McCall, Linda

1107 Background: The role of axillary ultrasound (AUS) after neoadjuvant chemotherapy (NAC) to assess for residual nodal disease in patients presenting with node positive breast cancer remains unclear. ACOSOG Z1071 is a prospective multi-institutional trial evaluating sentinel node biopsy in patients with biopsy proven node positive breast cancer (T0-4, N1-2, M0) receiving NAC. Herein we report on the secondary objective evaluating the correlation of lymph node (LN) features on AUS with residual nodal disease. Methods: AUS images from diagnosis and after NAC were centrally reviewed for cortex size, LN size and LN morphology. Morphologic features were defined as: type I, no visible cortex, type II, < 3 mm hypoechoic cortex, type III, > 3mm hypoechoic cortex, type IV, generalized lobulated hypoechoic cortex, type V, focal hypoechoic cortical lobulation, and type VI, totally hypoechoic node with no hilum. Type I and II are considered normal. Results: Surgical and imaging data are available on 294 patients. Median age was 50 years (range 23-93 years), mean initial tumor size 3cm (0 to 15cm) and clinical stage II in 64.5% and III in 35.5%. The maximum LN diameter decreased after NAC (mean 22mm pre-NAC to 14mm post-NAC)(p<0.0001); however, there was no significant difference after NAC between the pathologically N+ (13mm, range 5-46mm) and N0 cases (12mm, range 3-32mm)(p=0.13). LN cortical thickness correlated with residual nodal disease after NAC (p-value = 0.04). Using a cutoff point of cortical thickness of 3 mm, the sensitivity was 33% (48/145) and specificity 80% (66/82). AUS morphological features after NAC was associated with false negative rate 62%, false positive rate 28%, sensitivity 38%, and specificity 72%. Conclusions: AUS after NAC is useful to assess nodal response. Cortical thickness was the best predictor of residual nodal metastasis. LN size and morphological features do not reliably exclude residual nodal metastasis in patients after NAC. [Table: see text]

CRA506 Background: Sentinel node biopsy (SNB) eliminates the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND remains the gold standard for patients with a tumor-involved sentinel node. ALND achieves regional control, but its effect on survival remains controversial. The main objective of ACOSOG Z0011 was to compare outcomes of patients with hematoxylin and eosin (H&E) detected metastasis in SN managed with or without ALND and no axillary irradiation. Methods: Clinically node-negative patients who underwent SN biopsy and had 1 or 2 SN with metastases detected by H&E were randomized to ALND or no further axillary specific treatment. All patients were treated with lumpectomy and opposing tangential field irradiation. Adjuvant systemic therapy was at the discretion of their physicians. Overall survival (OS), disease-free survival (DFS), and locoregional control were evaluated. Results: 446 patients were randomized to SNB alone and 445 to SNB plus ALND. Patients treated with SNB alone were similar to those treated with SNB + ALND with respect to age, tumor size, Bloom-Richardson score, estrogen receptor status, adjuvant systemic therapy, tumor type, and T stage. Patients randomized to SNB alone had a median of two lymph nodes removed whereas patients randomized to ALND had a median of 17 lymph nodes removed. 17.6% of ALND patients had 3 or more involved nodes compared to 5.0% of SNB patients (p < 0.001). Median follow-up is 6.2 years. 5-year in breast recurrence after ALND was 3.7% compared to 2.1% for SNB (p = 0.16) while 5-year nodal recurrence was 0.6% compared to 1.3% (p = 0.44) respectively. The five-year OS for patients undergoing SNB + ALND is 91.9% compared to 92.5% for SNB alone (p = 0.24), and DFS is 82.2% compared to 83.8% respectively (p = 0.13). Conclusions: Despite the widely held belief that ALND improves survival, no significant difference was recognized by this study of SN node-positive women. Although the study closed early because of low accrual/event rate, it is the largest phase III study of ALND for node-positive women, and it demonstrates no trend toward clinical benefit of ALND for patients with limited nodal disease. [Table: see text]

