bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO1-07-07: Radiomics features for distinguishing true recurrence versus new primary tumor following breast-conserving treatment
Authors: Qu Feilin , Su Guan-Hua , Li Jin-Hui , You Chao , Shao Zhi-Ming
Published: May 2024

Background Despite modern surgical and irradiation techniques, ipsilateral breast tumor recurrence (IBTR) accounts for 5-15% of all cancer recurrences in women treated with breast conservative treatment. Historically, the methods to define true recurrence (TR) and new primary tumor (NP) for IBTR mainly rely on clinical and pathological criteria, limiting the accuracy of the discerption and causing misclassification. This study aimed to develop a preoperative, noninvasive model for distinguishing IBTR by integrating clinicopathological review with paired dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) at diagnosis and following in-breast recurrence. MethodsWe retrospectively extracted radiomics features from MRI to develop a radiomic cohort of IBTR (n =46), among which all patients underwent paired preoperative DCE-MRI. This radiomic cohort was divided into a training cohort (n =27) and a validation cohort (n =19) with stratified random sampling. Classification of IBTR as TR or NP on the basis of tumor location, histologic subtype, estrogen receptor, and HER2 status was set as the gold standard. The least absolute shrinkage and selection operator (LASSO) regression and logistic regression were utilized to perform radiomics feature selection and model training, respectively. The clinical utility of the model was determined via decision curve analysis (DCA). Results We selected three radiomics features (first-order feature Kurtosis from the first postcontrast phase on IBTR DCE-MRI, GLCM feature Imc2 from the first postcontrast phase on IBTR DCE-MRI, and the delta feature Correlation from the precontrast phase of the change between IBTR and primary tumor DCE-MRI) to develop an IBTR-classification predicting radiomic model, which performed well in the validation cohort (AUC 0.867, 95% confidence interval (CI) 0.694-1). Further investigation for sensitivity (73.3%) and specificity (100%) verified a favorable concordance between the radiomic classification and the conventional standard, with a diagnostic accuracy of 79%. Conclusions: Our study demonstrated the feasibility of the radiomics model in predicting IBTR classification and provided preoperative information about the nature of “recurrence”. This might have important implications in surgical approaches and multidisciplinary care for IBTR. Further efforts are needed to improve the reproducibility of radiomics features and models in multiple centers.

Citation Format: Feilin Qu, Guan-Hua Su, Jin-Hui Li, Chao You, Zhi-Ming Shao. Radiomics features for distinguishing true recurrence versus new primary tumor following breast-conserving treatment [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 PO1-07-07.
Abstract PO1-08-01: Identifying a founder BRCA1 variant in the Qatari population With unique genotype – phenotype correlations
Authors: Al-Bader Salha , Habish Hind , Sulaiman Reem Al , Al-Mulla Hajer , Ghazouani Hafedh
Published: May 2024

PURPOSE: Hereditary breast and ovarian cancer syndrome (HBOC) is the most common cause of hereditary breast & ovarian cancers in Qatar and worldwide which is caused by pathogenic variants in the BRCA1& BRCA2 genes. The aim of this retrospective study is to describe a common recurrent founder pathogenic variant in the BRCA1 gene that was observed in the native Qatari population with unique genotype-phenotype correlations. METHODS: Medical records of Qatari patients (affected & unaffected) with personal and/or family history of breast & ovarian cancers who carry pathogenic/likely pathogenic mutations in the BRCA1 & BRCA2 genes were reviewed between 2013- 2020. Epidemiological information and clinical data were reviewed including age, gender, ethnic background, personal history of cancer, tumour characteristics and family history. We used frequencies and proportions to describe the data and used Kaplan-Meier curves and log-rank analysis to compare survival rates. For the analysis, we used Stata Corp. 2015. Stata Statistical Software: Release 14, College Station, TX: Stata Corp LP. Result: Our result confirms the presence of a common recurrent pathogenic variant in BRCA1 gene [(c.4787 C>A) (p. Ser 1596*)] among Qatari patients who belong to 8 consanguineous large families followed by BRCA1[ c.4065_4068delTCAA]. BRCA1 c.4787 variant is highly associated with early onset breast cancer specifically Invasive ductal carcinoma (IDC) triple negative breast cancer (stage I, grade III), rather than ovarian cancer. In addition, the c.4787 C>A was found to be highly penetrant in families for young onset breast cancer. Conclusion: We showed that BRCA1 c.4787 C>A pathogenic variant is a highly recurrent variant among Qatari consanguineous families and contributes to the early onset breast cancer in Qatar. Early identification of this variant can aide to improve patient’s survival & guide early personalized treatment and prevention.

