bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2-13-07: Efficacy of short-course adjuvant trastuzumab in early stage breast cancer
Authors: Saifo M , Nikoula M
Published: May 2019

Background: A total of 12 months adjuvant Trastuzumab is still the optimal choice for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Still, the adjuvant short course 9-week trastuzumab may be considered as a cost-effective and safe option in developing countries such as Syria.

Purpose: The primary objective was disease-free survival after short course adjuvant Trastuzumab therapy in early breast cancer at AI-Bairouni university hospital compared with 6 month of adjuvant trastuzumab , the secondary objective was assessing toxicities especially cardiac toxicity.

Patients and methods: Women with histologically confirmed HER2 positive BC with either positive or negative hormone receptor of stages IA,IIA,IIB,IIC,IIIA,IIIB and IIIC were eligible for the study . Patients were assigned to 2 groups . The initial systemic treatment was similar in the 2 groups . Thereafter, no further Trastuzumab or chemotherapy was administered in Arm A; 90 patients (loading dose 4 mg/kg; then 2mg/kg weekly to complete 9 weeks of T), whereas in Arm B that included 157 patients single-agent T was administered to complete 6 months (loading dose 8 mg/kg then 6 mg/kg every 3 weeks) . The LVEF was measured pretreatment, and every 3 months afterword .

Results: After a median follow up of 24 months DFS was 89.06% and 89.81% in groups A and B respectively (P=0.11).No obvious side effects have been noticed during the follow up period in group A. otherwise congestive heart failure was reported in 2.55% of group B patients .

Conclusion: Short course 9 weeks adjuvant Trastuzumab achieved a good 2 years disease-free survival rate (DFS) compared to 6 month of treatment, with acceptable toxicity and good tolerability for treated patients with early-stage invasive breast cancer. Patients are being monitored for a longer follow up period.

Citation Format: Saifo M, Nikoula M. Efficacy of short-course adjuvant trastuzumab in early stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-13-07.
Abstract P2-14-15: Breast cancer-related lymphedema: Morbidity of sentinel node biopsy
Authors: Ju YW , Jung JG , Kim KE , Kim Y , Lee E , Lee H-B , Moon H-G , Han W , Noh D-Y
Published: May 2019

Purpose:

Sentinel lymph node biopsy (SLNB) lowers morbidity of lymphedema then axillary lymph node dissection (ALND). However, there has been concern about incidence of lymphedema after SLNB especially when the number of harvested nodes during sentinel node biopsy procedure is more than a few. In this study, we assessed lymphedema incidence and its risk factors including the number excised lymph nodes in patients who underwent SLNB.

Methods:

Between January, 2011 and April, 2012, the records of 910 consecutive patients who underwent breast surgery with axillary staging (SLNB/ALND) for breast cancer at Seoul National University Hospital were reviewed. Lymphedema was assessed by circumferential upper extremity measurements. The lymphedema was defined as > 1cm for either the upper arm or the forearm. Patients with clinical records of the treatment for lymphedema in the rehabilitation clinic were regarded as having lymphedema. Univariate and multivariate analyses were performed to identify potential risk factors associated with lymphedema. Association of number of excised lymph nodes with lymphedema was analyzed by Spearman rank correlation coefficient.

Results:

At median follow-up of 69.8 months, 231 patients (25.4%) presented with lymphedema. In univariate analysis, body mass index (BMI) (P<0.001), T stage (P<0.001), N stage (P<0.001), type of surgery (P<0.001), ALND (P<0.001), neoadjuvant chemotherapy (P<0.001) and adjuvant chemotherapy (P=0.027) were significantly associated with lymphedema. In multivariate analysis BMI (P<0.001), ALND (P<0.001), neoadjuvant chemotherapy (P=0.044), and radiation therapy (P=0.046) were significantly associated with lymphedema. In patients treated with SLNB only (n=595), the incidence of lymphedema was 16.3% (n=97). In SLNB only subgroup, BMI was only significant risk factor of lymphedema. There was no correlation between number of excised lymph nodes during sentinel lymph node biopsy procedure with incidence of lymphedema (P=0.138).

Conclusion:

The risk of lymphedema is multifactorial in breast cancer surgery and adjuvant treatments. In SLNB alone patients, higher BMI was only significant factor correlated with lymphedema. Excised number of lymph nodes during sentinel biopsy procedure was not associated with lymphedema.

Citation Format: Ju YW, Jung JG, Kim KE, Kim Y, Lee E, Lee H-B, Moon H-G, Han W, Noh D-Y. Breast cancer-related lymphedema: Morbidity of sentinel node biopsy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-15.
Abstract P3-01-01: Circulating tumor cells (CTCs) after neoadjuvant chemotherapy for triple negative breast cancer (TNBC)
Authors: Lucci A , Hall C , Hess K , Ravenberg E , Clayborn A , Mittendorf E , Rauch G , Candelaria R , Moulder S , Thompson A
Published: May 2019

Background: ARTEMIS (A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival) is a randomized trial to determine if precision guided neoadjuvant chemotherapy (NAC) impacts rates of pathologic complete response in the breast and axillary nodes (pCR). We hypothesized that CTCs in peripheral blood after completion of NAC would provide prognostic information beyond pCR alone in TNBC patients.

