tbuckley/cabot-search huggingface dataset:
Abstract PO4-26-04: Immunolocalization of cytoplasmic ER in ER-negative breast carcinoma as a potent favorable prognostic predictor
Authors: Akiko Ebata, Takashi Suzuki, Narumi Harada-Shoji, Yohei Hamanaka, Minoru Miyashita, Erina Iwabuchi, Kiyoshi Takagi, Yasuhiro Miki, Hiroshi Tada, Takanori Ishida
Journal: Cancer Research (2024)

Abstract Background: It is known that estrogen receptor (ER) has extranuclear signaling functions in addition to classical genomic pathway, and estrogenic actions have been reported in ER-negative breast carcinoma cells. However, significance of cytoplasmic-ER immunoreactivity has not been reported in ER-negative breast carcinoma tissues. Methods: We immunolocalized cytoplasmic ER in 155 ER-negative breast carcinoma tissues and evaluated its clinicopathological significance including the prognosis. As a comparative cohort set, we also used 142 ER-positive breast carcinomas. Results: Cytoplasmic-ER immunoreactivity was detected in the carcinoma cells, but not in the non-neoplastic mammary epithelium. Cytoplasmic-ER immunoreactivity was positive in the 35 out of 155 (23%) ER-negative breast carcinoma cases, whereas it was detected only in 2 out of 142 (1.4%) ER-positive cases. Cytoplasmic ER status was positively associated with cytoplasmic-PR status, but inversely associated with Ki67 labeling index or distant free-relapse survival rate. Moreover, cytoplasmic-ER status turned out to be an independent good prognostic factor for both distant relapse-free survival and breast cancer specific survival. Conclusion: These findings suggested that cytoplasmic ER plays important roles in the ER-negative breast carcinoma, and cytoplasmic ER is a potent good prognostic factor. (accepted in Acta Histochemica et Cytochemica, 2023/Jun/27) Citation Format: Akiko Ebata, Takashi Suzuki, Narumi Harada-Shoji, Yohei Hamanaka, Minoru Miyashita, Erina Iwabuchi, Kiyoshi Takagi, Yasuhiro Miki, Hiroshi Tada, Takanori Ishida. Immunolocalization of cytoplasmic ER in ER-negative breast carcinoma as a potent favorable prognostic predictor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-26-04.
Abstract PO4-22-04: Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation
Authors: Ahmed Shalaby, Zohaib Sherwani, Lara Hathout, Imraan Jan, Bruce Haffty, Mridula George, Shicha Kumar, Coral Omene, Deborah Toppmeyer, Nisha Ohri
Journal: Cancer Research (2024)

Abstract Purpose: Adjuvant capecitabine has been shown to improve disease-free survival and overall survival in breast cancer patients who have residual disease after neoadjuvant chemotherapy, particularly in those with triple negative breast cancer (TNBC). While adjuvant chemotherapy is often completed prior to adjuvant radiotherapy (RT), capecitabine may be administered concurrent with RT to reduce the time from surgery to RT. The purpose of this study was to evaluate the feasibility of concurrent therapy and the associated rates of acute loco-regional toxicity. Materials and Methods: A retrospective chart review was performed to identify all breast cancer patients who received adjuvant capecitabine and RT. Patients with a history of prior RT, patients who were treated with capecitabine and RT sequentially, and patients who were treated with palliative intent were excluded. Capecitabine was given Monday-Friday during RT. Patient and disease characteristics, capecitabine and RT treatment details, acute toxicity, and treatment breaks were recorded. Toxicity was scored by the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Results: A total of 27 patients with non-metastatic breast cancer who received concurrent capecitabine and RT with definitive intent treated from 2013 to 2023 were identified. Median age at diagnosis was 52 years [Interquartile Range (IQR) 40-60]. Adjuvant capecitabine dose ranged from 500-1500 mg twice daily. Adjuvant RT dose ranged from 42.56 Gray (Gy) to 50.4Gy. The majority of patients (92.6%) received a sequential 10-14 Gy boost to the lumpectomy site or mastectomy scar, and 70.3% of patients received elective regional nodal RT. During treatment, all patients developed Grade 1 or 2 radiation dermatitis, while Grade 3 radiation dermatitis was noted in 4 (14.8%) patients. Two patients required a treatment break from RT, and both patients were able to subsequently complete their planned RT course. Seven patients (25.9%) required a capecitabine dose reduction or capecitabine treatment break during RT. No Grade 4 or 5 toxicities were reported. Median follow-up from RT completion was 7 months [IQR 0.98-12.2]. At last follow-up, radiation dermatitis had improved to Grade 0-1 for all patients. Conclusion: Concurrent adjuvant capecitabine and RT is a feasible treatment approach that is well tolerated with acceptable acute toxicities. Citation Format: Ahmed Shalaby, Zohaib Sherwani, Lara Hathout, Imraan Jan, Bruce Haffty, Mridula George, Shicha Kumar, Coral Omene, Deborah Toppmeyer, Nisha Ohri. Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-04.
