Breast Cancer
Conditions
Keywords
stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer
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.
Interventions
DRUGsystemic chemotherapy
PROCEDUREaxillary lymph node dissection
PROCEDUREneoadjuvant therapy
PROCEDUREsentinel lymph node biopsy
PROCEDUREtherapeutic conventional surgery
PROCEDUREultrasound imaging
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria: 1. ≥ 18 years old 2. ECOG/Zubrod Performance Status 0-1 3. Female. Note: Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer. 4. Histologic diagnosis of invasive breast cancer, clinical stage T0-4 N1-2 M0 (excluding inflammatory breast cancer). 5. FNA biopsy or core needle biopsy of an axillary node documenting nodal disease at time of diagnosis and prior to preoperative chemotherapy. 6. Preoperative chemotherapy must be completed or planned for patient. NOTE: Patients enrolling on studies involving preoperative chemotherapy (through cooperative groups or institutional studies) may be eligible for this study, provided sentinel node surgery prior to preoperative chemotherapy was not required in the other studies. 7. No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis. 8. No prior SLN surgery/excisional lymph node biopsy for pathological confirmation of axillary status.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame |
|---|---|
| Disease-Free Survival | Up to 10 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| cN1 Cohort Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and 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. | 663 |
| cN2 Cohort Patients who were staged according to the AJCC staging system as cN2 (disease in fixed or matted axillary lymph nodes) and 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. | 38 |
| Total | 701 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Ineligible | 17 | 2 | 2 |
| Overall Study | Terminated prior to surgery | 27 | 7 | 0 |
Baseline characteristics
| Characteristic | cN1 Cohort | cN2 Cohort | Total |
|---|---|---|---|
| Age, Customized 18-39 years old | 120 participants | 4 participants | 124 participants |
| Age, Customized 40-49 years old | 213 participants | 15 participants | 228 participants |
| Age, Customized 50-59 years old | 197 participants | 10 participants | 207 participants |
| Age, Customized 60-69 years old | 112 participants | 5 participants | 117 participants |
| Age, Customized greater than 70 years old | 21 participants | 4 participants | 25 participants |
| Region of Enrollment United States | 663 Participants | 38 Participants | 701 Participants |
| Sex: Female, Male Female | 663 Participants | 38 Participants | 701 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 676 | 0 / 39 |
| other Total, other adverse events | 192 / 676 | 9 / 39 |
| serious Total, serious adverse events | 6 / 676 | 0 / 39 |
Outcome results
Primary
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]
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.
Time frame: At time of surgery
Population: Of the cN1 Cohort patients who Started the study (see Participant Flow), only patients with residual nodal disease were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| cN1 Cohort | 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] | 12.6 percentage of participants |
Secondary
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]
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.
Time frame: At time of surgery
Population: Of the cN2 Cohort patients who Started the study (see Participant Flow), only patients with residual nodal disease were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| cN1 Cohort | 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] | 0 percentage of false-negative SLN finding |
Secondary
False-negative Rate (FNR) Under the Selection Process by Axillary Ultrasound (AUS) Status After Completion of Neoadjuvant Chemotherapy (NAC)
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.
Time frame: At the time of surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| cN1 Cohort | False-negative Rate (FNR) Under the Selection Process by Axillary Ultrasound (AUS) Status After Completion of Neoadjuvant Chemotherapy (NAC) | 12.6 percentage of false-negative SLN finding |
Secondary
Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND)
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.
Time frame: At time of surgery
Population: Patients with post-chemotherapy AUS results were included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| cN1 Cohort | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | 1-3 | 173 Participants |
| cN1 Cohort | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | >10 | 10 Participants |
| cN1 Cohort | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | 4-10 | 42 Participants |
| cN1 Cohort | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | Missing/Unknown | 34 Participants |
| cN1 Cohort | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | 0 | 171 Participants |
| Post-chemotherapy AUS Suspicious | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | Missing/Unknown | 10 Participants |
| Post-chemotherapy AUS Suspicious | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | 0 | 47 Participants |
| Post-chemotherapy AUS Suspicious | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | 1-3 | 89 Participants |
| Post-chemotherapy AUS Suspicious | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | 4-10 | 28 Participants |
| Post-chemotherapy AUS Suspicious | Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) | >10 | 7 Participants |
p-value: 0.003t-test, 2 sided
Secondary
Pathologic Complete Nodal Response (pCR) Rate
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.
Time frame: At the time of surgery
Population: Patients in cN1 and cN2 Cohort who had at least two SLNs excised and went on to complete ALND were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| cN1 Cohort | Pathologic Complete Nodal Response (pCR) Rate | 41.0 percentage of SLN surgery/ALND |
| Post-chemotherapy AUS Suspicious | Pathologic Complete Nodal Response (pCR) Rate | 46.1 percentage of SLN surgery/ALND |
Secondary
Residual Cancer Burden Class
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.
Time frame: At time of surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| cN1 Cohort | Residual Cancer Burden Class | 0 | 182 participants |
| cN1 Cohort | Residual Cancer Burden Class | II | 136 participants |
| cN1 Cohort | Residual Cancer Burden Class | I | 33 participants |
| cN1 Cohort | Residual Cancer Burden Class | III | 150 participants |
| cN1 Cohort | Residual Cancer Burden Class | missing data | 162 participants |
| Post-chemotherapy AUS Suspicious | Residual Cancer Burden Class | III | 9 participants |
| Post-chemotherapy AUS Suspicious | Residual Cancer Burden Class | missing data | 6 participants |
| Post-chemotherapy AUS Suspicious | Residual Cancer Burden Class | 0 | 13 participants |
| Post-chemotherapy AUS Suspicious | Residual Cancer Burden Class | I | 0 participants |
| Post-chemotherapy AUS Suspicious | Residual Cancer Burden Class | II | 10 participants |
Other Pre-specified
Disease-Free Survival
Time frame: Up to 10 years