Methods: Blood was assessed for CTCs after NAC as part of two IRB approved studies, ARTEMIS (2014 – 0185/PA15-1050), and LAB04-0698. CTCs were identified using the Cell Search® System (Menarini Silicon Biosystems). Samples with one or more cells, also having morphologic criteria for malignancy, were deemed CTC positive. Log-rank test and Cox regression analysis were applied to evaluate associations between CTC positive, pCR, and overall survival.

Results: pCR was achieved in 24/68 (35%) patients with TNBC. Twenty four patients (35%) were CTC positive. Three year overall survival was evaluated in 4 groups of patients: pCR and no CTCs (n=20), pCR and CTC positive (n=4), non-pCR and no CTCs (n=24) and non-pCR and CTC positive (n=20). Three year overall survival was higher in the pCR and no CTCs cohort (100%), compared to pCR and CTC positive (50%), non-pCR and no CTCs (83%), non-pCR and CTC positive (19%); log rank p<0.0001. In the non-pCR and CTC positive patient cohorts, the presence of CTCs was associated with significant risk of death at 3 years [hazard ratio of 12.3 (95% CI 3.4-454, p=0.00002)], whereas a favorable, but non-significant trend was noted for pCR [hazard ratio of 0.2 (95% CI 0.0, 1.4, p=0.11)].

Conclusion: The identification of CTCs after NAC has prognostic significance beyond that of pCR, and should be considered in evaluation of patients for clinical trials of adjuvant therapies.

Citation Format: Lucci A, Hall C, Hess K, Ravenberg E, Clayborn A, Mittendorf E, Rauch G, Candelaria R, Moulder S, Thompson A. Circulating tumor cells (CTCs) after neoadjuvant chemotherapy for triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-01.
Abstract P3-01-07: Enabling HER2 and androgen receptor (AR) protein expression and localization in circulating tumor cells (CTCs) of ER(+/-)HER2(-) metastatic breast cancer (MBC) patients (pts)
Authors: Ontiveros P , Landaverde C , Graf R , Levin MK , Hippely S , Wang Y , Landers M , Dittamore R , O'Shaughnessy JA
Published: May 2019

Background:

Upregulation of HER2 and AR are mechanisms of acquired resistance to endocrine therapy, and are being investigated as treatment-guiding biomarkers. However, measurement of these proteins and their localization requires metastatic biopsies, which are costly, invasive, and prone to under-sampling which limits their utility to guide treatment in late stage metastatic patients. A CTC-based test could expand the clinical utility of these biomarkers. Here we utilized the Epic Sciences CTC platform for CTC detection and characterization. MBC blood samples were characterized for CTC prevalence, HER2 and AR expression at time of disease progression.

Material and methods:

HER2 and AR expression levels were determined based on model cell lines. A total of 72 blood samples were acquired from ER(+/-)/HER2(-) patients (by standard tissue pathology) at disease progression. 72 samples were analyzed for HER2 and 64 were analyzed for AR using the Epic Platform. Single-cell whole genome sequencing was performed to assess clonality and inter-patient heterogeneity of CTCs detected.

Results:

55/72 (76.4%) of patients had CTCs detected across two slides. 13/72 (18.1%) had at least one HER2(+) CTC, 14/64 (21.9%) had at least one AR(+) CTC, and 7/64 (10.9%) had at both AR(+) and HER2(+) CTCs detected on replicate slides. HER2 expression on individual CTCs showed distinctive cytoplasmic membrane staining, and AR expression on individual CTCs showed frequent nuclear localization. Most patient samples showed heterogeneous expression of these markers at disease progression indicating subclonal sensitivity to targeted therapies. Subsequently, these cells will be individually sequenced to better determine the clonality of resistance.

Conclusions:

CTCs are detected in most MBC pts upon disease progression, with expression of known endocrine therapy resistance markers, HER2 and AR, observed that CTCs could guide subsequent therapy selection. Prospective evaluation of HER2 and AR on MBC pts' CTCs as predictive biomarkers of benefit from inhibitors of these proteins is needed.

Citation Format: Ontiveros P, Landaverde C, Graf R, Levin MK, Hippely S, Wang Y, Landers M, Dittamore R, O'Shaughnessy JA. Enabling HER2 and androgen receptor (AR) protein expression and localization in circulating tumor cells (CTCs) of ER(+/-)HER2(-) metastatic breast cancer (MBC) patients (pts) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-07.
Abstract P3-01-11: A novel six-parameter assay for comprehensive phenotyping of circulating tumor cells
Authors: Liu MC , Sun Y , Ramirez A , Campton D , George T , Haselkorn KE , Clein A , Gadi V , Sabath D , Kaldjian E
Published: May 2019

