bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-05-01: Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas
Authors: Kern Joseph , Tilston-Lunel Andrew , Federico Anthony , Ning Boting , Peppler Grace , Stampouloglou Eleni , Lenburg Marc , Beane Jennifer , Monti Stefano , Varelas Xaralabos 
Published: March 2022

Abstract
Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells but undergo plasticity to a basal-like state upon transformation. Identifying cellular mechanisms underlying this luminal-basal plasticity will allow an improved understanding of the pathogenesis of basal-like breast cancers. The Hippo signaling pathway, an important cell fate regulator across many tissues, has been implicated in breast cancer development. Central to Hippo signaling are the tumor suppressor kinases LATS1 and LATS2 (LATS1/2), which function to inhibit the transcriptional regulators YAP and TAZ (YAP/TAZ). In this study, we investigated the roles of LATS1/2 in the maintenance of mammary epithelial homeostasis and tumorigenesis in vivo. Using genetic mouse models, we found that conditional co-deletion of LATS1/2 in adult luminal cells promotes rapid proliferation and acquisition of basal cell traits, leading to early development of basal-like ductal carcinoma in situ and an eventual transition to a metastatic state. Further co-deletion experiments demonstrated that these phenotypes are dependent on YAP/TAZ. Transcriptional analyses of LATS1/2-null cells sorted from mammary glands demonstrated that these cells adopt gene expression signatures that correlate with mammary basal cells and human basal-like breast cancers, and revealed an association with Sox9, a transcription factor implicated in luminal progenitor fate and basal-like carcinomas. Collectively, this study demonstrates that LATS1/2 are important mediators of luminal cell fate in mammary epithelial homeostasis and that dysregulation of Hippo signaling in vivo promotes luminal-basal cell plasticity leading to basal-like mammary carcinoma development.
Citation Format: Joseph Kern, Andrew Tilston-Lunel, Anthony Federico, Boting Ning, Grace Peppler, Eleni Stampouloglou, Marc Lenburg, Jennifer Beane, Stefano Monti, Xaralabos Varelas. Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas [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 P2-05-01.
Abstract P2-11-16: Rate of breast biopsy referrals in BRCA mutation carriers: A retrospective comparative study and matched analysis
Authors: Pomerantz Adi , Tsoref Daliah , Grubstein Ahuva , Wadhawker Sonya , Rapson Yael , Gadiel Itay , Goldvaser Hadar , Hammerman Ariel , Shochat Tzipora , Sharon Eran , Yerushalmi Rinat 
Published: March 2022

Abstract
Purpose: To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. Methods: The study group consisted of 330 BRCA mutation carriers attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients who were at age 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended in the international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. Results: The matched analysis revealed that the total biopsy rate per 1000 follow-up-years was 61.7 in the study group and 22.7 in the control group (p &lt;0.001). The positive biopsy rates per 1000 follow-up-years were 26.4 and 2.0, correspondingly (p &lt;0.001), and the positive biopsy percentages were 42.9% and 8.7% correspondingly (p &lt;0.0001).Conclusions: BRCA mutation carriers who attend a dedicated clinic, have a 2.7 times higher biopsy rate per 1000 follow-up-years, a 13.2 times higher positive biopsy rate per 1000 follow-up-years, and a 4.9 times higher positive biopsy percentage compared with women in the general population. Keywords: Biopsy, BRCA, breast cancer, screening, high risk
Citation Format: Adi Pomerantz, Daliah Tsoref, Ahuva Grubstein, Sonya Wadhawker, Yael Rapson, Itay Gadiel, Hadar Goldvaser, Ariel Hammerman, Tzipora Shochat, Eran Sharon, Rinat Yerushalmi. Rate of breast biopsy referrals in BRCA mutation carriers: A retrospective comparative study and matched analysis [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 P2-11-16.
Abstract P2-14-15: Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients
Authors: Makhoul Issam , Ibrahim Saddam M , Abu-Rmaileh Muhammad , Jousheghany Fariba , Siegel Eric , Rogers Lora J , Lee John J , Pina-Oviedo Sergio , Post Ginell R , Beck Thaddeus , Kieber-Emmons Thomas , Monzavi-Karbassi Behjatolah 
Published: March 2022

