Study Supports Role for ALND in Early Breast Cancer

Patients with early-stage breast cancer at high risk of residual nodal disease might benefit from axillary lymph node dissection (ALND), according to a simulation study that challenges certain findings of the controversial ACOSOG Z0011 trial.

The study results, presented at the 2012 Breast Cancer Symposium in San Francisco, suggest that ALND offers an improvement in long-term overall survival (OS) and quality of life for a segment of women weighing therapeutic options after undergoing breast-conserving surgery.

Researchers from Harvard Radiation Oncology set out to examine whether a subgroup of high-risk patients “were not adequately represented” in ACOSOG Z0011, lead investigator Monica Shalini Krishnan, MD, said at a press conference during the symposium. She is a resident in the Harvard Radiation Oncology residency program at Harvard University-affiliated hospitals in Boston.

Historically, patients with early-stage breast cancer who undergo breast- conserving surgery and have a positive sentinel lymph node biopsy have then received a completion ALND, Krishnan said.

She noted the Z0011 findings disputed that protocol. The Z0011 trial concluded that ALND did not significantly affect OS among patients who had limited sentinel lymph node metastases after breast-conserving surgery and systemic therapy, investigators reported in the Journal of the American Medical Association in February 2011.

In their simulation, the Harvard researchers applied algorithms to trial data to approximate results for hypothetical women aged 45, 55, and 75 with stage II breast cancer following breast-conserving surgery with positive sentinel lymph nodes. They then were treated with either ALND and whole-breast radiation (BRT) or BRT alone.

The study simulated patients’ axillary recurrence risk, lymphedema, and quality-adjusted life expectancy (QALE). The patients were stratified into two risk groups; “high risk” patients were those with a 30%-60% risk of residual nodal involvement while “low risk” patients had a <30% risk.

Patients in the high-risk group achieved a 20-year OS of 42% with ALND plus BRT, compared with 38% for BRT alone. The QALE was 14.36 years with ALND plus BRT, versus 13.55 years for BRT alone.

For the low-risk group, there was virtually no difference with ALND. The 20-year OS was 47% with and without ALND, and the QALE was 15.46 years with ALDN and 15.53 without it.

Krishnan said the hypothetical patients in her study would have been eligible for inclusion in ACOSOG Z0011, and therefore would be valuable in deciding upon therapeutic options.

“While it is not a substitute for clinical data, this simulation can at least inform what options physicians discuss with their patients and give physicians a basis for considering axillary lymph node surgery in patients with high risk of residual nodal disease,” Krishnan said.

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. JAMA. 2011;305(6):569-575.

Krishnan MS, Recht A, Bellon JR, et al. Trade-offs associated with axillary lymph node dissection: implications of the eligibility versus enrollment in ACOSOG Z0011. J Clin Oncol. 2012;30 (suppl 27; abstr 151).