bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES11-3: Optimizing immunotherapy efficacy in the clinic through biomarkers: Advances in single cell and spatial histology analyse
Authors: Kok M 
Published: March 2022

Abstract
Single cell technologies and spatial analyses are emerging as powerful tools to investigate tumor heterogeneity, cell state of key effector or suppressing immune cells and detailed distribution of cells within the tumor microenvironment. Their application will undoubtedly provide further understanding of the effects of cancer immunotherapy on the tumor microenvironment, which is particularly important for the largely non-immunogenic breast carcinomas. However, analyses of clinical samples require well-coordinated, multidisciplinary teams and specific expertise. Moreover, large scale analyses have major technical challenges and is still relatively costly. We will discuss the promise and hurdles of single cell and spatial analyses on the road to find biomarker for breast cancer immunotherapy and avenues for novel immunomodulatory treatments for breast cancer patients.
Citation Format: M Kok. Optimizing immunotherapy efficacy in the clinic through biomarkers: Advances in single cell and spatial histology analyse [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES11-3.
Abstract ES12-2: Single cell analysis of circulating tumor cells
Authors: Maheswaran S , Ebright R , Micalizzi D , D  , Toner M , Haber D 
Published: March 2022

Abstract
Epithelial to mesenchymal plasticity (EMP), an embryonic process, is reinstated in cancer and has been implicated in tumor metastasis and drug resistance. Tumor cells circulating in the blood of breast cancer patients show extensive EMP with dynamic shifts from one state to another. Comparison of the molecular characteristics of epithelial and mesenchymal circulating tumor cell (CTC) populations shows that epithelial CTCs compared with mesenchymal CTCs express multiple structural ribosomal proteins and exhibit enrichment of translational signatures; these epithelial CTCs are more proliferative and their presence in the blood correlates with poor clinical outcome. Mechanistically, overexpression of a single structural ribosomal protein, RPL15, which encodes a component of the large ribosomal subunit, increased the expression of multiple structural ribosomal proteins, global translation and cell proliferation coinciding with increased metastatic growth in multiple organs. Tumors overexpressing RPL15 were more sensitive to translational inhibitors suggesting that therapies targeting translation in this aggressive subset of epithelial CTCs may serve as potential suppressors of metastatic progression of breast cancer.
Citation Format: S Maheswaran, R Ebright, D Micalizzi, D , M Toner, D Haber. Single cell analysis of circulating tumor cells [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES12-2.
Abstract ES7-2: Emergent pharmacologic interventions for prevention: Non endocrine treatments
Authors: Heckman-Stoddard BM 
Published: March 2022

Abstract
Many agents have been examined in preclinical and early phase clinical trials for their potential to reduce the risk of breast cancer in additional to the traditional endocrine agents that have been shown in large, randomized phase III clinical trials to reduce the risk of hormone-receptor positive breast cancer. The focus on non-endocrine agents has included commonly used drugs such as statins, non-steroidal anti-inflammatory agents (NSAIDs), and metformin. There were also many trials that have examined nutraceutical agents such as soy and omega-3-fatty acids. In addition, there is interest in target agents such as rexinoids, Her-2 targeted agents, and PARP inhibitors because of their potential to inhibit hormone-receptor negative breast cancer. Finally, there is significant interest in developing immunoprevention strategies for breast cancer risk reduction. There is a renewed focus on examining lower doses, intermittent dosing strategies, and local delivery to maximize the benefit and reduce the toxicity. Results of preclinical and clinical studies will be presented and discussed as well as ongoing clinical trials that will further inform work in this area.
Citation Format: BM Heckman-Stoddard. Emergent pharmacologic interventions for prevention: Non endocrine treatments [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES7-2.
Abstract P3-07-08: Germline mutational profiling in Indian TNBCs
Authors: Koppiker C B 
Published: March 2022

Abstract
Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (&gt;25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of Indian breast cancer patients using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. In our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. Further analysis to investigate the association of tumor size, tumor grade, survival analysis with mutational profiles is in process. Similarly, we are also assessing. family history to underline the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings.
Citation Format: C B Koppiker. Germline mutational profiling in Indian TNBCs [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-08.
Abstract P3-12-04: Extending therapy after 5-year adjuvant hormone therapy in breast cancer patients: A population-based study
Authors: Zeng Erwei , He Wei , Bergqvist Jenny , Czence Kamila 
Published: March 2022

