Reducing Surgical Morbidity of Breast Cancer Staging

Institution: University of California, Davis
Investigator(s): Steven Chen, M.D. -
Award Cycle: 2009 (Cycle 15) Grant #: 15IB-0073 Award: $149,983
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure



Initial Award Abstract (2009)

Underarm lymph nodes are commonly removed to determine the extent of breast cancer spread. A feared complication of this operation is having arm swelling (lymphedema) after the operation, which can lead to loss of function, pain, or disfigurement. Such swelling has been related to the loss of lymphatics draining the arm (axillary) that are damaged or removed during removal of lymphatics draining the breast and can occur in up to 77% of patients. Any decrease in this complication can dramatically improve patients’ quality of life.

This project proposal seeks to utilize axillary reverse mapping (ARM) to improve axillary lymph node dissection (ALND) by preserving extremity lymphatics to potentially decrease the rates and severity of lymphedema occurrence after ALND. Decreasing the morbidity of those undergoing surgery has multiple impacts. The aims include:

1) Determine the proportion of women undergoing ALND at risk for lymphedema by characterizing the location of upper extremity draining lymphatics relative to breast draining lymphatics.
2) Determine if lymphatics identified by axillary reverse mapping contain lymph node metastases, and
3) To evaluate the incidence of lymphedema and associated other surgical related quality of life in those undergoing this procedure as compared to the current standard of care.

A two phase trial will be utilized. In the pilot phase, all patients will undergo mapping, but receive the standard ALND. First, we will note the location of the mapped upper extremity lymphatic drainage. All upper extremity related nodes identified in this manner will be marked for identification to determine if they contain tumor cells. Next, a randomized trial phase will then be undertaken. We will randomize patients between the standard ALND following by blue dye injection at the end of the case, and an ARM-guided ALND, utilizing mapping prior to starting the procedure and preserving all mapped lymphatics. To assess outcome we will measure of arm swelling, as well as use survey instruments for arm function and general quality of life to compare groups.

We hope that the use of ARM will increase the willingness of patients to undergo staging surgery, without which, patients would either be recommended to undergo axillary radiation with its attendant risks, or be inadequately staged. For those who currently undergo the surgery, this should reduce the number of people who suffer from this painful and sometimes disabling condition, improving the quality of life of survivors who suffer from this condition.




Final Report (2011)

Background:
The overall goals of this project were to pilot test the feasibility of adopting the experimental technique, “axillary reverse mapping” to identify lymph nodes draining the arm, so these can be spared dissection in staging breast cancer.

Progress on Specific Aims:
1) To produce a map of the lymphatic drainage of the upper extremity as it relates to breast drainage, to determine the proportion of women undergoing axillary lymphadenectomy at risk for lymphedema,

To date we have enrolled 12 patients into the pilot study, which had a minimum of of ten patients planned. Four surgeons have successfully performed the procedure. Of the 12 enrolled patients, only one has reported the incidence of lymphedema which is consistent with our expected incidence of 25%, when one considers the likelihood of a higher incidence on measurements than what is self reported. We have had 3 unsuccessful mappings, 2 were in patients with palpable lymph nodes who also received neoadjuvant chemotherapy. In each successful mapping, the specified blue lymphatic was identified as potentially able to be preserved, indicating promise in terms of the potential for increased rates of lymphedema when these lymphatics are removed. The pilot portion has now completed initial enrollment, allowing for randomization to begin for those surgeons who have completed the pilot phase. Initial review of the data demonstrates that the initial estimates of trial accrual size are reasonable. Continuing analysis of this will continue as more pilot patients are entered by new surgeons going the trial.

2) To determine if blue lymphatics identified by axillary reverse mapping contain lymph node metastases. No resected blue lymphatics to date have been noted to have cancer within them. This portion of the project will continue throughout the entire enrollment, but is promising in demonstrating the safety of the proposed procedure.

3) To evaluate the incidence of lymphedema and associated other surgical related quality of life in those undergoing this procedure as compared to the current standard of care.

Of the patients enrolled so far, 1 patient has self-reported lymphedema. We have not undertaken analysis of the measurement data yet, as that data has not reached the interim analysis point. It is likely that there will be a higher incidence of lymphedema based on measurements than via self-report. This bodes well in terms of having an adequate event rate in the randomized trial phase to detect a difference. Since the randomized trial phase has not started yet, there are no results as yet as to whether the experimental procedure will prove helpful in reducing lymphedema occurrence.




Symposium Abstract (2010)

Background: Axillary Lymph Node Dissection is a standard component of therapy in node positive breast cancer. Lymphedema continues to be one of the most feared complications of this operation. We hypothesized that lymphedema may be related to the resection of lymphatic channels from the upper extremity and that a novel technique, axillary reverse mapping, would be able to identify these lymphatics.

Methods: We identified patients planning to undergo an axillary lymph node dissection for breast cancer who had not had prior axillary dissections more extensive than sentinel node biopsy. These patients were then mapped intraoperatively using 2.5 mL of Lymphazurin Blue dye injected subcutaneously into the proximal arm prior to the start of their axillary dissection. A standard axillary dissection was then performed. Notation was made of the ability to localize a blue lymphatic channel, the location of any blue lymph nodes, and the status of blue lymph nodes in terms of harboring metastasis. Quality of life surveys, arm measurements, and a standardized lymphedema assessment survey were performed on all patients preoperatively and at regular intervals post-operatively.

Results: To date, we have performed eight reverse mappings. Our patients average age has been 45 years old. Our success rate has be 75% in identifying either a blue lymphatic or a blue lymph node. No resected blue lymph nodes have contained cancer. 1 of 8 patients has developed lymphedema. No patient has developed any adverse sequelae to the blue dye injection.

Discussion: This represents one of the first studies of this technique. Our results demonstrate the feasibility of surgeons who are otherwise experienced in lymphatic mapping to rapidly adopt this novel technique. Further refinement of the technique will be needed, once oncologic safety has been established to further increase its usability in this patient population. A randomized trial to ascertain the effect of saving these blue lymphatics/lymph nodes is warranted.