Breast Cancer

Understanding Targeted Therapy
. . . An Interview with Dr. Gabriel Hortobagyi

What is targeted therapy?

Targeted therapy is both a goal and a process. This type of treatment fulfills a long-standing wish to use the drug that is the most suitable and the most likely to work and, conversely, to avoid using drugs that are not suitable and are not likely to work. Targeted therapy is possible only because we have gained knowledge about the biology of tumors; for example, we have learned about many molecules that are involved in cell actions that cause cancer cells to grow. If we can interfere with these actions, we can prevent the growth of cancer cells. Targeted therapy is the use of specially developed drugs that are directed at specific molecules involved in these actions.

What targeted therapies are available for women with breast cancer?

Targeted therapy actually has its origin in breast cancer. The most important step in the development of targeted therapy was the discovery that female hormones can drive the growth of a breast cancer, and the use of hormone therapy is a pioneering event in targeted therapy across all types of cancer. Hormone therapy prevents estrogen from fueling the growth of cancer cells in breast tumors that test positively for estrogen and/or progesterone receptors (ER+/PR+ tumors). Another important targeted agent in breast cancer is trastuzumab (Herceptin), which is directed at the signaling pathway of human epidermal growth factor 2 (HER2), a protein expressed at high levels in some breast cancers. (Hormone therapy and targeted therapy are discussed in further detail in the Targeted Therapy According to ER/PR section.) These examples illustrate the importance of the development of technology to identify tumor markers. Without the ability to detect ER, PR or HER2 on breast cancer cells, researchers would not have known that these potential targets existed. Thus, tumor markers are an essential component of targeted therapy.

Another class of drugs, known as antiangiogenesis agents, has been developed to target vascular endothelial growth factor (VEGF), which is involved in the formation of new blood vessels. These agents interfere with signals between VEGF and its receptors. Without vessels to bring blood to the tumor, it cannot continue to grow.

How has the use of targeted therapy improved breast cancer treatment?

Twenty years ago, we treated all breast cancers in pretty much the same manner. Today, I cannot imagine treating all breast cancers the same. Our increasing understanding of the critical molecular abnormalities involved in breast cancers has allowed us to characterize breast cancers more specifically and to develop treatments that can be adapted for the type of breast cancer. Targeted therapy has significantly improved the disease-free survival and overall survival for many women with breast cancer. For example, HER2+ tumors are one of the most malignant types of breast cancer but the use of anti-HER2 agents, such as trastuzumab, has changed the clinical course of this breast cancer into one that is better controlled; HER2+ breast cancer treated with anti-HER2 agents is now associated with the highest cure rates among breast cancers. Similarly, there are increasingly more survivors with luminal A breast cancer, or ER+ breast cancer, which can now be controlled more effectively with the use of hormone therapy. Many drugs still being tested in clinical trials are showing great promise as treatment for other types of breast cancer, including triple-negative cancer, the most aggressive type of breast cancer.

How safe are targeted therapies?

Because targeted therapy agents act in specific ways, they do not carry the same risk as chemotherapy for damaging healthy tissues and so they usually cause fewer side effects than traditional chemotherapy. However, targeted therapy agents for breast cancer may cause some side effects (see Side Effects). The safety of targeted therapy — and any new cancer treatment — is a primary concern in clinical trials, and approval is granted only to drugs that are considered to have a good safety profile.

What does the future hold for targeted therapies?

Currently, hundreds of oncology drugs are in development, and they represent different classes of drugs and a variety of targets. In addition to HER2 and VEGF, other substances being evaluated as potential targets in breast cancer are poly (ADP-ribose) polymerase (PARP), the insulin-like growth factor receptor (IGFR)-1, and mammalian target of rapamycin (mTOR). The results of early trials with PARP inhibitors have been impressive, especially for metastatic triple-negative breast cancer and breast cancers with BRCA1/BRCA2 mutations.

The continued success of targeted therapy depends on research to better understand what cells, signals, and interactions are the most important in the growth and proliferation of breast cancer cells. Success also depends on clinical trials to evaluate targeted agents.

Where can I find information about clinical trials of targeted therapies?

Talking to a member of your treatment team is one of the best ways to learn about what clinical trials you may be eligible for depending on your particular type of breast cancer. You can also search for trials in the National Cancer Institute’s clinical trials database at www.cancer.gov/clinicaltrials/search.

 

Previous Next


Register Now! Sign Up For Our Free E-Newletter!

Read Inspiring Cancer Survivor Stories

Order Your Guides Here