Citation Format: Salha Al-Bader, Hind Habish, Reem Al Sulaiman, Hajer Al-Mulla, Hafedh Ghazouani. Identifying a founder BRCA1 variant in the Qatari population With unique genotype – phenotype correlations [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 PO1-08-01.
Abstract PO1-12-03: Quality of Life in Patients Diagnosed and Treated for Breast Cancer in Uruguay
Authors: Camejo Natalia , Amarillo Dahiana , Castillo Cecilia , Guerrina Maria , Savio Florencia , Carrasco Mariana , Strazzarino Noelia , Hernandez Ana laura , Herrera Guadalupe , Krygier Gabriel
Published: May 2024

Introduction: Breast cancer (BC) and its treatment can impair patient quality of life (QOL), and those undergoing more aggressive treatments may be more severely impacted. Objective: Assess the level of perception of the QOL of patients treated for BC at the Hospital de Clínicas and the Hospital Departamental de Soriano. Materials and Methods: A questionnaire for cancer patients (EORTC, QLQ-C30) and one specific for BC (EORTC QLQ-BR23) were used. Results: A total of 158 patients who had completed chemotherapy treatment at least one year prior to the evaluation were enrolled. The average age was 61 years old. QLQ-C30 questionnaire: the global QOL score (GQOL) was high: 70.9. Patients undergoing conservative surgery (CS) had better scores in physical and emotional functioning (p < 0.005) and presented less frequently with: pain, constipation and financial difficulties (p < 0.005). Those undergoing sentinel lymph node biopsy (SLNB) had higher scores for GQOL and for physical, role and social functioning scales (p < 0.001) and had less fatigue, pain, insomnia and financial difficulties (p < 0.005). Questionnaire QLQ-BR23: sexual functioning and sexual enjoyment scales were relatively low. Patients undergoing CS had better scores on the functional scales: body image and future outlook; and fewer breast symptoms (p < 0.005). Those undergoing SLNB also had better scores on the functional scales for body image and future outlook future and presented less frequently with symptoms (p < 0.005). Conclusion: Patients had high values on the GQOL scale, those undergoing CS and SLNB had better scores on most functional and problem/symptom scales. The implementation of intervention strategies aimed at improving the quality of life and the physical and emotional care of patients is recommended.

Citation Format: Natalia Camejo, Dahiana Amarillo, Cecilia Castillo, Maria Guerrina, Florencia Savio, Mariana Carrasco, Noelia Strazzarino, Ana laura Hernandez, Guadalupe Herrera, Gabriel Krygier. Quality of Life in Patients Diagnosed and Treated for Breast Cancer in Uruguay [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 PO1-12-03.
Abstract PO1-13-01: Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE study
Authors: Shao Zhimin , Zhang Qingyuan , Ouyang Quchang , Liu Qiang , Feng Jifeng , Li Hui-Ping , Wang Xiaojia , Liao Ning , Yang Liu , Zhu Qinyi , Qian Chenxi , Jiang Zefei
Published: May 2024

Aim:

Abemaciclib demonstrated efficacy with tolerable safety profile in Chinese patients (CN pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) and high-risk early breast cancer (EBC). The overall safety profile of abemaciclib in Chinese ABC and EBC pts was consistent with overall population in the MONARCH plus and monarchE studies. To better understand the safety of abemaciclib in CN pts, beyond the previously reported most frequent adverse events (AEs), we report a comprehensive summary of other selected AEs in CN pts in the two trials.

Methods:

Study designs of MONARCH plus (NCT02763566) and monarchE (NCT03155997) studies were reported previously. To report detailed characteristics of a selected AE profile, including alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, fatigue, nausea, and vomiting, data were pooled across all CN pts from these two phase 3 studies. The safety population was defined as all randomized patients receiving at least 1 dose of Abemaciclib or endocrine therapy. Data cutoff time is May 18, 2020 and July 1, 2022, respectively.

Results:

Among 6052 participants in the overall safety population, 875 CN pts (14.5%) were included (512/3100 abemaciclib, 363/2952 placebo). CN pts treated with abemaciclib indicated consistent AE profiles in combination with different endocrine therapies (aromatase inhibitors or Fulvestrant). Detailed characteristics of selected AEs are summarized in table. No deaths due to the selected AEs were reported in CN pts.

Conclusion:

The selected AEs of abemaciclib group were in low severity with limited grade 3-4 events. Those AEs were tolerable and generally manageable in CN pts in the MONARCH plus and monarchE trials.

Citation Format: Zhimin Shao, Qingyuan Zhang, Quchang Ouyang, Qiang Liu, Jifeng Feng, Hui-Ping Li, Xiaojia Wang, Ning Liao, Liu Yang, Qinyi Zhu, Chenxi Qian, Zefei Jiang. Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE 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 PO1-13-01.
Abstract PO1-13-08: Comparative analysis of stearoyl-CoA desaturase 1 expression and activity index in model cell lines of breast cancer subclasses
Authors: Feizi Hamid-Reza , Mehdizadeh Amir , Sanaat Zohreh , Abbasi Khadijeh , Gieseler Frank , Darabi Masoud
Published: May 2024

Introduction

Due to the unique conditions of the tumor microenvironment, such as hypoxia, poor angiogenesis, and mitochondrial dysfunction, cancer cells face challenges in obtaining nutrients and energy supply. However, monounsaturated fatty acids have been identified as preferred substrates for energy generation and maintenance of cellular structures in cancer cells. These fatty acids can be obtained through de novo fatty acid synthesis. Stearoyl-CoA desaturase 1 (SCD1) is the primary enzyme involved in the biosynthesis of monounsaturated fatty acids from saturated fatty acids and is known to be upregulated in various malignancies, including breast cancer. This study aimed to assess the expression and activity index of SCD1 in well-characterized MCF-7, SK-BR3, and MDA-MB231 breast cancer cell lines, representing luminal A/B, HER2-enriched, and triple-negative subtypes, respectively. Methods

