bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2-14-05: Can an internal surgical adhesive facilitate drain-free mastectomy and reduce overall invasiveness?-A prospective, randomized, controlled, multicenter non-inferiority trial
Authors: Eichler C , Paepke S , Ohlinger R , Mathias W , Scheffen I , Lux M , Hadad S , Kiernan T , Whisker L , Kaushik M , King P
Published: May 2019

Introduction: Mastectomy closure without drains has many potential advantages. Flap fixation techniques have shown to be an effective alternative to drains. This study tested the non-inferiority of a surgical adhesive in overall invasiveness compared to standard wound closure with drains. Methods: This trial (ClinicalTrials.gov Identifier: NCT02958449) recruited seventy-seven patients undergoing eighty-four mastectomies +/- SLNB (n=84) at eleven international centers. Procedures were prospectively randomized to standard wound closure with drains (SWC; n=41) or wound closure without drains using a high strength lysine-based adhesive named TissuGlu® (TG; n= 43). The primary outcome measured assessed overall invasiveness using the number of post-operative clinical interventions, including drain removals and needle aspirations. Secondary endpoints included total wound drainage, cumulative days of treatment, days to drain removal and wound healing related complications. A patient questionnaire evaluating quality of life measures was also administered. Results: Subjects in the TissuGlu® group required significantly fewer post-operative clinical interventions (1.25 ± 1.39 TG vs. 2.03 ± 1.45 SWC, p = <.0001) compared to the Control group and had fewer cumulative days of treatment (defined as days of drains being in place and / or days on which an aspiration occurred; 2.14 ± 4.15 TG vs. 5.76 ± 4.02 SWC, p = <0.0001). Presence of a drain was associated with significantly higher pain and lower mobility scores. Conclusion: The study demonstrates that flap fixation with this adhesive can permit drain-free mastectomy closure, reducing overall invasiveness and patient morbidity.

Citation Format: Eichler C, Paepke S, Ohlinger R, Mathias W, Scheffen I, Lux M, Hadad S, Kiernan T, Whisker L, Kaushik M, King P. Can an internal surgical adhesive facilitate drain-free mastectomy and reduce overall invasiveness?-A prospective, randomized, controlled, multicenter non-inferiority trial [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 P2-14-05.
Abstract P2-14-23: Successful intraoperative margin assessment in DCIS and invasive breast cancer with diffuison-weighted MRI using the Clearsight™ system
Authors: Thill M , Kelling K , van Haasteren V , Traub L , Nölke J , Szwarcfiter I , Shapiro M , Schon A , Aulmann S
Published: May 2019

Aim

Aim of our study is to evaluate the performance of the ClearSight™ system (ClearCut Medical, Ltd.) in assessing surgical margins for DCIS and IBC in breast conserving surgery

Material and Methods

The ClearSight™ system utilizes a diffusion-weighted-imaging (DWI) protocol to create 2D surface maps showing T2*, a MR parameter related to the tissue's apparent diffusion coefficient (ADC), with a depth penetration of 1.5mm. ADC is a highly accurate differentiator for irregular versus normal tissue.

From November 2017 a prospective, blinded post marketing study (N=63), evaluating the performance of the ClearSight™ system has been conducted in the Breast Centre at the Agaplesion Markus Krankenhaus, Frankfurt, Germany. After standard evaluation with ultrasound and/or X-ray, the specimens were scanned with the ClearSight™ system, and results were compared with the final histopathology results on a margin per margin bases, applying a simple T2* threshold to flag irregular tissue.

Results

Breast specimens' margins from 60 patients were analyzed. Pursuant to the breast conserving surgery (BCS), 348 margins were scanned by the ClearSight™ system. A rigid T2* threshold comparison with the pathology findings resulted in a sensitivity of 80% and specificity of 84%. Accuracy for invasive and in-situ cancers was found to be similar for tissues scanned within one hour after excision. After that sensitivity for DCIS started to drop and was found to be 56% after 2 hours. Further accuracy improvements can be achieved if the reading physician is free to apply an intuitive diffusion map interpretation rather than adhere to a fixed threshold.

Conclusion

The data suggest that ClearSightTM can reduce excision rates by a robust 80% if the excised breast tissue is scanned within one hour. Tissue drying impacts sensitivity for DCIS negatively. Free map interpretation leads to better results than a fixed threshold.

Citation Format: Thill M, Kelling K, van Haasteren V, Traub L, Nölke J, Szwarcfiter I, Shapiro M, Schon A, Aulmann S. Successful intraoperative margin assessment in DCIS and invasive breast cancer with diffuison-weighted MRI using the Clearsight™ system [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 P2-14-23.
Abstract P2-14-26: Withdrawn
Authors: Meybodi F , Sedaghat N , French J , Elder E
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Meybodi F, Sedaghat N, French J, Elder 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 P2-14-26.
Abstract P2-14-28: Local surgery improves survival in patients with primary metastatic breast cancer: A population-based study
Authors: Zhao Y , Sun H , Yang X , Zhao Y , Chen M , Jin W
Published: May 2019

Background

The aim of this study was to assess the prognosis of breast cancer patients with distant metastasis after surgery of the primary tumor and provide new understanding of treatment for these patients.

