Julie A. Margenthaler, M.D.
Project Overview:
The most important prognostic factor for a patient with breast cancer is the absence or presence of metastasis to the axillary lymph nodes. Survival correlates directly with the number of positive lymph nodes. Zero positive nodes is associated with a <20% treatment failure at 10 years, whereas more than four positive nodes is associated with a >70% treatment failure rate. Historically, all women with breast cancer underwent surgery to their breast (mastectomy or lumpectomy) plus removal of all of the axillary (i.e., armpit) lymph nodes on the side of their breast cancer. While this technique is very effective in determining the number of lymph nodes involved with cancer, it also subjects the patient to significant morbidity, including bleeding, infection, nerve injury, and permanent swelling of the arm (lymphedema). Currently, this procedure is still performed in women who have enlarged, suspicious lymph nodes by physical exam (approximately 10% to 20% of all patients) and the complication rates are reported to be 10% to 30%. More recently, a less invasive technology has emerged to examine the axillary lymph nodes in women who do not have enlarged lymph nodes on physical exam (approximately 80-90% of all patients). This is termed a sentinel lymph node biopsy and has been rigorously tested and proved effective in patients with breast cancer. The sentinel lymph node concept supports the notion that breast cancer cells spread in an orderly fashion from the primary tumor in the breast to a few lymph nodes in the axilla (i.e., the “sentinel” lymph nodes). By injecting blue dye and radioactive particles near the tumor, we can follow the lymph vessels to the sentinel lymph nodes and only these lymph nodes are removed. On average, one to three sentinel lymph nodes are removed.
There are several disadvantages to these techniques. Both procedures are invasive and subject the patient to additional surgical morbidity. Although the sentinel lymph node procedure results in fewer complications, the rate of bleeding, infection, nerve injury, or lymphedema remains at 5-10%. For patients undergoing sentinel lymph node biopsy, about 30% will have positive nodes on the final pathology and will require a second procedure to remove the remainder of the lymph nodes. Finally, the current methods of identifying and examining the lymph nodes results in false results approximately 5% to 15% of the time.
The goal of the current project is to study an advanced method of detecting metastasis in the axillary lymph nodes of breast cancer patients using molecular genetic testing called polymerase chain reaction or PCR. PCR has been shown to be superior to our current techniques and can pick up one tumor cell in the background of a million normal cells. Using ultrasound, we can identify the lymph node and obtain a small amount of tissue using a needle placed through the skin. This tissue is tested for an array of genes specific to breast cancer and allows us to construct a “fingerprint” of the cancer, providing the exact nature of the cancer and the way that it is likely to respond to various treatments. This procedure could be performed on all patients with breast cancer in lieu of removing the lymph nodes during surgery; only those patients with a positive genetic marker would need to have their lymph nodes removed. Therefore, 70% of patients would avoid surgery on their lymph nodes. In patients who have a positive lymph node, we can tailor their surgery and treatment to their specific cancer. This will allow us to treat patients with medications that will directly benefit their type of breast cancer, thus increasing their disease-free and overall survival. This technology is very promising and represents a significant potential advancement in the care of patients with breast cancer.
Final Report:
Sentinel lymph node biopsy (SLNB) has emerged as a less invasive alternative to axillary lymph node dissection (ALND) in the treatment of breast cancer. However, SLNB has a number of limitations, and we believe that alternative strategies for staging of the axilla should be explored. The hypothesis of this proposal was that the combination of preoperative high-resolution axillary ultrasound (AUS), fine needle aspiration biopsy (FNAB), and molecular analysis using real-time reverse transcription-polymerase chain reaction (RT-PCR) represents a viable, minimally invasive alternative to SLNB.