The breast cancer cell lines were cultured in RPMI-1640 medium with 10% fetal bovine serum at 37°C, 5% CO2, and 95% humidity for 72 hours. After harvesting the cells, SCD1 expression was analyzed using real-time quantitative PCR, and the activity index was determined by measuring the ratio of monounsaturated fatty acids to saturated fatty acids using capillary gas-liquid chromatography. Results

MCF-7 cell line showed a significantly higher SCD1 expression compared to MDA-MB231 (250-fold, p< 0.0001) and SK-BR3 (83-fold, p< 0.0001) cell lines. The activity index of SCD1 was significantly higher in both MCF-7 and MDA-MB231 cell lines with fold changes of 2.6 and 2.5, respectively, compared to SK-BR3 cell line (p=0.004 for both). Conclusion

Cell model assays demonstrated that the luminal A/B and triple-negative subtypes showed a higher capacity to convert saturated fatty acids to monounsaturated fatty acids through SCD1 enzyme activity, indicating a different lipid metabolism profile in the HER2-enriched subtype. These new findings reveal differences in SCD1 expression and activity among breast cancer subclasses. They highlight vulnerabilities in metabolism and identify potential therapeutic targets with clinical implications for managing breast cancer.

Citation Format: Hamid-Reza Feizi, Amir Mehdizadeh, Zohreh Sanaat, Khadijeh Abbasi, Frank Gieseler, Masoud Darabi. Comparative analysis of stearoyl-CoA desaturase 1 expression and activity index in model cell lines of breast cancer subclasses [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 PO1-13-08.
Abstract PO1-13-09: Programmed cell death ligand 1 (PD-L1) is constitutively expressed on tumorspheres cultured from circulating cancer stem cells in breast cancer patients
Authors: PIZON Monika , Schott Dorothea , Pachmann Ulrich , Pachmann Katharina
Published: May 2024

Background Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies revealed that enhanced PDL-1 expression in cancer stem cells is a novel mechanism to promoting cancer cell immune evasion and could crucially contribute to the maintenance of CSC self-renewal. Understanding the mechanisms behind this PDL-1 overexpression in cancer stem cells is critical for developing more effective anti-PD-1/PD-L1 therapy. Therefore the aim of the study was to determine the number of tumorspheres and expression of PD-L1 on tumorspheres cultured from cCSC in breast cancer patients. Methods: 110 patients with breast cancer in different stages of disease were included in this study. The determination of circulating cancer stem cells was performed using the sphere-forming assay. Additionally anti-PDL-1 antibody staining was applied to examine PDL-1 expression on breast tumorspheres. Results: We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres increased significantly with tumor progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p< 0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p< 0.05). The number of tumorspheres was positively correlated with Ki-67, Her2 status and grade score in primary breast tumors. We observed high PDL-1 expression and their considerable heterogeneity in enriched tumorspheres. Conclusion: The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with expression of PDL-1 might suggest their immunomodulating potential. Better understanding of the interaction between cCSCs and tumor immunology may help to identify strategies to eradicate the minor subpopulation that escapes conventional therapy attack, thus providing a solution to the problem of drug resistance and metastasis.

Citation Format: Monika PIZON, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. Programmed cell death ligand 1 (PD-L1) is constitutively expressed on tumorspheres cultured from circulating cancer stem cells in breast cancer patients [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 PO1-13-09.
Abstract PO1-21-01: A Case of High Grade Metastatic Encapsulated Papillary Carcinoma and a Look at Current Treatment Guidelines
Authors: Gore Nicholas , Silva Madeline , Calvo-Strube Carissia
Published: May 2024

Background: Encapsulated papillary carcinoma is a well-documented malignancy in the world of breast surgery. It is often described as a less invasive form of breast cancer, with a more indolent clinical course. Most EPC pathology demonstrates low grade tumors, with rare findings of metastases at time of diagnosis. EPC currently accounts for 1-2% of all breast cancers. It is distinguished by its fibrovascular core, which is covered with epithelium with or without a myoepithelial layer. Despite EPC being well-recognized, current management remains controversial. Most commonly, however, it is treated and managed as an in-situ disease. Case Presentation: We present a case of a 64-year-old female who initially presented with a painless lump in her left breast, which on biopsy demonstrated DCIS involved with a papillary lesion. On excision, the patient was upstaged to IDC in a background of EPC. She then underwent re-excision with confirmed negative margins. Despite this, over the following months, the patient continued to have increased pain, swelling, and an episode of superficial thrombophlebitis. She was taken back to the OR at this time and was found to have a new mass with a large feeding vein. Pathology was significant for high grade multifocal EPC with small and large vessel lympho-vascular invasion. Lesion noted to be metachronous. Additionally, metastases to the axilla were identified, requiring an axillary dissection. Conclusion: High grade encapsulated papillary carcinoma is a rare member of the indolent papillary breast cancer family. This unusually invasive type of cancer should be treated and managed in a more aggressive fashion, like its clinically similar cousin invasive ductal carcinoma. The current management standard of treating EPC as in situ disease is not robust enough and can lead to disease recurrence and need for repeat resection and treatment.