Methods

We retrospectively analyzed 8922 primary metastatic breast cancer (PMBC) patients from Surveillance, Epidemiology, and End Results (SEER) Database. The patients' clinical and pathological characteristics were investigated. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated by Kaplan-Meier method. Independent risk factors associated with disease special mortality were identified by Cox regression analysis.

Results

A total of 8922 PMBC patients from SEER database were identified, while 1724 (19.3%) of them received surgery therapy (ST) and 7198 (80.1%) patients were identified as no surgery therapy group (NST). Patients' underwent ST had dramatically increased OS (P<0.001) and BCSS (P<0.001) compared with those in NST group. And the result figured out that the patients with 1 or 2 distant metastatic sites might benefit most from local surgery, while the prognosis of patients with 3 or more showed no significant difference (p= 0.073 for OS, p= 0.091 for BCSS).

Furthermore, no differences were found in the survival rates between different surgical procedure groups (p= 0.886 for OS, p= 0.943 for BCSS). PMBC patients with ST tented to have increased OS (hazard ratio [HR] = 0.642; 95% confidence interval [CI], 0.583-0.707, p < 0.001) and BCSS (HR = 0.649; 95% CI, 0.587-0.718, p < 0.001), while age, grade, T stage, breast subtype, radiation, the number of metastatic site were also independent prognostic factors.

Conclusions

The current study demonstrated the survival benefit of ST in PMBC patients, especially those has 1 or 2 distant metastatic sites. Enlarged surgical range could not prolong survival. However, a large randomized clinical trial to validate the efficacy of ST in PMBC is essential in the future.

Key words: primary metastatic breast cancer; SEER Database; survival; surgery

Citation Format: Zhao Y, Sun H, Yang X, Zhao Y, Chen M, Jin W. Local surgery improves survival in patients with primary metastatic breast cancer: A population-based study [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 P2-14-28.
Abstract P3-01-05: Circulating tumor cell detection predicts early recurrence in patients with non-metastatic breast cancer
Authors: Hall C , Meas S , Bowman Bauldry J , Kuerer H , Lucci A
Published: May 2019

Background:

Our group and others have shown that CTCs are identified in 20-25% of non-metastatic breast cancer patients. Recent data suggests that circulating tumor cell (CTC) detection at 5 years follow-up predicts late recurrence for non-metastatic, estrogen receptor positive, HER2/neu negative (ER+/HER2-) breast cancer patients. The aim of this study was to determine if CTC detection at time of surgery in ER+/HER2- predicts early (less than or equal to 5 years) recurrence, and to compare the median recurrence-free survival (RFS) to triple negative (TN) patients.

Methods:

We performed CTC enumeration on 506 patients with non-metastatic breast cancer just prior to surgical resection as part of an IRB approved study. CTCs (per 7.5 ml blood) were identified using the Cell SearchSystem (Menarini Silicon Biosystems). The presence of one or more CTC meeting morphological criteria for malignancy was considered a positive result. Patients with inflammatory breast cancer were excluded from our analysis. Log-rank test and Cox regression analysis were applied to establish the association of CTCs with RFS.

Results:

Median follow-up was 68 months and mean age was 53 years. Eighty-four percent of patients (417/498) had T1/T2 tumors, 63% (307/487) had grade 1 or 2 tumors, and 58% (292/501) had negative lymph nodes. Eighty-three percent (419/506) had ER+/HER2- tumors, and 17% (87/506) were TN. One or more CTC was identified in 22% (91/419) ER+/HER2- patients, and in 28% (24/87) of TN patients. Nine percent (45/506) of patients recurred within 5 years of CTC assessment. Of the 45 patients who relapsed, detection of one or more CTCs predicted shortened RFS. Median RFS for CTC-positive patients was 1.2 years, vs. 2.5 years for CTC-negative patients, irrespective of ER+/HER2- or TN subtype (log-rank P<0.001, HR = 2.71, 95% CI, 1.50 to 4.87).

Conclusions: One or more CTCs identified at surgical resection predicted shortened RFS, irrespective of subtype, in non-metastatic breast cancer patients. This data warrants larger studies to determine if CTC positivity can be used to stratify both ER+ and TN patients who are at increased risk for early recurrence.

Citation Format: Hall C, Meas S, Bowman Bauldry J, Kuerer H, Lucci A. Circulating tumor cell detection predicts early recurrence in patients with non-metastatic 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 P3-01-05.
Abstract P3-01-14: Diverse inter- and intra-patient circulating tumor cells (CTCs) phenotypic heterogeneity identified in metastatic breast cancer (MBC) cohort
Authors: Wang Y , Hom B , Ontiveros P , Landaverde C , Roth E , Levin MK , Hippely S , Landers M , Dittamore R , O'Shaughnessy JA
Published: May 2019

Background: There is unmet need for biomarkers to guide the treatment selection in MBC. We described phenotypic CTC heterogeneity in metastatic castrate resistant prostate cancer(mCRPC), and showed that pts with CTC high heterogeneity have improved OS with chemotherapy, while with pts low CTC heterogeneity pts have longer OS with AR inhibitors (Scher et al. 2017 Cancer Research). Here, the same methodology was applied to evaluate the feasibility of CTC heterogeneity analysis in MBC pts.

