bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P5-11-11: A preliminary assessment of knowledge, attitudes, and awareness surrounding ESR1 mutations and biomarker testing amongst medical oncologists
Authors: Goldfarb SB , Goetz MP , Plourde PP , Attias E , Portman DJ
Published: May 2019

Background: Estrogen receptor gene (ESR1) mutations present in breast cancer patients are associated with resistance to endocrine therapy and worse patient outcomes. Recent findings suggest ESR1 mutations are present in up to 40% of metastatic breast cancer (mBC) patients' tumors. The objective of this study was to evaluate the perceptions of precision medicine and biomarker testing specific to ESR1 mutations among medical oncologists.

Methods: Ten 60-minute web-assisted, telephone interviews were conducted with medical oncologists. Each physician was prescreened prior to being interviewed to ensure board certification and practice experience between 2 and 35 years. Each participant spent greater than 30% of their time on direct patient care and managed the treatment of more than 30 different cancer patients per month, with a minimum of 15 breast cancer patients, including at least five who had metastatic breast cancer and at least one patient with an ESR1 mutation.

Results: A 10-20% prevalence of ESR1 mutation was estimated by the oncologists. However, the practitioners did accept the possibility of a 40% prevalence. Physician knowledge of ESR1 mutations included the relationship between ESR1 mutations and efficacy of endocrine therapies and its association with poorer outcomes. None of the medical oncologists interviewed were highly satisfied with the existing armamentarium of treatments for patients with an ESR1 mutation.

In general, the interview participants were highly comfortable ordering ESR1 companion diagnostics to test for an ESR1 mutation, pending viable treatment options are available. Nonetheless, most physicians will wait until the patient has progression of disease before ordering a biomarker test. Several areas of unmet need in the mBC arena were offered by the survey participants, including more efficacious hormonal options for later-line therapies, better durability of remission, improved drug tolerability profiles, and lower treatment costs.

Conclusion: Most oncologists acknowledged that personalized treatment is beneficial because it allows for better efficacy than a “one size fits all” approach. The study results also suggest that there are few barriers and drawbacks to the use of personalized medicine in the mBC arena, as most physicians expect precision medicine to account for the majority of advances in breast cancer treatments in the foreseeable future.

Support: Sermonix Pharmaceuticals

Citation Format: Goldfarb SB, Goetz MP, Plourde PP, Attias E, Portman DJ. A preliminary assessment of knowledge, attitudes, and awareness surrounding ESR1 mutations and biomarker testing amongst medical oncologists [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 P5-11-11.
Abstract P5-12-12: ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 breast cancer patients
Authors: Győrffy B , Fekete J
Published: May 2019

Prognostic biomarkers are capable to predict survival and predictive biomarkers are capable to predict therapy response. Systemic therapy of breast cancer can include chemotherapy, hormonal therapy, and targeted therapy. Here, we report the initial release of the first online available tool capable to identify gene expression based predictive biomarkers using transcriptomic data of a large set of breast cancer patients.

Published gene expression data of 44 publicly available datasets was integrated with treatment data into a unified database. The classification is based on either author-reported pathological complete response (n=1,775) or relapse-free survival status at five years (n=1,329). Treatment data includes chemotherapy (n=2,108), endocrine therapy (n=971), and anti-HER2 therapy (n=267). The transcriptomic database includes 20,089 unique genes and 54,675 probe sets. Gene expression and therapy response are compared using receiver operating characteristics and Mann-Whitney tests.

We demonstrate the utility of the tool by validating a set of established biomarkers including TP53 for chemotherapy in luminal breast cancer (p=5.2e-20, AUC=0.77), ERBB2 for trastuzumab therapy (p=8.4e-04, AUC=0.629), and PGR for hormonal therapy (p=8.6e-05, AUC=0.7).

The tool is designed to validate and rank new predictive biomarker candidates in real time. By analyzing the selected genes in a large set of independent patients, one can select the most robust candidate and quickly eliminate those which are most likely to fail in a clinical setting. The analysis tool is accessible at www.rocplot.org/breast.

Citation Format: Győrffy B, Fekete J. ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 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 P5-12-12.
Abstract P5-12-13: Changing level of serum heat shock protein 90 alpha as a diagnostic and predictive marker in breast cancer: Diagnosis of early breast cancer and prediction of response to neo-adjuvant and surgical therapy
Authors: Hu N , Li M , Zhu A , Du F , Yuan P
Published: May 2019

To analyze the correlation of the level of serum heat shock protein 90α (HSP-90α) in healthy and breast cancer patients, studying the evaluation of neoadjuvant efficacy and Clinical value of relapse monitoring.

A total of 102 healthy women were selected, 51 cases of breast benign tumor ,423 cases of female breast cancer all diagnosed by pathology,other system malignancies 62 cases. ALL the serum samples HSP-90αwas detected by double-antibody ELISA. The CEA, CA125,CA15-3 were detected by Roche Cobas ECL analyzer. The ROC curve was used to analyze the effectiveness of serum HSP-90α in the early diagnosis of breast cancer. The dynamic changes of HSP-90αlevel before and after treatment were analyzed by Wilcoxon's rank test. Moreover, we also combine the HSP-90αwith CEA,CA125,CA15-3 to evaluate the clinical value of monitoring the recurrence of breast cancer.