Abstract Background: In CALGB-49907 (NEJM 2009;360:2055), older patients (pts) with ESBC were randomized to standard adjuvant chemo (AC or CMF versus capecitabine). The objective of this secondary QoL analysis is to assess if pts’ BL chemo preference (CP, defined as high or low), is associated with the following during and after completion of chemo: self and professional-reported toxicity, changes in mental health, function, QoL, recurrence-free (RFS) and overall (OS) survival. Patients and Methods: Of 633 trial pts 350 participated in the QoL substudy; 145/350 pts completed the BL assessment regarding CP. CP was measured by asking the amount of benefit women would require to choose adjuvant chemo in a hypothetical situation, irrespective of chemo agents. Women who chose chemo for an increase in OS of ≤12 months (mo) were designated as high chemo preference (HCP) and those who chose &gt;12 mo were designated low chemo preference (LCP). CP associations were evaluated with: BL perception of self-health and perceived QoL on chemo; patient reported outcomes (PROs), changes in function and QoL (based on EORTC-QLQ-C30); anxiety and depression (Hospital Anxiety and Depression Scale); observed grade 3-5 adverse events (AEs) by NCI common toxicity criteria (CTC v2.0). Pts were assessed at midtreatment and at 1, 12, 18 and 24 mo post-treatment. Chi-square tests, t-tests, and Cox models were used for categorical, continuous, and time-to-event variables, respectively. Results: The demographic and tumor characteristics of women (median age 71) who provided CP at BL were not different from women in the QoL subset or from non-QoL pts. 68/145 (47%) women had a HCP. CP groups did not differ based on age, surgery type, tumor and nodal stage, hormone receptor status, performance status, chemo assignment, education, marital or employment status except the LCP group had a higher proportion of white women (95% vs. 78%, p=0.004). At BL, there were no differences in perception of self-health based on CP but women with LCP predicted QoL on chemo to be worse than women with HCP (p=0.006) and reported greater nausea/vomiting. Mid-treatment, LCP pts reported worse nausea/vomiting, financial worries, and cancer symptoms. Post-treatment, LCP pts had worse constipation (at 1 mo) and financial worries (at 24 mo). There were no differences based on CP for dyspnea, pain, fatigue, insomnia, anxiety or depression at any timepoint. Mid-treatment, LCP women reported lower QoL and worse social, emotional and physical function compared to HCP women. These scores were not significantly different after treatment completion. LCP women had significantly higher rates of grade 3-5 AEs (53 vs. 34%, p=0.02) during treatment but these did not persist post-therapy. CP was not significantly associated with OS (HR =0.75, p=0.36) or RFS (HR=0.94, p=0.84). Conclusions: LCP at BL was associated with lower QoL, worse physical symptoms, AEs and function mid-therapy, but not mental health. Mid-therapy declines in women with LCP largely reversed post-therapy. This information may be useful for oncology professionals to counsel older ESBC pts with LCP receiving adjuvant chemo. Citation Format: Ajeet Gajra, Linda McCall, Hyman B Muss, Harvey J Cohen, Aminah Jatoi, Karla V Ballman, Ann H Partridge, Linda Sutton, Barbara A Parker, Gustav Magrinat, Jaqueline M Lafky, Arti Hurria. Association of patient preference for adjuvant chemotherapy (chemo) at baseline (BL) with toxicity, mental health, function, quality of life (QoL) and survival in older women with early stage breast cancer (ESBC) [CALGB 49907 Alliance] [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-07.