Material and methods: 92 blood samples from MBC pts were processed for HER2 CTC analysis utilizing the Epic Sciences platform. Following enumeration, multi-dimensional phenotypic characterization analysis was performed utilizing protein expression and digital pathology features. 20 features from each CTC were clustered using unsupervised approach (K-means) and the optimal number of clusters was determined using the elbow method with greater than 85% of variance taken into account. Shannon Index was used to score intra-patient CTC heterogeneity.

Results: CTCs were detected in 77.2% (71/92) of the MBC pts. 1501 CTCs from 60 pts were clustered into phenotypic subtypes which are distinctively different in nuclear size, circularity, CK and HER2 intensity etc. HER2 expression was enriched in cell types that had higher CK intensity and was more circular morphologies often associated with replicative stress. A wide range of CTC phenotypic heterogeneity was observed across pts, Shannon Index scores from 0 (low heterogeneity) to 1.67 (high heterogeneity) with a median of 0.60. CTC heterogeneity was independent of CTC counts, some low count pts had heterogeneous CTC subtypes while some high count pts had homogeneous CTC subtypes.

Conclusions: Diverse inter- and intra-patient phenotypic CTC heterogeneity were observed in this MBC cohort, consistent with that seen in mCRPC and other MBC cohorts (Beverly H et al, ASCO 2018). Studies linking degree and patterns of CTC heterogeneity to therapeutic outcomes are ongoing.

Citation Format: Wang Y, Hom B, Ontiveros P, Landaverde C, Roth E, Levin MK, Hippely S, Landers M, Dittamore R, O'Shaughnessy JA. Diverse inter- and intra-patient circulating tumor cells (CTCs) phenotypic heterogeneity identified in metastatic breast cancer (MBC) cohort [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 P3-01-14.
Abstract P3-01-17: PD-L1 expression on circulating epithelial tumor cells (CETCs) correlates with aggressiveness of tumor in breast cancer patients
Authors: Schott D , Pizon M , Pachmann U , Pachmann K
Published: May 2019

Background: Strategies to improve the efficacy of the immune system against malignant tumors represent a major innovation focusing on the programmed death-1 receptor (PD-1), with its two ligands PD-L1 and PD-L2. The expression of PD-L1 has been evaluated in a number of different tumor types and can be used as a predictive biomarker for PD-1/PD-L1 checkpoint inhibitor treatment response. We used a non-invasive, real-time liquid biopsy to better characterize PD-L1 expression on circulating epithelial tumor cells (CETCs) in breast cancer patients.

Methods: CETCs were determined from blood of 72 patients suffering from breast cancer. The number of vital CETCs and their expression of PD-L1 was investigated using the maintrac® method.

Results: PD-L1 expressing CETCs were detected in 94.5 % of breast cancer patients. Breast cancer patients with metastatic disease had significantly more PD-L1 positive CETCs as compared to patients without metastasis (median 75% vs. 61.1%; p<0.05). Furthermore, patients with positive lymph node status had significantly more PD-L1 positive CETCs as compared to patients with negative lymph nodes (median 60% vs. 93%, p<0,05). Moreover, we observed a significant heterogeneity in PD-L1 immunostaining intensity across CETCs from the same patients.

Conclusion: Breast cancer patients have detectable CETCs with a high frequency of PD-L1 which correlates with progression of cancer disease. PD-L1 seems to be a major factor in immune evasion and may be a promising target of anticancer therapies. Monitoring the frequency of PD-L1 positive CETCs could reflect individual patient's response to an anti-PD-1/PD-L1 therapy.

Citation Format: Schott D, Pizon M, Pachmann U, Pachmann K. PD-L1 expression on circulating epithelial tumor cells (CETCs) correlates with aggressiveness of tumor in breast cancer patients [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 P3-01-17.
Abstract P3-03-03: Sentinel node biopsy (SNB) vs Low axillary sampling (LAS) in predicting nodal status of post-chemotherapy axilla in women with breast cancer
Authors: Parmar V , Nair NS , Vanamali V , Hawaldar RW , Siddique S , Shet T , Desai SB , Rangarajan V , Patil A , Gupta S , Badwe RA
Published: May 2019

Introduction

There is no safe method of avoiding complete axillary lymph node dissection in women with breast cancer after neo-adjuvant chemotherapy. sentinel node biopsy (SNB) has had prohibitively high false negative rate. We tested low axillary sampling (LAS) and SNB performed in same patient to predict axillary lymph node status in clinically node negative women undergoing breast conservation or modified radical mastectomy after neo-adjuvant chemotherapy.

Methodology

Post neo-adjuvant chemotherapy 751 women who had no palpable axillary lymph node underwent LAS (all lymph nodes below intercosto-brachial nerve). Of these 751 women, 730 also underwent SNB by dual technique after injection of blue dye as well as radio-isotope. SN was identified within and outside axillary sampling specimen. SN as well as LAS specimens were distinctly examined for nodal metastasis. The rest of the axillary dissection was completed in all patients. Post NACT 292/751(38.9%) had residual positive lymph nodes on pathology. The identification rate, false negative rate (FNR), and negative predictive value (NPV) of SNB and LAS were compared for predicting negative axillary lymph node status.