The levels of serum HSP-90α (123.49 ± 105.1ng / ml) in breast cancer patients wes significantly higher than that in healthy controls (40.33 ± 14.18ng / ml), benign breast disease (80.15 ± 103.09ng / ml) and carcinoma in situ (34.7 ± (114.31 ± 146.91ng / ml),the difference was statistically significant (P <0.001). .According to the ROC curve analysis of patients and healthy subjects, the cut-offvalue was set as HSP-90=59.7ng / ml, AUC=0.834, the sensitivity and specificity to diagnosis of breast cancer was 90.3% and 78.6% respectively ,the negative predictive value was 93.88%.The levels of serum HSP-90α was significantly decreased (P <0.05) after tumor resection and the patients who obtain PR from the neoadjuvant chemotherapy. When HSP-90=43.22ng / ml was set as the cut-off value for diagnosing the recurrence of breast cancer, AUC=0.877,the sensitivity and specificity were 95.7% and 74.5% respectively, and the negative predictive value was 96.2%. At the same time, we find that combined HSP-90α with CEA, CA125, CA15-3 can improve the accuracy of recurrence prediction.

Serum HSP-90α has a good clinical diagnostic value in breast cancer and can be used as a recurrence monitoring tool for post-adjuvant treatment patients.

Citation Format: Hu N, Li M, Zhu A, Du F, Yuan P. Changing level of serum heat shock protein 90 alpha as a diagnostic and predictive marker in breast cancer: Diagnosis of early breast cancer and prediction of response to neo-adjuvant and surgical 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 P5-12-13.
Abstract P5-14-02: Time to treatment discontinuation as a pragmatic endpoint: A U.S. Food and Drug Administration pooled analysis of CDK 4/6 inhibitors
Authors: Gao JJ , Gong Y , Cheng J , Schroeder RJ , Amiri-Kordestani L , Khozin S , Kluetz P , Sridhara R , Pazdur R , Blumenthal G , Beaver JA , Prowell TM
Published: May 2019

BACKGROUND: The primary endpoint in many registration trials is progression-free survival (PFS), defined as the time from randomization until objective tumor progression or death. In the clinical setting, however, PFS can be difficult to measure and explain, especially in patient-friendly language. For real-world evidence (RWE) based studies, time to treatment discontinuation (TTD), defined as time from randomization to discontinuation of the investigational study drug, may be a more practical endpoint. We hypothesize TTD will correlate with PFS and analyzed registration trials from recently FDA approved cyclin dependent kinase 4/6 inhibitors (CDKIs) to test this hypothesis. TTD was defined as time from randomization to discontinuation of the CDKI.

METHODS: We pooled data from five phase III randomized, controlled, registration trials of CDKIs with an aromatase inhibitor (AI) in the first-line or fulvestrant in the second-line setting. The CDKI discontinuation dates used to calculate TTD were derived from the patient-level datasets. We calculated patient-level correlation between TTD and PFS. We also summarized median TTD and PFS as well as the number of TTD and PFS events.

RESULTS: A total of 3017 patients were included in the pooled analysis (n=1899 treated with CDKI, n=1118 with placebo). The median PFS and TTD and the number of events are shown in Table 1. The patient-level Spearman correlation coefficient of TTD and PFS ranged from 0.87-0.95. The trial-level association was approximately R2=0.23.

Table 1:Primary ResultsTreatment ArmNPFS EventsTTD EventsMedian PFS, in mo (95% CI)Median TTD, in mo (95% CI)Spearman Correlation CoefficientCDKI1899873138320.7 (19.2-22.2)14.3 (13.6-14.9)0.87Placebo111871488311.7 (11.0-13.6)11.0 (9.7-12.0)0.95

CONCLUSION: Patient-level pooled cross-trial analysis show a relationship between TTD and PFS in registration trials of CDKIs. In all trials, the difference in time between median TTD and median PFS appeared greater in the CDKI arm than the placebo arm. This analysis is limited by the relatively small number of studies included. Further research is needed to determine both whether: 1) TTD can serve as a pragmatic endpoint for analyses of RWE, and 2) is a more meaningful endpoint to patients.

Citation Format: Gao JJ, Gong Y, Cheng J, Schroeder RJ, Amiri-Kordestani L, Khozin S, Kluetz P, Sridhara R, Pazdur R, Blumenthal G, Beaver JA, Prowell TM. Time to treatment discontinuation as a pragmatic endpoint: A U.S. Food and Drug Administration pooled analysis of CDK 4/6 inhibitors [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 P5-14-02.
Abstract P5-14-09: Integration of primary care practitioners in a breast multidisciplinary team meeting- A pilot study
Authors: Pitcher ME , Hornung I , Rangarajan P
Published: May 2019

Primary care practitioners are key to integrated patient care, as they often have an established relationship with patient and family, with knowledge of comorbidities and psychosocial factors. They can encourage compliance with cancer treatments and manage transition from acute care through survivorship.

Communication with primary care however has often been unsatisfactory, with information not helpful to that practitioner or not provided in a timely manner.

We recruited a general practitioner (GP) to attend the weekly breast cancer multidisciplinary meeting, with a responsibility to make contact with the primary care practitioner of patients presented prior to the meeting, so that relevant information from a primary care perspective could be taken into consideration for team deliberations. This also meant that the primary doctor was aware the patient was being discussed. Recommendations were fed back to that doctor after the meeting so that information was timely, and, being given by a peer, more useful.

