bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P1-03-10: Establishment and characterization of paired palbociclib-sensitive and resistant luminal A breast PDX models
Authors: Gamez Lizette , Moriarty Alyssa , Mashimo Tomoyuki , Papadopoulos Kyriakos , Rasco Drew , Patnaik Amita , Wick Michael J
Published: March 2020

Background: Palbociclib is one of three CDK 4/6 inhibitors approved in combination with an aromatase inhibitor for treatment of hormone receptor-positive breast cancer. Although this combination therapy has been found effective in some patients, resistance often develops. To aid in developing new therapies for CDK4/6-resistant breast cancer and better understand resistance mechanisms, we established a PDX model, designated ST1799, from a patient with luminal A breast cancer which was responsive to palbociclib in vivo and then conditioned the model with chronic drug administration until resistant. The resistant model, designated ST1799/PBR, and the parent were characterized for receptor expression, genomic alterations and in vivo drug sensitivity. Methods: ST1799 was established from an axillary lymph node FNA taken from a 66-year-old woman pretreated with various chemo and hormone therapies. The resulting model was passaged and a cohort challenged with chronic palbociclib treatment to produce drug resistance. The parent ST1799 and resistant ST1799/PBR were subjected to various comparative analyses including receptor expression, NGS and RNAseq and response to various relevant therapies. Results: Both models retained high ER staining (3+) expression and demonstrated comparable histopathology. DNA-based analysis of the parent model confirmed variants concordant with clinical mutation analysis. Comparison of the parent and resistant clone using RNAseq identified several alterations in variants and expression. In vivo palbociclib reported significant (p<0.0001) activity towards ST1799 (T/C=11%) while ST1799/PBR was resistant towards the therapy (T/C=80%). Tamoxifen or fulvestrant treatment of ST1799 resulted in partial tumor regressions while activity in ST1799/PBR was less pronounced. Activity of abemaciclib or ribociclib was greater in ST1799/PBR compared with palbociclib treatment. Conclusion: We have established and characterized paired palbociclib-sensitive and resistant breast PDX models which can be utilized as valuable tools in better understanding CDK4/6i resistance and in developing new therapies for CDK4/6 inhibitor resistant patients.

Citation Format: Lizette Gamez, Alyssa Moriarty, Tomoyuki Mashimo, Kyriakos Papadopoulos, Drew Rasco, Amita Patnaik, Michael J Wick. Establishment and characterization of paired palbociclib-sensitive and resistant luminal A breast PDX models [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-03-10.
Abstract P1-04-01: Breast cancer patient derived scaffolds as a platform for studying cancer promoting properties of the microenvironment
Authors: Garre Elena , Gustafsson Anna , del Carmen Leiva-Arrabal Maria , Fitzpatrick Paul , Gregersson Pernilla , Ståhlberg Anders , Landberg Göran
Published: March 2020

Despite great efficiencies of today’s anti-cancer therapies in breast cancer medicine, recurrences and metastasis still remains a major challenge. The tumor initiating population of cancer stem cells (CSC) is believed to promote metastasis and drug resistance, suggesting that selectively targeting CSC and their niche may be a potential beneficial therapeutic strategy. However, specific driving factors in the microenvironment influencing the CSC niche remains unknown. To study the influence of specific cancer microenvironments, we have developed a novel three-dimensional cell culture platform, using cell-free patient derived scaffolds (PDS) from decellularized breast cancer tumors. We confirmed that our novel patient derived scaffold (PDS) recapitulates the native microenvironment where the cancer cells originate and, retains their biological properties. Our data demonstrate that culturing breast cancer cell lines in PDSs promotes CSC and EMT-like properties and decreases proliferation, similarly to in vivo conditions. Additionally, global gene expression profiling revealed that PDS cultures exhibit transcriptional patterns more similar to patient derived xenografts than to traditional monolayer cultures. Moreover, we analyzed the expression of cells cultured in 108 PDSs made from breast cancer tumors with clinical follow-up data, using a gene panel representative of relevant breast cancer related processes. This revealed that expression changes of several EMT markers and other CSC related genes in the PDS cultured cancer cells were correlated to clinical parameters such as grade, lymph node metastasis, patient survival and disease recurrences. Altogether, our data shows that PDS can reveal unique additional information about the malignancy-inducing properties of specific tumor microenvironments, potentially provides a complementary diagnosis tool for breast cancer tumors in vitro, and is a promising platform for drug screening of anti-cancer therapies.