Results

The median clinical tumor size was 5cm (1-15cm) and 533(71%) patients were N1 or N2 at presentation. The SNB identification rate was 87.1% (636 of 730), with a median of 5 nodes and node positive in 238 of 636 (37.4%). LAS identification rate was 98% (736 of 751), with a median of 7 nodes and node positive in 292 of 736 (39.6%). In all but one case, the SN was found within the LAS specimen. The FNR of SNB (blue, hot and adjacent palpable nodes) was 19.7% (47 of 238, one sided 95% upper CI 24.0) compared to LAS with FNR of 9.9% (29 of 292, one-sided 95% upper CI 12.8) (p<0.001). Comparative NPV for SNB and LAS were 89.4% and 93.9% respectively. If SNB was confined to blue/hot node excluding adjacent palpable nodes, FNR was 31.6% (74 of 234, 95% upper CI 36.6).

Conclusions

LAS is superior to SNB in identification rate, FNR and NPV in predicting node negative axilla post-neoadjuvant chemotherapy. LAS can be safely used to predict negative axilla with less than 10% chance of leaving residual disease.

Citation Format: Parmar V, Nair NS, Vanamali V, Hawaldar RW, Siddique S, Shet T, Desai SB, Rangarajan V, Patil A, Gupta S, Badwe RA. Sentinel node biopsy (SNB) vs Low axillary sampling (LAS) in predicting nodal status of post-chemotherapy axilla in women with 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 P3-03-03.
Abstract P3-03-04: Withdrawn
Authors: Wu S , Wang Y , Li J , Zhang N , Liu G
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Wu S, Wang Y, Li J, Zhang N, Liu G. 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 P3-03-04.
Abstract P3-03-10: Pre-operative lymphoscintigraphy for sentinel lymph node localisation: Is it necessary?
Authors: Clark SL , Yilmaz D , Arun K , Javadzadeh S , Saeed S , Ullah MZ
Published: May 2019

Introduction

Sentinel lymph node biopsy (SLNB) has replaced lymph node clearance for staging of the axilla in patients with early invasive breast cancer and no evidence of lymph node involvement on ultrasound or needle biopsy. It is recommended that a dual technique, using isotope and blue dye, is used to locate the sentinel lymph node (SLN) intra-operatively. Often, at the time of radioisotope injection, a lymphoscintigram (nuclear medicine scan) is obtained to demonstrate the 'hot' sentinel lymph node with or without skin marking of its anatomical position.

Performing a lymphoscintigram adds time and cost to the localisation process. In our centre, this investigation costs £899-999 (˜US $1180-1300).

Aims

The aim of this study is to find out whether obtaining a pre-operative lymphoscintigram aids the surgeon in the localisation of the SLN or affects the number of sentinel lymph nodes biopsied in the axillary staging of patients with early invasive breast cancer.

Methods

We carried out a retrospective study of patients who underwent SLNB for breast cancer in our hospital Trust between March 2012 and November 2017. We identified those patients who had a lymphoscintigram performed pre-operatively for SLN localisation. We recorded the number of SLNs identified on imaging and compared this with the number of SLNs biopsied during the operation.

Results

349 patients underwent 354 SLNBs during the study period. One patient was male, the remainders were female. The mean age of patients was 57.2 years (range 25 to 98 years).

In 295 (83.3%) cases, a lymphoscintigram was obtained prior to SLNB for node localisation, and 268 (90.8%) of these scans were able to identify one or more SLNs. In 173 (58.6%) scans, a single SLN was identified. In 27 (9.1%) scans it was either unclear how many SLNs were demonstrated or no SLNs were seen (16/295 no SLN identified, 11/295 unclear how many SLNs).

In 102 (34.6%) cases, the number of SLNs biopsied matched the number of SLNs identified on imaging. Of those that did not match, 76.2% had more and 15.0% fewer SLNs excised than shown on imaging. In 8.8% it was unknown if the number of SLNs matched that seen on imaging due to lack of histopathology results.

Conclusion

Lymphoscintigraphy for SLN localisation is costly and time consuming. In a high proportion of cases, number of SLNs identified on imaging does not match the number biopsied and thus, we suggest, that it is not required prior to SLNB and should be removed from practice.

Citation Format: Clark SL, Yilmaz D, Arun K, Javadzadeh S, Saeed S, Ullah MZ. Pre-operative lymphoscintigraphy for sentinel lymph node localisation: Is it necessary? [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 P3-03-10.
Abstract P3-03-28: Withdrawn
Authors: Yoo T-K , Chae BJ , Ahn JY , Ryu J , Eom YH , Park WC , Song BJ
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Yoo T-K, Chae BJ, Ahn JY, Ryu J, Eom YH, Park WC, Song BJ. 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 P3-03-28.
Abstract P3-03-29: Evaluation of a direct reverse transcription loop-mediated isothermal amplification method without RNA extraction (direct RT-LAMP) for the detection of lymph node metastasis in early breast cancer
Authors: Lee IH , Jung J , Lee S , Lee J , Lee RK , Park H , Jung J , Kang J , Chae Y
Published: May 2019

Backgroud: The detection of lymph node metastasis by reverse transcription loop-mediated isothermal amplification method (RT-LAMP) had been studied previously. Even though, RT-LAMP method provides improved performance compared to intraoperative histology sentinel lymph node (SLN) evaluation, direct RT-LAMP method without RNA extraction can be more efficient and easily accessible process. Therefore, we evaluated the performance and efficacy of a direct reverse transcription loop-mediated isothermal amplification (direct RT-LAMP) assay for visual detection of CK19, CK20, and CEA mRNAs to identify lymph node metastasis in patients with early breast cancer.

