Targeted Therapy for Breast Cancer

Targeted therapy is treatment directed at genes, proteins, or other substances that contribute in some way to the growth and development of cancer cells. Targeted therapy is possible because of advances in technology that allow researchers to detect abnormal genes and determine how various proteins send signals to each other to generate the growth of new cancer cells. Chemotherapy is usually given along with targeted therapy to create a powerful combination: chemotherapy kills existing tumor cells while targeted therapy agents inhibit new growth by blocking signals.

Three targeted therapy agents have been approved for use in the treatment of breast cancer, and others continue to be developed and evaluated in clinical trials (Table 1). Two of the approved agents are known as anti-HER2 agents because they inhibit HER2; only tumors that are HER2-positive can respond to an anti-HER2 agent. The third targeted therapy agent inhibits vascular endothelial growth factor (VEGF), a protein that helps tumors form new blood vessels; without vessels to bring blood to the tumor, it cannot continue to grow. This type of drug is known as an antiangiogenesis agent.

Trastuzumab (Herceptin) was the first targeted therapy to be developed for any cancer. Studies have consistently shown that trastuzumab has helped women with HER2-positive breast cancer to live significantly longer overall and without cancer recurrence. Trastuzumab is usually used in combination with specific chemotherapy drugs.

Adjuvant treatment with trastuzumab is recommended for HER2-positive breast cancers that are larger than 1 cm, regardless of whether cancer has spread to the lymph nodes. Trastuzumab is given once weekly as an intravenous infusion over 30-90 minutes and treatment continues for 1 year. The agent is also recommended as first-line treatment of HER2-positive metastatic breast cancer and is given in the same manner for the same length of time.

Lapatinib (Tykerb) is another anti-HER2 agent. In combination with capecitabine, lapatinib has delayed the progression of breast cancer for nearly twice as long as capecitabine alone in women with metastatic HER2-positive breast cancer. Lapatinib is approved for use with capecitabine for the treatment of HER-positive metastatic breast cancer that has stopped responding to anthracyclines, taxanes (paclitaxel or docetaxel), and trastuzumab.

Bevacizumab (Avastin) has been effective for other types of cancer (most notably, colorectal cancer) and is now approved for use as first-line treatment in combination with paclitaxel (Taxol) for HER2-negative metastatic breast cancer. In one study, the combination enabled women to live nearly twice as long without progression of the cancer compared with paclitaxel alone.

Researchers continue to evaluate targeted therapy agents in combination with different chemotherapy drugs for neoadjuvant, adjuvant, and primary treatment of breast cancer. A class of targeted therapy agents that has shown promise in early clinical trials is PARP inhibitors. Drugs in this class block an enzyme called poly (ADP-ribose) polymerase (PARP), which cancer cells use to repair damage to their DNA. PARP inhibitors are being studied as treatment for triple-negative breast cancer (negative for HER2, ER, and PR), a type of breast cancer that is associated with defects in DNA repair and especially those with BRCA1 or 2 mutations.

Another targeted agent, erlotinib (Tarceva), is currently being investigated in several breast cancer clinical trials. This agent belongs to a class of drugs known as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. The clinical trials of erlotinib involve the use of the agent for metastatic, triple-negative breast cancers that overexpress EGFR. Erlotinib is also being evaluated for its effect as neoadjuvant treatment to shrink tumors before surgery and in combination with antiestrogens to overcome resistance to those drugs.

Large trials are needed of both PARP inhibitors and erlotinib before either can be used routinely in practice.

Because targeted therapy agents act in specific ways, they do not carry the same risk as chemotherapy for damaging healthy tissues. As such, these agents usually cause fewer side effects than traditional chemotherapy. However, targeted therapy agents for breast cancer may cause side effects. It is important to remember that not all side effects will occur in every individual who takes the same drug. Talk to your doctor about what side effects to expect and if they can be prevented and/or managed.

Table 1. Targeted Therapy for Breast Cancer
 

• American Cancer Society: www.cancer.org, Detailed Guide to Breast Cancer; Breast Cancer Profiler Tool(decision-making tool)
• ASCO's patient Web site: www.cancer.net, Breast Cancer Treatment
• Breastcancer.org: www.breastcancer.org, Treatment and Side Effects
• Susan G. Komen for the Cure: www.komen.org, Understanding Cancer: Treatment

• Trastuzumab for Targeted Therapy of Breast Cancer