Citation Format: Elena Garre, Anna Gustafsson, Maria del Carmen Leiva-Arrabal, Paul Fitzpatrick, Pernilla Gregersson, Anders Ståhlberg, Göran Landberg. Breast cancer patient derived scaffolds as a platform for studying cancer promoting properties of the microenvironment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-04-01.
Abstract P1-04-02: Multicellular spheroids to dissect the interplay between human immune system and cancer
Authors: Ahmadzadeh Elaheh , Martinek Jan , Marches Florentina , Aucello Gabby , Yu Chun I , Palucka Karolina
Published: March 2020

The interaction between various components in the tumor environment plays a pivotal role in tumor development, migration and metastasis. While the 2-dimensional (2D) in vitro culture methods fail to assimilate the complexity of tumor microenvironment, the 3D multicellular tumor spheroids support co-culture conditions and allow a more physiologically relevant environment. We are working to establish such 3D model to investigate the molecular mechanisms regulating the interactions between human cancer cells such as melanoma or breast cancer, myeloid cells and T cells. Spheroids were developed using hanging drop technique with multiple cancer cell lines, dermal fibroblasts and immune cells. Preliminary experiments were carried out to determine the optimum conditions for spheroid formation. Spheroid formation occurred within 72 hours and their integrity was maintained throughout the experiments. Immunofluorescence analysis of spheroid cryosections showed a homogeneous distribution of fibroblasts in spheroids. Addition of purified blood CD14+ blood monocytes to the mixture of cancer cells and dermal fibroblasts enabled monocyte integration into spheroids. Adding melanoma specific CD8+ T cells to tumor spheroids formed by melanoma cell line (Me275), dermal fibroblasts and monocytes resulted in homogeneous infiltration and increased number of cell death. Addition of PBMCs to the mix of breast cancer cells and fibroblasts enabled the discrimination of spheroids into two groups, tumor spheroids with immune cells at the margin preferentially located at tumor margin and tumor spheroids with infiltrating immune cells. These preliminary observations resemble those from our in vivo models of humanized mice, where different tumor xenografts show different level of immune cell infiltration. Thus, our 3D model might allow the classification of tumor cells based on immune cell infiltration and could potentially be used to assess the distribution of immune infiltrates and the interaction of cancer cells with immune compartments.

Citation Format: Elaheh Ahmadzadeh, Jan Martinek, Florentina Marches, Gabby Aucello, Chun I Yu, Karolina Palucka. Multicellular spheroids to dissect the interplay between human immune system and cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-04-02.
Abstract P1-05-04: miR551b-3p promotes Oncostatin M signaling in breast cancer
Authors: Geethadevi Anjali , Parashar Deepak , Aure Miriam Ragle , George Jasmine , Chen Changliang , Mishra Jyotsna , Tahiri Andliena , Nair Bindu , Camara Amadou , Kristensen Vessela N , Pradeep Sunila , Raghavan Pradeep Chaluvally
Published: March 2020

An increased expression of oncogenic microRNA miR551b-3p (also known as miR551b) occurs in a subset of breast cancer due to genomic amplification of 3q26.2 locus. Using in silico and clinical sample analysis of breast cancer patient datasets, we identified that those breast cancer samples that encompass miR551b amplification express high levels of STAT3 mRNA and Oncostatin (OSM) family genes in triple-negative breast cancer (TNBC). Furthermore, high expression of Oncostatin family genes associates with poor outcome in estrogen receptor- negative breast cancer patients. In this study, we identified a previously unexplored mechanism that miR551b-3p promotes breast cancer progression and tumor growth by direct interaction of miR551b-3p with STAT3 promoter thereby activating STAT3 transcription. As a consequence, STAT3 upregulates a cytokine Oncostatin and its receptor Oncostatin M receptor (OSMR) and their interaction further induces STAT3 phosphorylation and an autocrine self-reinforcing loop in TNBC cells. In this study, we demonstrate that overexpression of miR551b-3p promoted proliferation, invasion and migration, epithelial to mesenchymal transition (EMT) and spheroid formation of breast cancer cells and its inhibition decreased the expression of miR551b-3p by inhibiting OSM, OSMR, IL6ST, IL31RA, phosphorylated and total STAT3 in breast cancer cells and reduced tumor cell growth. Overall, our results provide the first evidence that miR551b regulates OSM family gene expression by activating STAT3 and thereby promoting tumor cell growth and metastasis in breast cancer cells. Therefore, targeting miR-551b-3p-STAT3-OSMR axis and inhibiting their levels will provide an unprecedented therapeutic opportunity in breast cancer.

Citation Format: Anjali Geethadevi, Deepak Parashar, Miriam Ragle Aure, Jasmine George, Changliang Chen, Jyotsna Mishra, Andliena Tahiri, Bindu Nair, Amadou Camara, Vessela N Kristensen, Sunila Pradeep, Pradeep Chaluvally Raghavan. miR551b-3p promotes Oncostatin M signaling in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-04.
Abstract P1-05-06: Functional characterization of lncRNA152 in ER+ and triple-negative breast cancers
Authors: Kim Daeseok
Published: March 2020