Abstract Background: The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial (Alliance) reported a false negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. Proposed methods to decrease the FNR include clip placement in the positive node at initial diagnosis with confirmation of resection of the clipped node at surgery and inclusion of residual metastatic cells identified by immunohistochemistry (IHC) for cytokeratins and disease measuring &lt;0.2mm on H&E in the definition of node positivity after chemotherapy. Herein we evaluate the impact of these methods on FNR. Methods: Z1071 was a prospective multi-institutional trial in which women with clinical T0-4,N1-2,M0 breast cancer underwent both SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. The primary endpoint defined nodal metastasis as disease &gt;0.2mm on H&E. Slides were submitted for central IHC staining when H&E-negative, unless performed locally. For this analysis, we expanded the definition of node positivity to include metastases less than 0.2mm on H&E and metastatic deposits identified by IHC. In 171 cases, a clip was placed in the node at initial biopsy and in these cases the SLNs and ALND were evaluated by x-ray or pathology to document clip location. FNR in the clip cohort is reported using the primary endpoint definition of node positive disease (&gt;0.2mm on H&E). Results: In the 113 cases where the clip was found in the SLN the FNR was 6.4% (1.8-15.5%). In the 29 cases where the clip was found in the ALND specimen, the FNR was 22.2% (6.4-47.6%). IHC was available on 470 of 525 patients with cN1 disease and 2 SLNs resected. Using the definition of H&E metastasis &gt;0.2mm, the FNR in these patients was 11.3% (34/301, 8.0-15.4%) which decreased to 8.7% (27/311, 5.6-11.8%) when including any disease &lt;0.2mm. SLNs from 16 patients had disease &lt;0.2mm in size. Seven patients previously classified as false negative SLN changed to true positive with identification of disease in the SLN. Nine patients changed from node-negative to node-positive with the only disease being &lt;0.2mm disease found in the SLN. Nodal pathologic complete response rate changed from 36.0% to 33.8% with the inclusion of metastases &lt;0.2mm. NResidual disease identified in SLNs or ALNDFNR (%)95% CINode positive definitionSLN metastases &gt;0.2mm by H&E470301 (64.0%)11.38.0-15.4SLN metastasis any size on IHC or H&E470311 (66.2%)8.75.6-11.8Clip locationClip in SLN11462 (54.4%)6.41.8-15.5Clip in ALND2918 (62.1%)22.26.4-47.6Clip location unknown2920 (69.0%)14.33.0-36.3Clip not placed354207 (58.5%)13.59.1-18.9 Conclusion: Placement of a clip at initial diagnosis of node positive disease with identification of the clip during the SLN surgery reduces the FNR. Use of IHC with inclusion of metastases &lt;0.2mm in the definition of residual nodal disease in women with node positive breast cancer after chemotherapy also improves the accuracy of SLN surgery. Use of one or both of these methods should be considered when performing SLN in this setting. Citation Format: Judy C Boughey, Karla V Ballman, William F Symmans, Linda M McCall, Elizabeth A Mittendorf, Gretchen M Ahrendt, Lee G Wilke, Bret Taback, Kelly K Hunt. Methods impacting the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4,N1-2) who receive neoadjuvant chemotherapy – Results from a prospective trial – ACOSOG Z1071 (Alliance) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-02.

Purpose The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients and Methods Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Results Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. Conclusion AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy.

Purpose The seventh edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer differentiates patients with T1 tumors and lymph node micrometastases (stage IB) from patients with T1 tumors and negative nodes (stage IA). This study was undertaken to determine the utility of the stage IB designation. Patients and Methods The following two cohorts of patients with breast cancer were identified: 3,474 patients treated at The University of Texas MD Anderson Cancer Center from 1993 to 2007 and 4,590 patients from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial. Clinicopathologic and outcomes data were recorded, and disease was staged according to the seventh edition AJCC staging system. Recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were determined using the Kaplan-Meier method and compared using the log-rank test. Results Median follow-up times were 6.1 years and 9.0 years for the MD Anderson Cancer Center and ACOSOG cohorts, respectively. In both cohorts, there were no significant differences between patients with stage IA and stage IB disease in 5- or 10-year RFS, DSS, or OS. Estrogen receptor (ER) status and grade significantly stratified patients with stage I disease with respect to RFS, DSS, and OS. Conclusion Among patients with T1 breast cancer, individuals with micrometastases and those with negative nodes have similar survival outcomes. ER status and grade are better discriminants of survival than the presence of small-volume nodal metastases. In preparing the next edition of the AJCC staging system, consideration should be given to eliminating the stage IB designation and incorporating biologic factors.