Patients with early-stage breast cancer whose sentinel lymph nodes with microscopic cancer cells (occult cells) are removed do not have better survival outcomes, researchers from Cedars-Sinai Medical Center reported in JAMA (Journal of the American Medical Association).
Study leader, Armando E. Giuliano, MD., in previous findings related to sentinel lymph node biopsy and diagnosing cancer, changed the accepted approach for early-stage breast cancer treatment. His studies challenged the belief that removing all lymph nodes, apart from the sentinel ones nearest to the tumors, was crucial for improving survival outcomes.
Those findings showed that female patients who underwent the removal of all lymph nodes had similar outcomes to those who only had the sentinel node removed. After Giuliano's research, women were spared the pain, discomfort and adverse events associated with total lymph node removal.
The authors wrote:
"Sentinel lymph node (SLN) dissection has revolutionized the approach to early-stage breast cancer by allowing minimally invasive axillary staging and more intensive examination of the SLN. This has led to the detection of micro metastases and isolated tumor cells of uncertain significance. Immunochemical staining of SLNs and bone marrow identifies breast cancer metastases not seen with routine pathological or clinical examination."
Giuliano and team wanted to find out whether survival rates were affected by the presence of microscopic cancer cells in nearby lymph nodes. These cancer cells cannot be detected in routine pathological or clinical examinations. They are identified with immunochemical staining of nearby lymph nodes and bone marrow specimens from early-stage breast cancer patients.
The American College of Surgeons Oncology Group trial (Z0010 trial) involved 5,210 female patients with breast cancer at 126 sites around the USA - it started in may 1999 and ended in May 2003. Breast-conserving surgery and sentinel lymph node dissection was performed on all of them.
Of 98.3% (5,119) of the specimens taken, 76.3% (3,904) were tumor-negative by hematoxylin-eosin staining. Of 3,326 sentinel nymph nodes examined by immunohistochemistry, 10.5% (349) were positive for tumor. Of 3,413 immunocytochemistry examinations of bone marrow specimens, 3% (104) were positive for tumors.
The patients were all followed up until April 2010 - they were followed-up for an average of 6.3 years. Over that period 435 patients died and 376 experienced breast cancer recurrence. Among those with hematoxylin-eosin-negative sentinel lymph nodes (SLNs), immunohistochemical evidence of cancer cells in the SLNs had no significant link to recurrence or death. The researchers wrote:
"Five-year rates of overall survival for patients with immunohistochemistry-negative SLNs were 95.7 percent and for those with immunohistochemistry-positive SLNs were 95.1 percent. Corresponding 5-year rates of disease-free survival were 92.2 percent and 90.4 percent, respectively."
The authors added:
"Bone marrow examination with immunocytochemistry may identify high-risk women; however, the incidence in the Z0010 trial was too low to recommend incorporating bone marrow aspiration biopsy into routine practice for patients with the earliest stages of breast cancer."
"This study shows that the presence of tiny sentinel lymph node metastases has no bearing on survival outcomes."
An adverse event linked to lymph node removal is lymphedema - painful and chronic swelling in the arm that can seriously debilitate the patients.
"Treating the patient doesn't end with stopping the cancer. We want to make sure we maximize the patient's quality of life even after cancer treatment is completed."
The findings of this trial have important implications for medical practice, the authors said.
"Many laboratories routinely perform-multiple sections and immunohistochemistry on hematoxylin-eosin-negative SLNs, even though the College of American Pathologists guidelines for SLN processing do not include their use. Data from Z0010 show that occult metastases detected by immunohistochemistry are not associated with survival differences in patients with the earliest stages of breast cancer. Although longer follow-up might reveal small differences in outcome, these are likely to be of no clinical significance as demonstrated by findings of National Surgical Adjuvant Breast and Bowel Project B-32 trial.
Routine immunohistochemical examination of hematoxylin-eosin negative SLNs and routine immunocytochemical examination of bone marrow are not clinically warranted for early-stage (clinical T1-T2N0) breast cancer. "
Accompanying EditorialRyan P. Merkow, M.D., and Clifford Y. Ko, M.D., M.S., M.S.H.S., of the American College of Surgeons, Chicago, wrote:
"(this study). . . . serves as an ideal illustration of how well-designed observational research can be conducted in surgery.
Randomized controlled trials (RCTs) should not be considered the de facto and sole source of high-level evidence. By considering RCTs and observational study designs complimentary, and recognizing the opportunities to use observational research when appropriate, it might be possible to address questions faster, cheaper, and perhaps even better than either approach alone. Above all else, it will be patients who will ultimately benefit."
"Association of Occult Metastases in Sentinel Lymph Nodes and Bone Marrow With Survival Among Women With Early-Stage Invasive Breast Cancer"
Armando E. Giuliano, MD; Debra Hawes, MD; Karla V. Ballman, PhD; Pat W. Whitworth, MD; Peter W. Blumencranz, MD; Douglas S. Reintgen, MD; Monica Morrow, MD; A. Marilyn Leitch, MD; Kelly K. Hunt, MD; Linda M. McCall, MS; Andrea Abati, MD; Richard Cote, MD
JAMA. 2011;306(4):385-393. doi: 10.1001/jama.2011.1034
Written by Christian Nordqvist