The GP attended 12 consecutive MDTs where 105 patients were discussed. In 55% contact was able to be made with the patient's GP prior to the meeting. This was perceived as not usually changing management plans, but reinforced known medical and social concerns. Feedback to the patients GP was regarded favourably, with reported greater confidence in managing the patient, particularly those with complex needs, as well as improving hospital to community communication in general.

This pilot has shown that it is feasible to include primary care practitioners in a multidisciplinary meeting and improve interdisciplinary communication.

Citation Format: Pitcher ME, Hornung I, Rangarajan P. Integration of primary care practitioners in a breast multidisciplinary team meeting- A pilot 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 P5-14-09.
Abstract P5-15-04: Oncotype DX cost effectivity to a Brazilian public hospital
Authors: Cabello C , de Andrade RN , Cabello TF , Teixeira S , da Costa LS , Ramalho S
Published: May 2019

Introduction: The Oncotype DX was associated to 14% of adjuvant chemotherapy administration to Hormonal Receptor positive (HR+) and HER2 negative, T1N0 or T2N0 breast cancer patients at Tailor X trial recently published (RS>25)

Objective: To describe the adjuvant chemotherapy administration to a Brazilian public hospital for HR+ HER2 negative, T1N0 or T2N0 breast cancer patients. And the estimate the cost effectivity of Oncotype DX in our low income scenary.

Materials and Methods:This retrospective cross-sectional study was conducted at the Oncology Division of the Women's Hospital - CAISM of the State University of Campinas (UNICAMP), Brazil. All patient data were found from the hospital records from 2007 to 2009. It was included T1N0 and T2N0 HR+/HER2 negative breast cancer patients. Patients submitted to neoadjuvant treatment were excluded.

We calculate the final cost of different types of chemotherapy used and the potential impact to oncotype DX introduction in this scenary.

Results: It was found 109 patients records. 66% (72/109) had received adjuvant chemotherapy. 35% (38/109) had AC (X6), 29% (32/109) had CMF (X6) and 2% (2/109) had AC-T (X4). The total cost for chemotherapy scheme were; AC (X6) US$ 346,9; CMF (X6), US$300,6; ACT (X4), US$395,9. The total cost of chemotherapy was US$ 23.596,83 to 72 patients. If we consider 14% (15/109) of adjuvant chemotherapy associate to a Oncotype DX use (Tailor X RS>25), It would reduce adjuvant chemotherapy administration to 15 patients. The chemotherapy cost would be US$ 4588,27. In our scenary, It could save US$ 19.008,56. Nevertheless, the Oncotype Dx cost to Brasil is US$ 3.200,00 for each test. To 109 patients the total cost would be (109 X US$ 3.200,00) US$ 348.800,00. Therefore, the total cost for Oncotype DX program plus adjuvant chemotherapy for our patients would be US$ 348.800,00 + US$ 4.588,27= US$ 353.388,27. While in the real situation we had spent US$ 23.596,83. The total estimate cost would be 15 times more.

Conclusion: At the moment, because of the assay high cost and the low cost of the adjuvant chemotherapy to HR+, HER2 negative T1N0 and T2N0, It would be difficult to consider Oncotype DX cost-effective to Brazilian public heath system. Even considering many advantages to spare chemotherapy to this population.

Citation Format: Cabello C, de Andrade RN, Cabello TF, Teixeira S, da Costa LS, Ramalho S. Oncotype DX cost effectivity to a Brazilian public hospital [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 P5-15-04.
Abstract P5-16-11: Intraoperative central nipple biopsy in subcutaneous mastectomies - A retrospective analysis of 200 patients
Authors: Eichler C , Stephan S , Thangarajah F , Puppe J , Mathias W
Published: May 2019

Background: Subcutaneous nipple sparing mastectomies (NSM) are an important tool in modern oncoplastic surgery. Especially when an immediate implant-based reconstruction (IBR) is desired, clean margins are of the utmost importance. Central nipple biopsies during surgery serve two main purposes. Most importantly, it is hypothesized that a general recurrence risk reduction occurs due to elimination of glandular and ductal components within the nipple. In addition, intraoperative pathological evaluation of this biopsy may increase clean margin resection rates. This trial aimed to evaluate complication rates, local recurrence and clean margin resection rates in a head-to-head retrospective manner.

Methods: Starting in 2015, intraoperative central nipple biopsy in NSM with IBR was introduced at the Municipal Breast Cancer Centre Cologne, Holweide, Germany. This trial evaluates global complication rates (necrosis, implant loss, seroma and hematoma), long term local recurrence and clean margin status for cohort 1 (n=100) SSM with nipple biopsy vs. cohort 2 (control, n = 100) without nipple biopsy. In case of an involved central nipple biopsy, the nipple areola complex was removed. This analysis is a single center, multi-surgeon, retrospective, head to head analysis. Median follow-up is three years. All IBR procedures used an epipectoral implant pocket.

Results: Global complication rates did not differ significantly between both cohorts. There was no increased rate of implant loss and or revision surgery. Within the medium three-year follow-up there was no case of local recurrence within nipple areola complex for both cohorts. An Involved central nipple biopsy was however found in 2% (n=2 /100) of the performed SSM procedures leading to the immediate removal of the nipple areola complex. Surgical time did not increase with central biopsy. A significantly higher rate of re-surgery due to involved margins was shown in the control cohort.

