Targeting Resistance to Endocrine Therapy in Advanced Breast Cancer
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.
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 and tamoxifen, 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 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.