Sentinel Node Biopsy Alone or With Axillary Dissection After Primary Chemotherapy

Sentinel Node Biopsy Alone or With Axillary Dissection in cT2 cN0/1 Breast Cancer Patients After Primary Chemotherapy: a Prospective Interventional Study

Many doctors believe that breast cancer patients scheduled for pre-operative chemotherapy whose cancer has spread to the axilla (determined by palpation plus ultrasound) should not receive sentinel node biopsy after chemotherapy, but proceed directly to removal of all the axillary lymph nodes.

In this study, breast cancer patients with operable medium-size cancer (T2) scheduled for pre-operative chemotherapy, and a disease-free or a metastatic axilla, are prospectively assigned to receive sentinel node biopsy as part of their post-chemotherapy surgical treatment (whose main aim is to remove the cancer in the breast).

Irrespective of whether the axilla is disease-free or metastatic before chemotherapy, if the removed sentinel nodes are disease-free on histological examination (pN0) after chemotherapy, then no further axillary treatment is given. If however the sentinel nodes contain cancer, then the other axillary lymph nodes will be removed surgically.

The study hypothesis is that, irrespective of whether the axilla is disease-free or metastatic before chemotherapy, patients with negative axillary sentinel nodes on histological examination (pN0) after chemotherapy, and who are no given further axillary treatment, will do as well as pN1 patients whose axillary lymph nodes are completely removed (a more aggressive treatment).

Study Overview

• Status: Completed
• Conditions: Breast Neoplasm Female
• Intervention / Treatment: Procedure: Sentinel Node Biopsy; Procedure: Axillary Dissection

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• cT2 cN0/1 breast cancer
• Scheduled for neoadjuvant chemotherapy,
• Informed consent,

Exclusion Criteria:

• Previous malignancy at another site
• Synchronous breast cancer at diagnosis
• Distant metastasis at diagnosis
• Clinically involved axilla (cN1) after neoadjuvant chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: SNB only; cT2 patients scheduled for primary chemotherapy (with or without a clinically involved axilla - cN0/1) who have disease-free sentinel nodes (pN0) after primary chemotherapy, are directed to "SNB only": i.e. no further treatment to the axilla.	Procedure: Sentinel Node Biopsy; Colloidal radiotracer (99Tc) is injected into the breast near the cancer. The radiotracer moves in the lymph ducts to accumulate in the first lymph nodes (almost always in the axilla) to receive lymph from the breast area containing the cancer. Lymphoscintigraphy is used to check for the presence of radioactivity in the axilla. Some hours later, during breast surgery, a radioactivity-detecting probe is used to identify "hot" lymph nodes (sentinel nodes) and aid their surgical removal from the axilla. These nodes are examined histologically (intraoperatively) for the presence of cancer. If they are disease-free the axilla will be left intact (no further axillary treatment given); if they contain cancer most lymph nodes in the axilla will be removed surgically (axillary dissection).; Other Names: Sentinel Lymph Node Biopsy
Other: SNB + AD; cT2 patients scheduled for primary chemotherapy (with or without a clinically involved axilla - cN0/1) who have metastatic sentinel nodes (pN1) on sentinel node biopsy (SNB) will undergo axillary dissection (AD) i.e. surgical removal of most axillary lymph nodes.	Procedure: Sentinel Node Biopsy; Colloidal radiotracer (99Tc) is injected into the breast near the cancer. The radiotracer moves in the lymph ducts to accumulate in the first lymph nodes (almost always in the axilla) to receive lymph from the breast area containing the cancer. Lymphoscintigraphy is used to check for the presence of radioactivity in the axilla. Some hours later, during breast surgery, a radioactivity-detecting probe is used to identify "hot" lymph nodes (sentinel nodes) and aid their surgical removal from the axilla. These nodes are examined histologically (intraoperatively) for the presence of cancer. If they are disease-free the axilla will be left intact (no further axillary treatment given); if they contain cancer most lymph nodes in the axilla will be removed surgically (axillary dissection).; Other Names: Sentinel Lymph Node Biopsy; Procedure: Axillary Dissection; Axillary dissection is the surgical removal of all Berg level I and II lymph nodes present in the axilla. The operation is carried out, at our Institute, during the surgery to treat the cancer in the breast (either breast-conserving surgery - quadrantectomy, or mastectomy).; Other Names: Axillary Lymph Node Dissection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) and Disease-Free Survival (DFS)	DFS and OS are reckoned from date of surgery. DFS is time to recurrence or death, whichever occurred first. OS is time to death for any cause. Time is censored for living patients who are event-free at most recent follow up. OS and DFS curves are estimated using the Kaplan-Meier method and compared using the log-rank test. To compare DFS and OS in the SNB only and SNB + AD groups, propensity scores are estimated to account for bias due to non-random assignment to SNB vs SNB + AD	Ten years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of axillary failure in those receiving only sentinel node biopsy	In patients given only sentinel node biopsy the proportion of patients who develop disease in the axilla will be calculated.	Ten years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pathological response to primary chemotherapy as predictor of outcome	The response of the cancer to primary chemotherapy (complete response, partial response, stable disease, disease progression) will be related to overall outcomes.	Ten years

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Gabriele Martelli, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2007
• Primary Completion (Actual): December 31, 2015
• Study Completion (Actual): December 31, 2015

Study Registration Dates

• First Submitted: June 14, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Breast cancer; Neoadjuvant chemotherapy; Sentinel node biopsy; Axillary dissection
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: INT180/13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No