Abstract
Background: Clinical guidelines have recommended breast cancer patients with certain characteristics to extend their therapy after 5-year adjuvant hormone therapy. However, no study thus far has described the prevalence, predictors, and outcomes of extending adjuvant hormone therapy in the real world. Methods: We identified 2,937 breast cancer patients who completed 5-year adjuvant hormone therapy during 2010-2019 in Stockholm, Sweden, by linking the Quality Register for Breast Cancer, Prescribed Drug Register, and Cause-of-death Register. We followed them until September 2020. Extended adjuvant hormone therapy was defined as having at least 2 prescriptions of tamoxifen and/or aromatase inhibitors after completing 5-year therapy. We used logistic regression to examine predictors of extended adjuvant hormone therapy and Cox regression to examine whether extended therapy is associated with distant metastasis-free survival, disease-free survival and all-cause mortality. Results: The proportion of extending therapy after 5-year adjuvant hormone therapy increased by 7 times during the past decade, from 8.8% in 2010 to 63.7% in 2019. Predictors of extended adjuvant hormone therapy included young age (≤50 years) at extension, positive lymph node status, high tumor grade and chemotherapy, among which chemotherapy was the strongest predictors [adjusted hazard ratio (HR), 4.64 (95% CI, 3.64-5.92)]. Among patients with chemotherapy, extended therapy improved distant metastasis-free survival [adjusted HR, 0.34 (95 CI%, 0.15-0.78)] and disease-free survival [adjusted HR, 0.61 (95 CI%, 0.39-0.95)]. Therapy discontinuation rates were similar during the first and second five years. Conclusion: Increasing number of breast cancer patients are extending adjuvant hormone therapy, even among patients without clear recommendations in clinical guidelines. Our findings support extended adjuvant hormone therapy in breast cancer patients with chemotherapy.
Citation Format: Erwei Zeng, Wei He, Jenny Bergqvist, Kamila Czence. Extending therapy after 5-year adjuvant hormone therapy in breast cancer patients: A population-based study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-04.
Abstract P4-06-04: The role of axillary lymph node status in residual cancer burden calculation of triple negative breast cancer post-neoadjuvant cytotoxic chemotherapy
Authors: Gandhi Shipra , Attwood Kristopher , Ji Wenyan , Aljabab Saif , Khoury Thaer 
Published: March 2022

Abstract
BACKGROUND: The residual cancer burden (RCB) is calculated utilizing these variables: tumor bed size, tumor/tumor bed ratio, percentage of DCIS, number of positive lymph nodes (LN) and the size of the largest LN. The aim of the study is to investigate if other variables related to the LNs correlate with the outcomes. METHODS: We conducted pathologic review of 129 patients who had triple negative breast cancer (TNBC) diagnosed between 2002 and 2006. The following variables were calculated, Finv: primary tumor/tumor bed ratio; dmet: diameter of largest involved LN; dprim= √d1d2 (d1 and d2 dimensions of the primary tumor bed); RCBprim = finv dprim ; RCBmet = 4 (1- 0.75LN) dmet; and RCB = 1.4 (finvdprim)0.17 + [4(1- 0.75 LN) dmet ]0.17. We calculated the LN tumor/tumor bed ratio (fLN), the number of resected LNs, and the number of LNs with therapy effect (with or without metastases). Clinical staging was abstracted from the medical records. Clinicopathologic variables were correlated with the recurrence free survival (RFS) and overall survival (OS). RESULTS: Most of the patients were treated with anthracycline based chemotherapy (CT) (90.7%). The median and range of follow up was 108.2 (15.0, 225.1) months. Pathology complete response (pCR) was achieved in 34.1% of the patients and correlated with age (p= 0.042) and clinical stage (p=0.004). pCR had better survival after 5-years (p&lt;0.001) and 10 years (p=0.001) follow up. In the univariate analysis the following variables were statistically significant correlating with RFS and OS including clinical stage, RCB, and fLN. These variables were statistically significant in the multivariate analysis for RFS including clinical stage with hazard ratio (HR) 0.37 (0.15, 0.89) (p=0.026) and fLN HR 1.01 (1.00, 1.02) (p=0.006); and for OS with HR 0.35 (0.14, 0.85) (p=0.02) and 1.01 (1.00, 1.02) (p=0.01), respectively. CONCLUSIONS: Adding LN tumor/tumor bed ratio (fLN) to the existing formula may improve the predictability power of the RCB index.
Citation Format: Shipra Gandhi, Kristopher Attwood, Wenyan Ji, Saif Aljabab, Thaer Khoury. The role of axillary lymph node status in residual cancer burden calculation of triple negative breast cancer post-neoadjuvant cytotoxic chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-06-04.
Abstract P4-07-06: Circulating lipids and breast cancer survival in the Malmö diet and cancer study
Authors: Harborg Sixten , Ahern Thomas P , Feldt Maria , Rosendahl Ann H , Cronin-Fenton Deirdre , Melander Olle , Borgquist Signe 
Published: March 2022

