Surgery to Remove the Sentinel Lymph Node and Axillary Lymph Nodes After Chemotherapy in Treating Women With Stage II, Stage IIIA, or Stage IIIB Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer

Interventions: Drug: systemic chemotherapy
Procedure: axillary lymph node dissection
Procedure: neoadjuvant therapy
Procedure: sentinel lymph node biopsy
Procedure: therapeutic conventional surgery
Procedure: ultrasound imaging

Registration Number: NCT00881361

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying surgery to remove the sentinel lymph node and axillary lymph nodes after chemotherapy in treating women with stage II, stage IIIA, or stage IIIB breast cancer.

Detailed Description: This is a multicenter study. Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes prior to registration to confirm eligibility and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection. The primary and secondary objectives of the study are described below.

Primary Objective:

1. To determine the false negative rate for sentinel lymph node (SLN) surgery. Among the patients who have at least one sentinel lymph node identified and removed, false negative rate is defined as the number of patients declared to have no evidence of cancer in the SLN and are found to have at least one positive lymph node in the ALND divided by the total number of patients with at least one positive axillary lymph node by ALND.

Secondary Objectives:

1. To determine how the axillary ultrasound status of the patient upon completion of preoperative chemotherapy (evidence of residual lymphadenopathy on the ultrasound examination versus no evidence of lymphadenopathy in the ultrasound examination) affects the false negative rate of SLN and how sonographic findings correlate with residual disease on final pathology.

2. To determine the node status of patients after preoperative chemotherapy. Patients will be classified as node positive if they were determined to have at least one positive lymph node by SLN or ALND. Patients will be classified as node negative if all nodes examined by SLN and ALND were negative.

3. To determine whether the false-negative rate for SLN surgery after preoperative chemotherapy is related to the extent of residual cancer burden (RCB) overall, or separately in the breast or regional nodal basin.

4. To evaluate pathological complete response (pCR) rates (defined as no invasive disease in breast or lymph nodes) and disease-free survival (DFS) rates in node-positive patients receiving preoperative chemotherapy.

After completion of surgery, patients will visit the office for follow-up exams at 1-2 weeks then patients are followed every 6 months for 2 years, yearly for 2 years, then every other year for 6 years. The study closed to accrual and treatment on 5/29/12.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 756

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study cohort	sentinel lymph node biopsy	Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.
Study cohort	ultrasound imaging	Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.
Study cohort	axillary lymph node dissection	Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.
Study cohort	systemic chemotherapy	Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.
Study cohort	neoadjuvant therapy	Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.
Study cohort	therapeutic conventional surgery	Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.

Primary Outcome Measures

Name	Time	Method
False Negative Rate (FNR) for Sentinel Lymph Node (SLN) Surgery After Chemotherapy When at Least 2 SLNs Were Excised in Women Initially Presenting With Biopsy-proven cN1 Breast Cancer [cN1 Cohort]	At time of surgery	False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy when at least 2 SLNs were excised in women initially presenting with biopsy-proven cN1 breast cancer, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients initially presenting with biopsy-proven cN1 breast cancer with at least one positive lymph node by SLN or ALND multiplied by 100. A 2-sided Bayesian credible interval (BCI) for the true FNR was constructed.

Secondary Outcome Measures

Name	Time	Method
False Negative Rate (FNR) for Sentinel Lymph Node (SLN) Surgery After Chemotherapy When at Least 2 SLNs Were Excised in Women Initially Presenting With Biopsy-proven cN2 Breast Cancer [cN2 Cohort]	At time of surgery	False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy when at least 2 SLNs were excised in women initially presenting with biopsy-proven cN2 breast cancer, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients initially presenting with biopsy-proven cN1 breast cancer with at least one positive lymph node by SLN or ALND multiplied by 100. An interval estimate of the SLN false negative rate will be constructed using the Duffy-Santner approach.
False-negative Rate (FNR) Under the Selection Process by Axillary Ultrasound (AUS) Status After Completion of Neoadjuvant Chemotherapy (NAC)	At the time of surgery	False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy in women with normal AUS and at least 2 SLNs were excised, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients with at least one positive lymph node by SLN or ALND multiplied by 100.
Residual Cancer Burden Class	At time of surgery	Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. The calculated RCB index value can also be categorized as one of four RCB classes. The number of patients classified in the four RCB classes along with the number of patients missing this data by cohort are reported below. RCB of 0 represents a path complete response while increasing levels (I, then II, then III) indicate an increase in the 'amount' of residual disease remaining.
Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND)	At time of surgery	Node status of patients after preoperative chemotherapy, as measured by the total number of positive nodes (SLN+ALND). Patients will be classified as node positive if they were determined to have at least one positive lymph node by SLN or ALND.
Pathologic Complete Nodal Response (pCR) Rate	At the time of surgery	Pathologic complete nodal response (pCR) rate (percentage) wherein a nodal pCR is pathologically node-negative (pN0) on the basis of SLN surgery and ALND. A 95% binomial confidence interval was constructed for the pCR rate.

Trial Locations

Locations (321): University of South Alabama Mitchell Cancer Institute
🇺🇸
Mobile, Alabama, United States
Providence Cancer Center
🇺🇸
Anchorage, Alaska, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
East Bay Radiation Oncology Center
🇺🇸
Castro Valley, California, United States
Valley Medical Oncology Consultants - Castro Valley
🇺🇸
Castro Valley, California, United States
Cancer Care Center at John Muir Health - Concord Campus
🇺🇸
Concord, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Valley Medical Oncology
🇺🇸
Fremont, California, United States
Todd Cancer Institute at Long Beach Memorial Medical Center
🇺🇸
Long Beach, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
🇺🇸
Los Angeles, California, United States
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University of South Alabama Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States