Methods: A total of 92 lymph nodes dissected from 40 patients with breast cancer were collected at the breast cancer center of Kyungpook National University Chilgok Hospital between November 2015 and February 2016. All of the samples were analyzed by direct RT-LAMP assay and routine histopathology examination. Cutoff values to distinguish metastasis and nonmetasis were determined by measuring cytokerain 19 (CK19) mRNA in histopathologically positive and negative lymph node using direct RT-LAMP.

Results: We set the cutoff value of direct RT-LAMP assay for CK 19 mRNA at 1ng to distinguish status of LN metastasis. The sensitivity and specificity of the RT-LAMP assay were 85.7% and 100%, respectively. The positive predictive value and negative predictive value were 100% and 94.4%.

Conclusion: Direct RT-LAMP assay can allow detection of SLN metastasis in breast cancer patients intraoperatively with a good sensitivity through cost-effective and time–saving manner.

Citation Format: Lee IH, Jung J, Lee S, Lee J, Lee RK, Park H, Jung J, Kang J, Chae Y. Evaluation of a direct reverse transcription loop-mediated isothermal amplification method without RNA extraction (direct RT-LAMP) for the detection of lymph node metastasis in 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 P3-03-29.
Abstract P3-03-33: Withdrawn
Authors: Blackhall VI , Bugelli M , Abbott NA , Mullen R
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Blackhall VI, Bugelli M, Abbott NA, Mullen R. 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 P3-03-33.
Abstract P3-03-39: Sentinel lymph node biopsy after surgery with removal of the primary tumor
Authors: Zhiltsova E , Krivorotko P , Dashayan G , Emelyanov A , Tabagua T , Bessonov A , Ivanova O , Kanaev S , Novikov S , Krzivickiyi P , Komayachov A , Nikolaev K , Gigolaeva L , Zernov K , Semiglazov V
Published: May 2019

Nowadays, sentinel lymph node biopsy (SLNB) is one of the basic methods for

diagnosing the lesion of regional lymph nodes (LN) and it is recommended by

experts as a standard method in determining the prevalence of the disease in breast

cancer patients (BC).

The aim of the study was the possibility of sentinel lymph node biopsy after

surgery with removal of the primary tumor.

Materials and methods

The study was conducted in the N.N. Petrov's National Medical Center of

Oncology from 2013 to 2018. SLNB was performed in patients who had a primary

tumorectomy in another medical institution. The study included patients with the

stage cN0. Radionuclide imaging of the sentinel lymph nodes (SLN) was

performed in 37 patients with breast cancer. The injection of radiopharmaceuticals

in postoperative scar was performed before the biopsy. Median of the period

between the operations was 21 days (14 to 30 days).

Results

After injection, the image of SLN was obtained in 91.9% (34 of 37) of patients.

During the operation, 1-5 sentinel lymph nodes were visualized. The lesion of the

sentinel lymph nodes (N+) was detected in 21.6% (8) patients, N0 in 78.4% (29)

patients, respectively.

There is no data for locoregional relapse for the period of observation from 2014 to

nowadays.

Conclusions

The obtained results are comparable with the results of sentinel lymph node biopsy

in primary patients with breast cancer stage cN0. This indicates the possibility of

biopsy after surgery with removal of the primary tumor.

Citation Format: Zhiltsova E, Krivorotko P, Dashayan G, Emelyanov A, Tabagua T, Bessonov A, Ivanova O, Kanaev S, Novikov S, Krzivickiyi P, Komayachov A, Nikolaev K, Gigolaeva L, Zernov K, Semiglazov V. Sentinel lymph node biopsy after surgery with removal of the primary tumor [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 P3-03-39.
Abstract P3-06-03: Copy number analysis identifies ESR1 and MDM4 as drivers of progression in invasive lobular breast carcinoma
Authors: Atkinson JM , Cao L , Basudan A , Sikora MJ , Bahreini A , Tasdemir N , Jankowitz RC , McAuliffe PF , Dabbs D , Haupt S , Haupt Y , Peter Lucas PC , Lee AV , Oesterreich S
Published: May 2019

Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma (IDC). While specific clinical and pathological features differ between ILC and IDC, both histologies are treated the same, due to a lack of knowledge of targetable pathways underlying the observed differences. To identify potential genetic drivers of ILC progression, we set out to identify genes with copy number (CN) alterations, comparing tumors with good outcome to those with poor outcome.

Method: We designed probes for a total of 67 genes known to be frequently altered in breast cancer and used sensitive nanoString technology to comprehensively investigate CN alterations of these genes in 70 well-curated primary ILCs. ILC cell lines MDA-MB-134-VI, SUM44PE, and BCK4 were used for functional studies including proliferation, apoptosis, colony formation, and analysis of gene expression.