Abstract
Rationale: Overweight and obesity are associated with inferior prognosis in breast cancer. The explanation is considered multifactorial, and dyslipidemia may be a contributing factor. The purpose of this study was to examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods: Circulating lipid levels were measured in the blood sampled upon enrollment in the female MDCS cohort (N=17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991-2014. The follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or five years of follow-up. We estimated the incidence rates of recurrence at five years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results: We enrolled 850 eligible patients. During the five years of follow up, 90 invasive recurrences with over 3,807 person-years occurred. In multivariable analyses, high levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR= 2.30 [95% CI: 1.13-4.68]). However, high levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR= 1.23 [95%CI: 0.68-2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR= 1.34 [95%CI: 0.70-2.58]) or all-cause mortality (tertile 3 vs. 1, HR=1.12 [95%CI: 0.61-2.05]). Conclusion: High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcome. These results warrant further investigation into the importance of lipid-regulation in breast cancer patients.
Citation Format: Sixten Harborg, Thomas P Ahern, Maria Feldt, Ann H Rosendahl, Deirdre Cronin-Fenton, Olle Melander, Signe Borgquist. Circulating lipids and breast cancer survival in the Malmö diet and cancer study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-06.
Abstract P4-07-07: Metaplastic carcinoma of the breast has comparable prognosis to non-metaplastic triple negative breast cancer despite poor response to chemotherapy
Authors: Lim Changjin , Kim Jang-il , Han Yireh , Cheun Jong-ho , Jung Ji Gwang , Kim Hong Kyu , Moon Hyeong-Gon , Han Wonshik , Lee Han-Byoel 
Published: March 2022

Abstract
Introduction Metaplastic carcinoma (MC) of the breast is a rare pathologic entity accounting for &lt;1% of all invasive breast cancers and is generally negative for hormone receptors and HER2. They often show more aggressive characteristics and are resistant to treatment. Although triple negative breast cancers (TNBCs) have good response to neoadjuvant chemotherapy (NAC) and a pathologic complete response (pCR) rate of about 40%, benefit of NAC for MC is not clear. The aim of this study was to compare the Clinicopathologic characteristics and prognosis of MC with non-MC TNBC, and assess the usefulness of NAC for MC. Methods Retrospective chart review of TNBC patients who underwent breast surgery at Seoul National University Hospital between January 2000 and December 2018 were included for analysis. Clinicopathologic features including age, TNM stage, Ki-67 and histologic grade were collected. For patients who had received NAC, tumor size on ultrasound before NAC and pathologic size of residual tumor was used to assess responsiveness to NAC. We used 3:1 propensity score matching according to age, neoadjuvant chemotherapy, pT stage, pN stage. Kaplan-Meier analysis and log-rank test were performed. Results Among 1783 TNBC patients included for analysis, 82 (4.59%) were MC and 1701 (95.34%) were non-MC. MC had a worse DFS and OS. After propensity score matching, there was no difference in survival outcomes. The 5-year disease-free survival and overall survival between MC vs. non-MC TN was 61.9% vs. 73.0% (HR 1.379, 95% CI 0.594-3.202, p-value = 0.430) and 71.4% vs. 74.6% (HR 1.007, 95% CI 0.393-2.579, p-value = 0.480), respectively. The proportion of patients who received NAC among MC and propensity matched non-MC TNBC were 21/82 (25.6%) and 63/1701 (3.7%), respectively. The pathologic complete response rate for all and propensity score matched non-MC TNBC was 76/364 (20.9%) and 11/63 (17.5%), respectively, whereas no MC patients achieved a pathologic complete response (HR 1.404 95% CI 1.213-1.624, p-value = 0.058). Conclusions MC has comparable prognosis compared to non-MC TNBC in terms of disease-free survival and overall survival, while showing lower rate of pathologic complete response after NAC. Upfront surgery may be more beneficial for MC. A prospective study with larger number of patients evaluating the role of NAC in MC is warranted.
Citation Format: Changjin Lim, Jang-il Kim, Yireh Han, Jong-ho Cheun, Ji Gwang Jung, Hong Kyu Kim, Hyeong-Gon Moon, Wonshik Han, Han-Byoel Lee. Metaplastic carcinoma of the breast has comparable prognosis to non-metaplastic triple negative breast cancer despite poor response to chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-07.
Abstract P4-12-05: Benefit of multidisciplinary consultation at initiation of oral antineoplastic agents in metastatic breast cancer patients
Authors: Morel Adeline , Jacobs Margaux , Da Silva Angelique , Allouache Djelila , Hrab Ioana , Segura Carine , Villemin Maud , Boscher Clémence , Johnson Alison , Ceintre Charlotte , Charles Rose-Marie , Lahaye François , Lequesne Justine , Divanon Fabienne , Levy Christelle , Emile Georges 
Published: March 2022