Abstract PO4-04-04: A Multicenter, Retrospective, Real World Study of Inetetamab Combined with Pyrotinib and Vinorelbine as Treatment for HER2-positive Metastatic Breast Cancer
Authors: Yongmei Yin, Wei Li, Xiang Huang, Nan Jin, Xinyu Wu, Chunxiao Sun, Yijia Hua
Journal: Cancer Research (2024)

Abstract Background Inetetamab, a new human epidermal growth factor receptor 2 (HER2) targeted antibody to optimize the ADCC effect, has shown great effectiveness in treating HER2-positive metastatic breast cancer. Pyrotinib, another HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. Here, we investigated the efficacy and safety of inetetamb combined with pyrotinib and vinorelbine as treatment or HER2-positive metastatic breast cancer. Methods From Jan 2020 to July 2023, 77 HER2-positive metastatic breast cancer patients received inetetamb combined with pyrotinib and vinorelbine were enrolled in this study. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles were reported. Results The patients’ median age at enrollment was 53 years, 35 patients (45.5%) had hormone receptor-positive disease and 54 patients (70.1%) had visceral metastasis. The median PFS was 10.03 months (95% confidence interval [CI] 6.66 to 13.41 months). ORR was 62.3% (48/77) and CBR reached 77.9% (60/77). The most common adverse event (AE) was diarrhea, occurring in 36 patients (46.8%). While the most common grade III/IV AEs included neutropenia (9[11.7%]), leukopenia (8[10.4%]) and diarrhea (5[6.5%]). No treatment-related serious adverse events or treatment-related deaths occurred. Conclusion The combination regimen of inetetamab combined with pyrotinib and vinorelbine showed an encouraging efficacy and favorable safety in patients with HER2 positive metastatic breast cancer. Citation Format: Yongmei Yin, Wei Li, Xiang Huang, Nan Jin, Xinyu Wu, Chunxiao Sun, Yijia Hua. A Multicenter, Retrospective, Real World Study of Inetetamab Combined with Pyrotinib and Vinorelbine as Treatment for HER2-positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-04.