Background. The presence and number of circulating tumor cells (CTCs) are prognostic for breast cancer treatment outcome. Direct imaging assays traditionally employ four markers to identify canonical epithelial CTCs: nucleus, exclusion (CD45), and inclusion (EpCAM and cytokeratin). There is intense interest in the ability to phenotype CTCs in order to provide a noninvasive means by which to predict treatment benefit from endocrine therapy and/or HER2-directed therapy in breast cancer. To address this, a 6-parameter assay for detection of ER and HER2 expression on CTCs was developed. We applied this assay to four well characterized breast cancer cell lines representative of various ER and HER2 phenotypes. Methods. BT474, MCF-7, SKBR3, or MDA-MB-231 cells were spiked into peripheral blood from healthy donors and processed using the AccuCyte® sample preparation system; nucleated cells, including CTCs, are captured onto glass slides (8 slides per 7.5 mL blood sample) for subsequent immunofluorescent staining. Slides were stained using the combined epithelial marker and ER/HER2 CTC assay and then analyzed with the CyteFinder® imaging system. CTCs were identified as nucleated cells with positive EpCAM and/or cytokeratin staining, and negative CD45 staining. ER and HER2 expression were assessed as present or absent. Results. All cell lines expressed both cytokeratin and EpCAM, except for MDA-MB-231 which was EpCAM-negative. The ER / HER2 expression patterns observed were consistent with reported phenotype: BT474 (+/+), MCF-7 (+/–), SKBR3 (–/+), and MDA-MB-231 (–/–). Conclusions. Identification of epithelial CTCs and phenotypic characterization of ER and HER2 status are feasible in a combined assay applied to a single blood sample. This approach has implications for efficiency and cost effectiveness, which are of particular importance given the interest in longitudinal testing. Assay evaluation is currently underway using blood samples from breast cancer patients with known receptor status, treatment history, and clinical outcomes. Results will be available for presentation at the meeting.

Citation Format: Liu MC, Sun Y, Ramirez A, Campton D, George T, Haselkorn KE, Clein A, Gadi V, Sabath D, Kaldjian E. A novel six-parameter assay for comprehensive phenotyping of circulating tumor cells [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-11.
Abstract P3-03-02: Redo sentinel lymph node biopsy for ipsilateral breast tumor recurrence after breast conserving surgery with negative sentinel nodes: A pooled analysis from a systematic review and two institutes
Authors: Yoon C-i , Bae SJ , Choi JE , Cha CH , Park SE , Ahn SG , Jeong J
Published: May 2019

Background:Cases of redo sentinel lymph node biopsy (SLNB) are growing according to the increase of ipsilateral breast tumor recurrence (IBTR) after breast-conservative surgery (BCS). To evaluate a feasibility of redo SLNB in patients with IBTR after negative SLN, we conveyed a pooled analysis using data from a systematic review and two institutes.

Materials and methods:A systematic search of PubMed was conducted to identify data of patient level from publications evaluating redo SLNB for cases with IBTR. Eligible patients who underwent BCS and were confirmed as negative axilla after SLNB were identified. An identification rate (IR) and a false-negative rate (FNR) were calculated. To identify FNR, we only included cases with back-up axillary node dissection (ALND) from retrieved data.

Results:In a systematic review, a total of 197 peer-reviewed publications were retrieved, of which 19 papers included patients who met eligibility criteria. Data from 464 patients were collected. In two-institutes, 38 cases with same criteria were identified. A total of 502 patient's data were pooled. The IR of redo-SLNB was 71.7% (360/502) in pooled data. For the FNR, data from 147 patients with back-up ALND after SLNB was analyzed. The FNR and accuracy of redo-SLNB were 9.8% (5/51) and 97% (142/147).

Conclusions:We found that the IR and the FNR of redo SLNB were 71.7% and 9.8%, respectively. Redo SLNB is reliable procedure for axillary staging in patients with IBTR after negative SLNB.

Citation Format: Yoon C-i, Bae SJ, Choi JE, Cha CH, Park SE, Ahn SG, Jeong J. Redo sentinel lymph node biopsy for ipsilateral breast tumor recurrence after breast conserving surgery with negative sentinel nodes: A pooled analysis from a systematic review and two institutes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-02.
Abstract P3-03-07: Withdrawn
Authors: Benson JR , Gnanakumar S , Dumitru D , Provenzano E
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Benson JR, Gnanakumar S, Dumitru D, Provenzano E. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-07.
Abstract P3-03-13: Not presented
Authors: Liang Y , Chen X , Zhan W , Yao J , Wu J , Huang O , He J , Zhu L , Li Y , Chen W , Shen K
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Liang Y, Chen X, Zhan W, Yao J, Wu J, Huang O, He J, Zhu L, Li Y, Chen W, Shen K. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-13.
Abstract P3-03-15: Patient reported outcomes in women undergoing sentinel lymph node biopsy in the SUNrISE randomized trial evaluating different doses of superparamagnetic iron oxide
Authors: Rubio IT , Esgueva A , Espinosa-Bravo M , Rodriguez-Revuelto R , Siso C , Rivero J
Published: May 2019

Background. Sentinel lymph node biopsy (SLNB) with 2 mL of superparamagnetic iron oxide (SPIO) tracer has shown to be non-inferior to the standard radioisotope technique in several studies. The SUNrISE randomized trial has shown non inferiority of 1mL vs. 1.5 mL vs. 2 mL dose of SPIO with the standard use of radioisotope 99m Tc. We present patient reported outcomes from this randomized trial.