Abstract
INTRODUCTION: The management of cancer patients changed in the recent years with increased in the number of oral antineoplastic agents (OANA) prescriptions. Recent guidelines encouraged improvement of information and patient education, and the coordination between health care professionals to secure and optimize the management of these drugs. To cope with current recommendations, a multidisciplinary consultation (MDC) for initiation of OANA was initiated at François Baclesse comprehensive cancer center in Caen, France. OBJECTIVE: The aim of this study was to evaluate the benefit of the MDC before the initiation OANA in patients with metastatic breast cancer. MDC consisted of a medical oncologist, hospital pharmacist, and oncology nurse consultations. Primary endpoint was the rate of hospitalizations. Secondary endpoints were treatment discontinuation and of adverse events rate. MATERIALS AND METHODS: We conducted a retrospective single center study comparing patients receiving MDC to the population with a single medical visit. RESULTS: A total of 482 patients were included in this study between January 2017 and December 2019 (329 patients had only a consultation with a medical oncologist before initiation of OANA and 153 had the MDC). A statistically significant decrease in the rate of hospitalizations for toxicity was found in the group of patients with MDC 3.9% (n=6) vs 18.5% (n = 61) in the group without MDC (p &lt; 0.001). A significant decrease in treatment interruption rate for toxicity was found in the group of patients with MDC 11% (n = 16) vs 26% (n=86) (p &lt; 0.001). Adverse events rate was not statistically significant between the two groups CONCLUSION: A statistically significant decrease in hospitalizations and rate of treatment interruption for toxicity was observed after initiation of MDC in patients with a metastatic breast cancer treated with an OANA. This process should be generalized for a better security in the management of the OANA.
Citation Format: Adeline Morel, Margaux Jacobs, Angelique Da Silva, Djelila Allouache, Ioana Hrab, Carine Segura, Maud Villemin, Clémence Boscher, Alison Johnson, Charlotte Ceintre, Rose-Marie Charles, François Lahaye, Justine Lequesne, Fabienne Divanon, Christelle Levy, Georges Emile. Benefit of multidisciplinary consultation at initiation of oral antineoplastic agents in metastatic breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-05.
Abstract P5-04-03: Prolactin drives a dynamic STAT5A/HDAC6/HMGN2 cis-regulatory landscape exploitable in ER+ breast cancer
Authors: Clevenger Charles V , Turner Tia , Harrell Chuck , Craig Justin 
Published: March 2022

Abstract
The hormone, prolactin, has been implicated in breast cancer pathogenesis and regulates chromatin engagement by the transcription factor, STAT5A. STAT5A is known to inducibly bind promoters and cis-regulatory elements genome wide, though the mechanisms by which it exerts specificity and regulation of target gene expression remain enigmatic. We previously identified HDAC6 and HMGN2 as cofactors that facilitate prolactin induced, STAT5A mediated gene expression. Here, multi-condition STAT5A, HDAC6, and HMGN2 ChIP-seq with parallel condition RNA-seq are utilized to reveal the cis-regulatory landscape and cofactor dynamics underlying prolactin stimulated gene expression in breast cancer. We find that prolactin regulated genes are significantly enriched for cis-regulatory elements bound by HDAC6 and HMGN2, and that inducible STAT5A binding at enhancers, rather than promoters, conveys specificity for prolactin regulated genes. The selective HDAC6 inhibitor, ACY-241, blocks prolactin induced STAT5A chromatin engagement at cis-regulatory elements as well as a significant proportion of prolactin stimulated gene expression. We identify functional pathways known to contribute to the development and/or progression of breast cancer that are activated by prolactin and inhibited by ACY-241. Additionally, we find that the DNA sequences underlying shared STAT5A and HDAC6 binding-sites at enhancers are differentially enriched for estrogen response elements (ESR1 and ESR2 motifs) relative to enhancers bound by STAT5A alone. Gene set enrichment analysis identifies significant overlap of ERα regulated genes with genes regulated by prolactin, particularly prolactin regulated genes with promoters or enhancers co-occupied by both STAT5A and HDAC6. Lastly, the therapeutic efficacy of ACY-241 is demonstrated in in vitro and in vivo breast cancer models, where we identify synergistic ACY-241 drug combinations and observe differential sensitivity of ER+ models relative to ER- models.
Citation Format: Charles V Clevenger, Tia Turner, Chuck Harrell, Justin Craig. Prolactin drives a dynamic STAT5A/HDAC6/HMGN2 cis-regulatory landscape exploitable in ER+ breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-04-03.