Conclusions: This analysis showed that intraoperative evaluation of the ductal components of the nipple is a safe procedure. At least 2% of the patients showed an immediate advantage of this procedure since clean margins were obtained by removing the nipple areola complex during the same surgery. The medium follow-up showed no significant difference in local recurrence. We therefore strongly, recommend a central nipple biopsy for all NSM procedures.

Citation Format: Eichler C, Stephan S, Thangarajah F, Puppe J, Mathias W. Intraoperative central nipple biopsy in subcutaneous mastectomies - A retrospective analysis of 200 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 P5-16-11.
Abstract P5-16-13: First results of the NOGGO-AWOGyn observational study: Skin and nipple sparing mastectomy and breast reconstruction with an implant and Epiflex®
Authors: Blohmer J-U , Ankel C , Faridi A , Krause-Bergmann B , Neumann C , Schnuppe K , Beier L , Mau C , Strittmatter H-J , Gerber-Schäfer C , Bauer L , Paepke S
Published: May 2019

Acellular dermal matrices (ADM) were used to cover the implant to reduce implant rotations and to improve esthetic results. Current retrospective data on complication rates are heterogeneous. Prospective data are rare. Primary objective was to evaluate the explantation rate.

11 German sites, with experience in breast reconstruction using ADM, have been selected for participation in this study. Patients were enrolled according to predefined in- and exclusion criteria into two cohorts: group A - primary reconstruction and group B - secondary reconstruction after capsular contracture.

After documentation of baseline characteristics and surgical parameters, endpoints such as rate of seroma, red breast syndrome, infection and explantation were assed at 1 day, 7 days, 1 month, 3, 6 and 12 months after surgery. In addition, patient- and surgeon-satisfaction were recorded.

Data of 83 patients were analyzed (A: 50, B: 33). In 29 patients Epiflex was used bilaterally, so that it was used 112-times in total. The average age of the patient was 45.1 years (A: 41.5; B: 50.3), the average BMI was 22.2 (A: 22.3; B: 22.1).

In total, 17.0 % seromas (A: 19.4 %; B: 12.5 %), 10.7 % red breast syndrome (A: 9.7 %; B: 12.5 %), 4.5 % infections (A: 6.9 %; B: 0 %) and 5.4 % explantations (A: 6.9 %; B: 2.5 %) were observed.

During the average observation period of 8 month, the satisfaction of the patients and surgeons was high at all measured time points. On a scale from (1 - very satisfied to 6 - not satisfied) the satisfaction of patients and surgeons was 2.3 (A: 2.3; B:1.9) and 2.0 (A: 2.2; B: 1.8) respectively.

Our data show, that both patients and surgeons are generally satisfied with the outcome of breast reconstruction using ADM. Complication rates were adequate and commonly lower in secondary reconstructions.

Citation Format: Blohmer J-U, Ankel C, Faridi A, Krause-Bergmann B, Neumann C, Schnuppe K, Beier L, Mau C, Strittmatter H-J, Gerber-Schäfer C, Bauer L, Paepke S. First results of the NOGGO-AWOGyn observational study: Skin and nipple sparing mastectomy and breast reconstruction with an implant and Epiflex® [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 P5-16-13.
Abstract P5-16-16: Reconstructive breast surgery with partially absorbable bi-component Seragyn® BR soft mesh: An outcome analysis
Authors: Machleidt A , Schmidt-Feuerheerd N , Blohmer J-U , Ohlinger R , Küper J , von Waldenfels G , Dittmer S , Paepke S , Klein E
Published: May 2019

Objective:

Synthetic meshes and acellular dermal matrices are increasingly used in implant based breast reconstruction. The objective of this study was to determine the incidence and severity of complications following the implantation of the partially absorbable bi-component soft mesh SERAGYN ® BR and assess risk factors for adverse operative outcomes.

Methods:

A retrospective clinical study was performed: The SERAGYN ® BR soft mesh was utilized in 148 operations (skin-sparing mastectomy, nipple-sparing mastectomy, breast conserving surgery, secondary reconstruction after mastectomy) in four different institutions in Germany from

June 2012 to February 2014. We analyzed whether the results were affected by tumor morphology (e.g. grading), patient characteristics and co-morbidities, previous surgery or therapies and use of alloplastic materials.

Results:

The SERAGYN ® BR soft mesh was successfully implanted in 131 of 148 operations. The rate of reconstructive failure was 11.5 %. The most common complication was seroma (25.7 %), followed by hematoma and skin infection (each 14.2%). Wound healing issues were detected in

13.5% cases, secondary wound infections in 10.8%. 83.8% of operations had no severe complications. Independent predictors for reconstructive failure were wound healing issues, nipple- or skin necrosis, wound- or skin infections, a high volume of excised tissue, hematomas, seromas and sentinel lymph node excisions. A higher body mass index was correlated with a higher

rate of infection.

Conclusion:

SERAGYN ® BR mesh can be used successfully in breast reconstructive surgery. Rates of major complications or reconstructive failure are comparable to the use of other synthetic or biological meshes.

