HER2+ (HER2-positive) breast cancer is a type of breast cancer subtype with strong aggressiveness and poor prognosis. With the approval of more new targeted drugs for clinical application, the prognosis of HER2+ breast cancer patients continues to improve. In the absence of previous anti-HER2 targeted therapy, patients with HER2+ have a higher risk of recurrence. After anti-HER2 therapy, the risk of recurrence is significantly reduced. In recent years, the emergence of antibody-coupled (ADC) drugs has brought the treatment of HER2+ breast cancer patients into a new era, but there are still some unsolved problems. At the 7th International Consensus Conference on Advanced Breast Cancer (ABC7), Oncology Frontier invited Dr.Javier Cortes of the Vall d’Hebron Institute of Cancer in Barcelona, Spain, to summarize and look forward to the changes in the field of HER2+ advanced breast cancer.
Oncology Frontier:What do you think is the biggest change or the most important research progress in HER2+ advanced breast cancer since ABC6?
Dr.Javier Cortes :I think that without any doubt, the data we have seen with trastuzumab deruxtecan（T-DXd）in both second line or third line and beyond, showing not only an improvement in progression free survival but also a very nice and dramatic improvement in overall survival has established this agent as the clear second line new standard of care.
Oncology Frontier:HER2 expression has certain spatial and temporal heterogeneity. When and how do you perform HER2 testing and evaluation in clinical practice?
Dr.Javier Cortes :I think that in my opinion we have to differentiate between HER2 low and HER2 overexpressing tumors. So although it is true that there is a clear heterogeneity in tumors, HER2 overexpressing tumors do not change that much. It changed in the range of 7% across time. So I think that for the HER2 low expression, that’s absolutely something very, very dynamic. So it is true that when we looked at the HER2 low expression, it happens in the range of 50 to 55% of all patients. But when we look at the sequential biopsies, we can observe this as high as 85 or even 90% of patients. So I think it is important to look for the HER2 low expression to give the patients the opportunity to receive T-DXd in the future.
Oncology Frontier:HER2 ADCs already have a new standard of second-line treatment and are making their way to the first-line. Looking ahead, what do you think will happen to the treatment of HER2+advanced breast cancer?
Dr.Javier Cortes:I think it’s very likely that T-DXd will be superior to the CLEOPATRA based strategy, involving taxane-trastuzumab-pertuzumab in the first-line setting. So this will mean that maybe T-DXd will be the standard of care in the first line. So nevertheless, there are open questions that have to be addressed in the future. So for example, do we need T-DXd forever or would it be possible to go for T-DXd as induction therapy followed by maintenance with trastuzumab and pertuzumab? Of this regard, we are conducting a clinical trial looking at this point, starting with T-DXd followed by maintenance of trastuzumab and pertuzumab. So I think that T-DXd is very likely to be positioned in the first line setting, but we have to understand better which is the optimal duration of this excellent drug.
Javier Cortes
Clinical Investigator, Breast Cancer Research Program, Vall d’Hebron Cancer Institute, Barcelona, Spain Head of Breast Cancer and Gynaecological Cancer, Ramon y Cajal University Hospital, Madrid, Spain