Material and methods. Patients with stage I breast cancer who underwent breast conservative surgery and sentinel lymph node biopsy were assigned consecutively (1:1:1) to one of the three groups defined by the different SPIO dose, group 1 (1mL), group 2 (1.5 mL) and group 3 (2 mL). Patients filled a questionnaire related to the presence of skin staining, staining intensity ( mild, moderate, intense) and whether the stain worried them. Patient also completed a quality of life (QoL) EORTC C30 questionnaire at 1 month postoperative visit, at 6 months and at 12 months. First analysis from the 1 month postoperative outcomes are reported here. Follow up on the 6 months will be available for the meeting.

Results. One hundred and thirty five patients were included in the trial, 45 in each group. Median age in group 1 was 58 years old, 63 y/o in group 2 and 65 y/o in group 3. (p=0.03) At 1 month follow up, patients in group 1 had less skin tattoo when compared with patients in group 2 and 3 (p= 0.02). There were no significant differences related to skin staining intensity by doses. Seventy percent of patients felt no concern about the tattoo.

On the multivariate analysis including age, SPIO dose, body mass index and breast density, only younger age (p = 0.037), and higher SPIO doses (p= 0.029) were significantly associated with increased skin staining.

There were no statistically significant differences in responses in the QoL questionnaire at 1 month postoperative visit. There were no severe reactions to the procedure or complications in any patient.

Conclusions. SLN with 1mL dose of SPIO has shown non-inferiority in the detection of SLN when compared to 1.5 and 2 mL. Being young and the use of 1.5 and 2 mL increased the risk of developing skin staining. Even though, most of the patients were not concern about the skin staining. Rates of discontinuation of skin discoloration will be assessed at 6 months follow up.

Citation Format: Rubio IT, Esgueva A, Espinosa-Bravo M, Rodriguez-Revuelto R, Siso C, Rivero J. Patient reported outcomes in women undergoing sentinel lymph node biopsy in the SUNrISE randomized trial evaluating different doses of superparamagnetic iron oxide [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-15.
Abstract P3-03-30: Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy
Authors: Matsumoto A , Umemoto Y , Jinno H
Published: May 2019

Background:American College of Surgeons Oncology Group Z0011 trial showed that axillary lymph node dissection (ALND) had no impact on recurrence and survival in patients with positive sentinel lymph node (SLN) after breast-conserving surgery. However, it is still unknown if the omission of ALND can be applicable to patients treated with mastectomy. The aim of this study wasto evaluate whether ALND could be safely omitted for patients with SLN–positive breast cancer after mastectomy.

Methods: From a prospective database of 296 patients with clinically node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy (SLNB) from March 2006 to December 2016, 81 patients who had positive SLNs were selected. Patient characteristics and prognosis were compared between SLN-positive patients with and without ALND. Patients treated with neoadjuvant chemotherapy were excluded from the analysis. Lymphatic mapping was performed using a combined method of blue dye and radioisotope.

Results: The median age of entire patients was 57.0 (range: 32-85) years and the median tumor size was 2.5 (range: 0.6-7.9) cm. Of 81 patients, 23 (28.4%) patients omitted ALND. Patients with SLNB alone were more likely to have smaller SLN involvements (p<0.001): micrometastasis was identified in 13 (56.5%) patients in SLNB-alone group and 9 (15.5%) patients in ALND group. The number of positive SLN was comparable between SLNB-alone (median: 1.0, range: 1-6) and ALND groups (median: 1.0, range: 1-5) (p=0.063). There was no significant difference in characteristics including age, tumor size and tumor subtypes between the two groups. Post-mastectomy radiotherapy was performed in 5 (21.7%) patients with SLNB alone and 16 (27.6%) patients with ALND (p=0.588). The majority of patients with macrometastatic SLN received adjuvant chemotherapy in both groups (83.3% vs. 75.5%, p=0.562). Twenty (87.0%) and 51 (87.9%) patients received adjuvant endocrine therapy in SLNB-alone and ALND group, respectively (p=0.584). After a median follow-up of 54.7 months, no axillary recurrence was observed in both groups and 5-year disease-free survival was not significantly different between the two groups (75.0% vs. 88.8%, p=0.489). Lymphedema was observed significantly more often after ALND than after SLNB (22.4% vs. 4.3%, p=0.045).

Conclusions: These data suggested that ALND could be safely omitted in SLN-positive breast cancer patients treated with mastectomy and appropriate systemic therapy.

Citation Format: Matsumoto A, Umemoto Y, Jinno H. Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-30.
Abstract P3-03-34: Sentinel lymph node biopsy is unnecessary in ductal carcinoma in situ patients diagnosed by biopsy
Authors: Uemoto Y , Kondo N , Wanifuchi-Endo Y , Hisada T , Nishikawa S , Katagiri Y , Kato H , Takahashi S , Toyama T
Published: May 2019

Background: Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer 2018 state that sentinel lymph node (SN) biopsy is unnecessary for patients treated with breast-conserving therapy (BCT) and with an expected final pathological diagnosis of ductal carcinoma in situ (DCIS). Regardless of whether they were diagnosed with DCIS by biopsy before surgery, 78% of patients currently undergo axial procedures in Japan because invasive lesions may be detected in surgical specimens. This study examined whether SN biopsy can be omitted in DCIS patients diagnosed by biopsy and which factors are associated with invasion.