Citation Format: Machleidt A, Schmidt-Feuerheerd N, Blohmer J-U, Ohlinger R, Küper J, von Waldenfels G, Dittmer S, Paepke S, Klein E. Reconstructive breast surgery with partially absorbable bi-component Seragyn® BR soft mesh: An outcome analysis [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 P5-16-16.
Abstract P5-16-17: Titanium-coated polypropylene mesh for immediate implant-based breast reconstruction – Our initial experience
Authors: Munir A , Holt S , Huws A , Khan S , Shariaha Y , Khawaja S
Published: May 2019

Background: The use of titanium-coated polypropylene mesh (TCPM) is an alternative to a-cellular dermal matrix for the implant based breast reconstruction by providing extra implant coverage especially in the lower half. The aim of our study was to analyze short-term outcomes of TCPM based implant breast reconstruction and compare the patient- and procedure-related factors to implant loss and surgical complications.

Methods: Between 2013and 2016, implant breast reconstructions after conservative mastectomies using TCMP was performed in 50 patients (with 58 reconstructions). Complications were divided into major (need for additional surgery), minor (conservative treatment), and implant loss. Univariate analyses were performed to determine the influence of the patient- and procedure-related factors on postoperative complications and implant loss.

Results: Fifty patients had therapeutic mastectomies with 8 of them also had contra lateral risk reducing mastectomies. With median follow-up of 17.5 months, four of 50 patients had implant loss. Reasons for implant loss were skin necrosis in 2 cases, infection in 1 case and necrosis with infection in another case. One of these patients had a revised reconstruction one year later. One additional patient required implant replacement because of capsule contracture. No risk factors were observed for patient-associated complications. Univariate analysis revealed an increased risk for implant loss in patients with skin necrosis (p < 0.01).

Conclusions: This titanium-coated polypropylene mesh shows acceptable complication rates and its use in immediate implant breast reconstruction is safe and effective.

Citation Format: Munir A, Holt S, Huws A, Khan S, Shariaha Y, Khawaja S. Titanium-coated polypropylene mesh for immediate implant-based breast reconstruction – Our initial experience [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 P5-16-17.
Abstract P5-16-18: Oncologic outcomes and reconstruction quality of immediate autologous breast reconstruction in intermediate and locally advanced breast cancer
Authors: Yoon WS , Yang DS , Son GS , Woo SU , Kim D-W , Dhong E-S , Chang YW
Published: May 2019

Purpose: We analyzed oncologic outcomes and reconstruction quality in locally advanced stage breast cancer after performing immediate autologous breast reconstruction (IABR).

Methods: From 2007 to 2014, data of patients with stage II-III breast cancer of ≤ 70-years-old who received total mastectomy (TM) from two institutions were extracted. Exclusion criteria were: previous contralateral breast cancer, follow-up loss before adjuvant therapy completion, and artificial reconstruction. Patients were divided into two groups; 1) TM alone and 2) TM+IABR. Overall survival (OS) and loco-regional recurrence free survival (LRRFS) were calculated and minor revision, abnormal volume on CT, and breast height change were observed.

Results: Sixty-one of 188 patients received IABR after TM. Neoadjuvant chemotherapy and postoperative radiotherapy was done in 27 and 80 patients, respectively. Fifty-nine percent, 19.2%, and 21.8% of patients were in stage II, IIIA, and IIIB-C, respectively. Stage IIIB-C was the most important prognostic factor for OS and LRRFS. In a median of 56.8 follow-up months, 5-year TM and TM+IABR OS rate were 96.8% and 100% for stage II (P=0.324) and 57.6%, 95.5% and 91.7% for stage IIIA (P=0.698), and 62.5% for stage IIIB-C (P=0.544), respectively. Five-year TM and TM+IABR LRRFS were 98.1% and 95.7% for stage II (P=0.998)91.1% and 100% for stage IIIA (P=0.277), and 70.8% and 62.5% for stage IIIB-C (P=0.378), respectively. However, two locoregional failures after 5-years were developed in stage IIIB-C of TM+IABR at 71 and 94 months. Minor revisions 3 months of IABR, including two major complications, were done in 49.2%. The reduction of breast height was 21.2% (11/52) and 31.9% (15/47) in about 18 months and about 42 months observations after IABR, respectively. The volume of abnormal imaging was over 10 cc in 27.3% (15/55) on CT of 6 months after IABR. Although minor revisions, abnormal volume on CT, and breast height change were common, they were not related to therapeutic methods, including radiotherapy and tumor stage.

Conclusions: In about 5-years follow-up, IABR did not aggravate oncologic outcomes, and adjuvant radiotherapy was not closely related with quality of reconstruction. It must be considered, however, that absolute oncologic outcomes of advanced stage were not sufficient, and minor problems post-IABR were commonly developed.

Citation Format: Yoon WS, Yang DS, Son GS, Woo SU, Kim D-W, Dhong E-S, Chang YW. Oncologic outcomes and reconstruction quality of immediate autologous breast reconstruction in intermediate and locally advanced 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 P5-16-18.
Abstract P6-01-01: Immunohistochemical staining and in vitro analysis of HER2-positive breast cancer using trastuzumab and pertuzumab to develop an appropriate tracer in image-guided surgery
Authors: Otsubo R , Kuppen PJ , Bhairosingh S , Vahrmeijer AL , Smit VT , Nagayasu T , van de Velde CJ , Sier CF
Published: May 2019

Background: Pre- and intraoperative visualization of cancer cells using monoclonal antibody-based multimodal tracers can demarcate tumor margins in breast-conserving surgery. We focused on trastuzumab (Tmab) to develop a tracer for HER2-positive breast cancer by conjugation with a fluorescent dye. However, whether Tmab can be used as an imaging tracer for patients who receive Tmab as neoadjuvant therapy (NAD) is unclear, because tumor-cell HER2 could be bound by NAD Tmab at the time of surgery. This study evaluated immunohistochemical (IHC) staining and in vitro experiments with Tmab and pertuzumab (Pmab) as primary antibodies to find a suitable tracer. Pmab has a different antigen epitope than Tmab.

