NSABP B-32

Published

Krag DN, et al. "Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial". Lancet Oncology. 2010. 11(10):927-933.
PubMed • Full text • PDF

Clinical Question

In women with clinically node-negative breast cancer, how does sentinel lymph node biopsy compare to axillary lymph node dissection in terms of overall survival?

Bottom Line

Among women with clinically node-negative breast cancer, there is no difference in overall survival between sentinel lymph node biopsy and axillary lymph node dissection, but sentinel lymph node biopsy is associated with fewer nerve palsies, neuropathies, and less lymphedema.

Major Points

Sentinel lymph node biopsy (SLNB) is a surgical technique used to screen for metastasis in which the sentinel lymph nodes (SLNs) draining a tumor bed are identified using dye and radioactive tracers. Given the hierarchical anatomy of lymph nodes, more distant nodes are almost guaranteed to be negative for tumor when SLNs are negative, obviating the need for more extensive axillary lymph node dissection (ALND). Originally devised for melanoma, SLNB remains a major advancement towards reducing the surgical morbidity associated with ALND in women with breast cancer. Several smaller studies have demonstrated no survival difference between SLNB and ALND, but NSABP B-32 was the largest trial to validate the SLNB technique.

The National Surgical Adjuvant Breast and Bowel Project Trial B-32 randomized 5,611 women with clinically node-negative breast cancer to one of two strategies for lymph node evaluation: the first group received SLNB followed by ALND, while the second group received SLNB followed by ALND only if metastasis was discovered in any SLNs. After a mean follow-up of 8 years, there were no differences in overall survival (92.9% vs. 91.6%), disease-free survival (75.1% vs. 76.1%), or locoregional control among SLN-negative patients. The false-negative rate of SLNB was 9.8% in NSABP B-32, which is roughly comparable to an average false-negative SLNB rate of 7.3% in a large meta-analysis. Importantly, NSABP B-32 used only simple H&E preparations to evaluate for nodal metastases; the follow-up Effect of Occult Metastases on Survival in Node-Negative Breast Cancer evaluated advanced techniques including immunohistochemistry.

Modern guidelines recommend SLNB for routine axillary staging in patients with early stage breast cancer and clinically negative lymph nodes. Previously, women with an involved node identified on SLNB were advised to undergo completion ALND. This guideline was withdrawn based in part on ACOSOG Z0011, which demonstrated no difference in locoregional recurrence rate among women with a positive SLNB who were randomized to either completion ALND or to no further surgical staging.

Design

• Multicenter, non-blinded, randomized, controlled trial
• N=5,611 women with clinically node-negative breast cancer
  • SLNB followed by ALND (n=2,807)
  • SLNB followed by ALND only if SLNB was positive (n=2,804)
• Setting: 80 centers in the US and Canada
• Enrollment: 1999-2004
• Follow-up: 8 years
• Analysis: Intention-to-treat
• Primary outcome: Overall survival

Population

Inclusion Criteria

• Female >18 years
• Invasive breast cancer
• Clinically node-negative

Exclusion Criteria

• None specified

Baseline Characteristics

• Age ≥50 years: 75.5%
• White: 90.5%; Black: 4.7%
• Tumor size:
  • ≥2.0 cm: 83.8%
  • 2.1-4.0 cm: 14.7%
  • ≥4.1 cm: 1.5%
• Lumpectomy: 87.5%
• Total Mastectomy: 12.5%
• Systemic adjuvant therapy: 84.6%
• Radiation therapy: 82.3%

Interventions

• Stratified by age, tumor size, and surgery (lumpectomy vs. mastectomy), patients were randomized to either:
  • SLNB followed by ALND
  • SLNB followed by ALND if ≥1 SLN was positive intraoperatively or at a later date if final pathology demonstrated malignancy
• All patients underwent SLNB, identifying SLNs as blue, radioactive, or palpably suspicious at time of surgery
• Subsequent therapies were directed by the medical and surgical oncology teams

Outcomes

Comparisons are SLNB followed by ALND vs. SLNB followed by ALND if SLNB was positive.

Primary Outcome

Overall survival

92.9% vs. 91.6% (P not specified)

Log-rank comparison: HR 1.20 (95% CI 0.96-1.50; P=0.12)

Cox proportional hazard analyses: HR 1.19 (95% CI 0.95-1.49; P=0.13)

Disease-free survival

75.1% vs. 76.1% (P=NS)

Local recurrences

54 vs. 49 events (P=0.55)

Secondary Outcomes

Death without disease recurrence

HR 1.03 (95% CI 0.71-1.50; P=NS)

Second cancers

HR 1.20 (95% CI 0.901.58; P=NS)

Contralateral breast cancer

HR 0.77 (95% CI 0.52-1.15; P=NS)

Distant recurrences

HR 1.14 (95% CI 0.80-1.64; P=NS)

Local regional recurrences

HR 1.05 (95% CI 0.90-1.22; P=NS)

Alive and event-free

84.1% vs. 83.3% (statistics not given)

Adverse Events

Allergic reactions occurred in 0.8% of patients, mostly from the dye.

Criticisms

As 15 year mortality is a significant outcome for local disease progression with mastectomy, a 15 year follow-up may be a more relevant endpoint in this trial.

Funding

US Public Health Service, National Cancer Institute, and Department of Health and Human Services.