bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO4-10-07: Understanding Psychological distress in patients prior to breast cancer diagnosis:Mixed Methods Study
Authors: Gao Yan , Gao Jinnan
Published: May 2024

Purpose:While the association between diagnosis of breast cancer and post-diagnosis psychological distress has been well documented, data regarding pre-diagnosis psychological distress in the breast cancer population are limited. The purpose of the current study is to measure the distress levels of patients prior to breast cancer diagnosis, to identify the categories of distress they have, and describe the experience of distress of patients before diagnosis.

Methods: This study uses a mixed research method of cross-sectional survey and qualitative interviews. In the quantitative part, a cross-sectional survey of 118 patients with completed breast biopsies awaiting pathological diagnosis was conducted using the National Comprehensive Cancer Network’s (NCCN’s) Distress Thermometer(DT) and Problem List (PL), In the qualitative part, 15 patients were invited using convenient and purposive sampling. Data was collected using a semi-structured face-to-face interview and recorded. The transcribed text was analyzed using Colaizzi's phenomenological method.

Results: The results reveal that 63.6% of patients reported a higher level of psychological distress (n=75, scoring≥4).Most patients had emotional (98%) or physical (64%) problems. Among these, worry or anxiety (47.5%), fear (33.1%), finances (21.2%), sadness and depression(18.6%), and grief or loss(15.3%) were the most frequently reported problems. Multivariate logistic regression analysis showed that the factors associated with psychological distress before the diagnosis of breast cancer patients were age, education level. The experience of patients before diagnosis emerged five themes: Very high psychological distress index; Strong uncertainty; The demand of information; Guilt for the family; Hoped for psychological support from the health care team.

Conclusions: Psychological distress is prevalent prior to breast cancer diagnosis and may merit early intervention. Understanding patients’ distress may help guide future psychosocial needs assessments and interventions to promote patient quality of life.

Table 1 Sample characteristics (n=118).

Table 2 Univariate analysis of predictors associated with psychological distress

Table 3 The binary logistic regression model of psychological distress

Citation Format: Yan Gao, Jinnan Gao. Understanding Psychological distress in patients prior to breast cancer diagnosis:Mixed Methods 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 PO4-10-07.
Abstract PO4-12-05: Immediate breast reconstruction is associated with reduced incidence of ipsilateral lymphedema in breast cancer patients undergoing mastectomy
Authors: Byeon Jin Young , Shin Ik Beom , Lee Hawjeong , Kang Eunhye , Jung Ji-Jung , Lim Changjin , Han Wonshik , Kim Hong-Kyu , Lee Han-Byoel , Moon Hyeong-Gon
Published: May 2024

Purpose: The number of patients undergoing immediate breast reconstruction after mastectomy is increasing. A study of ipsilateral lymphedema after immediate breast reconstruction is also needed.This retrospective study aimed to identify the risk factors associated with lymphedema incidence after mastectomy in breast cancer patients, particularly focusing on the impact of the immediate breast reconstruction.

Methods: A retrospective analysis was conducted on 6,105 patients who underwent mastectomy for breast cancer with or without immediate breast reconstruction from Jan 2012 to Dec 2022 at Seoul National University Hospital to identify the potential risk factors for developing ipsilateral lymphedema.

Results: A total of 6,105 breast cancer patients with a mean age of 50.1 years were included in this study, with a median follow-up period of 52.0 months. In univariate analysis, the incidence of lymphedema was significantly lower in the immediate breast reconstruction group (4.47%) compared to the no reconstruction group (9.15%) (p < 0.001). Other significant risk factors included the number of dissected axillary lymph nodes, number of metastatic lymph nodes, body mass index (BMI) over 25 kg/m2, the use of neo-adjuvant chemotherapy or adjuvant radiation therapy, and older age at the time of operation. In multivariate analysis, the immediate breast reconstruction remained to be an independent predictor of developing lymphedema (OR: 0.71, 95% CI: 0.55-0.91, p = 0.008), along with the number of dissected lymph nodes (OR: 1.06, 95% CI: 1.05-1.08, p < 0.001), neoadjuvant chemotherapy (OR: 1.83, 95% CI: 1.44-2.33; p < 0.001), adjuvant radiation therapy (OR: 6.77, 95% CI: 5.16-8.96, p < 0.001), BMI >25 kg./m2 (OR: 1.58, 95% CI: 1.26–1.97, p < 0.001) and older age at surgery (OR: 1.01, 95% CI: 1.00-1.02, p = 0.007).

Conclusion: Our data demonstrates significantly lower rates of ipsilateral lymphedema for the patients undergoing immediate reconstruction after mastectomy when compared to that of the mastectomy alone. While these observations require further validation, our study provides useful information for the surgical decision making in patients who are considering the option of immediate reconstruction after mastectomy.

Citation Format: Jin Young Byeon, Ik Beom Shin, Hawjeong Lee, Eunhye Kang, Ji-Jung Jung, Changjin Lim, Wonshik Han, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon. Immediate breast reconstruction is associated with reduced incidence of ipsilateral lymphedema in breast cancer patients undergoing mastectomy [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 PO4-12-05.
Abstract PO4-13-05: Spotlight on PSMA as a new theranostic biomarker for breast cancer
Authors: Bravaccini Sara , Cortecchia Stefania , Foca Flavia , Martinelli Giovanni , Ravaioli Sara , Tumedei Maria Maddalena , Matteucci Federica , Maltoni Roberta , Paganelli Giovanni , Poli Francesca , Puccetti Maurizio
Published: May 2024

