ABSTRACT
Breast cancer frequently metastasizes to the axillary lymph nodes (ALN). The cancer spread from the
primary breast tumor can occur during the early stages, and ALN metastasis is usually the earliest detectable
cancer spread. Sentinel lymph node (SLN) biopsy is the standard approach for axillary staging in breast
cancer patients with no palpable axillary adenopathy or when ALN metastasis is not detected during the
presurgical diagnosis. Currently, SLN is identified by a peritumoral injection of a radioactive tracer, technetium
99mTc and/or blue dye, followed by a SLN biopsy for pathological examination. Although this peritumoral
injection method can identify the location of SLN, it does not intraoperatively distinguish between LN
metastases and healthy LN as it stains SLN regardless of the status of LN metastases. Thus, once SLN is
identified by 99mTc and/or blue dye, SLN is surgically removed regardless of cancer metastases status in SLN,
and sent for pathological assessment. The majority of patients with breast cancer (~70%) who undergo a SLN
biopsy are pathologically negative. Although the clinical benefits of a SLN biopsy have been observed, SLN
biopsies are often associated with postoperative complications such as lymphedema, seroma formation,
sensory nerve injury, and limitation in range of motion. Moreover, after a SLN biopsy, if pathological reports
show cancer negative in the SLN, then a complete ALN dissection can be avoided. When SLN is cancer
positive, patients need a second operation to complete the ALN dissection. This decision can be made during
the primary tumor resection or SLN biopsy if surgeons can detect LN involvement intraoperatively. Therefore,
a new intraoperative method for a clinically translated surgical visualization tool that can accurately detect LN
involvement is clinically needed to eliminate any delay in treatment and prevent unnecessary surgeries.
To overcome previous and current challenges in identifying LN with cancer cells, our approach in this
application aims to intraoperatively distinguish LN with cancer cells from normal LN with a real-time
visualization tool. Our preliminary results with one breast cancer cell line showed that ICG-p28 preferentially
accumulated at the primary breast tumor and LN metastases, but not in healthy LN. Based on our preliminary
data, we hypothesize that our real-time imaging approach with ICG-p28 can intraoperatively/accurately
distinguish between LN metastases and healthy LN which will substantially improve the health of breast
cancer patients. We will test our hypothesis in mimicked intraoperative settings. Each aim/sub-aim will occur
in the collaborative and interdisciplinary environment to carry out our proposed research. Our unique imaging
approach can potentially provide a significant impact on SLN biopsy procedures. It will potentially provide
better treatments for breast cancer patients, which is a major milestone and relevant to the NIH focus area.