PROJECT ABSTRACT
Lymphedema is a debilitating, life-long iatrogenic sequalae of cancer treatment which is becoming an
important survivorship issue due to improved cancer survival. Patients with inflammatory breast cancer (IBC), a
highly aggressive form of breast cancer, require systemic therapy, surgery, and radiation therapy for
oncological control. These treatments place them at the highest risk of developing lymphedema, with
approximately 50% developing it within 12 months following surgery. Therefore, developing strategies to
predict and prevent treat lymphedema would significantly impact the well-being of patients with IBC.
General strategies for treating lymphedema include physical therapy and the continuous use of compression
garments, and surgical treatments have recently been introduced that can provide some improvement in the
swelling and symptom burden. Given the incomplete outcomes of these interventions, especially for a high-risk
group like IBC patients, focus has recently shifted to risk-reducing surgeries. Immediate lymphatic
reconstruction (ILR) of lymphatic vessels at the time of axillary lymphadenectomy (ALND) has resulted in
significantly lower rates of lymphedema among breast cancer patients for patients who received ILR.
Unfortunately, none of the studies on ILR have focused on IBC patients, or have investigated longitudinal
outcome measures, which would enable comprehensive outcome assessment, including identification of
potential biomarkers. We propose a single-arm, clinical trial investigating the impact of ILR on the development
of lymphedema in IBC patients at a single, high-volume center specializing in treatment of IBC patients.
We hypothesize that ILR in patients with IBC is preventative against lymphedema development as defined by
objective clinical threshold measurements, and prevents changes in lymphatic architecture and pumping
characteristic of lymphedema visualized using near-infrared fluorescence lymphatic imaging (NIRFLI), as well
as functional alterations in peripheral blood immune cells associated with lymphedema development.
This hypothesis will be addressed in the following Specific Aims: (1) to determine the incidence of clinical
lymphedema in IBC patients following ILR; (2) to establish a longitudinal, dynamic, imaging-based profile of
IBC patients following ILR using NIRF-LI to provide real-time visualization and objective characterization of
changes in lymphatic vessel architecture and function; and (3) to identify a blood-based, inflammation-related
signature of lymphedema in patients with IBC through longitudinal analysis of serum samples from our clinical
trial cohort, using an inflammatory cytokine/ chemokine array.
The proposed trial will allow objective assessment of lymphatic vessel anatomy and functional changes in
lymphedema, as well as to define immune characteristics that correlate with lymphedema development. If
successful, this work would provide impetus to change the surgical standard-of-care for patients with IBC and
help direct highest risk patients to specialized treatment centers for surgical intervention.