Citation Format: Nicholas Gore MD, Madeline Silva MD, Carissia Calvo-Strube MD. A Case of High Grade Metastatic Encapsulated Papillary Carcinoma and a Look at Current Treatment Guidelines [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 PO1-21-01.
Abstract PO1-22-11: Use of magnetic tracer and magnetic resonance imaging for sentinel lymph node detection after breast cancer recurrence and previous axillary surgery: The SentiRecur feasibility study
Authors: VikhePatil Eva , Chin Kian , SegerbardPlanoudis Amalia , Dussan Carlos , Leonhardt Henrik , Zaar Pontus , Gialis Pantelis , Wärnberg Fredrik
Published: May 2024

Background: Preoperative imaging increases the chance of finding the sentinel lymph node (SLN) in patients with previous axillary surgery. Current clinical routine for preoperative localization is Technetium (Tc99) and lymphoscintigraphy. An alternative method has been proposed using superparamagnetic iron oxide nanoparticles (SPIO) and non-contrast enhanced magnetic resonance imaging (MRI) of the axillae. In this feasibility study, SPIO+MRI was used in parallel with Tc99+scintigraphy for SLN localization. Methods: Twenty patients with recurrent breast cancer and previous axillary surgery at Sahlgrenska and Linkoping University Hospitals scheduled for SLN-biopsy will be included. All patients received Tc99+scintigraphy as per standard practice. In addition, a SPIO injection and bilateral axillary MRI was performed up to four weeks before surgery. Both preoperative and perioperative SLN-detection rates were studied. Rates and number of concordant SLNs were presented as percentages. Results: So far, ten patients received both SPIO+MRI and Tc99+scintigraphy. The SLN-detection rates per patient were 70% (7/10) for SPIO+MRI and 50% (5/10) for Tc99+scintigraphy, respectively. The perioperative SLN-detection rates per patient were 60% (6/10) for SPIO using the magnetic probe (SentiMagTM) and 30% (3/10) for Tc99 using a gamma-probe. In total, eleven SLNs were detected with SentiMag and four with gamma-probe. Of all SLNs, only four (36%) contained both SPIO and Tc99. Conclusion(s): Although preliminary, the results suggest that Tc99+scintigraphy may be replaced by the magnetic technique for detecting SLNs after earlier axillary surgery. The magnetic technique enables logistic advantages as tracer injection and SLN identification during a wider time frame. Table 1. Sentinel lymph node detection in patients with recurrent breast cancer

Table 1. Sentinel lymph node detection in patients with recurrent breast cancer

Citation Format: Eva VikhePatil, Kian Chin, Amalia SegerbardPlanoudis, Carlos Dussan, Henrik Leonhardt, Pontus Zaar, Pantelis Gialis, Fredrik Wärnberg. Use of magnetic tracer and magnetic resonance imaging for sentinel lymph node detection after breast cancer recurrence and previous axillary surgery: The SentiRecur feasibility 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 PO1-22-11.
Abstract PO1-23-07: The effect of intra-operative margin assessment during breast conserving surgery for breast cancer in a Dutch cohort
Authors: Wooldrik Sophie , Voort Elles van de , Klem Taco , van Dalen Thijs , Verhoef Cornelis , Struik Gerson , Birnie Erwin
Published: May 2024

Background

Pre-operative tumour localisation and intraoperative specimen radiography are necessary to perform adequate resection of non-palpable breast tumours. Intraoperative digital specimen mammography (IDSM), is an alternative to conventional specimen radiography (CSR) and has the benefit of providing immediate specimen evaluation and the potential of decreasing operation time. IDSM may also reduce positive margins and re-excision rates. IDSM was implemented in our hospital in 2018. The study objective was to evaluate the surgery time, radicality and re-excisions in IDSM and CSR.

Methods

A single centre retrospective cohort study with two cohorts: CSR (n=532) and IDSM (n=475). The primary outcome was duration of surgery. Secondary outcomes were margin status of the primary surgery, the perioperative cavity shave rate and the re-excision rate. Differences between cohorts were compared using univariate statistics and multiple regression to adjust for variables that were statistically significantly associated with duration of surgery.

Results

IDSM use was associated with 8 minutes shorter surgery time (B -8.242, p < 0.001). Treatment variables independently associated with the duration of surgery were use of IDSM, type of (axillary) surgery and the performance of cavity shaving. Cavity shaves were more often performed when IDSM was used (24% versus 14% in CSR group, p < 0.001), while the proportion of radical first surgeries (93% versus 96% respectively, p = 0.070) was comparable.

Conclusion

IDSM was associated with a modest reduction in duration of surgery. Surgeons performed more cavity shaves since IDSM but this was not reflected by a lower proportion of patients with positive margins.

Table 1. Baseline characteristics of the CSR versus the IDSM cohort

Table 2. Results of surgery in the CSR versus the IDSM cohort.

Citation Format: Sophie Wooldrik, Elles van de Voort, Taco Klem, Thijs van Dalen, Cornelis Verhoef, Gerson Struik, Erwin Birnie. The effect of intra-operative margin assessment during breast conserving surgery for breast cancer in a Dutch cohort [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 PO1-23-07.
Abstract PO1-24-07: LYSOSOMAL-ASSOCIATED TRANSMENBRANE 4B (LAPTM4B) AS POTENTIAL BIOMARKER IN BREAST CANCER
Authors: Murillo Serafin Morales , Cudós Ariadna Gasol , Der-Abrain Noemí Tuset , Urdanibia Izaskun , Sánchez Ana Velasco
Published: May 2024

LAPTM4B is a transmembrane that promotes autophagy and renders tumor cells resistant to metabolic and genotoxic stress. Increased expression of LAPTM4B has been found in breast, liver, lung, ovarian, uterine and gastric cancers. Overexpression of LAPTM4B contributes to chemotherapy resistance, proliferation and metastases.