Genomic analyses have revealed that many RNA species other than protein-coding mRNAs are transcribed from mammalian genomes and may have profound effects on cellular physiology and pathology. One such class of RNAs are the long noncoding RNAs (lncRNAs). In our previous work using Global Run-On and sequencing (GRO-seq), we identified and annotated ~1,900 lncRNAs in MCF-7 human breast cancer cells, which are differentially expressed across the distinct molecular subtypes of breast cancer. Further meta-analysis identified lncRNA152 as a predictor of increased metastasis-free survival. Thus, lncRNA152 levels may serve as a biomarker to track disease progression in breast cancer patients. However, the precise mechanisms by which lncRNA152 regulates these clinical outcomes remain largely unknown. Interestingly, lncRNA152 is highly expressed in the luminal subtypes of breast cancer, but downregulated in triple-negative breast cancers (TNBC), suggesting that lncRNA152 expression may be associated with more aggressive cancer features. Through multiple complementary experimental approaches, we found that (1) FoxA1 regulates lncRNA152 transcription, (2) knockdown of lncRNA152 inhibits the growth, but promotes cell migration and invasion, of luminal breast cancer cell subtypes, and (3) ectopic overexpression of lncRNA152 inhibits TNBC cell growth, migration, and invasion. Importantly, our xenograft studies provide evidence that lncRNA152 inhibits estrogen-dependent tumor growth of luminal and TNBC cells. In addition, transcriptome analysis of TNBC cell-derived xenografts indicates that lncRNA152 expression downregulates many genes that are involved in biological processes such as cell growth, migration, invasion, and angiogenesis. Collectively, these results suggest that lncRNA152 is a novel tumor suppressor in luminal and basal subtype of breast cancer.

This work is supported by grants from the Cancer Prevention and Research Institute of Texas (CPRIT RP160318/RP190235) to W.L.K.

Citation Format: Daeseok Kim. Functional characterization of lncRNA152 in ER+ and triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-06.
Abstract P1-05-11: Breaking “vicious cycle”? The role of miR-223 in breast cancer metastasis to bone
Authors: Shan Zhen , Li Wen , Lin Ying , Zeng Huijuan , Qi Yunling , Lin Zefei , Fan Yuanjian
Published: March 2020

The “seed and soil” theory of metastasis was proposed by Stephen Paget in 1889. The theory suggests that bone acts as a fertile environment (soil) for cancer cells (seeds) colonization and growth. The theory successfully explains how bone and breast cancer cells interact to support breast cancer cell growth within the bone microenvironment.Breast cancer cells that metastasize to bone secrete growth factors and cytokines into the bone microenvironment that promote the production of receptor activator nuclear factor κ β ligand (RANKL), which, in turn, leads to osteoclast formation. The osteoclasts then cause bone resorption and the subsequent release of growth factors, include transforming growth factor-beta (TGF-β), bone morphogenetic proteins (BMPs), insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), and platelet-derived growth factors (PDGF) into the bone microenvironment, which further stimulate the growth of breast cancer cells. Growth factors and cytokines produced by both breast cancer cells and bone cells result in a “vicious cycle” of bone breakdown: factors released from the bone promote breast cancer cell proliferation, which leads to more bone loss, and the subsequent release of more growth factors from the bone. The concept of the “vicious cycle” was proposed in 1997 by Mundy and Guise. Currently, the “vicious cycle” model provides the best description of our understanding of the interaction between breast cancer and bone. We found in miR-223 knockout mice, the bone volume of lowe limb bones is significantly lower than C57BL/6 mice (wild type), the osteoclastic resorption is more severe in miR-223 knockout mice according to H&E sections. Then, we hypothesized miR-223 may inhibit osteoclast formation. In vitro study, We found miR-223 can suppress RANKL activating osteocalst formation by targeting NF1A protein. These results indicated miR-223 may disturb the establishment of osteolytic lesion, which may destroy the “soil” in bone microenvironment. Besides, we also found in miR-223 knockout mice, the IGF-1R is over expressed and the PI3K-Akt pathway was excessively activated. miR-223 up-regulation can inhibit MDA-231 cell proliferation but enhance apoptosis, which may destroy the “seed” in bone microenvironment. In conclusion, we hypothesized that miR-223 may break the “vicious cycle” and suppress breast cancer metastasis to bone.

Citation Format: Zhen Shan, Wen Li, Ying Lin, Huijuan Zeng, Yunling Qi, Zefei Lin, Yuanjian Fan. Breaking “vicious cycle”? The role of miR-223 in breast cancer metastasis to bone [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-11.
Abstract P1-10-21: PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers
Authors: Harada Yurina , Kubo Makoto , Mori Hitomi , Kai Masaya , Yamada Mai , Kurata Kanako , Kawaji Hitomi , Kaneshiro Kazuhisa , Hayashi Saori , Shimazaki Akiko , Morisaki Takafumi , Yamaguchi Rin , Arima Nobuyuki , Nishimura Reiki , Okido Masayuki , Nakamura Masafumi
Published: March 2020

[background] In general, TNBC has a high distant metastasis rate and is highly aggressive. Despite good response to chemotherapy, it has a poorer prognosis compared to other subtypes. There is a need to develop new treatments for the selection of appropriate treatments. At present, treatments using an immune check point blockade are attracting attention, and the evaluations as biomarkers of and, PD-1 / PD-L1 expression on immune cells for therapeutic effects and prognosis in TNBC are controversial. In order to select patients with TNBC for who immunotherapy is likely to be effective, new biomarkers need to be explored.