Abstract PS15-07: Proxalutamide plus Endocrine Therapies in Women with HR+/HER2-/AR+ Metastatic Breast Cancer: A Phase Ic Study
Authors: Hui-Ping Li, Guohong Song, Hanfang Jiang, Xu Liang, Xiaojia Wang, Hua Yang, Lili Zhang, Youzhi Tong
Journal: Cancer Research (2024)

Abstract Abstract Background: Resistance to endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is a major obstacle to the management of hormone-receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer (mBC). Targeting the AR signaling pathway has been demonstrated with promising results in this population. This phase Ic study aimed to assess the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic (PD) characteristics of the combination of proxalutamide, a high-affinity AR antagonist, with ETs in androgen receptor (AR)+/HR+/HER2- mBC. Methods: Patients in part 1 regimen-finding phase received proxalutamide plus specific ETs (letrozole [cohort A], exemestane [cohort B], or fulvestrant [cohort C]) and were assessed for dose-limiting toxicity (DLT), PK, PD, and anti-tumor activity. Part 2 expansion phase evaluated the safety and efficacy of proxalutamide plus fulvestrant. The primary endpoint was safety and tolerability. Results: Between June 18, 2019, and Sep 15, 2022, 38 (18 in part 1 and 20 in part 2) patients were treated. Efficacy analysis indicated that the ORR was 16.7% (2/12, 95% CI, 2.1%-48.4%) for cohort C and 15.0% (3/20; 95% CI, 3.2%-37.9%) for part 2. Patients achieved a median progression-free survival (PFS) of 6.4 months (95% CI, 2.7-19.3) in cohort C while an mPFS of 11.0 months (95% CI, 5.5- not estimable) in part 2. In part 1, no DLTs were reported. Grade 3 or more treatment-emergent adverse events (TEAEs) were observed in 11 (29.7%) patients (7 [18.9%] in part 1 and 4 [10.8%] in part 2) and mainly included neutrophil count decreased (8.1%) and platelet count decreased (5.4%). Seven (18.9%) had serious AEs (4 [10.8%] in part 1 and 3 [8.1%] in part 2)[1]. PD results showed a greater reduction of estradiol in cohort C compared with that in cohort B. In addition, proxalutamide was absorbed rapidly into the body with the plasma concentrations of proxalutamide and metabolites reaching a nearly steady state on day 29. Patients with AR/ER of ≤1 seemed to achieve longer PFS over those of &amp;gt;1 (8.4 months vs. 4.1 months). Conclusions: These findings suggested favorable clinical outcomes and safety profiles of the combination of proxalutamide and fulvestrant in AR+/HR+/HER2- mBC patients who have progressed on the first-line therapy, and maybe with better efficacy in patients with lower AR/ER ratio. Trial registration: NCT20191063 Citation Format: Hui-Ping Li, Guohong Song, Hanfang Jiang, Xu Liang, Xiaojia Wang, Hua Yang, Lili Zhang, Youzhi Tong. Proxalutamide plus Endocrine Therapies in Women with HR+/HER2-/AR+ Metastatic Breast Cancer: A Phase Ic Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS15-07.
Abstract PS15-08: Final Overall Survival (OS) analysis of the SAKK 21/12 trial. CR1447 in HR+/HER2- metastatic breast cancer and androgen receptor positive triple negative breast cancer
Authors: Marcus Vetter, Holer Lisa, Karin Rothgiesser, Wolfgang Schönfeld, Salome Riniker, Roger von Moos, Andreas Torjan, Elena Kralidis, Manuela Rabaglio, Mathias K. Fehr, Andreas Müller, Beat Thürlimann
Journal: Cancer Research (2024)

Abstract Introduction: CR1447 (4-Hydroxytestosteron) is a compound with aromatase inhibitor and anti-androgen receptor activity and is applied transdermally. We assessed its activity and safety in metastatic breast cancer (mBC). The primary endpoint (disease control rate at week 24) was reported in 2019. We now present the final overall survival (OS) analysis of the trial. Methods In cohort A (ER+/HER2-negative metastatic disease), one prior treatment line was allowed and 29 patients (ITT 21 patients) were included. In cohort B (triple negative mBC), eight patients were included. The trial was closed in 2018 due to futility (cohort A) and slow accrual (cohort B). Results At data cut-off on 11.04.2023 92% of all patients had died. Median OS for cohort A was 35.4 months (95% CI: 24.6-49.1) in the ITT population and 19.4 months (95% CI: 2.3-36.8) in the non-ITT population (patients with more than one line of endocrine therapy). In cohort B, median OS was 10.8 months (95% CI: 3.3-28.6). Treatment was well tolerated with no new safety signals and the majority of treatment-related adverse events (TRAE) were Grade 1 and 2. The most common TRAEs were dry skin (43%), rash (16%), fatigue (16%) and nausea (16%). Discussion Despite the trial being negative in terms of the primary endpoint, cohort A (ITT) had a median OS of 35.4 months. There were no new safety signals. Mutational analysis of AR/ER is ongoing to determine benefit of this treatment in specific subgroups. CR1447 might be a candidate drug to combine with other agents (CDK4/6 inhibitors or other targeted therapies). Citation Format: Marcus Vetter, Holer Lisa, Karin Rothgiesser, Wolfgang Schönfeld, Salome Riniker, Roger von Moos, Andreas Torjan, Elena Kralidis, Manuela Rabaglio, Mathias K. Fehr, Andreas Müller, Beat Thürlimann. Final Overall Survival (OS) analysis of the SAKK 21/12 trial. CR1447 in HR+/HER2- metastatic breast cancer and androgen receptor positive triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS15-08.