Methods: We included 43 patients with HER2-positive breast cancer, who were treated between 2010 and 2016. The NAD cohort (n=10, with 26 lesions) received chemotherapy and Tmab before surgery. The Tmab-naïve cohort (n=33, with 95 lesions) did not receive chemotherapy or Tmab before surgery. We excluded NAD patients with pathological complete responses. We evaluated the lesions, using IHC with Tmab and Pmab. We also performed flow cytometry and fluorescent microscopic analysis (FMA) using Tmab and Pmab conjugated with a fluorescent agent for the HER2-negative MCF7 and HER2-positive HCC1954 cell lines, which were pre-treated with Tmab to model NAD conditions.

Results: IHC with anti-HER2 antibody showed positive staining in all patients. Tmab staining was less intense, but positive Tmab IHC reactions were detected on tumor cell membranes in 77.8% of lesions in the naïve cohort and 70.8% in the NAD cohort. Pmab staining was seen in 46.3% of naïve cohort lesions and 22.2% of NAD lesions. Notably, we observed cytoplasmic staining in 87.8% of Pmab-negative cases in the NAD cohort. Flow cytometry showed less Tmab binding than Pmab binding in HCC1954 cells. After 24 hours' pretreatment incubation with Tmab, FMA showed a clear decrease in Tmab binding from 73.3% (without pretreatment) to 5.7%(after pretreatment), and a smaller decrease in Pmab binding from 72.7% (without pretreatment) to 66.4% (after pretreatment) in HCC1954 cells.

Conclusions:Pmab might be a suitable tracer for image-guided surgery after NAD, but identifying a suitable tracer for HER2-positive breast cancer will require further study.

Citation Format: Otsubo R, Kuppen PJ, Bhairosingh S, Vahrmeijer AL, Smit VT, Nagayasu T, van de Velde CJ, Sier CF. Immunohistochemical staining and in vitro analysis of HER2-positive breast cancer using trastuzumab and pertuzumab to develop an appropriate tracer in image-guided surgery [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 P6-01-01.
Abstract P6-02-03: Interpretation schema for optical coherence tomography images in breast tissue
Authors: Yemul KS , Zysk AM , Richardson AL , Tangella KV , Jacobs LK
Published: May 2019

Purpose

Optical coherence tomography (OCT) is an attractive technology for surgical imaging because it permits the real-time visualization of microscopic tissue morphology with a handheld probe without the need for exogeneous agents, tissue manipulation, ionizing radiation, or histological processing. While initial studies have shown that OCT is an effective margin-evaluation tool for breast conserving surgery (BCS), image interpretation and feature identification have not been directly studied. In this work, breast pathologies were assessed with a handheld OCT probe and the images were compared to histology.

Methods

Mastectomy and BCS specimens from 26 women were imaged with a handheld OCT probe, and histology slides from the same region were digitally photographed. OCT and histology images from the same region were paired by selecting the best structural matches. Because image characteristics in OCT are akin to those in ultrasound, descriptive OCT image feature terminology similar to that of ultrasound was developed. Each of these characteristics was used to select and describe OCT-histology image matches.

Results

In total, 2880 OCT images were acquired from 26 breast specimens, and 48 matching OCT-histology image pairs were identified. These matched image pairs illustrate tissue types including adipose tissue, dense fibrosis, fibroadipose tissue, blood vessels, regular and hyperplastic ducts and lobules, cysts, fibroadenoma, IDC, ILC, DCIS, calcifications, and biopsy cavities. Differentiation between pathologies was achieved by considering feature boundaries, interior appearance, posterior shadowing or enhancement, and overall morphologic patterns.

Conclusions

This is the first work to systematically catalog the features of breast OCT images. The results indicate that OCT can be used to identify important structures and distinguish between benign and malignant breast pathologies.

Citation Format: Yemul KS, Zysk AM, Richardson AL, Tangella KV, Jacobs LK. Interpretation schema for optical coherence tomography images in breast tissue [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 P6-02-03.
Abstract P6-02-13: Withdrawn
Authors: Huang C-S , Fann JC-Y , Chen H-H , Hsu G-C , Ho M-F , Chen S-C , Chen Y-J , Chen S-T , Chen C-Y , Sheen-Chen S-M , Chang H-T , Yeh D-C , Chao M , Yeh H-T , Cheng L , Chen D-R , Chang Y-C , Chang K-J
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Huang C-S, Fann JC-Y, Chen H-H, Hsu G-C, Ho M-F, Chen S-C, Chen Y-J, Chen S-T, Chen C-Y, Sheen-Chen S-M, Chang H-T, Yeh D-C, Chao M, Yeh H-T, Cheng L, Chen D-R, Chang Y-C, Chang K-J. 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 P6-02-13.
Abstract P6-02-17: Hand-held impulse-radar detector for breast cancer: development and a pilot study
Authors: Sasada S , Masumoto N , Song H , Goda N , Kajitani K , Emi A , Kadoya T , Arihiro K , Kikkawa T , Okada M
Published: May 2019

Background: Microwave breast imaging, which using the difference in the dielectric properties between breast cancer and normal breast tissue, is a painless and non-radiation method. We have created a novel hand-held prototype of breast cancer detector using impulse-radar based imaging system, and conducted a pilot clinical study.