Abstract
Background: We have developed P10s-PADRE, a carbohydrate-mimetic-based peptide, cancer vaccine and demonstrated its safety and immunogenicity in a Phase I clinical trial performed in stage IV breast cancer patients. HR+/HER2- breast cancer is the most common form of breast cancer diagnosed in the United States. These patients face a persistent risk of distant recurrence long after completion of their treatment and new strategies to activate anti-tumor immune responses can improve outcomes of standard therapies. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2− early-stage breast cancer patients. Methods: Five combination schedules were designed based on the timing of immunizations relative to a standard-of-care neoadjuvant chemotherapy regimen. Induction of on-treatment antibody and cellular responses, including T-cells, natural killer (NK) cells, and cytokines was determined. Tumor-infiltrating lymphocytes were quantified in core and surgical biopsies. The data were used to define the treatment effect in general and the vaccine contribution in particular. Results: Combination of P10s-PADRE with chemotherapy was safe and immunogenic. Antibody response was superior in a particular combination schedule, called schedule C, where 3 weekly immunizations preceded the first dose of chemotherapy. We observed that the schedule C, relative to other schedules, displayed an increase in CD16 expression on NK cells, a drop in serum IFN-γ, and an increase in quantity of stromal TILs in residual tumors. Subjects demonstrated a significant reduction in the size of their primary tumor and three subjects achieved pCR. Conclusions: The timing of the immunization relative to the chemotherapy seems to define the type and strength of the immune responses elicited. A particular combination schedule, schedule C, appears promising and the results warrant the conduct of randomized phase II trials.
Citation Format: Issam Makhoul, Saddam M Ibrahim, Muhammad Abu-Rmaileh, Fariba Jousheghany, Eric Siegel, Lora J Rogers, John J Lee, Sergio Pina-Oviedo, Ginell R Post, Thaddeus Beck, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ 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 P2-14-15.
Abstract P3-09-10: NTRK1/2/3 fusions are observed in both secretory and non-secretory breast cancers
Authors: Sokol Ethan , Maund Sophia , Ross Jeffrey , Wilson Timothy 
Published: March 2022

Abstract
Background NTRK1/2/3 kinase fusions are rare oncogenic drivers found in &lt;1% of solid tumors. NTRK fusion-positive (NTRK+) solid tumors have shown meaningful clinical response to small molecule NTRK inhibitors such as entrectinib and larotrectinib, and broad genomic testing will help identify patients (pts) with these rare alterations. NTRK fusions occur more frequently in some cancers than others. For example, NTRK fusions are characteristic of secretory breast cancers (BCa), and it has been posited that non-secretory BCa lack druggable NTRK fusions (PMID: 30707464). However, these conclusions were drawn on limited patient populations. Here we show evidence of NTRK fusions in both secretory and non-secretory breast tumors in the largest real-world cohort of NTRK+ breast tumors reported to date. Methods Comprehensive genomic profiling of at least 324 cancer-related genes, including NTRK1/2/3, was done at Foundation Medicine on de-identified all-comer BCa pts during the course of routine clinical care. Pathology reports and hematoxylin and eosin (H&E) images of NTRK+ breast tumor tissue were examined by a board-certified pathologist for designation of secretory vs. non-secretory phenotype. Results NTRK fusions were identified in 23 BCa specimens. H&E images were available for review in 22 cases, and another was confirmed as secretory via the pathology report. Pathologist review of those 23 cases revealed that NTRK fusions were present in 11 with secretory phenotypes, 11 with non-secretory phenotypes, and 1 with a mixed secretory phenotype. Secretory cases most often harbored a ETV6-NTRK3 fusion (n=7) with additional recurrent fusions seen in TPM3-NTRK1 (n=2) and LMNA-NTRK1 (n=2). Non-secretory breast cancers also harbored ETV6-NTRK3 (n=2), TPM3-NTRK1 (n=1), and LMNA-NTRK1 (n=1) fusions, as well as several unique fusion events that retain the NTRK kinase domain. Conclusions While rare, NTRK fusions occur in a wide variety of tumor types. Within BCa, this includes both secretory and non-secretory phenotypes, with half of the identified alterations occurring in non-secretory BCa. Recurrent events, including ETV6-NTRK3, were observed in both populations. These data support NTRK fusion testing for all BCa pts with both secretory and non-secretory histologic subtypes.
Citation Format: Ethan Sokol, Sophia Maund, Jeffrey Ross, Timothy Wilson. NTRK1/2/3 fusions are observed in both secretory and non-secretory breast cancers [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 P3-09-10.
Abstract P3-12-33: Breast cancer incidence rates in Japan showed unimodal age distribution
Authors: Uchida Ken , Ohashi Hitoshi , Nogi Hiroko 
Published: March 2022