Methods: Patients who underwent definitive surgery for DCIS diagnosed by preoperative biopsy at our institution from May 2004 to January 2018 were investigated retrospectively. The factors associated with upstaging to invasive cancer from DCIS were examined with Fisher's exact test and the t-test. (Age, Tumor size, Operation (Mastectomy or BCT), Biopsy method (Core Needle Biopsy or Vaccume-Assisted Biopsy), Mammography (ditected or not-detected), Ultrasound (ditected or not-detected, mass or non-mass), Comedo, ER, PgR, HER2)

Results: A total of 311 patients were enrolled in this study, of whom 277 (89.1%) underwent SN; six of these (2.2%) had SN metastasis. All six cases were upstaging to invasive cancer: five (1.8%) had micrometastasis and one had macrometastasis (0.4%). From a surgical viewpoint, SN metastasis were detected in 3/161 (1.9%) cases treated with mastectomy and 3/150 (2.4%) cases treated with BCT. Although all three cases treated with BCT had micrometastasis, one case treated with mastectomy had macrometastasis (the other two cases had micrometatastasis). A total of 80/311 cases (25.7%) upstaged to invasive cancer and the only predictor of invasion was tumor size on images (p=0.0002). We could not determine the effective cut-off for tumor size because the area under the receiver operating characteristic curve was 0.63<0.70.

Tabule 1.Tumor size on images was the only predictor of invasion. Upstaging (N=80)DCIS (N=231)P valueTumor size: mm (95% Confidence Interval)47.5 (41.9-53.2)33.9 (30.5-37.3)0.0002

Conclusion: Tumor size was found to be the only predictor of invasion. Only 2.2% of DCIS patients had SN metastasis despite the fact that 25.7% patients were upstaged to invasive cancer. We conclude that SN biopsy is not necessary for DCIS patients diagnosed by biopsy.

Citation Format: Uemoto Y, Kondo N, Wanifuchi-Endo Y, Hisada T, Nishikawa S, Katagiri Y, Kato H, Takahashi S, Toyama T. Sentinel lymph node biopsy is unnecessary in ductal carcinoma in situ patients diagnosed by biopsy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-34.
Abstract P3-03-43: Incorporation of MSKCC nomogram to guide the application of intra-operative sentinel lymph node frozen section evaluation in patients with early breast cancer
Authors: Yang H , Wang S , Shen D , Cao Y , Tong F , Chen D , Liu P , Peng Y
Published: May 2019

Background and Objectives:

Although de-escalation of axillary surgery becomes more popular, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node(SLN) positive patients not meeting the criteria of ACOSOG Z0011 in many hospitals, and frozen section (FS) of SLN is one of the valuble intra-operative assesments to avoid axilla re-operation although it was controversial due to accuracy and efficiency concerns. This study was to assess the performance of selective use of frozen section evaluation guided by MSKCC lymph node metastasis risk prediction nomogram to optimize the proceudure to be more accurate and cost effective.

Methods:

Surgical pathology records of consecutive 2582 biopsies in 2552 patients breast cancer patients from 2011 to 2017 were reviewed, intra-operative frozen section diagnosis were compared to post-operative paraffin reports. We calculated the sensitivity, specificity, accuracy and FNR for different MSKCC risk, the axilla re-operation rate with or without FS and the number needed to treat (NNT) to avoid second ALND was also analyzed.

Results:

The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3% respectively. The axilla re-operation rates were significantly decreased if FS was done(4.7%±0.4% with FS versus 35.8%±5.8% without FS, P<0.001). The estimated axilla re-operation rate without FS was positively correlated with MSKCC risk(r=0.99, P<0.001), while NNT to avoid second ALND by FS were negatively correlated with MSKCC risk(r=-0.98, P<0.001). When patients were divided into four groups according to quartile MSKCC risk, the axilla re-excisional rates were 18.4%, 25.1%, 38.7%, 58.7% without FS, while 4.8%, 3.2%, 5.6%, 3.2% with FS, and NNT correspondingly decreased from 7.3, 4.5, 3.0 to 1.8. An decision-making algorithm for application of FS was proposed.

Conclusion:

Stratified decision-making algorithm based on MSKCC prediction model improved the efficiency of FS to avoid axilla re-operatioin in patients undergoing sentinel lymph node biopsy. We recommend FS be restricted to patients with MSKCC risk higher than 0.5 who do not meet ACOSOG Z0011 criteria.

Citation Format: Yang H, Wang S, Shen D, Cao Y, Tong F, Chen D, Liu P, Peng Y. Incorporation of MSKCC nomogram to guide the application of intra-operative sentinel lymph node frozen section evaluation in patients with early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-43.
Abstract P3-06-12: Genetic heterogeneity of DCIS is a predictor of invasive cancer
Authors: Fortunato A , Mallo D , King L , Hardman T , Hall A , Marks JR , Hwang S , Maley CC
Published: May 2019

Background: Heterogeneity is a hallmark of human cancers that is apparent both between and within individual tumors. Intra-tumor heterogeneity provides the genetic fuel for natural selection in clonal evolution and cancer progression. Tumors with high levels of genetic heterogeneity are hypothesized to be more likely to progress to invasion and metastasis

Methods: We measured the mutational loads from separate areas of pure DCIS and compared this to genetic heterogeneity in DCIS lesions that co-exist with invasive cancer, as a surrogate for progression. Cases of pure DCIS and DCIS diagnosed concurrent with invasive cancer were identified. Two areas of DCIS from each case a minimum of 0.8 cm apart and control tissues were macro-dissected and the DNA extracted from FFPE samples. To analyze the data, we developed new bioinformatics methods that allowed analysis of small amounts of degraded DNA extracted from FFPE samples across multiple regions. Our bioinformatics pipeline was optimized on a series of 28 independent technical replicates of the same DNA sample sequenced twice, as training tools to find the best filtering parameters.