We analyze the expression of LAPTM4B in serum by ELISA method in a series of breast cancer patients in different clinical situations to assess its possible potential as a biomarker.

A total of 135 patients were analyzed, 95 patients were in early breast cancer and 50 in metastatic disease. Of the 95 patients with early disease, 52 had a luminal A phenotype, 19 luminal B, 15 HER2 positive and 9 triple negative. And of the other 50 they were luminal in 34, HER2 positive in 11 and triple negative in 5.

The attached table specifies the values of the LAPTM4B expression in the different clinical situations.

GLOBAL LUMINAL A LUMNAL B HER2 TRIPLE NEGATIVE

SITUATIONS Laptm4b n Laptm4b n Laptm4b n Laptm4b n Laptm4b n

EARLY 9,6 ng/ml 95 7,7 ng/ml 52 12,8 ng/ml 19 13,4 ng/ml 15 7,1 ng/ml 9

METASTATIC 16,8 ng/ml 50 13,7 ng/ml 34 7,2 ng/ml 11 58,9 ng/ml 5

We found a statistic difference in the expression of LAPTM4B in patients with early and metastatic disease (ANOVA test p:0,028 ). LAPTM4B was higher in the luminal B and HER2 subtypes in early breast cancer while in metastatic disease was overexpressed in triple negative.

An interesting finding was that in metastatic disease, LAPTM4B was overexpressed in patients with progression compared to patients in response. 30 ng/ml vs 10 ng/ml (ANOVA test p:0,011)

LAPTM4B expression may be a potential biomarker in breast cancer since its expression is statistically different in early and metastatic disease (9,6 vs 16,8 ng/ml).In addition, patients with metastatic breast cancer who re in response also have lower levels of LAPTM4B compared with patients in progression. Monitoring the levels of LAPTM4B in serum can help us to predict the treatment response.

Citation Format: Serafin Morales Murillo, Ariadna Gasol Cudós, Noemí Tuset Der-Abrain, Izaskun Urdanibia, Ana Velasco Sánchez. LYSOSOMAL-ASSOCIATED TRANSMENBRANE 4B (LAPTM4B) AS POTENTIAL BIOMARKER IN 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 PO1-24-07.
Abstract PO1-27-09: TRIPTORELIN (11.25MG) vs TRIPTORELIN (3.75MG) IN PREMENOPAUSAL WOMEN WITH HIGH-RISK EARLY STAGE BREAST CANCER RH(+) and HER2(-) REAL WORLD EXPERIENCE. TRIPTO3 RESULTS
Authors: Limon Ronald , Lopez-Pereyra Mariano , Gianella Mario , Espinoza Neysa , Ramirez Denize , Antelo Carlos , Sitic Claudia , Cortez Wara , De Guzman Oscar Niño , Neciosup Silvia , Valdivieso Natalia
Published: May 2024

Background. Premenopausal women with high risk early stage BC HR+/Her2- present as a complex disease and generally have worse survival outcomes compared to postmenopausal women with the same disease. There are pathological clinical factors and genomic platforms that help us in therapeutic decisions. The use of triptorelin 3.75mg associated with AI promotes favorable results in terms of survival for premenopausal women with high-risk Early stage BC. TEXT/SOFT trial. TRIPTO3 study evaluates the use of Triptorelin 11.25mg vs. Triptorelin 3.75mg in this specific patient population. Methods: We reviewed medical records of premenopausal female patients with high-risk early stage breast cancer who have been treated and received triptorelin 3.75mg and triptorelin 11.25mg as part of their treatment. All patients were treated at a private Oncology Center between 2013 and 2020. The primary objective was disease-free survival. Results: 52 patients were found who met the inclusion criteria. 28(53.8%) patients received triptorelin 11.25mg and 24(46.2%) patients received triptorelin 3.75mg respectively. The median follow-up was 63 months and the disease-free survival for the Triptorelin 11.25mg group was 91.2% and for the Triptorelin 3.75mg group was 86.8% respectively (Hazard Ratio of disease-free survival was 1.2; 95% IC (0.2-7.2). Disease-free survival for both groups regardless of triptorelin dose was 89% at 5 years. The median disease-free survival was not reached in both groups. Conclusions: Our findings show that triptorelin 11.25 mg is similar to the use of triptorelin 3.75 mg in terms of disease-free survival for premenopausal women with high-risk early stage breast cancer.