[Purpose] Our aim is to investigate the possibility as a biomarker of PD-L1 expression on immune cells(PD-L1/IC) in TNBC. We also assess the relationship among PD-L1/IC, PD-L1 expression on tumor cells(PD-L1/TC) and TIL.

[Methods] This study included 248 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at Kyushu University Hospital(Fukuoka, Japan) and related hospitals between January 2004 and December 2014.

[Results] PD-L1/IC was positive in 129 cases (52.0%) of 248 TNBCs. Although there was no significant difference in RFS and OS between the positive and negative groups, PD-L1/IC-positive and TIL-High group showed the best prognosis, considering the combination whether PD-L1/IC was positive or negative, and TIL was high or low. PD-L1/IC was significantly correlated with PD-L1/TC(p<0.001). In addition, there was a significant correlation between TIL rate and PD-L1/IC(p<0.001). Moreover, PD-L1/IC-positive group showed stronger therapeutic effects of anthracycline both in OS and RFS, compared with the PD-L1/IC-negative group.

[Conclusion] In TNBC, the relationship between PD-L1/IC and prognosis is still not clear, but in IMpassion130 trial, PD-L1/IC is a predictive marker for the effect of Atezolizumab. PD-L1/IC has potential as an immune biomarker in TNBCs. This study also found that PD-L1/IC was related to the therapeutic effect of anthracycline. PD-L1/IC may be a predictive marker of the efficacy of various treatments.

Citation Format: Yurina Harada, Makoto Kubo, Hitomi Mori, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Saori Hayashi, Akiko Shimazaki, Takafumi Morisaki, Rin Yamaguchi, Nobuyuki Arima, Reiki Nishimura, Masayuki Okido, Masafumi Nakamura. PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-21.
Abstract P1-15-08: Real world data on treatment patterns before and after reporting of the KATHERINE trial: A phase 3 study of adjuvant Ado-trastuzumab emtansine (TDM1) versus trastuzumab in early stage HER+ breast cancer
Authors: Margolis Neil , Kozlovsky Vlad , Flood William , Reddy Sandeep
Published: March 2020

BACKGROUND: At SABCS 2018 and simultaneous publication in the NEJM, results of the phase 3 KATHERINE clinical trial comparing TDM1 vs trastuzumab as adjuvant therapy in patients with HER2-positive early-stage breast cancer with residual invasive disease after receiving neoadjuvant chemotherapy and trastuzumab, showed that TDM1 reduced the risk of invasive recurrence or death by 50%. We sought to determine the effect of the release of this data on clinical practice of general medical oncologists in the US by comparing the requests for treatment authorization for TDM1 in the quarters preceding and following SABCS 2018. METHODS: data from a pre-authorization platform used by multiple commercial insurance companies in the US (Eviti) was analyzed. Analysis for request for use of TDM1 was limited to 2nd and 3rd line of therapy in patients with a diagnosis of HER2+ breast cancer in stage <4 patients. Between 1/1/2018 and 6/30/2019, 29,525 breast cancer treatment plans were identified, of which 7,969 were identified as HER2-NEU+ (27%), either IHC3+ or FISH+. TDM1 was prescribed at any line of therapy in 886 patients (11%). RESULTS: Before April 5th 2019, when the adjuvant TDM1 regimen was published, users who entered the drug would have to pick one of the other 2 TDM1 regimens (1st line or 2nd line+). They could change the line of therapy to adjuvant if appropriate. TDM1 authorizations are shown in TABLE 1, indicating an immediate increase in TDM1 use in the quarter following SABCS and based on the quarter 2, 2019 data showing a 42% adjuvant-use rate, we model that 99 cases would have received adjuvant TDM1 in Q1 2019 after 0 in Q4 2018.

Q 1, 2018Q 2, 2018Q 3, 2018Q 4, 2018Q 1, 2019Q 2, 2019TDM1 Adjuvant097TDM1 First Line11178195925TDM1 Second Line+104939276177108

CONCLUSIONS: Clinical uptake of practice changing data presented at SABCS 2018 regarding TDM1 was relatively rapid. SABCS and rapid simultaneous publication serves as an important and effective mechanism to communicate practice changing clinical data to practicing oncologists in the US.

Citation Format: Neil Margolis, Vlad Kozlovsky, William Flood, Sandeep Reddy. Real world data on treatment patterns before and after reporting of the KATHERINE trial: A phase 3 study of adjuvant Ado-trastuzumab emtansine (TDM1) versus trastuzumab in early stage HER+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-08.
Abstract P1-15-09: What are the outcomes of importance for patient education in breast cancer?
Authors: Kazemi Ghazaleh , Levine Mark , Reiter Harold , Sinding Christina
Published: March 2020

Background: Patient education is an important component of quality cancer care. However, there remains much debate about its effects, merits and limitations. There is a lack of consensus on the intended effects of educational interventions and a lack of standardized outcome measures to assess quality. As a result, multiple outcomes measures are used without consistency and in differing combinations in the literature making it difficult to compare relative efficacy of interventions. The primary objective of this study was to identify outcomes of importance for patient education interventions in breast cancer.

