We Are Now Stronger in Targeted Drug Treatment for Breast Cancer!

With early diagnosis awareness becoming very widespread in many societies, breast cancer has become a disease diagnosed at early stages in up to 90% of cases. However, because it is the most common type of cancer in women worldwide, we still frequently encounter advanced breast cancer. In addition, approximately 30% of patients whose disease is early-stage at diagnosis develop metastases later. For these reasons, treatment of metastatic breast cancer remains a focus of interest, and new treatments developed in this area make significant contributions to patients’ survival.

Not all breast cancers are the same, and their treatments differ according to tumor type and extent of spread!

Treatment decisions for breast cancer depend on whether the tumor’s hormone and HER2 receptors are positive. Breast cancers are roughly classified into four different types, and two groups have positivity for the Her2 receptor. Cancer cells carrying this receptor are not sufficiently affected by chemotherapies and hormonal drugs without targeted drugs. Therefore, correctly identifying this patient group and planning targeted drugs at the right time is extremely important.

Human epidermal growth factor receptor (HER2) positivity

The receptor called HER2 is one of the mediators of cell growth signals. In HER2 + tumors, cancer cells overproduce this receptor. This causes more aggressive cancer behavior. Before new-generation targeted drugs targeting the HER2 receptor were developed, HER2 positivity was associated with a poor disease course and more frequent recurrence. About 20% of breast cancers are positive for HER2.

Targeted drugs directed at HER2 have become indispensable in combination with chemotherapy, particularly because they significantly increase survival in patients with metastatic (stage 4) HER2-positive breast cancer. So far, agents targeting HER2 have received approval in 4 treatments. All these drugs are accessible in our country and covered by reimbursement.

1. Trastuzumab (Herceptin®)

It is an antibody-based drug developed to bind the part of the HER2 receptor outside the cell. It is administered intravenously in an infusion. Trastuzumab, which received FDA approval in 1998, is approved for use in both early and advanced HER2-positive breast cancers. The discovery of this drug is one of the important milestones in cancer medicine because it was one of the first targeted molecular treatments.

In our country, as worldwide, it is started together with chemotherapy in early-stage disease to reduce recurrence risk and is used for 1 year. In patients with locally advanced disease, it is used together with chemotherapy to shrink the disease and make it suitable for surgery. After surgery, its use for preventive purposes is completed to a duration of one year.

In fourth-stage, that is, metastatic disease, it is used together with the chemotherapy drug docetaxel and the newly approved new-generation targeted drug pertuzumab. The use of pertuzumab, approved in our country in recent months, as part of a triple-drug combination enables us to achieve encouraging results in our patients.

2. Lapatinib (Tykerb®)

It is a small-molecule targeted drug in pill form that enters the cell and stops the cancer cell’s growth signal. It achieves this effect by suppressing the intracellular tyrosine kinase activity of the HER2 receptor. This drug, which received FDA approval in 2007, is approved for use in advanced HER2-positive breast cancers. It is used with the chemotherapy pill called Capecitabine. It is preferred in patients who previously used trastuzumab, that is, the drug called Herceptin, together with chemotherapy and developed a lack of response.

3. Pertuzumab (Perjeta®)

It prevents the HER2 receptor from becoming activated by binding to other similar receptors. It is an antibody-based targeted drug. Rather than being used alone, it is mostly used together with trastuzumab and a chemotherapy drug. This achieves dual inhibition (double suppression) against tumor growth.

Pertuzumab, which received FDA approval in 2012, was first approved for use with trastuzumab and the chemotherapy drug docetaxel in metastatic HER2-positive breast cancer. This form of administration was approved in our country only in July 2016. In 2013, it was approved by the FDA for neoadjuvant (shrinking = preparing for surgery) treatment of locally advanced HER2-positive breast cancers, but its use in this setting has not yet been approved in our country.

4. Ado-trastuzumab emtansine (Kadcyla®)

This new-generation drug, called T-DM1, consists of a combination of two different drugs (one trastuzumab (T), the other an antimicrotubule agent (DM1)). In other words, it combines a targeted drug and chemotherapy as a single drug. This drug, which received FDA approval in 2013, is used in treating advanced (metastatic) HER2-positive breast cancer. In our country, in September 2016, T-DM1 was approved for patients whose disease progressed after chemotherapies combined with Trastuzumab.

In the figure below, you can see the mechanisms of action of all these targeted drugs approved for use in our country in HER2-positive breast cancer.