- Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes:
- The SOUND Randomized Clinical Trial. Gentilini et al. JAMA Oncol. 2023 Sep 21:e233759. doi: 10.1001/jamaoncol.2023.3759
- The SOUND trial that was published in JAMA Oncology concluded:
- That patients with small breast cancer (less than 2 cm) and sonographically normal appearing lymph nodes:
- Can be safely spared any axillary surgery:
- Whenever the lack of pathological information does not affect the postoperative treatment plan
- Can be safely spared any axillary surgery:
- That patients with small breast cancer (less than 2 cm) and sonographically normal appearing lymph nodes:
- This study was designed to evaluate whether omission of sentinel lymph node (SLN) surgery in patients with negative axillary ultrasound:
- Was noninferior to SLN surgery in terms of 5 year distant disease free survival
- While this trial is unlikely to change practice immediately:
- It is a thought provoking study that will likely generate multidisciplinary discussion
- Phase III Randomized Controlled Trial:
- Conducted at 18 European hospitals from 2012 to 2017:
- Italy, Spain, Switzerland, and Chile:
- Recruitment Feb 6, 2012 – Jun 30, 2017
- Italy, Spain, Switzerland, and Chile:
- Enrolled patients with invasive breast cancer up to 2 cm, cN0, planning for breast conserving surgery (BCT) and adjuvant radiation therapy (XRT) who had an axillary US showing no LN involvement on imaging:
- If doubtful – FNA performed and had to be negative:
- 1406 negative AUS, 57 with negative FNA
- If doubtful – FNA performed and had to be negative:
- Patients were randomized to SLN surgery vs no axillary surgery
- Analysis cohort:
- 1405 women:
- 708 SLN
- 697 no axillary surgery
- Median age 60
- Tumor size 1.1 (IQR 0.8-1.5cm)
- ER+ / Her2- disease in 87.8%
- In the SLN group:
- 13.7% had positive nodes on SLN:
- 5.1% macrometases
- 8.6% micrometastases
- 2.0% had ≥ 2 positive SLNs, 0.6% had pN2 disease
- 13.7% had positive nodes on SLN:
- Recommended adjuvant systemic therapy and radiotherapy were similar in the two groups:
- 20.1% of SLN group and 17.5% of no axillary surgery group received chemotherapy
- 98.0% of SLN group and 97.6% of no axillary surgery received radiation
- 83.3% (593 pts) vs 81.1% (565 pts) had whole breast radiation over 3 to 5 weeks
- 10.7% (76 pts) vs 10.8% (75 pts) had partial breast radiotherapy
- 3.4% (24 pts) vs 5.6% (39 pts) had intraoperative boost of ELIOT (12 Gy) followed by a hypofractionated course of whole-breast radiotherapy (37.05 Gy in 13 fractions)
- 1405 women:
- Conducted at 18 European hospitals from 2012 to 2017:
- The study authors concluded that patients with patients with small breast cancer with sonographically normal appearing lymph nodes:
- Can be safely spared any axillary surgery:
- Whenever the lack of pathological information does not affect the postoperative treatment plan
- Can be safely spared any axillary surgery:
- This study provides further data:
- Supporting that axillary sentinel lymph node surgery does not provide therapeutic benefit
- In the no axillary surgery group:
- The cumulative incidence of lymph node recurrences in the axilla was very low:
- 0.4% at 5 years:
- Despite a 13.7% rate of nodal involvement in the SLNB group
- 0.4% at 5 years:
- The cumulative incidence of lymph node recurrences in the axilla was very low:
- However, SLN surgery likely still has a role in certain patients for staging to guide adjuvant therapies:
- In particular in young patients:
- Where chemotherapy is associated with survival benefit for node positive disease (Rx-Ponder patient)
- Furthermore, while adjuvant treatment recommendations in terms of rate of chemotherapy was similar between the two groups:
- Identification of nodal positivity in ER+ breast cancer:
- Also influences treatment options in terms of:
- CDK4/6 inhibitor eligibility as well as consideration of extended endocrine therapy (to 10 years)
- Also influences treatment options in terms of:
- Identification of nodal positivity in ER+ breast cancer:
- Many patients are interested in potential for omission of radiation therapy:
- The trial required radiation, with 90% of patients having whole breast radiation and 10% partial breast radiation
- Some of the patients in this trial with small breast cancers aged > 65 would be candidates for consideration of omission of radiation
- This creates a dilemma regarding de-escalating axillary surgery leading to potential escalation of adjuvant radiation
- It should be noted that tumor grade was not an inclusion / exclusion factor:
- However, 18% had grade 3 disease
- Patients with grade 3 disease have higher likelihood of nodal positivity:
- Should omission of SLN surgery be limited to grade 1 and 2 disease at outset
- Especially as grade 3 disease with 1 to 3 positive nodes:
- Would make patients eligible for CDK4/6 inhibitor
- In particular in young patients:
- Genomic scores were not included on this trial:
- Most patients with ER+ / Her2- disease (with tumors > 1 cm in size) would be considered for genomic testing to guide systemic treatment recommendations
- In summary:
- Multidisciplinary discussion will be important before implementing any changes in practice as a result of the SOUND trial
- I look forward to additional data from several other trials evaluating this question over the upcoming years:
- INSEMA (published)
- BOOG 2013-08
- NAUTILUS
Rodrigo Arrangoiz MS, MD, FACS, FSSO 