Abstract PO4-23-03: The Influence of Reconstruction Type on Outcomes in Women Undergoing Mastectomy with Immediate Reconstruction: A Nationwide Study
Authors: Lucia Castro Hernandez, Joshua Parreco
Journal: Cancer Research (2024)

Abstract INTRODUCTION: Outcomes after mastectomy with immediate reconstruction may vary depending on the type of reconstruction, but the evidence is limited and inconsistent. The purpose of this study was to compare the most common reconstruction techniques in a large national cohort of women undergoing these procedures. METHODS: The Nationwide Readmissions Database for 2016-2020 was queried for all women aged 18 years or older undergoing mastectomy for breast cancer with immediate reconstruction. The primary outcome was prolonged length of stay (LOS) greater than 7 days. The secondary outcomes were readmission within 30 days and readmission to a different hospital. The types of reconstruction were compared along with all other relevant variables from the database. Univariable comparison was performed using chi-squared tests for each outcome. Multivariable logistic regression was performed using all significant confounders. RESULTS: During the study period, 35,430 patients were identified undergoing mastectomy for breast cancer with immediate reconstruction. The rate of prolonged (LOS) was 2.4% (n= 840) and the readmission rate was 5.4% (n=1,919). From the readmitted patients, the rate of readmission to a different hospital was 14.2% (n=273). Controlling for confounders with multivariable logistic regression revealed the strongest risk factors for prolonged LOS were latissimus dorsi flap (OR 5.4 [4.0-7.4] p&amp;lt; 0.001) and an investor-owned hospital (OR 4.3 [3.5-5.2] p&amp;lt; 0.001). The highest risk of readmission was a transverse rectus abdominis flap (OR 1.3 [1.1-1.6] p&amp;lt; 0.001) and the highest risk of readmission to a different hospital was a small hospital (OR 2.2 [1.6-3.1] p&amp;lt; 0.001). CONCLUSION: Reconstruction type influences outcomes in women undergoing mastectomy. These outcomes have significant implications for surgical decision-making and fragmentation of care. Further research to identify ways to reduce adverse outcomes and improve patient satisfaction is warranted. Citation Format: Lucia Castro Hernandez, Joshua Parreco. The Influence of Reconstruction Type on Outcomes in Women Undergoing Mastectomy with Immediate Reconstruction: A Nationwide Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-03.
