SLNB IS SAFE-BIGGEST TRIAL ANNOUNCED

September 28, 2010 — In women with breast cancer and clinically negative lymph nodes, a less invasive approach to lymph node surgery provides the same survival and regional control as a more aggressive approach.

This is the most definitive word to date on the subject of sentinel lymph node (SLN) biopsy vs axillary lymph node dissection (ALND) in these women, according to the authors of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial.

The results from this study, the largest-ever randomized surgical trial of breast cancer, which were presented earlier this year at the American Society of Clinical Oncology annual meeting, were published online September 20 in the Lancet Oncology.

The trial enrolled 5611 women with invasive breast cancer, and randomly assigned them to either SLN biopsy plus ALND or to SLN biopsy alone (with ALND only if the SLNs were positive).

SLN surgery is the "highly targeted removal of the lymph nodes that receive direct drainage from a solid tumor in the breast," explain the study authors, led by David Krag, MD, from the University of Vermont in Burlington.

Anytime that SNL surgery is performed without follow-up ALND, there is the chance that there is residual disease in the nonsentinel nodes, according to an editorial that accompanies the study.

"It is of crucial importance to ascertain whether the finite proportion of patients with residual disease in nonsentinel nodes have impaired overall survival," writes editorialist John Benson, MD, from Cambridge University Teaching Hospitals Trust in the United Kingdom.

There was a slight difference in survival among patients assigned to SLN biopsy plus ALND and those assigned to SLN alone. But the difference was not statistically significant and, thus, could have been due to chance.

The 8-year Kaplan–Meier estimates for overall survival were 91.8% (95% confidence interval [CI], 90.4 - 93.3) for SLN biopsy plus ALND and 90.3% (95% CI, 88.8 - 91.8) for SLN biopsy alone.

The new data vindicate the "contemporary practice of SLN biopsy and provide support for a reduction in extent of axillary surgery for most patients with breast cancer," writes Dr. Benson.

However, this is not the final word on the subject — more follow-up is needed, says Dr. Benson.

For instance, there were more regional recurrences with SLN biopsy alone (14 vs 8 events). "Low volume axillary disease might arguably be clinically relevant if it translates into overall survival differences with longer-term follow-up," he points out.

However, the study authors placed a different emphasis on these data.

Dr. Krag and his coauthors say the results confirm the low rate of regional node recurrences after SLN surgery. Furthermore, the trial shows that in patients with negative SLNs, "the number of regional node recurrences does not differ significantly between patients who have axillary dissection or SLN resection only," they write.

"SLN surgery represents the next major step in reducing the extent of surgical procedures to treat breast cancer," the authors conclude, citing breast-conserving surgery as the previous major step.

Adverse Effect Advantage Too

In the editorial, Dr. Benson points out that this study is a step forward in understanding how SLN influences outcomes in clinical node-negative breast cancer, where disease in the nodes cannot be palpably detected in the clinic.

"Most published data on [SLN] biopsy come from validation studies in which clinically node-negative patients have undergone SLN biopsy and then immediate complete [ALND]," he writes.

What's been missing is comparative data for SLN biopsy alone without concomitant ALND, he adds.

There are actually 5 randomized controlled trials currently comparing SLN biopsy with conventional ALND in clinically node-negative patients. Notably, 3 of the trials have the exact same design: SLN biopsy plus ALND vs SLN biopsy alone. But the NSABP B-32 trial is the biggest.

In the B-32 trial, which is taking place at 80 centers in Canada and the United States, SLN biopsy was done in the more than 5000 patients with a blue dye and radioactive tracer, note the authors.

Previously reported results from the B-32 trial showed that morbidity related to range of motion, edema, pain, and sensory defects is lower in the SLN group than in the ALND group (J Clin Oncol. 2010;28:3929-3936; J Surg Oncol 2010;102:111-118).

This is key because the whole point of SLN surgery is to reduce morbidity.

However, as Dr. Krag and colleagues point out, SLN surgery is not without complications. There is a small increase over baseline of extremity edema and functional and neurologic deficits, they note.

The authors have disclosed no relevant financial relationships.

Lancet Oncol. Published online September 20, 2010. Abstract, Abstract