Virginia F. Borges, MD

2008-2010 BCRF-AACR Project:
"Targeting the Inflammatory Milieu of Pregnancy-Associated Breast Cancer"

Pregnancy exerts complex effects on the risk of breast cancer. The risk of breast cancer diagnosis increases immediately following the completion of a pregnancy and this risk persists for approximately 10 years. The diagnosis of invasive breast cancer in temporal proximity to a completed pregnancy is associated with an increased risk of subsequent metastatic spread and a significant decrease in breast cancer survival for reasons unrelated to standard breast cancer prognostic markers. Pregnancy-associated breast cancer (PABC) is defined as a breast cancer diagnosed within six years of a completed pregnancy, reflecting this period of increased risk.

Among women under the age 40 diagnosed with breast cancer, almost 50% fulfill the definition of PABC. As many American women continue to delay childbearing until later ages, this proportion will continue to increase. Therefore, PABC is a high-risk, increasing sub-population of breast cancer in the US with significant negative impact on a vital component to society—young mothers. In setting of post-pregnancy, post-nursing when the mother weans, the breast undergoes a process called involution that returns the breast to its pre-pregnant state.

Dr. Borges has previously reported that during this process of involution the breast tissue, called the microenvironment, takes on attributes similar to a wound, with inflammation that promotes breast cancer growth and risk of breast cancer metastatic spread. It has also been increasingly recognized that the tumor itself causes an inflammatory microenvironment for itself and can trick the immune system into failing to recognize it as a threat, allowing the cancer to progress. Therefore, Dr. Borges has begun a project to investigate the immune response to the pro-inflammatory tumor microenvironment in PABC as it compares to non-PABC. By utilizing the unique window between initial breast cancer diagnosis and definitive surgery, her team will also conduct a randomized, short-term drug intervention study to target this pro-inflammatory environment with a short term anti-inflammatory intervention. She hypothesizes that the anti-inflammatory interventions will result in a decrease of inflammatory markers in the breast microenvironment, a decrease in the cancers ability to evade the immune system and a decrease potential for metastasis in newly diagnosed PABC. The clinical trial has been set up and the laboratory work needed to answer the immunology questions is in progress. It is anticipated that accrual will begin in August 2009.

Mid-Year Progress Report:
Dr. Borges's project is investigating the immune response to the pro-inflammatory tumor microenvironment in pregnancy-associated breast cancer (PABC)as it compares to non-PABC. By utilizing the unique window between initial breast cancer diagnosis and definitive surgery, her team is also conducting a randomized, short term, drug intervention study to target this pro-inflammatory environment with a short term anti-inflammatory intervention. They hypothesize that the anti-inflammatory interventions will result in a decrease of inflammatory markers in the breast microenvironment, a decrease in the cancers ability to evade the immune system and a decrease potential for metastasis in newly diagnosed PABC. The clinical trial is underway and the researchers are actively accruing women onto the study.

Bio:
Dr. Borges received her medical degree from the University of Medicine and Dentistry of New Jersey in 1993 and received her Masters of Medical Science in Clinical Investigation from Harvard Medical School/MIT-HST program in 2001. She completed her Internal Medicine and Hematology/Oncology training at the Beth Israel Deaconess Medical Center in Boston. She is currently an Associate Professor at the University of Colorado Denver and is the Director for the Young Women’s Breast Cancer Translational Program. The Borges Lab is currently working on the role of pregnancy-induced immune suppression in pregnancy-associated breast cancer and the impact of tumor-induced immune suppression by biologic subtype of breast cancer.