Susan G Komen  
I've Been Diagnosed With Breast Cancer Someone I Know Was Diagnosed Share Your Story Join Us And Stay Informed Donate To End Breast Cancer
    Home > Research & Grants > Grants Program > Research Grants > Research Grants Awarded > Abstract
    Awarded Grants
    Linking Lymphedema to Disorders of Lymphangiogenesis

    Scientific Abstract:
    Background: For breast cancer survivors, the risk of disabling secondary lymphedema (LE) after treatment continues throughout a lifetime. Furthermore, a majority show early LE within the first year that persists beyond a year. It may be a problem of healing injured lymphatics. The genes involving lymphatic development (lymphangiogenesis) are being elucidated, and are likely involved in lymphatic healing. At the same time, some variably inherited autosomal dominant mutations have been identified in the inherited primary LE syndromes. Some genes are found in both the lymphangiogenesis pathway and inherited LE syndromes. There are likely many disorders of lymphatic vessel formation that have not yet been identified. Hypothesis: Inherited genetic variations in the genes related to primary lymphedema (LE) syndromes and the lymphangiogenesis pathway influence the phenotype of secondary LE in breast cancer survivors. Specific Aims: 1) Determine variation in the Flt4 gene which codes for a growth factor receptor VEGFR3, in breast cancer survivors with secondary LE who have undergone axillary surgery and/or radiation therapy as compared to those survivors without secondary LE who have undergone the same treatment. 2) Determine variation in the VEGF-C gene which codes for a growth factor, in the same breast cancer survivors with and without secondary LE, and 3) Determine mutations in the FOXC2 gene which codes for a transcription factor, in the same breast cancer survivors with and without secondary LE. Study Design: To quantify gene mutations, blood samples will be collected from a) survivors who are currently enrolled in LE clinic with the diagnosis of secondary LE and controls who visited the clinic and were determined not to have secondary LE (case-control), and b) breast cancer patients who agree to participate before receiving treatment (cohort). Preoperative and quarterly standard measurements of the upper extremities will be obtained and limb volume calculated. A LE nurse specialist will confirm LE cases. DNA genomic testing results will be coordinated with molecular epidemiology. Potential Outcome/Benefits: New information about inherited variations in lymphatic healing may direct targeted studies to test alternative approaches to breast cancer treatment, including avoidance of any axillary dissection, and reduction of secondary LE. In addition, this new knowledge may direct new basic science and translational studies about metastasis formation in breast cancer by the lymphatic route with the goal to reduce metastasis formation.

    Lay Abstract:
    Rationale: For breast cancer survivors, the risk of disability from secondary lymphedema (LE) after treatment continues throughout a lifetime. LE is a swelling of the arm resulting from the blockage of channels (lymphatics) that collect fluid in the body and direct it back to the bloodstream. These channels are damaged by surgery, including surgery of the axilla (armpit) and radiation therapy (RT). Some genes that are involved in the formation of lymphatics may also be involved in the healing of injured lymphatics. If this doesn’t go well, LE may result. There are also inherited (primary) forms of LE that have nothing to do with breast cancer. Some of the genes responsible have been identified that coincide with some of the genes used to make and possibly heal lymphatics. Purpose: To identify mutations in the genes that are involved in both the formation of lymphatics and in the inherited primary LE in breast cancer patients who develop secondary LE after treatment. Specific Aims: 1) Determine the variation in the Flt4 gene which codes for a growth factor receptor VEGFR3, in breast cancer survivors with secondary LE who have undergone axillary surgery and/or RT as compared to those survivors without secondary LE who have undergone the same treatment. 2) Determine variation in the VEGF-C gene which codes for a growth factor, in the same breast cancer survivors with and without secondary LE, and 3) Determine mutations in the FOXC2 gene which codes for a transcription factor, in the same breast cancer survivors with and without secondary LE. Study Design: Blood samples will be collected from a) survivors who are currently enrolled in LE clinic with the diagnosis of secondary LE and controls who visited the clinic and were determined not to have secondary LE (case-control), and b) breast cancer patients who agree to participate before receiving treatment (cohort). The genes will be tested from the DNA in the blood. Preoperative and quarterly standard measurements of the upper extremities will be obtained and limb volume calculated. A LE nurse specialist will confirm LE cases. Potential Outcome/Benefits: By identifying gene mutations that will interfere with healing lymphatics in breast cancer survivors, we may direct alternative approaches to breast cancer treatment such as avoiding axillary surgery or certain kinds of RT, if at all possible. This would reduce the incidence of LE. The information about gene mutations in lymphatic healing will also assist basic science studies that are trying to reduce the spread of breast cancer by the lymphatics.