Targeted Therapy
Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target,” targeted therapies may slow cancer cell growth or increase cancer cell death.
HER2-targeted therapy: Twenty to thirty percent of breast cancers overexpress (make too much of) a protein known as HER2.[1] Overexpression of this protein leads to increased growth of cancer cells. Fortunately, the development of treatments that specifically target HER2-positive cells has improved outcomes among women with HER2-positive breast cancer.
Herceptin® (trastuzumab): Herceptin is an agent that recognizes and binds to HER2-positive cells. The effects of Herceptin are thought to include decreased cell growth and increased cell death.[2] Results from an important clinical trial indicate that adding Herceptin to chemotherapy improves survival for patients with advanced HER2-positive breast cancer.[3]
Avastin® (bevacizumab): Avastin is a targeted therapy that blocks a protein known as vascular endothelial growth factor (VEGF). VEGF stimulates the growth of new blood vessels. Drugs that interfere with VEGF can slow or stop the growth of cancer cells, and may also improve the delivery of chemotherapy to cancer cells by normalizing blood supply.
CancerConnect Breast Cancer Community & Discussions
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Among women with advanced, HER2-negative breast cancer who have not received prior treatment for metastatic disease, treatment with Avastin plus paclitaxel resulted in a longer time to cancer progression than treatment with paclitaxel alone.[4] The addition of Avastin did not, however, significantly improve overall survival.
Management of Bone Metastases
Breast cancer cells that have spread to the bones are called bone metastases. Cancer can spread to the bones when individual cancer cells break off from the original tumor and travel in the circulatory or lymph system until they get lodged in a small vessel in a new area. The cell then grows into another tumor. Management of bone metastases may include a bisphosphonate drug.
Bisphosphonates: Bisphosphonates are a class of drugs that decrease the rate of bone destruction in patients with cancer. Clinical studies have demonstrated that bisphosphonates can significantly decrease the number of fractures occurring from cancer that has spread to the bone and reduce the pain associated with cancer involving the bone.
In November 2003, the American Society of Clinical Oncology recommended the use of the bisphosphonates Zometa® (zoledronic acid) or Aredia® (pamidronate) for treatment of patients with bone metastasis from breast cancer. The optimal duration of use or the optimal time to administer bisphosphonates is still being evaluated in clinical trials. Researchers are hopeful that bisphosphonates may help to prevent some patients from developing bone metastasis if they are administered prior to bone spread.
For more in depth information, go to the Bone Complications and Cancer.
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of metastatic breast cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of metastatic breast cancer include the following:
New Approaches to Managing Bone Metastases
Targeted Therapy
Epidermal Growth Factor Receptor (EGFR) Inhibitors
Vaccines
Advances in Hormonal Therapy
New Approaches to Managing Bone Metastases: Denosumab
Denosumab is an investigational drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab has shown promising results in the management of patients with bone metastases as well as the management of bone loss due to cancer treatment.
Denosumab was directly compared with the bisphosphonate drug Zometa in a Phase III clinical trial that enrolled more than 2,000 breast cancer patients with bone metastases. The results indicated that denosumab was more effective than Zometa at delaying skeletal complications such as fracture, spinal cord compression, surgery to the bone, and radiation to the bone.[5]
Targeted Therapy
Epidermal Growth Factor Receptor (EGFR) inhibitors: Epidermal growth factor receptors (EGFR) are small proteins that are found on the surface of all cells. EGFR binds exclusively to small proteins circulating in the blood called growth factors. The binding action between EGFR and growth factors stimulates biological processes within the cell to promote controlled cellular growth. However, in many cancer cells, EGFR is either abundantly overexpressed, or the EGFR biological processes that normally stimulate cell growth are constantly active, leading to the uncontrolled and excessive growth of the cancer cell. Several drugs that inhibit EGFR have been developed and are currently being evaluated in the treatment of breast cancer.
Tarceva (erlotinib) is an EGFR inhibitor that is approved for the treatment of advanced non-small cell lung cancer and is being evaluated in the treatment of other cancers, including advanced breast cancer.
Vaccines: One strategy for stimulating the immune system to attack cancer cells is the use of vaccines. Cancer cells often display certain small proteins and/or carbohydrates (antigens) on their surface that are not displayed by healthy cells. Vaccines are often comprised of these specific antigens, which can be taken directly from the patient’s cancer cells, other patient’s cells, or produced in a laboratory. If these antigens are injected into the patient, the immune system recognizes them as “foreign” and will attack the cancer cells displaying the antigens. Researchers are now evaluating various strategies to enhance the immune response against the injected antigens, including combining the patient’s own immune cells with the specific antigens in a laboratory prior to injection.
Advances in Hormonal Therapy
Researchers continue to evaluate ways to improve hormonal therapy for breast cancer by evaluating new agents or different ways to administer drugs that are already in use. Aromasin and Faslodex® (fulvestrant) are approved for treatment of women with metastatic breast cancer that has stopped responding to tamoxifen, but not as initial treatment. However, research now indicates that these two anti-estrogen agents appear to be superior to tamoxifen as initial treatment of metastatic disease. Anti-cancer responses were three times more prevalent among patients treated with Aromasin compared to patients treated with tamoxifen (41% versus 17%).[6] Treatment with Faslodex also resulted in more anti-cancer responses than tamoxifen, and patients who received Faslodex experienced a longer time before their cancer progressed.[7]
Stage IV Breast Cancer
Hormonal Therapy
Chemotherapy
CancerConnect Breast Cancer Community & DiscussionsYou are not alone—The CancerConnect Breast Cancer Community is the leading Social Media Application for Breast Cancer patients and caregivers seeking information, inspiration, and support in the wake of a cancer diagnosis. With over 50,000 members the network offers patients and caregivers a thriving community to support the many ongoing needs from diagnosis to survivorship. Login or register here.
References
[1] National Cancer Institute FactSheet. Herceptin® (Trastuzumab): Questions and Answers. Available at: http://www.cancer.gov/cancertopics/factsheet/therapy/herceptin. Accessed October 11, 2007.
[2] Hobday TJ, Perez EA. Molecularly targeted therapies for breast cancer. Cancer Control. 2005;73-81.
[3] Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. New England Journal of Medicine. 2001;344:783-792.
[4] Genentech. FDA Grants Accelerated Approval of Avastin in Combination With Paclitaxel Chemotherapy for First-Line Treatment of Advanced HER2-Negative Breast Cancer. Available at: http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=11027. Accessed February 2008.
[5] Amgen press release. Denosumab demonstrates superiority over Zometa in pivotal phase 3 head-to-head trial in breast cancer patients with bone metastases. Available at: http://wwwext.amgen.com/media/media_pr_detail.jsp?year=2009&releaseID=1305355 Accessed July 8, 2009.
[6] Paridaens L, Dirix C, Lohrisch L, et al. Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Annals of Oncology. 2003;14:1391-1398.
[7] John F, Robertson A, Howell P, et al. Faslodex versus Nolvadex for the first-line treatment of advanced breast cancer (ABC) in postmenopausal women. Annals of Oncology. 2002;13:46 (Abstract #164).