Omission of Completion Axillary Lymph Node Dissection for Patients with Breast Cancer Treated by Upfront Mastectomy and Sentinel Node Isolated Tumor Cells or Micrometastases

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The study evaluates the impact of omitting completion axillary lymph node dissection (cALND) in breast cancer (BC) patients with isolated tumor cells (ITC) or micrometastases in sentinel lymph nodes (SN), treated with up-front mastectomy. Analyzing data from 554 patients across 13 French cancer centers, the study found a non-sentinel node (NSN) involvement rate of 13.2%. Multivariate analysis revealed that omitting cALND was significantly associated with poorer outcomes in terms of overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and metastasis-free survival (MFS), particularly in HER2-positive, triple-negative, and ER-positive HER2-negative BC subtypes. The study highlights a potential negative prognostic impact of cALND omission.

The study is very interesting and reaches opposite conclusions according to present literature. Many clinical trials are on-going and I am confident we are going to see definitive results very soon.

Author Response

Reviewer 1 comments: The study evaluates the impact of omitting completion axillary lymph node dissection (cALND) in breast cancer (BC) patients with isolated tumor cells (ITC) or micrometastases in sentinel lymph nodes (SN), treated with up-front mastectomy.

Analyzing data from 554 patients across 13 French cancer centers, the study found a non-sentinel node (NSN) involvement rate of 13.2%. Multivariate analysis revealed that omitting cALND was significantly associated with poorer outcomes in terms of overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and metastasis-free survival (MFS), particularly in HER2-positive, triple-negative, and ER-positive HER2-negative BC subtypes. The study highlights a potential negative prognostic impact of cALND omission.

The study is very interesting and reaches opposite conclusions according to present literature. Many clinical trials are on-going and I am confident we are going to see definitive results very soon.

Answer: Thank you for your review and comments. We agree with your comments: "The study highlights a potential negative prognostic impact of cALND omission." 

Yes, the study reaches opposite conclusions according to present literature, but only for sentinel node micrometastases and mastectomy with or without post mastectomy radiotherapy. Yes: "Many clinical trials are on-going and I am confident we are going to see definitive results very soon", particularly for our SERC randomized trial.

Reviewer 2 Report

Comments and Suggestions for Authors

Title : Omission of completion axillary lymph node dissection for patients with breast cancer treated by up-front mastectomy and  sentinel node isolated tumor cells or micrometastases.

The current work shows application and difference in outcome of cALND with SLNB or without cALND.

Comments:

1.Authors have shown strong comparison regarding application of SLNB with cALND or only SLNB.Can Author explain status of micro or Macro metastastases after SLNB or cALND or SLNB with cALND treated patient?

2.After treatment with SLNB or cALND or SLNB with cALND treated patient with a age window of 50years showed increase or decrease in micro or Macro metastastases tumor cells?

3.In Current version of manuscript, page 1 line 34-35 states there is “These findings suggest potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC”, but survivual curve analysis showed cALND showed increase survival rate the untreated ? This statement need to revised with respect to the findings.

 

 

Author Response

Thak you for your review and comments.

Reviewer 2 Comments:

1. Authors have shown strong comparison regarding application of SLNB with cALND or only SLNB. Can Author explain status of micro or Macro metastastases after SLNB or cALND or SLNB with cALND treated patient?  Answer: In chapter methods (lines 90-91), it is reported that axillary surgery was sentinel lymph node biopsy (SLNB) or SLNB and completion axillary lymph node dissection (cALND). (Not only ALND). SLNB status were: 391 pN1mi sn and 163 pN0(i+) sn with 44 pN1 status (11.3%) and 8 pN1 status (4.9%) after cALND, respectively (Table1). cALND was performed in 55.8% (91/163) of pN0(i+)sn and 71.6% (280/391) of pN1mi sn, respectively (Table 2).

2.After treatment with SLNB or cALND or SLNB with cALND treated patient with a age window of 50 years showed increase or decrease in micro or Macro metastastases tumor cells? Answer: In Table 3, we report that patients 50.1-74.9 years had more cALND after SLNB with an Odd Ratio of 2.392 (p=0.007) and 75.3% of cALND (198/263) in Table 2. In Table 1, there was no difference between pN1mi sn or pN0(i+)sn according to patients age (p=0.157). We added, line 132: Distribution between pN0(i+)sn and pN1mi sn was 66 pN0(i+)sn and 150 pN1mi sn for patients 50 years or lower, 97 pN0(i+)sn and 241 pN1mi sn for patients > 50 years (p=0.640). For patients without cALND, pN0(i+)sn rate was 48.5% (32/66) and 34.2% (40/117) for patients 50 years or lower and > 50 years, respectively (p=0.057). For patients with cALND, pN0(i+)sn rate was 22.7% (34/150) and 25.8% (57/221) for patients > 50 years, respectively (p=0.492). For patients with cALND, pN1 with macro metastases rates were 11.3% (17/150) and 14.5% (32/121), pN1 mi rates were 66.7% (100/150) and 62.4% (138/221) and pN0(i+) rates were 22.0% (33/150) and 23.1% (51/221), for patients 50 years or lower and > 50 years, respectively (p=0.618). 

3.In Current version of manuscript, page 1 line 34-35 states there is “These findings suggest potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC”, but survivual curve analysis showed cALND showed increase survival rate the untreated ? This statement need to revised with respect to the findings. Answer: Yes, we removed "potential": These findings suggest negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. However, as we report in chapter Discussion, Limitations: "Despite multivariate analysis adjusted on numerous criteria, several biases can persist in the comparison between SLNB alone and SLNB with cALND. These results underline a possible negative prognostic effect of cALND omission in patients with SN micrometastases or isolated tumor cells".