Removal of More Lymph Nodes May Not Be Necessary for Some Patients with Early-Stage Breast Cancer

The Bottom Line

Results from a randomized phase III clinical trial demonstrate that axillary lymph node dissection (ALND) provided no additional survival benefit when compared with sentinel lymph node biopsy (SLNB) in women with breast tumors 5cm in diameter or smaller and minimal lymph node metastasis who were treated with lumpectomy, whole-breast radiotherapy, and adjuvant systemic therapy.

The Whole Story

ALND, or the removal of most of the lymph nodes under the arm, has served for decades as the standard method for determining the regional spread of tumors in patients with breast cancer. It has also been viewed as having a therapeutic benefit—by removing lymph nodes that may harbor cancer cells that could eventually produce new tumors. However, ALND can cause side effects, such as lymphedema (arm swelling), paresthesia (numbness or tingling of the skin), and infection or seroma (accumulation of fluid) at the surgical site.

More recently, in an attempt to avoid the morbidity associated with ALND while retaining the ability to determine whether tumor cells have infiltrated the axillary lymph nodes, surgeons have begun evaluating the one or two lymph nodes to which cancer cells are most likely to spread first, called the sentinel lymph nodes. If no cancer cells are found in the sentinel nodes, patients might be able to forgo ALND. If, however, cancer cells are found in the sentinel nodes, patients would then undergo a full ALND.

Because women receive similar treatments after breast cancer surgery no matter how many axillary lymph nodes are involved, and because it is not known whether the presence of isolated tumor cells and micrometastases in axillary nodes is relevant to prognosis, doctors began to wonder whether the burdensome side effects of ALND were worth its potential benefits. Recent data from women without sentinel lymph node metastasis suggested that ALND in addition to SLNB is unnecessary for such women, but it was not clear whether this finding also applied to women with cancer cells in the sentinel nodes.

To answer this question, the American College of Surgeons Oncology Group (ACOSOG), an NCI Clinical Trials Cooperative Group, initiated trial Z0011. The trial’s goal was to compare the survival of women with early-stage breast cancer and metastasis to only one or two sentinel lymph nodes who were randomly assigned to undergo either no further lymph node surgery or ALND. Between May 1999 and December 2004, 891 patients with tumors 5 cm or less in diameter, no more than two metastasis-positive sentinel lymph nodes, and no other obvious lymph node involvement (such as swollen lymph nodes) were enrolled.

All of the women were treated with lumpectomy and received radiation therapy to the entire breast. Most of the women also received systemic therapy, which included hormonal therapy, chemotherapy, or both. The trial was closed early at the recommendation of its independent data and safety monitoring committee because of very low rates of tumor recurrence and patient death. At a median follow-up of 6.3 years, the 5-year overall survival for both groups of patients was nearly identical: 92.5% for the SLNB-only group versus 91.8% for the ALND group. The 5-year disease-free survival was also similar, at 83.9% for the SLNB-only group versus 82.2% for the ALND group. The researchers also observed less morbidity in women who received SLNB only, including fewer infections and seromas and less patient-reported paresthesia and lymphedema.

These results suggest that, for certain women with breast cancer, SLNB alone is not inferior to ALND when combined with lumpectomy, whole-breast radiotherapy, and systemic therapy. The whole-breast radiotherapy and systemic therapy appear to be effective in killing cancer cells that have spread to lymph nodes covered by the field of radiation exposure and cancer cells that have spread to other parts of the body, respectively. Therefore, the use of SLNB without more-extensive lymph node surgery may improve the quality of life of some breast cancer patients without adversely affecting their survival.

References: Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. Journal of the American Medical Association 2011; 305(6):569-575.