Methods: The detector consists of complementary metal-oxide-semiconductor (CMOS) integrated circuits covering the ultrawideband width from 3.1 to 10.6 GHz, which enable the generation and transmission of Gaussian monocycle pulse (GMP) trains and single port eight throw switching matrices (SP8T-SW) for controlling a 4×4 cross-shaped dome antenna array. The size of the detector was 19.1 × 17.7 × 18.8 cm. After evaluation using a breast tumor phantom and the resected breast specimens obtained through mastectomy, we recruited 5 patients with histologically confirmed breast cancers in the clinical study. The detector was placed on the breast with the patient in a supine position. The primary endpoint was a detection rate of breast cancers, and the secondary endpoints were positional accuracy and adverse event. This study was registered with the UMIN Clinical Trials Registry (UMIN000026181).

Results: The three-dimensional positions of the tumors in the imaging results using a phantom and resected specimens are consistent with the results of histopathology analysis. In the clinical study, all 5 targeted breast cancers were detected and were visualized at the sites confirmed by other diagnostic modalities. Among 5 tumors, one was not detected via mammography because of heterogeneously dense breast and another was a microinvasive carcinoma of invasive tumor size 0.5 mm. No study-related adverse events occurred.

Conclusions: We succeeded in creating a new device of hand-held impulse-radar detector for breast cancer. The detector has sufficient detective capability, is safe for clinical use, and might detect an early stage breast cancer. In the future, we will proceed with the development to clinical application.

Citation Format: Sasada S, Masumoto N, Song H, Goda N, Kajitani K, Emi A, Kadoya T, Arihiro K, Kikkawa T, Okada M. Hand-held impulse-radar detector for breast cancer: development and a pilot 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 P6-02-17.
Abstract P6-03-03: Withdrawn
Authors: Penzvalto Z , Chen JQ , Cardiff RD , Willis B , Hubbard NE , Piersigilli A , Borowsky AD
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Penzvalto Z, Chen JQ, Cardiff RD, Willis B, Hubbard NE, Piersigilli A, Borowsky AD. 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 P6-03-03.
Abstract P6-03-05: Not presented
Authors: Guangping L , Wei L , Xiang H , Shidai J , Dengshun M , Ziyi F , Jinhai T , Yongmei Y
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Guangping L, Wei L, Xiang H, Shidai J, Dengshun M, Ziyi F, Jinhai T, Yongmei Y. 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 P6-03-05.
Abstract P6-05-04: NEAT1 enhances drug sensitivity by inhibiting cancer stem-like cells in triple-negative breast cancer
Authors: Kwong A , Chen J , Siu J , Chuek I , Shin V
Published: May 2019

Background: Accumulating evidence showed that long non-coding RNAs (lncRNAs) dysregulation is the hallmark of cancer. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to overexpress in many cancers, and promote cell growth and disease progression. However, the role of NEAT1 on drug sensitivity and stem-cell like property in triple-negative breast cancer is largely unknown.

Methods: LncRNA expression profile were compared between breast cancer patients and healthy individuals using lncRNA array. Large scale validation of NEAT1 expression in blood samples were performed by real-time PCR. Triple-negative breast cancer (TNBC) cells, MDA-MB-231 and its cisplatin resistance subline (MDA-MB-231/cis) were used. Stable transfection of cells with NEAT1 knockdown by shRNA, and evaluated single cell clonogenic assay, aldehyde dehydrogenase (ALDH) activity, CD44+/CD24- and other cancer stem cell (CSC) markers. Drug sensitivity assay, flow cytometry analysis, immunofluorescence staining and xenograft model were used to assess the functional role of NEAT1.

Results: Array data showed that NEAT1 was the top upregulated lncRNAs in the plasma of breast cancer patients. Consistent with the array data, validation of larger cohort of patients and healthy individuals (n=369) also demonstrated a higher expression of NEAT1 in breast cancer patients, in particular TNBC subtype. Knockdown of NEAT1 by shRNA sensitized breast cancer cells to cisplatin and taxol treatment. Cell proliferation and colony formation abilities were reduced with S-phase cell cycle arrest in shNEAT1 cells. Flow cytometry analysis revealed an induction of apoptosis with increased cleaved caspase-3. Cells expressing shNEAT1 abrogated ALDH activity, CD44+/CD24- subpopulation and expression of CSC markers (SOX2, NANOG and OCT4). More importantly, shNEAT1 cells retarded tumor growth in xenograft mice model and reduced CSC markers.

Conclusion: Taken together, NEAT1 expression is differentially expressed in breast cancer patients, and particularly higher in patients with TNBC. These findings suggest a potent therapeutic target to improve drug sensitivity in patients with TNBC.