Results: Our studies reveal that ESR1 is frequently amplified in primary ILC (14% gains and 10% amplification), and that tumors with amplified ESR1 are more likely to recur compared to those with normal CN. Our analysis also identified a subset of ILCs with HER2 amplification (19%) despite a negative clinical IHC score, and these tumors expressed high HER2 mRNA, protein, and demonstrated enrichment of a molecular HER2 signature. The other most frequently amplified genes included CCND1 (33%), MDM4 (17%), and MYC (17%), and most frequently lost genes were NCOR2 (7%), FGFR4 (6%) and TP53 (6%). MDM4, a negative regulator of p53, has previously been reported to play a role in breast cancer, though little is known about its role in ILC. We demonstrate that decreasing MDM4 levels in p53 wild type ILC cell lines results in increased apoptosis, decreased proliferation associated with cell cycle arrest, and activation of p53 target genes. Intriguingly, a similar induction of G0/G1 cell cycle arrest and increase in apoptosis was observed in p53 mutant ILC cells after MDM4 downregulation, suggesting a p53-independent function of MDM4.

Conclusion: Sensitive detection of CN changes identified amplifications of ESR1 and MDM4 as potential drivers of ILC. Functional studies demonstrate that MDM4 has both p53 dependent and independent functions that warrant further study.

Citation Format: Atkinson JM, Cao L, Basudan A, Sikora MJ, Bahreini A, Tasdemir N, Jankowitz RC, McAuliffe PF, Dabbs D, Haupt S, Haupt Y, Peter Lucas PC, Lee AV, Oesterreich S. Copy number analysis identifies ESR1 and MDM4 as drivers of progression in invasive lobular breast carcinoma [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 P3-06-03.
Abstract P3-06-05: Whole genome sequence analysis of 77 breast cancer patients reveal increased somatic transposable element insertions responsible for early onset of cancer
Authors: Paul R , Solzak JP , Radovich M
Published: May 2019

More than 50% of the human genome consists of transposable elements (TE). However only certain classes of retrotransposons (ALU, SVA, ERV and L1) are believed to be active. They transpose using an RNA intermediate causing target-site duplications along with a poly-A tail. They can also insert into intronic regions and disrupt normal transcription of protein-coding genes. However, most TEs are repressed using various epigenetic mechanisms such as DNA methylation, histone modifications and RNA silencing. The piRNA pathway also plays an important role in retrotransposon silencing by establishing a repressive chromatin state. In this study, somatic and germline TE insertions in 77 TCGA breast cancer cases were characterized. These studies have revealed that somatic TEs can insert into intronic regions of tumor suppressor genes such as LRP1B, RAD51B and WNK2. Characterization of germline TE insertions, reveal insertions in intronic regions of predisposition genes such as CDH1 and BRCA2. Analysis of germline SNPs in high somatic TE patients reveals the presence of deleterious variants in genes such as NRDE2, RAD51C and DDX3X which are known to regulate TEs using RNA silencing via the piRNA pathway and other DNA-damage response mechanisms. Patients having high somatic TE insertions were found to have lower age of diagnosis suggesting a role in the early onset of cancer (median age of patients with high TE=43.37yrs; low TE=59.77yrs, Wilcoxan p=0.023). Further comparison of somatic TE insertion burden against somatic point-mutation burden revealed an inverse correlation suggesting analysis of TE insertions is indispensable to get the complete mutation profile of breast cancer genomes.

Citation Format: Paul R, Solzak JP, Radovich M. Whole genome sequence analysis of 77 breast cancer patients reveal increased somatic transposable element insertions responsible for early onset of 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 P3-06-05.
Abstract P3-06-13: Whole exome sequencing of HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary durable complete responses (ExdCR) to trastuzumab (T)
Authors: Walsh N , Gullo G , Quinn C , Furney SJ , Crown J
Published: May 2019

Background: Trastuzumab (T) has shown clinical efficacy in early-stage and MBC. However, within 1-year 40-50% develop resistance to T. The exact mechanism of the development of T resistance is not completely understood. Anecdotal observations suggest that a small fraction of patients with HER2+ MBC may be "extraordinary durable complete responders (ExdCR)". Indeed, we previously reported that 9% of MBC achieve dCR following T and chemotherapy. Understanding the genomic mechanisms underlying exceptional dCR to T may improve patient selection and treatment rationale to identify HER2+ MBC pts who are more likely to achieve dCR following T treatment.

Methods: Genomic DNA was extracted from paraffin embedded formalin fixed (FFPE) tissue. Whole exome sequencing (WES) on primary tumours from 9 MBC ExdCR > 60 mo (5 matched T:N) and 6 non-responders (NR) or PR < 6 mo (3 matched T:N). Tumours were analysed for single nucleotide variants (SNVs) point mutations, insertions/deletions (indels), copy number alterations (CNA), and tumour mutational burden. Detailed clinicopathologic data was collected for each patient and linked to the genomic information.

Results: WES of matched tumour:normal samples revealed differences in SNVs and indels between the ExdCR pts compared to NR. Mutations in TP53 were found in 2/5 ExdCR pts and in 0/3 NR. Initial analysis of CNA revealed that HER2 is significantly more amplified in ExdCR pts compared to NR, and this was also shown by IHC and FISH.

