Predictive Model of Axillary Nodal Status After Neoadjuvant Chemotherapy in Breast Cancer Patients (LNNEO)

Retrospective, Observational, Multicentric Study Aimed at Developing a Model for Prediction of Axillary Lymph Node Status After Neoadjuvant Chemotherapy in Breast Cancer Patients

The management of patients diagnosed with breast cancer (BC) with axillary nodal involvement is still a controversial topic. These patients' treatment usually involves the administration of a neoadjuvant chemotherapy (NAC) in order to improve survival rates and increase local disease control. Depending on the tumor subtype, an axillary pathologic complete response (pCR) is achieved in 40-70% of initially axillary node-positive patients (cN+). Concerning patients with an axillary pCR, thus a clinically negative node status (cN0), axillary lymphadenectomy (ALND) might be replaced by less invasive surgical approaches and sentinel lymph node biopsy (SLNB) is considered, in these cases, an effective alternative treatment.

However, the relatively high false negative rates, reported in several validation trials, points out the complexity concerning these patients' treatment. Moreover, histological findings' predictive and prognostic value, after SLNB, of micrometastases and isolated tumor cells (ITCs) is still unclear.

Currently, dual-tracer-guided lymph node biopsy and the surgical removal of ≥ 3 sentinel lymph nodes are known as effective strategies aimed to reduce the false negative rates.

There are several ongoing clinical trials to understand and define the best approach for these patients.

Nowadays, there's great interest in potential prognostic role of systemic inflammation's biochemical markers such as neutrophil-to-lymphocyte ratio (NLR). Systemic inflammation's markers may be nodal pCR's predictors after NAC in node-positive breast cancer patients.

The aim of the study is to develop and validate a pre-operative model, able to predict pCR after NAC to select the patients suitable for a surgery de-escalation strategy.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer

Detailed Description

This is a retrospective, observational, multicentric and no profit study. The study involves patients with diagnosis of cN+ breast cancer who underwent neoadjuvant treatment and then treated with lymph node biopsy or axillary lymphadenectomy, referring to the participating centers.

For each patient the following clinical-anamnestic information will be collected: age, pre-NAC blood cell count, tumor dimension, clinical staging (cT, cN), histological information (tumor subtype, grading, receptors' status, Ki-67 value), neoadjuvant treatment regimen, clinical and radiological local response after NAC, clinical and radiological nodal response after NAC, type of surgery, number of examined lymph nodes, number of positive lymph nodes, pathological staging after surgery (ypT, ypN).

• Study Type: Observational
• Enrollment (Actual): 1950

Contacts and Locations

Study Locations

• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Istituti Clinici Scientifici Maugeri SpA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study involves patients with diagnosis of cN+ breast cancer who underwent neoadjuvant chemotherapy and afterwards treated with lymph node biopsy or axillary lymphadenectomy, referring to the participating centers.

Description

Inclusion Criteria:

• Diagnosis of breast cancer confirmed by histological examination
• Patients who underwent neoadjuvant chemotherapy
• Axillary lymph nodes involvement at diagnosis (cN≥1), identified by clinical examination and/or imaging techniques and/or axillary lymph node cytology aspirate positive for breast cancer cells.

Exclusion Criteria:

• Patients with M+ at diagnosis
• Contraindications for neoadjuvant chemotherapy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with diagnosis of cN+ breast cancer who underwent neoadjuvant treatment; Patients with diagnosis of cN+ breast cancer who underwent neoadjuvant treatment and then treated with lymph node biopsy or axillary lymphadenectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Selection of features	Identification of pre-operative clinical-pathological features predictive for ypN0 status after NAC in patients with cN+ breast cancer (Logistic regression model will be performed)	48 months
Nomogram	Development and validation of a nomogram, based on selected clinical-pathological features, able to predict nodal status after neoadjuvant chemotherapy	48 months

Collaborators and Investigators

• Sponsor: Istituti Clinici Scientifici Maugeri SpA

Publications and helpful links

General Publications

• Gasparri ML, Albasini S, Truffi M, Favilla K, Tagliaferri B, Piccotti F, Bossi D, Armatura G, Calcinotto A, Chiappa C, Combi F, Curcio A, Della Valle A, Ferrari G, Folli S, Ghilli M, Listorti C, Mancini S, Marinello P, Mele S, Pertusati A, Roncella M, Rossi L, Rovera F, Segattini S, Sgarella A, Tognali D, Corsi F. Low neutrophil-to-lymphocyte ratio and pan-immune-inflammation-value predict nodal pathologic complete response in 1274 breast cancer patients treated with neoadjuvant chemotherapy: a multicenter analysis. Ther Adv Med Oncol. 2023 Sep 15;15:17588359231193732. doi: 10.1177/17588359231193732. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Actual): May 25, 2021
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: March 22, 2023
• First Posted (Actual): April 5, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 2394

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No