Citation Format: Kwong A, Chen J, Siu J, Chuek I, Shin V. NEAT1 enhances drug sensitivity by inhibiting cancer stem-like cells in triple-negative 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 P6-05-04.
Abstract P6-05-09: Exosome microRNA contents are altered during breast cancer progression
Authors: Hannafon BN , Gin AL , Behbod F , Ding W-Q
Published: May 2019

Background: The progression of breast cancer involves the transformation of normal mammary epithelial cells to ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). This process is initiated by genetic alterations and characterized by changes to gene expression programs and microenvironmental alterations. However, the specific drivers of DCIS progression to IBC are not well understood nor has an indicator of progression been identified. Exosomes are small secretory vesicles that can contribute to cancer progression by transferring oncogenic factors, such as microRNAs (miRNAs), to surrounding cells in the tumor microenvironment, and enter the circulation to act at distant sites. miRNAs are short noncoding RNAs that regulate the expression of a target messenger RNA (mRNA). Altered regulation by miRNAs is implicated in cancer progression. In this study, we sought to characterize the exosome miRNAs in the MCF10 isogenic model of breast cancer progression in order to identify potential drivers of breast cancer.

Methods: Exosomes were isolated from the conditioned media of the MCF10 isogenic cell line model of breast cancer progression representing the following stages: normal, benign proliferative, carcinoma in situ, and invasive carcinoma. RNA was extracted from the exosomes and next generation RNA sequencing was performed. Exosome miRNA expression was validated in breast cancer cell lines and in plasma exosomes collected from a mouse-intraductal transplantation (MIND) model implanted with MCF10DCIS.com (DCIS) cells that can mimic human DCIS progression in vivo.

Results: Comparisons were made between differentially expressed miRNAs among each condition (fold change >1.5; Kruskal-Wallis p<0.05,). Twenty-nine miRNAs were differentially expressed among invasive and DCIS exosomes. The expression of 5 oncogenic miRNAs (miR-30c-5p, -210, -182-5p, -200c-3p, and -200b-3p) were consistently increased, while 2 tumor suppressive miRNAs (miR-423-5p and -92b-3p) were consistently decreased with invasive progression. Exosome miRNA expression was confirmed in breast cancer cell lines and mouse plasma exosomes.

Conclusion: This work demonstrates that the microRNA contents of exosomes change upon malignant transformation to invasive breast cancer and indicate that certain exosome microRNAs are consistently up- or down-regulated and may contribute to breast cancer progression.

Citation Format: Hannafon BN, Gin AL, Behbod F, Ding W-Q. Exosome microRNA contents are altered during breast cancer 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 P6-05-09.
Abstract P6-08-01: Not presented
Authors: Guimarães I , Gimba E , Castelo-Branco M , Sternberg C , Silva I , Rangel L
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Guimarães I, Gimba E, Castelo-Branco M, Sternberg C, Silva I, Rangel L. 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 P6-08-01.
Abstract P6-09-03: Association of Caspase 8 polymorphisms with TILs and disease-free survival in primary breast cancer patients
Authors: Wimberger P , Bachmann HS , Kuhlmann JD , Link T , Kröber E , Thomssen C , Malle B , Vetter M , Kantelhardt EJ
Published: May 2019

BACKGROUND: The minor allele of two caspase-8 polymorphisms, namely CASP8 -652 6N InsDel and CASP8 Asp302His, were shown to promote survival of T-lymphocytes and were repeatedly associated with reduced breast cancer susceptibility. However, besides some preliminary findings, clinical relevance of these polymorphisms in patients with already existing primary breast cancer has not yet been established. Considering an immunomodulatory and potentially tumor-protective role of these caspase-8 variants, we genotyped 785 primary breast cancer patients and correlated caspase-8 variants with i) disease-free survival (DFS) and ii) the presence of tumor infiltrating lymphocytes (TILs).

METHODS: Primary breast cancer samples were collected at the Martin-Luther University, Halle-Wittenberg between 2009 and 2011 as part of the multicenter prospective PiA trial (NCT 01592825). The majority of patients had luminal-like tumors (75.9%), followed by triple negative (10.1%), luminal-Her2-like (9.6%) and Her2-enriched tumors (4.5%). Genotyping was performed by pyrosequencing, TILs status was assessed by hematoxylin and eosin staining.

RESULTS: The CASP8 -652 deletion was significantly associated with improved DFS in an allele-dose dependent manner (p=0.027). Homozygosity for the -652 6N Del variant was an independent predictor for improved DFS (p=0.005). In patients with a 302His/His genotype, there was no event of recurrence during the entire observation time. Combined analysis of diplotypes revealed that both polymorphisms had an influence on DFS (p=0.029). Interestingly, patients with the 302His/His variant among the unstratified patient cohort and among the luminal-like subtype alone had tumors with very low lymphocyte infiltration (0-10% TILs in 65% of cases compared to 31% of cases for other genotypes, p=0.025).

CONCLUSION: In line with previous epidemiological findings, we propose a prognostically favorable role of the CASP8 -652 6N Del and the Asp302His variant in primary breast cancer patients. Moreover, we suggest for the first time a role of the Asp302His variant in immunosurveillance and lymphocyte infiltration of breast cancer. Our findings strongly encourage further analyze of these genetic variants as a biomarker for prognostic and immunotherapeutic considerations.

Citation Format: Wimberger P, Bachmann HS, Kuhlmann JD, Link T, Kröber E, Thomssen C, Malle B, Vetter M, Kantelhardt EJ. Association of Caspase 8 polymorphisms with TILs and disease-free survival in primary 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 P6-09-03.