Citation Format: Ronald Limon, Mariano Lopez-Pereyra, Mario Gianella, Neysa Espinoza, Denize Ramirez, Carlos Antelo, Claudia Sitic, Wara Cortez, Oscar Niño De Guzman, Silvia Neciosup, Natalia Valdivieso. TRIPTORELIN (11.25MG) vs TRIPTORELIN (3.75MG) IN PREMENOPAUSAL WOMEN WITH HIGH-RISK EARLY STAGE BREAST CANCER RH(+) and HER2(-) REAL WORLD EXPERIENCE. TRIPTO3 RESULTS [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 PO1-27-09.
Abstract PO1-29-04: Spatial tumor microenvironment profiling identifies immune features that correlate with response to T-DXd treatment in patients with metastatic breast cancer
Authors: Zhao Hong , Vasquez Matthew , Zhang Jeffrey , Das Glori , Lee Ji-Hoon , Gao Yuan , Zhang Jilun , Li Xiaoxian , Chang Jenny , Wong Stephen
Published: May 2024

Objective: It is unclear which patients with metastatic breast cancer respond to the new antibody drug conjugate T-DXd treatment. Methods: We profiled 22 pre-T-DXd treatment metastatic tissue samples from patients using Nanostring GeoMX digital spatial profiler of tumor infiltrating immune cells and stroma components. Among the 22 metastatic samples, 10 were bone metastases 7 of the patients were defined as responder (R) and 3 were defined as non-responder (NR) to T-DXd treatment; 4 brain metastases with 2 R and 2 NR; 4 lymph node metastases with 2 R and 2 NR, and 3 liver metastases with all patients were NR to T-DXd. In each metastatic tissue section, 6-8 circular regions of interest (ROI) with 300µm diameter were selected by tumor epithepial marker (pan CK) and immune cells marker (CD45) throughout different areas of the tumor. The spatial quantification of 22 immune markers and 3 stroma elements (fibronectin, fibroblast activation protein, and smooth muscle actin) in each ROI was analyzed. Results: Based on the segmented CD45-positive cell numbers, a total of 144 ROIs were classified into high tumor-infiltrating immune ROIs (high-TIL, n=47) and low-TIL ROIs (n=97). Within the high-TIL ROIs, none immune markers showed significant difference in either the R or NR group across all metastasis sites (P >0.05, Figure 1). Within the low-TIL ROIs, several immune markers, including PD-L1, PD-1, CD3, CD56, CD20, CD14, CD11c, CTLA-4, CD45, and B2M (Beta-2-microglobulin, an antigen presentation marker) showed significant elevation in the R group than those in the NR group (P < 0.05, Figure 2). Other immune markers including CD4 and CD8 were not significantly different in the R vs. NR groups in the low-TIL ROIs. High Ki-67 was correlated with R in both high and low-TIL ROIs. None of the three stroma markers was associated to treatment response to T-DXd. Conclusions: Enrichment of PD-L1, PD-1, CD3, CD56, CD20, CD14, CD11c, CTLA-4, CD45, and B2M in the metastatic tumor sites favors the treatment response to T-DXd in patients with metastatic breast cancer. Our study provides novel evidence that immune-suppression is associated with patients’ response to T-DXd treatment, which may due to the unique mechanism of action of T-DXd.

Citation Format: Hong Zhao, Matthew Vasquez, Jeffrey Zhang, Glori Das, Ji-Hoon Lee, Yuan Gao, Jilun Zhang, Xiaoxian Li, Jenny Chang, Stephen Wong. Spatial tumor microenvironment profiling identifies immune features that correlate with response to T-DXd treatment in patients with 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 PO1-29-04.
Abstract PO2-05-07: Which treatment is done in patients with metastatic breast cancer who received a prior treatment with CDK4/6 inhibitors? A real-world experience in a single italian Institution
Authors: Bravaccini Sara , Balzi William , Roncadori Andrea , Virga Alessandra , Ulivi Paola , Martinelli Giovanni , Maltoni Roberta
Published: May 2024

Patients with HR positive (HR+) and c-erb-b2 negative (HER2-) advanced breast cancer are treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with hormone therapy (HT). At the time of disease progression with these treatments, no established guidelines are defined for the subsequent therapeutic options.Treatment options after progression can be different, in terms of use of chemotherapy or ET alone, or the combination of the two, or of other biological agents (such as everolimus) or the HT combined with other therapies.

We aimed to verify in our Institute (IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy) how HR+ mBC patients are treated after having received a treatment with HT plus CDK4/6 inhibitors (ribociclib, palbociclib, abemaciclib). 105 mBC patients, 32 of whom were treated with CD4/6 inhibitors plus letrozole and 73 treated with CDK4/6 inhibitors and fulvestrant were included in the study. 83 were treated with palbociclib, 16 with ribociclib and 6 with abemaciclib. The median age was 65 years (range 40-86), 58 were younger than 65 years. 90 were in postmenopausal status. On the total 105 patients, 46 (43.8%) were treated with a single chemotherapy regimen while 25 (23.8%) with a combined schedule of chemotherapies (Table 1). Only 9 (8.6%) have been treated with HT alone. 22 (20.95%) patients received combined treatments with ET or chemotherapy+targeted therapy or chemotherapy +immune checkpoint inhibitor. 1 (0.95%) patients was treated with a triplet chemotherapy regimen (cyclophosphamide+capecitabine +vinorelbine), 2 (1.9%) for whom the re-biopsy of the tumor resulted HER2 + were treated with taxol +pertuzumab +trastuzumab. 82/105 (78%) patients performed more lines of therapies after CDK4/6 inhibitors.

In conclusion, patients with mBC were treated heterogeneously. The major part of them have been treated with chemotherapy alone or with combination of more chemotherapies. The evaluation of the patient response in relation to the different therapies is still ongoing as well as the effect of all the other therapies beyond the first line of treatment.