Methods: A generic qualitative study using interpretive description was conducted to discover what key stakeholders in the process of patient education in breast cancer (patients, physicians and nurses) would identify as outcomes of importance. The study population included breast cancer patients, physicians and nurses caring for breast cancer patients at the Juravinski Hospital and Cancer Centre in Hamilton, Ontario. Four focus groups and one semi-structured interview was conducted using purposeful sampling and an iterative design.

Results: Eight patients, five nurses and four physicians participated in this study. Five common themes to all groups with respect to outcomes of importance in patient education were discovered: improving knowledge, improving coping ability, providing an orientation to the cancer system, enabling shared decision making and impacting behaviour during cancer treatment.

Conclusion: Despite the surprising variability and inconsistency of outcomes discovered in the patient education literature, this qualitative study demonstrated that patients, physicians and nurses generally agree on what constitute important outcomes and serves as a first step in the process of developing validated outcomes for patient education interventions in cancer.

Citation Format: Ghazaleh Kazemi, Mark Levine, Harold Reiter, Christina Sinding. What are the outcomes of importance for patient education in breast cancer? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-09.
Abstract P1-17-07: Objective measurement of cognitive impairment in breast cancer survivors who received chemotherapy with the use of novel computerized testing
Authors: Godbole Manasi M , Singal Mukul , Benabou Reina , Choudary Iqra , Patel Mehul P
Published: March 2020

Background: Breast cancer is the most common cancer in women worldwide. With early detection and advancement in treatment, majority of women diagnosed with breast cancer will be cured. Some of these breast cancer survivors report Cognitive Impairment (CI) also known as “chemo-brain” or “mental fog”, especially those who have received chemotherapy. Few studies using functional neuroimaging have been conducted to foresee possible neurological alterations that could be linked to CI but research in this area remains in its early stages. Cognivue ® is an FDA cleared medical device that helps in assessment of cognitive dysfunction using novel computerized technology and is reported to be useful in detecting early stages of CI. Methods: We conducted a pilot study at the Lipson Cancer Institute/Rochester General Hospital for evaluation of CI in patients with breast cancer who received curative chemotherapy within the last 12 months of enrollment and self-reported CI. We enrolled 23 female patients between ages 19 and 90 years. Patients were subjected to Mini Mental Status Examination (MMSE) and St. Louis University Mental Status examination (SLUMS) as well as Cognivue ® testing. MMSE and SLUMS were scored according to scoring range guidance and digital data was obtained from the Cognivue® software. Analysis was performed using correlations of numeric data, ANOVA with Tukey’s post-hoc tests for categorical data, and Positive/Negative Percent Agreement (PPA/NPA) analysis for comparison of all cognitive testing methods. Results: Cognivue ® provides higher sensitivity to evaluate CI than MMSE and SLUMS, mainly in detecting earlier stages of CI. The cognitive domains most affected were executive function, abstraction and memory. There was a statistically significant correlation between Cognivue/CI score and duration of chemotherapy (p = 0.02). Age, type of chemotherapy or hormonal status of breast cancer were not significantly related with CI. Conclusions: Cognivue appears to be beneficial in its ability to detect CI in breast cancer patients. Specifically, detection of impairment in executive function domain could be predictive of daily life activity issues in such patients post-chemotherapy. This study also provides a possibility of detecting early cognitive dysfunction as well as the potential to develop a predictive algorithm of early intervention strategies for better patient outcomes.

Citation Format: Manasi M Godbole, Mukul Singal, Reina Benabou, Iqra Choudary, Mehul P Patel. Objective measurement of cognitive impairment in breast cancer survivors who received chemotherapy with the use of novel computerized testing [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-07.
Abstract P1-17-12: The influence of social demographics on genomic sequencing in metastatic breast cancer
Authors: Wecht Zoe , Brufsky Adam , Hsia Tiffaney , Rosenzweig Margaret Q
Published: March 2020

BACKGROUND: With the potential for medications targeted to somatic mutations, the utilization of whole genome sequencing (WGS) in MBC is increasingly important. The current clinical protocols surrounding the routine testing of WGS in MBC are amorphic.

AIMS: We explored a cohort of patients with MBC to determine the prevalence and timing of WGS. Demographic and tumor characteristics of sequenced vs. non sequenced women with MBC were compared. Patient understanding of genomic sequencing was assessed.

METHODS: Retrospective chart review of all MBC patients of the Magee-Womens Cancer Center between October 2016 and May 2019 for collection of demographic information, including neighborhood deprivation index (NDI) (zip code derived 0-10; higher scores= higher deprivation), clinical data and sequencing results (FoundationOne®, Guardant360®, Tempus, Caris®). Of those sequenced - Patient questionnaires included test of genetic knowledge (higher = more knowledge). Descriptive statistics, chi square and independent sample t tests used for analysis.