Results: Whole exome sequencing was performed on two geospatially separated blocks for each case (41 pure DCIS and 30 DCIS adjacent to invasive disease). Minimum coverage for inclusion in this study was 40X over at least 50% of the exome. We used the ratio of private mutations (only in 1 area) to public (found in both areas) mutations as a measure of intra-tumor heterogeneity. Overall mutational load of DCIS was not a significant predictor to progression; however notably, DCIS adjacent to invasive disease patients had a higher ratio of private/public mutations (heterogeneity) in coding domains (Mann-Whitney p=0.016. Functional analysis of mutated coding genes (DAVID 6.8) shows a statistically significant enrichment in signal transduction, olfactory receptors (G-protein-coupled receptors) and cell-matrix interactions in both tumor types, after FDR correction. DCIS adjacent to invasive disease had an enrichment of mutated genes involved in additional cellular functions such as microtubule activity (fold enrichment =7.6, FDR=0.002), protein-protein interactions (fold enrichment =3.65, FDR=5.11E-04) and extracellular matrix remodeling (fold enrichment =8.3, FDR=0.02).

Conclusion: We present an approach to measure clonal heterogeneity using a bulk sequencing strategy applied to geospatially distinct foci of DCIS. Our findings suggest that functional heterogeneity may play an important evolutionary role as a driver for invasive progression.

Citation Format: Fortunato A, Mallo D, King L, Hardman T, Hall A, Marks JR, Hwang S, Maley CC. Genetic heterogeneity of DCIS is a predictor of invasive cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-06-12.
Abstract P3-07-03: Withdrawn
Authors: Rinkenbaugh AL , Sinha VC , Zhang X , Shao J , Piwnica-Worms H
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Rinkenbaugh AL, Sinha VC, Zhang X, Shao J, Piwnica-Worms H. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-07-03.
Abstract P3-07-07: Withdrawn
Authors: Jiang Y-Z , Ma D , Suo C , Shi J , Xue M , Stover DG , Verschraegen C , Kaklamani V , Wang P , Shi L , Huang W , Shao Z-M
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Jiang Y-Z, Ma D, Suo C, Shi J, Xue M, Stover DG, Verschraegen C, Kaklamani V, Wang P, Shi L, Huang W, Shao Z-M. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-07-07.
Abstract P3-08-12: PIK3CA mutations in breast cancer: Mutational landscape and clinical implications in ER+/HER2- subtype
Authors: Ahn HK , Park S , Hyun SH , Park K , Lee E , Kim J-Y , Nam SJ , Kim SW , Lee JE , Lee SK , Yu JH , Ahn JS , Im Y-H , Park YH
Published: May 2019

Introduction: PIK3CA mutation is one of the most frequent genomic alterations in breast cancer. We evaluated PIK3CA mutational status including spatial and temporal heterogeneity, clinical characteristics and prognostic impact focused on ER+/HER2- subtype.

Methods: We performed targeted ultra-deep sequencing (CancerSCAN™) of breast cancer tissue in a prospective cohort. Burden of disease was assessed by metabolic tumor volume(MTV) in 18F-FDG-PET scan. Association with clinical characteristics or survival were tested in ER+/HER2- subtype, using Chi square test or Kaplan-Meier method.

Results: PIK3CA analyses were performed in 1274 breast cancer specimens from 1091 patients. 957 patients had early breast cancer. PIK3CA alterations were found in 397 patients(36.3%), and frequency of PIK3CA mutation was significantly lower in triple negative breast cancer(19.0%), compared with 40.4% in ER+/HER2-, 40.9% in ER+/HER2+, and 45.2% in ER-/HER2+ subtype(p<0.0001). 158 patients had more than two biopsies. Among 92 patients with second biopsy within one month, 11%(10/92) had spatial heterogeneity of PIK3CA mutation. After neoadjuvant chemotherapy, 10%(3/30) of patients had change of PIK3CA mutational status. Serial biopsy at time of recurrence revealed loss or gain of PIK3CA mutation in 10 out of 59 patients (17%). In ER+/HER2- subtype, PIK3CA had a trend toward longer distant disease free survival without statistical significance. In patients with stage IV ER+/HER2- disease, PIK3CA hotspot mutations were associated with significant longer overall survival(OS) (71.0 vs. 37.8 months, p=0.048) and better progression free survival(PFS) at 1st line palliative treatment (37.7 vs. 9.4 months, p = 0.0004). Frequency of symptomatic recurrence, recurrence as oligometastases, and specific metastatic sites were not associated with PIK3CA mutational status, except that bone metastases at first distant metastases was less prevalent in patients with PIK3CA hotspot mutations(35.6% vs. 53.8% in PIK3CA wt, p=0.048). Metabolic tumor volume(MTV) at time of first distant metastases was not associated with presence of PIK3CA mutation.