Table 1. Type of treatments done in mBC patients (Nf105) after treatment with HT+ CDK4/6 inhibitors

*1 performed only 1 cycle

** 1 was treated also with a metronomic schedule of therapy

Citation Format: Sara Bravaccini, William Balzi, Andrea Roncadori, Alessandra Virga, Paola Ulivi, Giovanni Martinelli, Roberta Maltoni. Which treatment is done in patients with metastatic breast cancer who received a prior treatment with CDK4/6 inhibitors? A real-world experience in a single italian Institution [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 PO2-05-07.
Abstract PO2-05-13: HER2 status presented an unstable switching from primary to recurrent breast cancer
Authors: Zhu Anjie , Li Hui-Ping
Published: May 2024

Background: Breast cancer patients with HER2-2+ expression had heterogeneous characteristic. Treatment decision is of great importance after progression. Objective: We explored patients with HER2-2+ in matched primary or recurrent/metastatic tumor samples from January 2010 to June 2022 in our institute were included to evaluate the evolution from or to HER2-2+ expression. Meanwhile, with an emerging of novel entity as HER2-low expression breast cancer, we included this category when analysis as well. Results: In the cohort of a total of 159 breast cancer patients with HER2-2+ expression in either primary tumor or locoregional/distant metastases samples, HER2-2+ breast cancer accounted for 44.0% in primary tumor and 88.8% in recurrent diseases. There were 18.5% and 15.2% patients with HER2 gene amplification on ISH assay among primary and recurrent/metastatic HER2-2+ breast cancers, respectively. The overall rate of HER2 IHC discordance was 67.1%. Among primary HER2-2+ cases, 74.6% maintained in HER2-2+ when disease relapsed. Discordance was mostly driven by cases switching from HER2-2+ to HER2-1+ (64.7%). In HER2-2+ recurrent/metastatic cases, discordance was mostly driven by cases switching from HER2-0 to HER2-2+ (47.1%). The proportion of HER2 discordant cases got a higher statistically trend among HR-positive patients in compared with HR-negative patients (44.1% vs. 21.7%, p = 0.062). There were 35.0% in primary HR-positive/HER2-negative patients and 11.8% in primary triple-negative patients switching from HER2-0 to HER2-low when disease progressed, respectively. Meanwhile, HER2 discordance rate had a significant difference across different metastatic sites (p = 0.026). All contralateral breast and skin metastasis presented with discordant HER2 results. While, all central nervous system metastasis maintained the same HER2-low expression. HER2-positive phenotype in primary breast cancer samples loss their positivity in 42.1% cases. There was a total of 6.6% cases gained HER2 positivity in recurrent breast cancer samples. Conclusion: HER2 expression from primary to relapse breast cancer samples were highly unstable. Biopsy of recurrent sites was necessary to find novel treatment.

Citation Format: Anjie Zhu, Hui-Ping Li. HER2 status presented an unstable switching from primary to recurrent 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 PO2-05-13.
Abstract PO2-18-12: Updated Results of a Phase II Study: Neoadjuvant Inetetamab Combined with Pertuzumab, Paclitaxel and Carboplatin for Locally Advanced HER2-Positive Breast Cancer
Authors: Chai Yue , Liu Jiaxuan , Jiang Mingxia , He Maiyue , Wang Xin , Wang Yipeng , Yang Xue , Wang Jing , Xu Binghe , Li Qiao
Published: May 2024

Background:

Inetetamab is a neotype HER2-targeted monoclonal antibody with amino acids modified Fc segment which optimizes the antibody-dependent cellular cytotoxicity effect. However, robust evidence evaluating the combination of inetetamab combined with pertuzumab, paclitaxel and carboplatin (TCbIP) for neoadjuvant therapy is still lacking. This study aimed to evaluate the efficacy and safety of TCbIP as a neoadjuvant therapy for patients with locally advanced HER2-positive breast cancer. We now present the updated results of this trial.

Methods:

This phase II trial included female patients with histologically confirmed stage IIA to IIIC HER2-positive primary invasive breast cancer. Eligible patients received TCbIP treatment every three weeks for a maximum of six cycles followed by surgery. The primary endpoint was pathologic complete response (pCR, ypT0/is ypN0) rate. Key secondary endpoints included near pCR (npCR, residual breast disease < 1cm) rate, objective response rate (ORR) and safety.

Results:

From November 2021 to July 2023, 40 patients were enrolled in the trial. One patient received one cycle of the study treatment but was lost to follow-up without surgery, and five patients received one cycle of the study treatment and were still undergoing treatment, leaving 34 patients in the intention-to-treat (ITT) population. Among these 34 patients (82.4% in stage III), 22 patients completed the study treatment and surgery (per-protocol [PP] population) and 12 patients were still undergoing neoadjuvant treatment. The ORR was 91.2% (31/34) in the ITT population and 86.4% (19/22) in the PP population. Among the 22 patients in the PP population, 12 patients (54.5%) achieved pCR, and18 patients (81.8%) achieved npCR. The pCR rates for patients with hormone receptor (HR) negative and positive tumors were 80.0% (8/10) and 33.3% (4/12), respectively. The most common grade 3 adverse event was neutropenia (17.6%). No significant reduction in the left ventricular ejection fraction was observed in any patient.