Results: There has been an overall increase in the frequency of WGS in MBC; n=15 in 2016, n=30 in 2017, n=39 in 2018 and n=25 in the first 5 months of 2019.

Of 418 total MBC patients, 31.3% (N=131) had whole genome sequencing, while 68.7% (N=287) did not. The sequenced patients were more likely to be triple negative, 74.4%, (n=96) than non-sequenced 25.6%, (n=33), p=.001. Most patients were sequenced once (n=112, 88.2%). First sequencing occurred within a mean of 4.9 months (SD 2.2; range 1-9) from MBC diagnosis. No clinical trials were accessed as a direct result of sequencing. There was no racial difference in sequencing prevalence, but non sequenced patients were from more highly deprived neighborhoods (p=.000).

Of the patients sequenced, n=27 were interviewed. Mean knowledge of basic genetics was high at 12 (SD-2.1; Range 8-16). Knowledge of WGS and implication was poor. N=15 (80%) patients did not understand reasons and implications of sequencing while n=5 (20%) did. All who understood WGS and its implications were from non-deprived neighborhoods.

Conclusion: WGS is increasingly being utilized as a tool in MBC, particularly for triple negative patients, without strict clinical protocol or direct change in treatment. Patient understanding of WGS and its implication is poor.

Citation Format: Zoe Wecht, Adam Brufsky, Tiffaney Hsia, Margaret Q Rosenzweig. The influence of social demographics on genomic sequencing in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-12.
Abstract P1-17-13: Design of a cognitive bias modification eHealth app to improve implicit vitality in breast cancer patients: A co-creation process
Authors: Wolbers Roos G.M. , Bode Christina , Siemerink Ester J.M. , Siesling Sabine , Pieterse Marcel E.
Published: March 2020

Objective: More than 50% of all breast cancer patients experience fatigue symptoms during and after their treatment course. Recent evidence shows that fatigue is partly driven by cognitive biases, such as the self-as-fatigued identity bias, which may be corrected with computer-based Cognitive Bias Modification (CBM) techniques. The aim of the current study was the intervention design of such a CBM-training by adopting a co-creation approach.

Methods: Semi-structured interviews were conducted with seven health professionals, three breast cancer patients and two patient advocates. Aim of the interviews was to collect input for the design of the CBM-training taking the attitude and preferences of the stakeholders into account and to determine the timing and implementation of the training in the treatment course.

Results: Overall, the interviews showed that CBM was accepted among all stakeholders. Important requirements were revealed, such as that the training needs to be simple, undemanding, yet engaging and persuasive. Based on the results, eHealth app IVY (Implicit VitalitY) was created. Interviews suggested that IVY should be offered early in the treatment course and should be carefully aligned with clinical treatment.

Conclusion: CBM training tasks seem to be suitable for targeting fatigue in breast cancer patients. It is innovative to use CBM techniques for cancer-related fatigue in a preventive approach. The current study suggests CBM has several benefits, such as being simple, time-effective and possibly increase levels of self-control in patients. In the next step, effectiveness of the CBM-training will be tested.

Citation Format: Roos G.M. Wolbers, Christina Bode, Ester J.M. Siemerink, Sabine Siesling, Marcel E. Pieterse. Design of a cognitive bias modification eHealth app to improve implicit vitality in breast cancer patients: A co-creation process [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-13.
Abstract P1-17-14: Physical activity platform to improve bone health in cancer survivors
Authors: Skinner Cathy
Published: March 2020

Cancer treatment-induced bone loss and the subsequent risk of fractures in both men and women is a significant burden on national health care. The number of cancer survivors in the United States will reach 18 million by 2022 and by 2025, the projected burden of osteoporosis is $25.3 billion. Cancer patients treated with medications that lower hormone levels face an increased risk of fractures. Clinical studies report that moderate- intensity resistance exercises prevent a decline in bone health in female cancer survivors, and that strength training may reduce complications associated with cancer such as fatigue, muscle wasting, and bone loss. Unfortunately, only a small percentage of female cancer survivors engage in and adhere to a strength training exercise routine. Several factors account for this low level of engagement such as poor awareness of the benefits of exercise, lack of motivation, and the lack of affordable and easily accessible exercise programs designed for cancer survivors. Internet-based self-managed programs of exercises and guidance can potentially address these problems, and can be scaled for broader dissemination. The Thrivors™ internet-based platform seeks to shift the current paradigm of poor adherence to exercise by providing an affordable and accessible means of improving outcomes for cancer survivors. The product, Thrivors plus Bone Health (Thrivors+BH), will be a first-of-its-kind offering of clinically validated bone health exercises that can be customized to a cancer survivor's pain and energy levels, with several novel interactive feedback features. The product has supportive modules for connecting with a community of other users, mindfulness training, nutritional advice and a repository of educational information. The Thrivors™ platform is scalable, device-agnostic, and allows analysis of de-identified usage data. With commercialization potential for healthcare providers and health insurance payers, Thrivors™ provides a value-based care delivery model focused on outcomes. There are multiple important physiologic and psychosocial secondary conditions that could be positively impacted by the Thrivors™ platform. For this specific clinical trial, we focus on adherence to bone health exercises.