Abstract
Purpose: Breast cancer incidence rates in Japan have been increasing recently. The incidence rates show bimodal age distribution in the developed countries. The latest studies have thrown new light on a close association between etiologic subtypes and the bimodal age distribution. To determine whether bimodal age distributions are also present in Japanese breast cancer, we investigated Japanese breast cancer incidence rates by age and biological features involved in incidence rates.Methods: Using Japanese breast Cancer Registry data, we examined age-at-diagnosis frequency distributions of breast cancer for 2017 and their hormone receptors (estrogen and progesterone) and HER2 status. Japanese female population data were referred to the registry of Statistics Bureau of Japan. Results: We included 94,612 breast cancer cases for 2017 in Japan. The number of breast cancer cases showed bimodal age distributions at 45-49 years and 65-69 years. However, the age distributions altered to unimodal age distribution with slight peaked at 45-49 years by adjusting with Japanese female population. Estrogen and progesterone receptor rates showed higher level at 45-49 years than other age groups (92.3% and 86.8%, respectively). HER2 expression rates showed lower rates (12.2%) at 45-49 years than other age groups.Conclusions: Japanese breast cancer incidence rates showed unimodal age distribution with slight peaks at 45-49 years. Luminal type breast cancer accounted for younger ages at 45-49 than elderly. Etiology of Japanese female breast cancer was different from the developed countries represented as bimodal age distribution.
Citation Format: Ken Uchida, Hitoshi Ohashi, Hiroko Nogi. Breast cancer incidence rates in Japan showed unimodal age distribution [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 P3-12-33.
Abstract P3-19-24: Long-term follow-up results of intensity modulated radiotherapy in early-stage breast cancer patients
Authors: Zolcsák Zita , Loap Pierre , Fourquet Alain , Henry Alexandre Arsene , Landherr László , Hamar Péter , Kirova Youlia 
Published: March 2022

Abstract
Introduction: Early breast cancer patients with complex anatomy received adjuvant intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) in our Institute. The aim of this study was to evaluate our results in terms of local control, overall survival, progression free survival and adverse events. Materials and methods: This study is a retrospective data analysis, enrolling patients treated with helical tomotherapy irradiation technique. Overall survival (OS) and progression free survival (PFS) curves were plotted with Kaplan-Meier method. We also analyzed the OS and PFS data by molecular subgroups. Long-term toxicities were evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 4.0. Multivariable analysis was performed to determine the predictors of the toxicities. Results: Between 2009 and 2015, 174 patients with 194 treated breasts were irradiated with helical tomotherapy. The median follow-up was 65 months. The 8-year OS was 89,2 % (IC95: 83.5% - 95.4 %), the 8-year PFS was 85,4% (IC95: 80.2%- 91%). The best therapeutic response shown by the 5 year OS data was in the HER2 receptor positive subroup 95% (IC95: 85.9% - 100%). Long-term skin toxicity was the most common long-term side effect, seen in 20.7% of the patients. 5 patients had second primary breast cancer, always located at the contralateral breast. In multivariant analysis, BMI&gt;25 kg/m2 was found to be a predictor of skin toxicity, and pre-existing cardiovascular disease was independently associated with the risk of cardiovascular toxicity. Conclusion: HT can be safely used for adjuvant breast cancer irradiation. In patients with complex anatomy, HT improves clinical target volume coverage and reduces the dose to OARs. Further prospective studies with long follow-up are needed to confirm and validate these results.
Citation Format: Zita Zolcsák, Pierre Loap, Alain Fourquet, Alexandre Arsene Henry, László Landherr, Péter Hamar, Youlia Kirova. Long-term follow-up results of intensity modulated radiotherapy in early-stage 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 P3-19-24.
Abstract P3-19-26: The impact of post-mastectomy radiotherapy on the survival of breast cancer patients aged 70 years or older: A study based on SEER database
Authors: Lin Jingyi , Luo Shiping , Zhang Jie , Song Chuangui 
Published: March 2022

