# ACOSOG Z1071 — Sentinel Lymph Node Surgery after Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer

**Autores:** Boughey JC, et al. (American College of Surgeons Oncology Group)
**Revista:** JAMA (2013)
**PMID:** 24101169 | **PMCID:** PMC4075763
**DOI:** [10.1001/jama.2013.278932](https://doi.org/10.1001/jama.2013.278932)
**Fuente:** PubMed Central (open access full-text)

## Relevancia
Ensayo pivotal fase II que estableció la tasa de falsos negativos (FNR) de la biopsia del ganglio centinela (SLNB) tras quimioterapia neoadyuvante en pacientes que se presentan con enfermedad ganglionar (cN1). Resultado: FNR global 12.6% (>10% prespecificado), pero con dual mapping y ≥3 SLN extraídos baja a 10.8% y 9.1% respectivamente. Tasa de respuesta patológica completa axilar (ypN0): 41%.

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## Resumen estructurado (PubMed)

**Importance:** Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for clinically node-negative (cN0) breast cancer patients. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive breast cancer (cN1) is unclear because of high false negative results reported in previous studies.

**Objective:** To determine the false negative rate (FNR) for SLN surgery following chemotherapy in patients initially presenting with biopsy-proven node-positive breast cancer.

**Design, Setting, and Patients:** The ACOSOG Z1071 trial enrolled women with clinical T0–4 N1–2, M0 breast cancer who received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. SLN surgery using both blue dye and a radiolabeled colloid mapping agent was encouraged.

**Main Outcome Measure:** The primary endpoint was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease.

**Results:** Seven hundred fifty-six patients were enrolled from 136 institutions. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. A SLN could not be identified in 46 patients (7.1%). Only one SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients yielding a **pathological complete nodal response of 41.0% (95% CI: 36.7%–45.3%)**. In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND resulting in a **FNR of 12.6% (90% BCI, 9.85%–16.05%)**.

**Conclusions and Relevance:** Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND.

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## Texto completo

### INTRODUCTION

Axillary lymph node status is an important prognostic factor in breast cancer and is used to guide local, regional, and systemic treatment decisions. In patients with large primary tumors or involved lymph nodes, chemotherapy is often delivered preoperatively in order to assess response to chemotherapy and to increase the likelihood of breast conserving surgery. Residual axillary nodal disease is found in only 50–60% of breast cancer patients initially presenting with node-positive disease (cN1) who receive neoadjuvant chemotherapy. Accurate determination of axillary involvement after chemotherapy is important; however removing all axillary nodes to assess for residual nodal disease subjects many patients to the morbidity of surgery while potentially only a subset will benefit.

To avoid the complications associated with axillary lymph node dissection (ALND), it is preferable to identify nodal disease with the less invasive SLN procedure which results in less morbidity. SLN surgery is considered reliable for identifying axillary nodal disease in women initially presenting without clinically evident nodes (cN0). False negative results can occur when the SLNs do not contain cancer, but cancer is found in nodes obtained on completion ALND. False negative rates for SLN surgery range from 0% to 20% after chemotherapy in cN0 patients, with a meta-analysis reporting a FNR of 12%. Subsequently, investigators from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-27 trial including both cN0 and cN1 disease and reported a SLN FNR of 10.7% after chemotherapy. However, the utility of SLN surgery following neoadjuvant chemotherapy for cN1 patients has been questioned, as the only available data has been from small series reporting FNRs ranging from 7% to 29.6%. Anthracyclines and taxane-based chemotherapy regimens have been shown to eradicate nodal disease in approximately 30–40% of patients. These patients would not benefit from ALND but may suffer complications of the procedure. ACOSOG Z1071 was designed to determine the FNR of SLN surgery after chemotherapy in women initially presenting with axillary node-positive disease.

### PATIENTS AND METHODS

The ACOSOG Z1071 trial was a phase II clinical trial designed to determine the FNR for SLN surgery performed after neoadjuvant chemotherapy in women presenting with pathologically proven node-positive breast cancer.

**Eligibility:** Women >18 years with clinical T0–4 N1–2 M0 invasive breast cancer (AJCC 6th edition), ECOG 0-1, completed or planning neoadjuvant chemotherapy, with pre-chemotherapy axillary nodal disease confirmed by FNA or core needle biopsy. Excluded: prior ipsilateral axillary surgery, prior SLN surgery, or excisional lymph node biopsy.

**Surgery:** Within 84 days post-chemo. Both SLN surgery (dual-agent mapping recommended: blue dye + radiolabeled colloid) and ALND performed. ≥2 SLNs required per protocol. Positive SLN defined as metastasis >0.2 mm.

**Statistics:** Bayesian design — FNR considered too high if >95% chance FNR >10%. Sample size 300 cN1 patients.

### RESULTS

756 women enrolled (July 2009 – June 2011, 136 institutions). After exclusions: 663 cN1 and 38 cN2. Chemotherapy: 74.6% anthracycline+taxane; median 4 months.

- SLN identified in 92.7% (639/689)
- 525 cN1 patients with ≥2 SLNs + completion ALND analyzed
- **Nodal pCR (ypN0): 215/525 = 41.0% (95% CI 36.7-45.3%)**
- **FNR: 39/310 = 12.6% (90% BCI 9.85-16.05%)**

**Factors associated with lower FNR (bivariable):**
- Dual-agent mapping vs single agent: 10.8% vs 20.3% (p=0.052)
- ≥3 SLNs vs 2 SLNs: 9.1% vs 21.1% (p=0.007)

**cN2 cohort (n=26):** pCR 46.1%, FNR 0% (95% CI 0-23.2%, small numbers).

### DISCUSSION & CONCLUSION

FNR exceeded the 10% threshold globally but optimization with dual tracer and ≥3 SLNs brings it below. Recommend SLN surgery NOT be performed in patients with clinically evident residual nodal disease or poor response to chemotherapy.

The findings of ACOSOG Z1071 led to refined approaches including targeted axillary dissection (TAD) — combining clip placement in biopsy-proven node + SLNB.

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*Texto recuperado de PubMed Central (PMC4075763). Citar siempre el artículo original: doi 10.1001/jama.2013.278932*