Conclusions: We present a genomic landscape of extraordinary durable complete responders compared to non-responders using WES. High variability exists in mutation profile of ExdCR pts with few overlapping genes. Further analysis into clinically relevant genomic and molecular alterations will be performed to potential aid in patient selection and choice of therapy, and novel drug targets.

Citation Format: Walsh N, Gullo G, Quinn C, Furney SJ, Crown J. Whole exome sequencing of HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary durable complete responses (ExdCR) to trastuzumab (T) [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 P3-06-13.
Abstract P3-06-18: Comprehensive genomic profiling of carcinosarcomas of the breast
Authors: Gay LM , Elvin JA , Vergilio J-A , Killian JK , Ramkissoon S , Severson E , Daniel S , Hammerich A , Sokol E , Frampton G , Chung J , Trabucco S , Ali S , Reddy P , Schrock AB , Miller VA , Ross JS
Published: May 2019

Background:

Carcinosarcomas of the breast (BCSC) are exceptionally rare and the underlying genomic drivers are still being elucidated. Comprehensive genomic profiling (CGP) determines the tumor mutation burden (TMB) and identifies all four classes of genomic alterations (GA) that have potential to direct personalized treatment strategies.

Methods:

CGP by hybridization capture of exons from up to 315 cancer-related genes and select introns of 28 genes commonly rearranged in cancer was applied to ≥ 50ng of DNA extracted from 9 consecutive BCSC and sequenced to high, uniform median coverage (>500X). Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined by principal components analysis of optimized loci.

Results:

The 9 BCSC patients had a median age of 57 yrs (range 49-78 yrs). CGP was performed on the primary BCSC in 4 cases and on metastasis biopsies in 5 cases (4 lung and 1 lymph node). The mean GA/tumor was 6.6 and clinically relevant GA (CRGA)/tumor was 1.3. The most frequent non-CRGA were in TP53 (89%), MYC (56%) and LYN (40%). The most frequent CRGA were in PIK3CA (33%), and NF1, BRCA1, PTEN, RICTOR, FGFR1, AKT2 and STK11 (all at 11%). The median TMB for all BCSC was 2.4 mut/Mb with 1 (11%) tumor with a TMB > 20 mut/Mb and 8 BCSC (88%) with TMB < 5 mut/Mb. Five of 5 BCSC (100%) that were available for MSI status testing were microsatellite stable.

Conclusions:

On CGP, BCSC feature a high frequency of GA, but only a modest frequency of CRGA and high TMB. However, when the CRGA and TMB positive cases are combined (77.8% overall in this series), the opportunity for personalized targeted and immunotherapies are significant. Thus, further investigation of precision therapies for BCSC in the clinical trial setting appear warranted.

Citation Format: Gay LM, Elvin JA, Vergilio J-A, Killian JK, Ramkissoon S, Severson E, Daniel S, Hammerich A, Sokol E, Frampton G, Chung J, Trabucco S, Ali S, Reddy P, Schrock AB, Miller VA, Ross JS. Comprehensive genomic profiling of carcinosarcomas of the breast [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 P3-06-18.
Abstract P3-06-19: MUC17 and PCNX1 as mediators of chemotherapy response in breast cancer
Authors: Al Amri W , Verghese E , Stead L , Hanby A , Sharma N , Hughes T
Published: May 2019

Breast cancer is a heterogeneous disease and accumulating evidence suggests that treatment failure may be driven by intra-tumour heterogeneity (ITH). Utilising the current protocol for neoadjuvant (pre-surgery) chemotherapy (NAC) provides the opportunity to study molecular genetic changes between pre- and post-therapy by assessing pre-therapy biopsies and post-therapy surgical resections.

Whole exome sequencing was performed on matched pre- and post-treatment cancer cells from 6 patients with oestrogen receptor positive breast cancers that showed partial responses to the chemotherapeutic epirubicin. Data analysis was performed to determine differences in genetic aberrations between pre- and post-NAC, and in particular to identify evidence of consistent selection by therapy of aberrations that therefore may define chemotherapy resistance or sensitivity.

There were extensive differences in the range of genetic aberrations between pre- and post-NAC. 48 genes were identified for further study based on evidence of mutations conferring a selective advantage or disadvantage during chemotherapeutic response. The relevance of these was screened using siRNA knock-down and assessment of response to chemotherapeutic drug using cell viability assays in vitro. Two genes were taken forward. Potential loss-of-function mutations in the MUC17 gene were selected against during therapy in patients, and in accordance with this MUC17 knock-down was associated with increased sensitivity in vitro. Potential loss-of-function mutations in the PCNX1 gene were selected for during therapy in patients, and in accordance with this PCNX1 knock-down was associated with resistance. Further work was done to investigate mechanisms by which these genes modify cellular chemotherapy response, by examining drug loading and ABC transporter expression levels. Data indicate that both genes impact on drug loading, potentially through modulating ABC transporter activities. Using available transcriptomic datasets, expression of neither gene correlated with breast cancer outcomes in mixed cohorts that received a wide-range of therapies, however, analysis of correlations between protein expression and outcomes specifically after chemotherapy are on-going. We conclude that MUC17 and PCNX1 are potential markers of response to chemotherapy in breast cancer, and therapeutic modulation of their activities could enhance chemotherapy responses.

