HER2 positive breast cancer accounts for about 20% of all breast cancers and tends to occur in younger women. It used to be the most feared type of breast cancer due to its aggressive nature. However, in September 1998 a miracle called Trastuzumab happened, which changed the face of HER 2 positive breast cancer. It is a drug which blocks the HER2 receptor and when used along with chemotherapy works to eradicate the cancer cells. Since its FDA approval, it has saved thousands of lives. Very few drugs have had this kind of an impact on cancer management!

Building upon the success of Trastuzumab (Herceptin), additional agents designed to switch off the HER2 receptor have been approved including Pertuzumab (Perjeta), Lapatinib (Tykerb), Neratinib (Nerlynx), and Ado-trastuzumab emtansine (Kadcyla). In the last 20 years, with the help of all these drugs, we have been able to successfully change the outcomes of women with HER2 positive breast cancer. Today, prognosis of HER positive breast cancer is no worse than other less aggressive forms of breast cancer – leveling the playing field.

Inspite of all these advances in management, some women with advanced HER2 positive breast cancer develop and die from brain metastases (breast cancer that spreads to the brain). The HER2CLIMB trial examined a new drug called Tucatinib in this context. This drug works to treat HER2 positive breast cancer, even that which has spread into the brain. Patients who were enrolled into this trial had advanced HER2 positive breast cancer that was already resistant to multiple other treatments. About 50% of these patients had brain metastases. In this trial, all patients received Trastuzumab along with a chemotherapy agent called Capecitabine (Xeloda). In addition about 2/3rd of the patients received Tucatinib (test drug). The other 1/3rd received a placebo. The results of this trial were presented at the San Antonio Breast Cancer Symposium in December 2019. It was exciting to see that not only did Tucatinib keep the cancer at bay for a longer time, but also women who took this medication lived longer than those who did not. Most importantly, Tucatinib improved the overall survival even in those women who had brain metastases!

Another new drug known as Trastuzumab Deruxtecan was discussed at the SABCS. It belongs to a novel class of drugs called antibody-drug conjugates. The DESTINY Breast01 was a phase II trial which tested this medication in patients with advanced HER2 positive breast cancer that was extensively pre-treated.  Most of these women in this trial had received at least 6 prior treatments. Amazing responses were seen with this medication, the overall response rate was about 67%, with a disease control rate of 97%. The duration of response was about 16 months, with a median estimated survival rate of 86% at one year!

Hopefully, both these new drugs will be approved in the near future by the FDA, thus further improving the outcomes of women with HER2 positive breast cancer!

Padmaja Venuturumilli, MD.FACP.

Hematology Oncology Consultants.
Assistant Professor, OUWB School of Medicine, Michigan.