Investigators: Cathy Skinner, MA - CEO and Founder, Thrivors (https://www.linkedin.com/in/cathyskinner/) Doug Yee, MD - Director of the Masonic Cancer Center, University of Minnesota (https://www.linkedin.com/in/douglas-yee-50402a14/) Kerri Winters-Stone, PhD - Professor, OHSU (https://www.linkedin.com/in/kerriwintersstone/) Kathryn Schmitz, PhD, MPH - Professor, Penn State - (https://www.linkedin.com/in/kathryn-schmitz-32a3891b/)

Citation Format: Cathy Skinner. Physical activity platform to improve bone health in cancer survivors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-14.
Abstract P1-17-16: Deconstructing breast cancer reconstruction
Authors: Allison Cecelia , Fear David
Published: March 2020

Background: The American Cancer Society currently invests more in breast cancer research than any other cancer type. However surgical treatments for breast cancer have been studied as far back as 3,000 BCE. Until the mid 19th century, the surgical treatment of breast cancer was limited either by sociocultural and religious views or technology. The advent of anesthesia and sterile practice in the late 1800s and early 1900s paved the way for innovation and precision.

Synopsis: Despite being completely against breast reconstruction, Dr. William Halsted completely reconstructed breast cancer surgery. At the turn of the 20th century, Halsted’s new mastectomy procedure demonstrated to the world how technological advancements showed promise for a cure for breast cancer. The “Halsted Radical Mastectomy” recommended the removal of all diseased tissue including the pectoralis major muscle. Halsted later recommended further dissection of rectus abdominis, serratus anterior, subscapularis, latissimus dorsi and the teres major muscle without any breast reconstruction. With a local recurrence rate of 7% - an unheard of figure among the surgeons of the time- the “Halsted Radical Mastectomy” dominated the field for almost a century. With Halsted’s domination of technique came domination of thought. Halsted’s strong opinion against breast reconstruction influenced the American standard of care for breast cancer surgery for decades to follow. His treatment plan of mastectomy without reconstruction was the standard, so much so that other procedures for reconstruction, such as the latissimus dorsi pedicle flap (the first myocutaneous flap for breast reconstruction) were forgotten about for almost 70 years. Despite Halsted’s tight grasp on surgical thought, later 20th century innovations in breast reconstruction showed aesthetic results. Gradually, immediate breast reconstruction began to be advocated for all patients who were eligible. Breast cancer surgery and treatments continued to evolve and improve to ultimately lead to personalized medicine plans which have greatly improved patient outcomes. The shift in American surgical culture around breast reconstruction after mastectomies provide a lesson on how the power of cultural context shapes modern medical treatments.

Significance: The medical recognition and treatment of breast cancer long outdated the modern day anesthetized, sterile, evidence-based procedures. Today, most women with early stage breast cancer will have some type of surgery. Therefore, it is important to appreciate the advancements and improvements in technology that have led us to the personalized medicine plans that have greatly improved outcomes.

Citation Format: Cecelia Allison, David Fear. Deconstructing breast cancer reconstruction [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-16.
Abstract P1-18-27: Developing a novel combination therapy using EZH2i for HER2+ breast cancer
Authors: Watanabe Marina , Kuzmickas Rysn , Cichowski Karen
Published: March 2020

The receptor tyrosine kinase (RTK) human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers and acts as a driver of tumor growth. Though there are FDA-approved agents in the clinic that specifically target HER2, metastatic HER2+ breast cancer remains incurable with a median overall survival of 56.5 months. In addition, the response rates of patients with metastatic disease vary considerably, with 20-50% and 60-80% of patients unresponsive to first- and second-line therapies respectively. Therefore, it is necessary to discover a new therapy able to overcome the therapeutic resistance of HER2+ breast cancer that currently leads to patient relapse, and ultimately, death.

One approach that our lab has successfully used to develop more effective therapies for other tumor types is to co-target different oncogenic pathways for a more potent effect. A target of interest is the histone methyltransferase enhancer of zeste homolog 2 (EZH2), which is overexpressed in many cancer types including breast, prostate, bladder, gastric, lung, and hepatocellular carcinoma. Interestingly, in breast cancer, EZH2 is overexpressed in the more aggressive subtypes including HER2+. EZH2 expression levels correlate with a worse prognosis and parallels cancer progression. We chose to investigate the therapeutic potential of combining EZH2 inhibitors (EZH2i) with lapatinib, an FDA-approved HER2-targeted therapy for late stage HER2+ breast cancer. In vitro assays show that the combination has a potent cytotoxic effect and renders lapatinib-sensitive HER2+ breast lines more sensitive, and causes lapatinib-resistant lines to become sensitive. In addition, in vivo testing of both lapatinib-sensitive and resistant HER2+ xenografts showed potent regression with the combination, confirming the extremely promising results. Using RNA-Seq and ChIP-Seq, we have identified that the Rb/E2F pathway may be involved in the combination’s mechanism of action. We will identify the biological settings in which this combination may be most effective and elucidate its molecular mechanism of action. This work will not only validate a promising new therapeutic combination, but will also provide insight into additional vulnerabilities of HER2+ breast cancer, possibly leading to additional therapeutic strategies.