Citation Format: Al Amri W, Verghese E, Stead L, Hanby A, Sharma N, Hughes T. MUC17 and PCNX1 as mediators of chemotherapy response in 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 P3-06-19.
Abstract P3-06-21: Withdrawn
Authors: Minhas S , Veldore V , Ramprasad V , Ganvir M , Aggarwal S
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Minhas S, Veldore V, Ramprasad V, Ganvir M, Aggarwal S. 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 P3-06-21.
Abstract P3-07-09: Tumour clonality in paired invasive breast carcinomas
Authors: Biermann J , Parris TZ , Nemes S , Danielsson A , Engqvist H , Werner Rönnerman E , Forssell-Aronsson E , Kovács A , Karlsson P , Helou K
Published: May 2019

Background: Multiple invasive breast tumours may represent either independent primary tumours or clonal recurrences of the first tumour, where the same progenitor cell gives rise to all of the detected tumours. Consequently, the driver events for the progenitor cell need to have been identical in early tumour development. Molecular classification of tumour clonality is not currently evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. Furthermore, there is no consensus about which type of biological data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.

Methods: Thirty-seven invasive breast tumour pairs were stratified by laterality (bilateral vs. ipsilateral) and the time interval between the diagnoses of the first and second tumours (synchronous vs. metachronous). Both tumours from the same patient were analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), distance measure, shared segment analysis etc., were used to classify the tumours from the same patient as clonally related recurrences or independent primary tumours.

Results: The SI applied on DNA copy numbers derived from aCGH (array comparative genomic hybridization) data was determined as the strongest indicator of clonal relatedness as it showed the highest concordance with all other methods. The distance measure was the most conservative method and the shared segment analysis most liberal. Concordant evidence for tumour clonality was found in 46% (17/37) of the patients. Notably, no significant association was found between the clinical characteristics and molecular tumour features.

Conclusions: A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. In cases of extremely similar or different tumour pairs, the results showed consistency regardless of the method used. The SI can be easily integrated into clinical routine using FFPE samples to obtain copy number data. However, clinical guidelines with exact thresholds need to be defined to standardize clonality testing in a routine diagnostic setting.

Citation Format: Biermann J, Parris TZ, Nemes S, Danielsson A, Engqvist H, Werner Rönnerman E, Forssell-Aronsson E, Kovács A, Karlsson P, Helou K. Tumour clonality in paired invasive breast carcinomas [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 P3-07-09.
Abstract P3-08-19: Proteomic tracking of breast cancer metastasis progression
Authors: Hajjaji N , Aboulouard S , Robin YM , Bertin D , Fournier I , Bonneterre J , Salzet M
Published: May 2019

Background

Metastases from breast cancers have not yet reached curability mainly because of the continuous evolution of cancer cells leading to treatment resistance and tumor progression. Despite the identification of the main genomic drivers of breast cancer resistance, and the development of specific targeted therapies, resistance has not been eradicated. A deeper understanding of tumor biology underlying treatment escape and tumor progression is necessary to find new targets. The aim of this study was to determine whether mass spectrometry based imaging and microproteomics are able to capture changes in protein expression and pathways occurring during metastasis progression.

Methods

Ten tumor samples from five progressing metastatic breast cancer patients treated at Oscar Lambret Cancer Center (France) were selected based on the availability of paired metastasis biopsy performed at two time points during the evolution of the disease. The proteomic profiles of paired tumor samples were analyzed using MALDI mass spectrometry imaging combined with microproteomics, a spatially resolved proteomic technology.

Results

Comparison of paired samples showed gain and loss of proteins associated with tumor progression. However, few were shared between patients. The pathways and biological processes mainly represented during tumor progression, and which were found in at least two patients, were those involved in the negative regulation of leukocyte mediated cytotoxicity, the metabolism of carboxilic acid, peptides and nucleosides, in response to stress, oxidation-reduction process, endocytosis, catabolic processes, actin regulation, and extracellular matrix organization. During metastasis evolution, few shared proteins were identified in at least 3 patients such as SRPX2, CILP1, collagen alpha-2(V) chain, Ras-related C3 botulinum toxin substrate 1, filamin-C, PDZ and LIM domain protein 2 and chloride intracellular channel protein 4. The main proteins lost during progression and found in at least 2 patients were cell surface glycoprotein MUC18, collagen alpha-2(IV) chain, polyadenylate-binding protein 2, and latent-transforming growth factor beta-binding protein 4 (LTAGP4). Results from an expanded cohort will be presented at the meeting.

Conclusion

MALDI mass spectrometry proteomics identified private and shared changes in proteins and biological processes associated with breast cancer metastasis progression.

Citation Format: Hajjaji N, Aboulouard S, Robin YM, Bertin D, Fournier I, Bonneterre J, Salzet M. Proteomic tracking of breast cancer metastasis progression [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 P3-08-19.
Abstract P3-08-21: Not presented
Authors: Stanek L , Tesarova P , Vocka M , Petruzelka L , Musil Z
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Stanek L, Tesarova P, Vocka M, Petruzelka L, Musil Z. 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 P3-08-21.