Conclusion: We observed variations in PIK3CA mutational status in more than 10% of patients with >1 repeated biopsy. In stage IV ER+/HER2- disease, PIK3CA hotspot mutation seemed to be associated with longer PFS and OS, however metabolic tumor burden was not associated with PIK3CA alterations.

Citation Format: Ahn HK, Park S, Hyun SH, Park K, Lee E, Kim J-Y, Nam SJ, Kim SW, Lee JE, Lee SK, Yu JH, Ahn JS, Im Y-H, Park YH. PIK3CA mutations in breast cancer: Mutational landscape and clinical implications in ER+/HER2- subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-12.
Abstract P3-08-24: Mutational characterization of HER2-positive breast cancer
Authors: Velasco Sánchez A , Gasol Cudos A , Morales S , Veas Rodriguez J , Serrate López A , Mele Olivé J , Canosa Morales C
Published: May 2019

Background: Studies of mutational analysis have been widely reported in various global series of breast cancer. However, in the era of different phenotypes of breast cancer, these analyses should be more specific in order to find differences in each phenotype that could predict response to treatment. Particularly HER2 positive is a special subtype with different connotations that make the analysis of its genotype very interesting.

Methods: Cohorts of 47 consecutive samples of HER2 positive breast cancer, treated in our institution were analyzed. It was conducted a mutational study with NGS technique of the most common genes involved in breast cancer.

Results: 10 patients were metastatic at diagnostic, 17 with negative estrogen receptor expression, the median value of Ki67 was 45 (20-95) and the median initial tumor size was 33.5 mm (18-111). Inmunohistochemical expression of HER2 was +3 in 31 tumors and +2 in 15 with a median ratio by FISH of 3,2 (1,18-8,3). We also analyzed the expression of HER by PCR of mRNA in 35 samples with a median expression of 2,49 (0,26-33,15). 38 patients underwent surgical excision of the tumor with a pathologic complete response observed in 19.

We found a total of 38 significant mutations and the genes with more frequent mutations were MCPH1 (100%), HNF1 (98%), p53 (96%), somatic BRCA1 (62%), TSC1 (30%), PIK3CA (23%), ATM (21%), ALK (15%) and somatic BRCA2 (13%). Although the aim of the study was to find the most frequent mutations in this subtype, we have also analyzed possible correlations of those with pathological response or with more common variables, finding no significance in any of them.

Conclusions: In our series, we found a high percentage of mutations in MCPH1, HNF1 and p53 genes with almost 100% of mutations in p53 that are also limited in a very specific area. Also interesting is the 62% of mutations found in BRCA1 and 13% in BRCA2 that could allow more specific treatments in this subgroup. Although the study did not have the power to assess the predictive factor of these mutations, it is very suggestive that in the 7 patients with BRCA mutations, 6 achieved a complete pathological response.

Citation Format: Velasco Sánchez A, Gasol Cudos A, Morales S, Veas Rodriguez J, Serrate López A, Mele Olivé J, Canosa Morales C. Mutational characterization of HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-24.
Abstract P3-09-03: RelB facilitates cell migration and invasion in breast cancer via MMP1 upregulation
Authors: Wang M , Tang J
Published: May 2019

Background: RelB is a subunit of the nuclear factor-κB (NF-κB) signaling famliy and appears aberrant expression in breast cancer. The aim of the present study was to further investigate the role of RelB in breast cancer and whether RelB might be a therapeutic target.

Methods: 120 cases of breast cancer patients were collected from the Jiangsu Province Hospital during 2015-2017. Immunohistochemistry (IHC) was performed to detect RelB expression in breast cancer tissues and para-cancer tissues. The relationship between RelB expression and clinical pathologic parameters were investigated. Detection the expression of RelB in 4 kinds of human breast cancer cell lines (MCF-7, T47D, MDA-MB-231, BT-549) by Western blot and RT-qPCR.Knockout of RelB in TNBC cell lines (BT-549 and MDA-MB-231) was using the CRISPR/Cas9 genome editing system. CCK-8 and flow cytometry were performed to observe the proliferation, cycle and apoptosis of MDA-MB-231 and BT-549 after knockout of RelB. Transwell and wound healing experiments were performed to observe cell invasion and migration ability. RT-PCR and Western blotting were performed to detect the expression of mRNA and protein of EMT marker and MMP1 respectively. The luciferase reporter gene was performed to detect whether RelB binding with MMP1 promoter region. In vivo efficacy was tested using the xenograft model and lung metastasis model.

Results: RelB was highly expressed in triple-negative breast cancer (TNBC) tissues compared with that in adjacent tissues. RelB levels were remarkably associated with the pTNM stage (p=0.01981) and ER expression (p=0.4689). RelB expressions in TNBC cell lines were higher than that of hormone receptor positive MCF-7 cells. In vitro studies showed that RelB deletion promoted apoptosis and suppressed breast cancer cell survival, migration and invasion by decreasing snail, vimentin and MMP1. RelB deletion inhibited cell cycle progression and G1/S transition by upregulating p21 and p27 expression. In vivo studies showed that 231-RelB-KO cells completely impaired tumor formation in xenograft models and lung metastasis model in nude mice.