Citation Format: Marina Watanabe, Rysn Kuzmickas, Karen Cichowski. Developing a novel combination therapy using EZH2i for HER2+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-27.
Abstract P1-20-20: Intraoperative ultrasound localization (IOUS) for non-palpable breast cancer
Authors: Zahed Shideh Pour , Andersen Thor Knudsen
Published: March 2020

Background: With the introduction of breast cancer screening the number of non-palpable breast cancers and so the number of breast conserving surgery (BCS) has increased. Wire-guided localization (WGL) is used as invasive standard method for localization. IOUS is an alternative non-invasive, time-sparing and safe localization method with many cost benefits.

Patient and methods: A retrospective observational study was performed in a single breast unit where IOUS was used as localization method by two surgeons in the period June 2013 to October2016. The surgeons did not have any special experience with Ultrasound (US) apart from one week of bed-side training.

Results: During a 41 months period the two surgeons treated 452 with BCS. Of them 126 were non-palpable and visible by US 28%. The 126 cancers were identified with IOUS at surgery and removed successfully by the surgeons. In the period a total of 156 had a BCS with WGL. These cases had a nonpalpable cancer which were non-visible on US with either calcifications, DCIS or non-specific lesions. In the study we also found that the re-lumpectomy rate for BCS with IOUS was lower than without IOUS. In the entire breast unit, the number of BCS were 848 and number of BCS+WGL were 320 in the same period. Of them 263 (22.5%) had a re-lumpectomy. The number BCS with IOUS were 452 and the number of BCS+WGL with IOUS were 156. Of them 72 (11.8%) had a re-lumpectomy.

Conclusion: In our breast unit, IOUS was used after a short bed-side training, with 100% success rate, to remove non-palpable cancers if visible on US. IOUS is easy to learn and easy to use and offers many financial and time-sparing benefits. IOUS has a reasonable learning curve and can reduce the work load on the Radiology Department.

Citation Format: Shideh Pour Zahed, Thor Knudsen Andersen. Intraoperative ultrasound localization (IOUS) for non-palpable breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-20.
Abstract P1-20-21: The use of intraoperative ultrasound and guidewire placement to obtain low re-excision rates and increased accuracy of excision in impalpable breast lesions at the Cambridge Breast Unit
Authors: Wignarajah Primeera , Papalouka Vasiliki , Forouhi Parto
Published: March 2020

INTRODUCTION: Increasingly we are dealing with more and more impalpable breast lesions thanks to screening programmes, chemotherapy and in situ disease. There are various techniques already employed for assisting in surgery for impalpable lesions such as radioactive and magnetic markers. All of these have limitations and are only useful in surgery. Ultrasound can be used in clinic and theatre to locate tumours and sonographically visible markers. In our experience in the Cambridge breast unit we have found it is more satisfactory to use guidewires that are intraoperatively or preoperatively placed using ultrasound guidance. This allows for direct approach to the lesion at the same time limiting the dissection and volume of resection. The guidewire allows tactile feedback and helps with precision and accuracy of the excision as reflected in the specimen weights. In this study we look at the outcomes of intraoperatively and preoperatively placed guidewires using ultrasound for impalpable breast lesions between 2015 -2018 in the Cambridge Breast Unit. The primary outcomes are re-excision rate and average specimen weights.

METHODS: Patients undergoing breast conservation surgery for impalpable lesions from 01/01/2015 to 30/07/2018 were included. Data was collected retrospectively from our electronic records system EPIC and analysed.

RESULTS The results were divided into intraoperative localisations and preoperative localisations. A total of 441 lesions in 415 patients were included in this study.

Preoperative localisationIntraoperative localisationNumber of patients193222Number of lesions210231*Re-excision rate per patient %19.2%14.0%Specimen weight per patient (grams)39.4g24.2g*Fishers exact 0.24 (NS)

CONCLUSION: Impalpable lesions can be successfully localised using ultrasound guidance and a guidewire both intraoperatively and preoperatively with good outcomes. Intraoperative localisation has lower re-excision rates and specimen weights in our study as well as many other benefits for the patient and surgeon. We have looked into how easily and quickly we can train ultrasound naïve trainees in this technique and have achieved good results.

Citation Format: Primeera Wignarajah, Vasiliki Papalouka, Parto Forouhi. The use of intraoperative ultrasound and guidewire placement to obtain low re-excision rates and increased accuracy of excision in impalpable breast lesions at the Cambridge Breast Unit [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-21.