Conclusions:

Neoadjuvant therapy with TCbIP demonstrated promising efficacy and manageable toxicity in patients with HER2-positive locally advanced breast cancer.

Registration number: NCT05749016 (www.clinicaltrials.gov).

Citation Format: Yue Chai, Jiaxuan Liu, Mingxia Jiang, Maiyue He, Xin Wang, Yipeng Wang, Xue Yang, Jing Wang, Binghe Xu, Qiao Li. Updated Results of a Phase II Study: Neoadjuvant Inetetamab Combined with Pertuzumab, Paclitaxel and Carboplatin for Locally Advanced HER2-Positive 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 PO2-18-12.
Abstract PO2-24-12: Tumor-specific circRNAs elicit anti-tumor immune response via encoding cryptic antigenic peptides
Authors: Huang Di , Chen Jianing , Su Shicheng , Song Erwei
Published: May 2024

Emerging data have shown that previously defined noncoding genomes might encode human leukocyte antigen (HLA) binding peptides as cryptic antigens to stimulate adaptive immunity. However, the significance and mechanisms of cryptic antigens in anti-tumor immunity remain unclear. Here, mass spectrometry for HLA class I (HLA-I) peptidome coupled with ribosome sequencing of human breast cancer samples identified HLA-I binding cryptic antigenic peptides, which were noncanonically translated by a tumor-specific circular RNA CEIP (circCEIP). Importantly, the cryptic peptides efficiently primed naive CD4+ and CD8+ T cells in an antigen-specific manner and elicited anti-tumor immunity. Clinically, the expression of circCEIP and its encoding peptides was associated with massive infiltration of antigen-specific CD8+ T cells and better survival of breast cancer and melanoma patients. Mechanistically, circCEIP-encoding peptides had strong binding affinity to both HLA-I and II molecules, respectively. In vivo, administration of vaccines devised by tumor-specific circRNA or its encoding peptides in breast cancer or melanoma-bearing mice dramatically enhanced the infiltration of tumor-antigen specific cytotoxic T cells, leading to effective tumor control. Overall, our findings revealed that noncanonical translation of circRNAs can drive efficient anti-tumor immunity, suggesting that vaccination exploiting tumor-specific circRNAs may serve as an appealing immunotherapeutic strategy against malignant tumors.

Citation Format: Di Huang, Jianing Chen, Shicheng Su, Erwei Song. Tumor-specific circRNAs elicit anti-tumor immune response via encoding cryptic antigenic peptides [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 PO2-24-12.
Abstract PO2-26-05: Disparities at the Convergence of Race and Ethnicity: Examining Trends and Outcomes in Young Women Diagnosed with Breast Cancer
Authors: Gopalakrishnan Ragisha , Gandhi Esha , Fernandez Maria
Published: May 2024

Purpose: In breast cancer, research has shown that race/ethnicity can be associated with disease predisposition, access to care, and outcomes. There are numerous studies that combine Hispanic and Haitian women of all races into a single group may overlook opportunities to identify important characteristics within this heterogeneous group that could more accurately predict outcomes and reveal opportunities to improve care. While these groups have been studied, there is limited data about the impact race and ethnicity has on young adult populations with breast cancer. In this study, we sought to compare tumor subtype, stage at diagnosis, time to surgery (TTS), and overall survival (OS) among Hispanic and Haitian patients to patients of non-Hispanic descent. Methods: Women 18 years of age or older who had been diagnosed with stage 0-IV breast cancer and who had undergone lumpectomy or mastectomy were identified in the National Cancer Database (2015-2021). Tumor subtype and stage at diagnosis were compared by race/ethnicity. Multivariable linear regression and Cox proportional hazards modeling were used to estimate associations between race/ethnicity and adjusted TTS and OS, respectively. Results: A total of 48,150 patients were included in this study. Age ranged from 18-40. (American Indian [AI]: 79 [0.2%]; Haitian: 15,011 [31.2%]; White: 20,109 [85.48%]; Hispanic: 13,030 [27%]. Hispanic women had higher rates of triple-negative disease (23.9%) than did Haitian women (11.5%) and white women (10.9%; P < .001). Hispanic women had higher rates of node-positive disease (26.2%) in comparison to Haitian women (17%) and Non-Haitian/Hispanic women (10% P < .001). Hispanic women had worse PFS when diagnosed at Stage II and III (37 and 39 months, respectively) than Haitian women (57 and 59 months, respectively) and Non-Haitian/Hispanic women (82 and 87 months). Hispanic women had worse OS when diagnosed at Stage II and III (45 and 49 months) than Black women (70 and 75 months) and non- women (95 and 99 months). Conclusion: Hispanic women had worse PFS versus non-Hispanic and Haitian women as well as present with high-risk characteristics and nodal disease at the time of presentation. This suggests that racial differences in tumor subtype and nodal stage among Hispanic women highlight the importance of developing additional studies which can investigate the disparity in patient outcomes with young Hispanic women in breast cancer research.

Citation Format: Ragisha Gopalakrishnan, Esha Gandhi, Maria Fernandez. Disparities at the Convergence of Race and Ethnicity: Examining Trends and Outcomes in Young Women Diagnosed with 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 PO2-26-05.