Conclusion: RelB is aberrant constitutive expressed in clinical specimens and cell lines of breast cancer, especially in TNBC. RelB regulates malignant phenotypes of breast cancer, including cell survival, migration and invasion, as well as apoptosis and the cell cycle. Moreover, RelB can induce MMP1, which facilitates the invasion of tumor. Collectively, our findings highlight that RelB might serve as a therapeutic target for triple negative breast cancer.

Citation Format: Wang M, Tang J. RelB facilitates cell migration and invasion in breast cancer via MMP1 upregulation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-09-03.
Abstract P3-09-06: CXCL1 chemokine stimulates migration and invasion in ER-negative breast cancer through activation of the ERK/MMP-2/9 signaling axis
Authors: Liu S , Yang C , Guo S , Chen R
Published: May 2019

Chemokine (C-X-C motif) ligand 1 (CXCL1), a member of the CXC chemokine family, has been reported to be a critical factor in inflammatory diseases and tumor progression. However, its functions and molecular mechanism in estrogen receptor α (ER) negative breast cancer (BC) has little been known. In this study, we discovered that CXCL1 is overexpression in ER-negative breast cancer tissues and cell lines compared with ER-positive patient tissues and cell lines. Treatment with recombinant human CXCL1 protein promotes ER-negative BC cell migration and invasion in dose-dependent manner and stimulates the activation of p-ERK1/2, but not p-STAT3 or p-AKT. Whereas, knockdown of CXCL1 in BC cells attenuates these effects. Moreover, CXCL1 induces the expression of MMP2/9 via ERK1/2 pathway. The blockage of ERK by its antagonists (U0126) can abolish the effect of CXCL1 on MMP2/9 expression. Furthermore, immunohistochemical (IHC) analysis revealsa strong positive correlation between CXCL1 and p-ERK1/2 expressions in BC tissues. In conclusion, our study illustrates that CXCL1 is highly expressed in ER-negative BC and stimulates cell migration and invasion through ERK/MMP2/9 pathway, which may serve as a potential therapeutictarget in ER-negative breast cancer.

Citation Format: Liu S, Yang C, Guo S, Chen R. CXCL1 chemokine stimulates migration and invasion in ER-negative breast cancer through activation of the ERK/MMP-2/9 signaling axis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-09-06.
Abstract P3-10-17: mRNA expression of HER2 by PCR as a strong predictor of pathologic response to neoadjuvant antiHER2 therapy
Authors: Gasol Cudós A , Morales Murillo S , Veas Rodriguez J , Velasco Sánchez A , Serrate López A , Melé Olivé J , Canosa Morales C
Published: May 2019

Background: Pathologic response to neoadjuvant therapy is the most important prognostic factor so new agents should aim to improve it. HER2 expression in breast cancer provides prognostic and predictive information of response to antiHER2 therapy. The quantification of HER2 expression by mRNA is one of the most potent markers of cellular dependence to HER2 pathway.

Methods: From a series of 160 patients with early or locally advanced HER2 positive breast cancer who received neoadjuvant treatment with chemotherapy and antiHER2 drugs, mRNA expression of HER2 was analyzed in 69 specimens and it was correlated to pathologic complete response (pCR).

Results: Median age was of 52.5 years (29-86), tumor size of 33mm (10-111), 39 (53%) patients had nodal involvement. Median ki67 expression was of 45% (17-80), 28 (38%) tumors were estrogen receptor (ER) positive and 46 (62%) negative. We also analyze the expression of tumor-infiltrating-lymphocytes (TILs) by immunohistochemistry in 43 samples because their expression is also a strong predictive of pathologic response. A total of 31/69 patients (45%) achieved a pCR with a median of mRNA expression of 7,55 (3,8 – 11) in comparison with 2.03 (1,2 -2,8) in patients without pCR (p: 0,002). In the univariable analysis, variables correlated to pCR were estrogen receptor=0 (OR 0,186 IC 95% 0,063-0,549, p: 0,002), mRNA (OR 5,689 IC 95% 1,854-17,452, p: 0,002) and TILs (OR 15,167 IC 95% 3,223-71,38, p: 0,001) and in the multivariable analysis, TILs and mRNA expression were found to be independent predictive factors for pCR. The quantification of HER2 by mRNA obtained an impressive response specially in ER negative patients with a rate of pCR of 100% in samples of mRNA expression upper of 3,6 and ER negative. However, patients with mRNA expression lower than 3,6 with a pCR rate of 32%, could reach to an 80% rate if they had high TILs expression.

Conclusions: Quantification of HER2 expression by mRNA is a strong predictive factor of pCR (OR 5,689); achieving a 100% pCR in ER negative tumors. TILs are also a predictive factor for pCR (OR 15,167) and its combination with mRNA expression could improve pCR rates; thus, patients with mRNA expression lower than 3,6, if they had a higher TILs expression could reach to an 80% pCR.

Citation Format: Gasol Cudós A, Morales Murillo S, Veas Rodriguez J, Velasco Sánchez A, Serrate López A, Melé Olivé J, Canosa Morales C. mRNA expression of HER2 by PCR as a strong predictor of pathologic response to neoadjuvant antiHER2 therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-17.