Abstract PO5-18-06: On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy
Authors: Katherine Tkaczuk, Paula Rosenblatt, Ranee Mehra, Katherine Scilla, Nancy Tait, Binbin Yue, Ginette Serrero
Journal: Cancer Research (2024)

Abstract Progranulin (PGRN/GP88) is an 88 kDa glycoprotein characterized by seven and a half double cysteine rich repeats which is the largest member of the granulin-epithelin protein family. PGRN/GP88 has been demonstrated as a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC), lung prostate, ovarian and digestive cancers. PGRN/GP88 tissue expression is an independent prognostic factor of recurrence in breast, lung cancers while elevated serum PGRN/GP88 level in metastatic breast, lung, ovarian and prostate cancer patients. Elevated PGRN/GP88 levels are associated with poor outcomes such as progression and shortened survival. An anti-human PGRN/GP88 monoclonal antibody able to inhibit the the in vitro and in vivo action of human PGRN/GP88 has been developed, chimerized and expressed in CHO cells. All IND enabling activities including pharmacology, GMP manufacturing, formulation and GLP toxicology studies have been conducted. The IND application has been filed and cleared by the Food and Drug Administration. A first-in-human, first-in-class phase 1 safety and efficacy clinical study of AG01 in patients with solid tumors and advanced disease with special focus on patients with breast, lung and ovarian cancers has been initiated and is on-going at the University of Maryland Greenebaum Cancer Center. The trial is registered as NCT05627960 to clinicaltrials.gov site. The presentation will provide an update on the number of patients enrolled in this on-going phase 1A trial. Supported by grants R44CA162629 and R44CA224718 from the National Cancer Institute to GS. Citation Format: Katherine Tkaczuk, Paula Rosenblatt, Ranee Mehra, Katherine Scilla, Nancy Tait, Binbin Yue, Ginette Serrero. On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-06.
Abstract PO4-25-09: HER2-Low and Ultra-Low expression in young women with luminal breast cancer in México
Authors: Jesus Edgardo Hernandez Hernandez, César Octavio Lara Torres, Bryan Moreno Moran, Cynthia Villareal Garza, Fany Iris Porras Reyes, Víctor Manuel Pérez Sánchez, Alejandro Mohar
Journal: Cancer Research (2024)

Abstract Background and objective HER2-Low in breast cancer is a biomarker with new approaches for prognosis and medical treatment decisions. However, HER2-Ultra-Low is an area of novel research. Our objective was to describe the clinicopathologic characteristics and HER2 expression status of a group of Mexican young patients with luminal breast cancer. Methods One hundred and fifty-seven young patients (&amp;lt; 40 years) with luminal breast cancer diagnosed from 2014 to 2020 were included. Clinicopathologic features, hormone receptors, HER2 expression, and tumor infiltrating lymphocytes (TILs) were assessed. We categorized patients in three groups: HER2 negative (n=95, 60.5%), HER2-Low (n=33, 21.0%), and HER2-Ultra-Low (n=29, 18.5%). Descriptive statistics were used to report demographic, clinical and histopathological characteristics. Kaplan-Meier curves and log-rank or Mantel-Cox tests were used to determine survival. Statistical significance was established using a P value &amp;lt; 0.05. This analysis was performed using R (version 4.0.4) through R Studio interface (version 1.4.1106). Results The median of age at diagnosis was 36.1 years [range 32.8-38.8], with a median of follow-up of 5.08 years [range 3.58-6.52]. The most frequent histologic type was ductal infiltrating carcinoma (81%), and 49.4% presented grade two of differentiation. T2, N0 and clinical stage II were the most common (45.2%, 44.5, and 48.1%, respectively), and fourteen patients (9.0%) presented clinical stage IV. We found statistically significant differences in Ki67 and total TILs quantification between HER2 negative and HER2-Low. Progesterone receptor levels were higher for HER2 negative and Ultra-Low in comparison to HER2-Low. The total population had a 5-year overall survival of 84.9%. We found statistically significant differences in the median of survival between HER2 groups, with a shorter survival for HER2-Low. Conclusion To date, there are no studies that describe the clinical profile and OS of HER2-Low and Ultra-Low in young patients with luminal breast cancer in México. These preliminary findings could indicate the need for further investigation in prognosis, outcomes, and specific treatment in these patients. This study contributes to better understand the clinicopathologic profile of the HER2-Ultra-Low group and its differences with the HER2-Low group. Citation Format: Jesus Edgardo Hernandez Hernandez, César Octavio Lara Torres, Bryan Moreno Moran, Cynthia Villareal Garza, Fany Iris Porras Reyes, Víctor Manuel Pérez Sánchez, Alejandro Mohar. HER2-Low and Ultra-Low expression in young women with luminal breast cancer in México [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-09.