About 15-20% of women diagnosed with breast cancer have the HER2 positive breast cancer subtype. The HER2 protein in these breast cancers is increased in amount and becomes the most important driving force responsible for cancer cell growth.

Trastuzumab is a lab-synthesized drug that attaches to the HER2 protein in breast cancer cells and stops cancer cells from growing and dividing. It was approved in 1998 to treat women with metastatic HER2 positive breast cancer. Then later approved for use in early breast cancer patients in 2005.

This type of HER2 targeted treatment has dramatically improved the life span and increased cure rates in women with metastatic and early breast cancer, respectively. As shown in Figure 1 below, newer HER2-targeted drugs have since been approved. This was after being rigorously tested in large clinical trials, proving that they could further improve patients’ survival.

Timeline of HER2 targeted therapies approved by the EMA & FDA.

HER2 Positive Targeted Therapies at Present

At present, both trastuzumab and pertuzumab are approved to be used as the first treatment with chemotherapy, specifically in women with metastatic HER2 positive breast cancers in Australia. When such women were followed-up by the original Cleopatra trial designed to test this treatment combination, 37% of these women remain alive eight years after starting treatment. This is a remarkable achievement in the history of breast cancer treatment.

If metastatic breast cancers become resistant to these initial treatments (trastuzumab, pertuzumab and chemotherapy) and no longer work, patients are usually switched to T-DM1, otherwise known as “trastuzumab emtansine”. As shown in Figure 2 below, T-DM1 is an antibody drug conjugate (ADC) with a small amount of chemotherapy attached to the monoclonal antibody that targets the HER2 protein.

Types of HER2 targeted treatment available.

Chemotherapy is released into the breast cancer cell when the drug is locked onto the HER2 protein. Because the small molecule of chemotherapy is only released within the HER2 positive breast cancer cell, this is called targeted treatment and is not referred to as “chemotherapy”. When TDM-1 no longer works, the small molecule inhibitor drug lapatinib can then be used.

Recently, pertuzumab and T-DM1 have both been adopted into the treatment of early HER2 positive breast cancers. Before surgery, pertuzumab is added to trastuzumab and chemotherapy to shrink the size of the breast cancer (but this drug is not funded by Medicare and requires payment for at least part of the cycles of pertuzumab treatment).

It has been shown to improve the probability of shrinking the HER2 positive breast cancer completely without any cancer cells left in the breast. At the time of surgery, if any residual breast cancer cells are found in the breast or adjacent lymph nodes after initial trastuzumab +/- pertuzumab and chemotherapy, switching to T-DM1 treatment has been shown to improve cancer survival outcomes when compared to staying on trastuzumab for up to 12 months.

Adding 12 months of neratinib (again not currently PBS funded) after completion of 12 months of trastuzumab in some early breast cancers can also improve cancer-free survival in women with both HER2 positive and hormone positive subtypes.

Looking to the future

Newer ADC such as trastuzumab-deruxtecan (T-Dxd) has recently been approved by the American and European health agencies. This is a result of two trials that showed that T-Dxd can outperform the current standard treatment of T-DM1.

Another new drug called tucatinib has also been approved overseas. It also works to shrink cancers even after trastuzumab and T-DM1 have stopped working.

We are hopeful that these drugs may be funded by Medicare so that patients with HER2 positive metastatic breast cancer can access these effective treatments when and if they are needed.

In summary, research into new ways of targeting breast cancer cells to improve outcomes for women with breast cancer is a continuous process. We are dedicated to finding the best treatments for all of our patients.