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Name of the Trial

Phase III Randomized Study of Tamoxifen Citrate or Letrozole With Versus Without Bevacizumab in Women With Hormone Receptor-Positive Stage IIIB-IV Breast Cancer (CALGB-40503). See the protocol abstract ³.

Principal Investigator

Dr. Maura Dickler Principal Investigator

Dr. Maura Dickler, Cancer and Leukemia Group B

Why This Trial Is Important

The female hormone estrogen, which is an endocrine hormone, can stimulate the growth many breast cancers. In addition, estrogen can promote the growth of new blood vessels (angiogenesis) to tumors, which helps the tumors get the oxygen and nutrients they need for continued growth. Hormonal therapies, such as letrozole ⁴ and tamoxifen ⁵, can help delay the progression of breast cancers that grow in response to estrogen. Letrozole, an aromatase inhibitor, interferes with the body's ability to produce estrogen, and tamoxifen, an antiestrogen, competes with estrogen for binding to estrogen receptors. However, most patients with advanced breast cancer eventually develop resistance to hormonal therapy and experience relapse.

Some preclinical research has suggested that a possible cause for this resistance is the hormone-independent growth of blood vessels to tumors. Doctors want to know if inhibiting this angiogenesis with an antibody known as bevacizumab ⁶ can help delay the development of resistance to hormonal therapy. Bevacizumab blocks the activity of vascular endothelial growth factor (VEGF), a protein that is important for angiogenesis.

In this trial, women with advanced, hormone receptor-positive breast cancer will be randomly assigned to receive hormonal therapy (with letrozole or tamoxifen) and either bevacizumab or a placebo. The decision of whether to take letrozole or tamoxifen will be made by patients and their doctors. Researchers want to determine whether the addition of bevacizumab will slow disease progression in women receiving hormonal therapy.

"This trial is intended to provide definitive proof of whether anti-VEGF therapy adds to the benefit of endocrine therapy in advanced breast cancer," said Dr. Dickler.

"One important aspect of this trial is that women do not have to have a measurable tumor to be included," she added. "Many women experience recurrence in the form of non-measurable disease, such as bone metastases, pleural effusions, or lymph node metastases, and these women may be eligible for this study."

The investigators plan to answer additional questions with the trial as well. For example, women will be monitored to see if the addition of bevacizumab causes more, or different, side effects than does letrozole or tamoxifen alone.

For More Information

See the lists of entry criteria ⁷ and trial contact information ⁸ or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

Glossary Terms

A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

A substance that prevents cells from making or using estrogen (a hormone that plays a role in the formation of female sex characteristics, the menstrual cycle, and pregnancy). Antiestrogens may stop some cancer cells from growing and are used to prevent and treat breast cancer. They are also being studied in the treatment of other types of cancer. An antiestrogen is a type of hormone antagonist. Also called estrogen blocker.

A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone-dependent breast cancer.

Cancer that has spread from the original (primary) tumor to the bone.

Refers to tissue that makes and releases hormones that travel in the bloodstream and control the actions of other cells or organs. Some examples of endocrine tissues are the pituitary, thyroid, and adrenal glands.

Treatment that adds, blocks, or removes hormones. For certain conditions (such as diabetes or menopause), hormones are given to adjust low hormone levels. To slow or stop the growth of certain cancers (such as prostate and breast cancer), synthetic hormones or other drugs may be given to block the body’s natural hormones. Sometimes surgery is needed to remove the gland that makes a certain hormone. Also called endocrine therapy, hormone therapy, and hormone treatment.

A cell protein that binds a specific hormone. The hormone receptor may be on the surface of the cell or inside the cell. Many changes take place in a cell after a hormone binds to its receptor.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

An abnormal collection of fluid between the thin layers of tissue (pleura) lining the lung and the wall of the chest cavity.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

A substance made by cells that stimulates new blood vessel formation. Also called VEGF.