therefore, the potential effect is great and the side effects are comparatively low."
The KATHERINE study now shows that the risk of metastasis and relapse can be reduced by 50 percent compared to current standard therapy with trastzumab alone, thus potentially improving the survival prognosis. As Steger continues: "I am sure that the substance will permanently change the adjuvant (preventive) therapy for this indication once it has been approved."
About the drug
Trastuzumab emtansine is a combination of two drugs, a so-called drug conjugate. This compound creates a single substance. In this case, an antibody and a cytostatic drug (active ingredient of a chemotherapy drug) are combined to unify the therapeutic principles of HER2 antibody therapy and chemotherapy. The cytostatic agent is chemically bound to the HER2 antibody, which transports it, virtually piggybacked, to the HER2-positive cancer cell. There, the antibody binds to the specific receptor and the cytostatic drug is introduced into the cancer cells. Inside the cancer cells, it triggers the death of the cell (apoptosis).
“A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)”. DOI: 10.1056/NEJMoa1814017