Abstract
The impact of post-mastectomy radiotherapy on the survival of breast cancer patients aged 70 years or older: a study based on SEER databaseIntroduction: This study aimed to investigate the role of post-mastectomy radiotherapy (PMRT) in the female aged 70 years or older diagnosed with breast cancer, which is still controversial.Methods: This retrospective study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database. Women aged 70 years or more diagnosed with breast cancer between 2004 and 2016 following mastectomy were enrolled. Propensity score matching (PSM) was performed to reduce covariable imbalance. The univariable and multivariable analyses calculated the prognostic factors. Kaplan-Meier survival curves and multivariable Cox regression model were applied to compare breast cancer-specific survival (BCSS) and overall survival (OS) between two arms and among subgroups stratified by various clinicopathological factors. Results: Of the 27,636 female were eligible, 17.2%(n=4,747) received PMRT while 82,8%(n=22,889) not. By multivariable Cox analysis, radiotherapy was still founded to be independent prognostic factors for BCSS and OS. After 1:1 matching, PMRT were associated with significant improvement in BCSS and OS(p &lt;0.001). By contrast, the BCSS and OS benefit from PMRT were not statistically significant in patients with T1 tumor and 1-3 positive lymph nodes(BCSS:HR = 0.716,95%CI 0.406-1.263,p = 0.249;OS:HR = 0.908,95%CI 0.648-1.270,p = 0.572), and the results were consistent in patients with T2 tumor and 1-3 positive lymph nodes(BCSS:HR = 0.866,95%CI 0.664-1.130,p = 0.289;OS:HR = 0.879,95%CI 0.732-1.055,p = 0.166). Stratified by grade, number of positive lymph nodes, and HR status, there were still not survival advantage of PMRT observed for patients with T1-2N1 breast cancer(all p&gt;0.05).Conclusions: This study demonstrates that post-mastectomy radiotherapy has a definite role in improving the survival of females with elderly breast cancer. After a comprehensive assessment of the side effects and the quality of life, the omission of PMRT could be considered in patients with T1-2N1 breast cancer.
Citation Format: Jingyi Lin, Shiping Luo, Jie Zhang, Chuangui Song. The impact of post-mastectomy radiotherapy on the survival of breast cancer patients aged 70 years or older: A study based on SEER database [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 P3-19-26.
Abstract P4-04-10: Pharmacological targeting of cholinergic receptors as a novel breast cancer immunotherapy
Authors: Eliceiri Brian P. , Qian Jin , Blair Sarah 
Published: March 2022

