Vermont Cancer Center Breast Cancer Research

Over 120 physicians and scientists at the Vermont Cancer Center at the University of Vermont and Fletcher Allen Health Care are engaged in a full range of basic, translational, clinical, and outcomes research that seeks to uncover new knowledge and understanding about cancer and the issues that affect people with the disease. Highlighted here are a few current research projects led by VCC members.

Harnessing the Body to Fight Cancer

Chris Holmes, M.D., Ph.D., is investigating how the 4 trillion platelets in our blood, which aid with clotting, can be coaxed to act as anti-cancer agents. Platelets, specifically, have been found to release proteins that promote angiogenesis — the growth of new blood vessels — in cancer cells. One key cancer-promoting protein Holmes is studying is vascular endothelial growth factor (VEGF), which is released by activated platelets.

“Studies in cancer patients routinely show that cancer works to increase platelet numbers, and the higher the number of platelets in your body, the worse the prognosis is for the cancer,” says Holmes. Recently, she and colleagues published an encouraging study about the effects of platelets on ovarian cancer cells. The research revealed that platelets and the proteins inside them cause ovarian cancer cells to spread and that when protein release was prevented from the platelets, the cancer spreading was severely decreased.

Building on this research with the help of an American Cancer Society grant, Holmes is now looking at how proteins are released from platelets and how current drugs, including aspirin, may affect that release to see whether platelets can become part of the fight against cancer. Using patient blood samples, Holmes is working to identify which activation systems affect the release of cancer-promoting proteins, such as VEGF, in platelets the most, so they can be effectively targeted with anti-platelet therapy.

Customizing Breast Cancer Therapies

David Krag, M.D., is exploring how the body — specifically, the immune system — can be taught to destroy cancer cells. Krag’s goal is to customize safe and effective therapies tailored to breast cancer patients’ specific biology and type of cancer, which could later be applied to patients with other cancers.

To achieve this, Krag is working to develop customized therapeutic antibodies that he hopes will attack and destroy the specific cancer cells of individual breast cancer patients. Such a treatment could reduce the toxic side effects, such as nausea and vomiting and suppression of the immune system, often associated with lifesaving cancer therapy.

Krag believes that white blood cells called t-cells can also be programmed to recognize cancer cells and target them for mass destruction by t-cells. Making t-cells recognize cancer cells as foreign invaders involves a complex molecular biological process. To test his theory, Krag will use immunodeficient mouse models implanted with patient tumor samples and samples of patients’ white blood cells to generate a patient’s immune system and unique cancer biology in the research model. Krag plans to study whether antibodies can be made for each patient that will bind to and send a signal to t-cells to attack the patientís specific cancer.

Exploring the Obesity-Breast Cancer Connection

Cancer researchers have now established solid evidence that 25 to 30 percent of postmenopausal and recurrent breast cancers are linked to excess weight, and there is a growing incentive among cancer experts to discover why excess weight increases malignancy risk.

Kim Dittus, M.D., Ph.D., and Jean Harvey-Berino, Ph.D., R.D., are collaborating to better understand the biologic links between obesity, weight loss, and postmenopausal breast cancer. Individuals who are overweight are more likely to die of their breast cancer and also have a higher risk of recurrence, says Dittus.

Because women with breast cancer have reported reluctance to participate in lifestyle-focused studies due to time and travel requirements, Dittus, Harvey-Berino, and colleagues will be conducting a randomized clinical trial at the Vermont Cancer Center to test the effectiveness of an Internet-based weight loss intervention for postmenopausal breast cancer patients.

Both scientists agree that the ultimate outcome of such studies would be the addition of weight loss regimens as standard of care, and health policy and clinical guidelines to support it, as well as health insurance to cover the costs. Dittus will present a talk on exercise and breast cancer therapy in Session 2.1. Harvey-Berino will address breast cancer and weight gain in Session 5.1.

Investigating Vitamin D3 as Chemoprevention for Breast Cancer

Breast cancer specialist Marie Wood, M.D., recently received a National Cancer Institute R21 award to lead a randomized, placebo-controlled clinical study evaluating the effects of vitamin D3 on several breast cancer biomarkers (including mammographic density), the results of which could provide valuable information regarding the usefulness of vitamin D3 as a chemoprevention strategy for breast cancer. Investigating the impact of vitamin D3 on breast cancer biomarkers will provide clear evidence of the chemopreventive properties of vitamin D3 and give rise to sorely needed agents for the prevention of Estrogen Receptor negative (ER-) breast cancer and greater options for premenopausal women. A pilot study of this research was initially funded by a Lake Champlain Cancer Research Organization Pilot Project Grant, which allowed Wood to assess the association between Vitamin D and mammographic density in women at high risk for developing breast cancer. Wood will speak to physicians and other providers about breast cancer screening and prevention in Session 1.2.