Axillary Dissection Based on the Histological Result of the Sentinel Node, in Patients With Breast Carcinoma
|Breast Carcinoma||Procedure: quadrantectomy and axillary dissection Procedure: quadrantectomy + sentinel node biopsy|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Clinical Trial Comparing Axillary Dissection "by Principle" and Axillary Dissection Based on the Histological Result of the Sentinel Node, in Patients With Breast Carcinoma of Small Size|
- disease free survival, overall survival [ Time Frame: every 6 months for the first 5 years and every 8 months afterwards ]
- number of axillary metastases [ Time Frame: every 6 months for the first 5 years and every 8 months afterwards ]
|Study Start Date:||March 1998|
|Study Completion Date:||April 2010|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
Active Comparator: QUART
Patients in this arm will receive quadrantectomy, axillary dissection and radiotherapy (the current standard therapy).
Procedure: quadrantectomy and axillary dissection
standard quadrantectomy and axillary dissection
Experimental: QURT (SN-)
Patients will receive quadrantectomy, sentinel node investigation and radiotherapy. Selective axillary dissection will be performed if sentinel node is positive.
Procedure: quadrantectomy + sentinel node biopsy
standard quadrantectomy and selective axillary dissection only if sentinel node biopsy is positive
The axillary lymph nodes represent the most frequent site of metastasis from breast carcinoma. In previous studies, it has been shown that the process of metastasis to the axillary nodes proceeds in an orderly and progressive fashion from the I to the II and to the III level and that a "saltatory" event of metastasis represents a rare event described in only 2% to 6% of cases.
The risk of metastasis is directly correlated with the size of the primary tumor. When smaller than 1 cm in diameter, the risk of metastasis is about 10%; when larger than 5 cm in diameter, the risk increases to more than 70%.
The involvement of axillary lymph nodes by metastases constitutes today the most important prognostic factor in breast cancer. Massive invasion is most certainly associated with a poor outcome and therefore, the information that the lymph node status can provide, is indispensible for administration of appropriate therapies in the postoperative period. Nevertheless, in those cases where the lymph nodes are found to be free of metastases, axillary dissection is a useless treatment that can prove harmful if one considers all the possible short and long term complications.
Presently, there are no diagnostic modalities that are able to provide an accurate lymph node staging preoperatively. This information can only be gained by histologic examination of all lymph nodes after complete axillary dissection.
Standard treatment for operable breast cancer today always involves the dissection of the axillary lymph nodes, regardless of the surgical procedure used for resection of the primary tumor, i.e. conservative or demolitive. This not only results in a large expenditure of resources (longer surgical procedures under general anesthesia), but most notably, in an increased risk of complications (lymphedema and functional limitations of the involved extremity) for the patient, secondary to a more aggressive intervention on the axilla.
A method utilizing preoperative lymphoscintigraphy and intraoperative use of a gamma-ray probe in order to evaluate the possibility of metastasis in the first axillary lymph node, i.e. the "sentinel node", has recently been put into practice at our institute. This method, which in its first part consists in the subcutaneous or peritumoral administration of a radiolabeled (99Tc) human albumin colloid (see methods section), has allowed isolation and excision of the sentinel lymph node with the use of the gamma-ray probe in 98.8% of cases.
In the case that this procedure should prove highly predictable of patient outcome, numerous axillary lymphadenectomies could be avoided and with such, numerous complications associated with such aggressive intervention.
A first phase study has evaluated 238 patients with breast carcinoma that would be candidates for complete axillary dissection. Patients with intraductal carcinoma, those candidates for primary chemotherapy, those diagnosed during pregnancy or lactation, and those with tumors less than 1 cm in size (because of inclusion in the randomized trial (053) evaluating the role of radiotherapy on the axilla in patients undergoing conservative surgery without axillary node dissection) were excluded from the study. The results of this first phase have shown a concordance in the histologic findings between the sentinel lymph node and all remaining axillary lymph nodes, subdivided into three levels, in 96.7% of cases. Furthermore, concordance was 100% in 18 patients with breast carcinoma of a size equal or less than 1.0 cm.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00970983
|European Institute of Oncology|
|Milano, Italy, 20141|
|Study Director:||Umberto Veronesi, MD||European Institute of Oncology|