Abstract
There is a general consensus that the devastating effect of malignant breast cancers (MBCs) is due in part to the ability of breast tumors to exploit host immune functions by subverting normal mechanisms of immunosurveillance. For example, while immunotherapies based on immune checkpoint inhibition in lymphocytes have been associated with better prognosis in other cancers, the efficacy in breast cancer has been limited. We focus here on activating biochemical pathways in antigen-presenting dendritic cells (DCs) that are otherwise immunosuppressive to stimulate the activity of tumor-infiltrating lymphocytes through a novel mechanism. To this end, we recently discovered using an immune-competent mouse model of MBC that breast cancer cells exploit adaptive immune cells such as DCs that express CHRNA7, the α7 nicotinic acetylcholine receptor. Based on the importance of the CHRNA7 signaling pathway in the control of normal inflammation in macrophages in general, we show here that CHRNA7 stimulation in DCs leads to an activation of lymphocytes associated with a reduction in MBC. Specifically, mice lacking the CHRNA7 gene have (a) decreased survival, (b) increased tumor growth kinetics, (c) immunophenotyping revealed a reduction in the “cancer-permissive” phenotype in CHRNA7 KO mice, and (d), a commensurate reduction in T cell proliferation. Based on these mechanistic proof of principle studies, we demonstrate that in contrast to the loss of CHRNA7 in KO, pharmacological activation of CHRNA7 with AR-R17779 has the opposite effect by stimulating DCs to activate the adaptive immune response which leads to tumor progression and increased survival. These findings demonstrate the preclinical potential of AR-R17779 as a clinically relevant approach to stimulate the adaptive immune system through a novel pathway that has not been examined to date, and with a small molecule drug that is stable, specific and well-tolerated.
Citation Format: Brian P. Eliceiri, Jin Qian, Sarah Blair. Pharmacological targeting of cholinergic receptors as a novel breast cancer immunotherapy [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 P4-04-10.
Abstract P4-11-12: Integrating the patient and partner distress and perceptions about prognosis in women with metastatic breast cancer guides the medical oncology consultation
Authors: Mortimer Joanne , Waisman James , Yuan  , Lavasani Sayeh , Stewart Daphne , Sedrak Mina , Patel Niki , Bitz Courtney , Clark Karen , Razavi Marianne , Loscalzo Matthew J 
Published: March 2022

Abstract
Methods: Women with metastatic breast cancer and their partners completed couples’ tailored biopsychosocial screening and alignment in perception of prognosis immediately before consultation with a Medical Oncologist. In addition, couples were offered a standardized couples’ session before the medical consultation, individual couples’ counseling, and a strengths-based group intervention. As a component of biopsychosocial screening, each patient and her partner were asked individually their understanding of prognosis. They were asked their perception of likelihood of cure with supporting text and percentages provided: 76-100%; 51-75%; 26-50%, or 0-25%. Results: To date 254 women were considered eligible for this program. Complete data for both partners is available on 205. All the patients had metastatic breast cancer prior to their Medical Oncology appointment. The average age of the patient was 54 years (Range 25-84) and 55 years (Range 26-84) for the partner. In the perception of prognosis, 48.7% of patients and their partner were aligned and 51.3% were misaligned. The patient was more likely to have considered their prognosis worse in 59% and the partner 41%. The most commonly endorsed distress items for the patient were: Worry about the future 61%; Side effects of treatment 60%; Fatigue 59%; How my family will cope 58%; and Sleeping 49%. Distress for the partner included: Feeling anxious or fearful 49%; Wanting to best help my partner 37% and Sleeping 37%. Both the patient and partner sought assistance with Understanding treatment options 73.6%; Feeling anxious or fearful 62.5%, Worry about the future 57.3% Fatigue 56.3%, and Pain 56.3%- Partner practical distress was significantly higher for those couples who were not in alignment, p&lt;.05. Conclusions: It is possible to openly ask patients and their partners about prognosis. In women with metastatic breast cancer, lack of alignment with understanding prognosis was common with the patient being more likely to have realistic expectations than their partner. A better understanding of the patient/partner’s expectations about treatment outcome has the potential to guide the Medical Oncologist to individualize communications including discussion about goals of care.
Citation Format: Joanne Mortimer, James Waisman, Yuan, Sayeh Lavasani, Daphne Stewart, Mina Sedrak, Niki Patel, Courtney Bitz, Karen Clark, Marianne Razavi, Matthew J Loscalzo. Integrating the patient and partner distress and perceptions about prognosis in women with metastatic breast cancer guides the medical oncology consultation [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 P4-11-12.