Breast cancer patients are risk-stratified on the basis of the subtype classification. However, this parameter is not completely accurate in discriminating between high- and low-risk disease, creating a need for a reliable marker to determine aggressiveness. Prostate-specific membrane antigen (PSMA) could fulfill this need given that it has been reported to be expressed by breast cancer tumor cells and the endothelial cells of tumor vessels. We analyzed 68 breast cancers (BC) of whom 14 luminal A, 28 Luminal B, 15 HER2 positive and 11 triple negative BC to assess whether PSMA expression by immunohistochemistry was different in the several tumor subtypes and was related to ki67 expression and stromal TILs. PSMA positivity was calculated as the number of positive vessels on 10 fields at 40X magnifications. Kruskal Wallis’s test was used to assess difference in PSMA positivity among BC subgroups and Dunn’s test was performed for post-hoc comparisons; Spearman’s rho coefficient was calculated to analyze the correlation among PSMA, KI67 and TILs. Our results show that median PSMA was higher both considering the number of positive vessels and the staining intensity in TNBC compared to Luminal A and B tumors (p< 0.001). Ki67 was higher in TNBC compared to Luminal A tumors (p< 0.001). We saw a correlation between PSMA and ki67, especially in HER2+ tumors (p=0.002), while a correlation between PSMA and TILs was observed in TNBC (p=0.014). The analysis of PSMA expression on the lymph nodes showed the same trend observed for the primary tumors given that it was higher in TNBC compared to HER2 positive and luminal cancers.

Our results suggest that PSMA could be used as theranostic biomarker in BC considering that it is highly expressed in more aggressive tumors and the possibility to treat PSMA-expressing patients for anti-angiogenesis and/or radionuclide treatment.

Citation Format: Sara Bravaccini, Stefania Cortecchia, Flavia Foca, Giovanni Martinelli, Sara Ravaioli, Maria Maddalena Tumedei, Federica Matteucci, Roberta Maltoni, Giovanni Paganelli, Francesca Poli, Maurizio Puccetti. Spotlight on PSMA as a new theranostic biomarker for 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 PO4-13-05.
Abstract PO4-14-04: Comprehensive genomic profiling results in patients with metastatic breast cancer due to germline BRCA1/2 status and their HER2-low status
Authors: Tada Hiroshi , Miyashita Minoru , Harada-Shoji Narumi , Hamanaka Yohei , Sato Miku , Yanagaki Mika , Tsunokake Satoko , Motonari Tokiwa , Kon Tomomi , Yamazaki Asumi , Ishida Takanori
Published: May 2024

Objective: To determine the usefulness of comprehensive genomic profiling testing and the percentage of HER2-low in patients with germline BRCA1/2 (gBRCA1/2) variants metastatic breast cancer.

Methods: We included 3404 patients with metastatic recurrent breast cancer who underwent CGP testing from June 2019 to June 2023 in Japan. We examined the proportion of patients with or without recommended therapy, the proportion of patients who received matched therapy, and the proportion of patients with HER2 low by gBRCA1/2 variant due to CGP testing.

RESULTS.: Of the 3404 patients, 69 (2.0%) had gBRCA1, 136 (4.0%) had gBRCA 2, 5 (0.1%) had gBRCA1 & gBRCA2, 1807 (53.1%) were negative, and 1388 (40.1%) were untested or unknown. The overall percentage of patients who recommended targeted therapy due to CGP testing was 37.4%(1272/3404), with gBRCA1 at 31.9%(22/69), gBRCA2 at 43.4%(59/136), and gBRCA1&gBRCA2 at 50%(2/4). The percentage of matched therapy performed in the 1st line after the expert panel was 8.3% overall, 2.9% for gBRCA1, 14.0% for gBRCA2, and 0% for gBRCA1&gBRCA2. The rate of tumor mutation burden (TMB) high was 7.4% overall, and gBRCA1 at 2 .9%, gBRCA2 at 9.6%, and gBRCA1&gBRCA2 at 50%. On the other hand, the percentage of HER2-low was 38.3% overall, 29% for gBRCA1, 58.1% for gBRCA2, and 25% for gBRCA1 & gBRCA2.

Conclusion.: Germline BRCA2 variants had a higher rate of reaching matched therapy based on CGP test results. The higher rate of TMB high was suggested to be the reason for this. The high percentage of patients with HER2-low is also expected to improve the prognosis.

Citation Format: Hiroshi Tada, Minoru Miyashita, Narumi Harada-Shoji, Yohei Hamanaka, Miku Sato, Mika Yanagaki, Satoko Tsunokake, Tokiwa Motonari, Tomomi Kon, Asumi Yamazaki, Takanori Ishida. Comprehensive genomic profiling results in patients with metastatic breast cancer due to germline BRCA1/2 status and their HER2-low status [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 PO4-14-04.
Abstract PO4-20-12: Case Report: Should core needle biopsy showing primary leiomyosarcoma of the breast warrant a second look for accurate diagnosis and management?
Authors: Ritter Amanda , Shimunov Sergey
Published: May 2024

A 68-year-old female with unknown medical history presented to the emergency department with an exceptionally large necrotic mass of the right breast. Initial core needle biopsy showed morphology consistent with the exceedingly rare leiomyosarcoma of the breast. This patient’s necrotic, fungating tumor with abscess warranted urgent surgical excision. The pathology report that followed revealed malignant phyllodes tumor as her final diagnosis. The patient did well after surgery with no sign of metastasis and continued to follow-up with oncology. Lack of clinical guidance for breast leiomyosarcoma begs the question as to when further workup is indicated since it is known to imitate the histological and radiological features of other breast lesions. We discuss the need for updated guidance from prospective future studies to change national guidelines.

Citation Format: Amanda Ritter, Sergey Shimunov. Case Report: Should core needle biopsy showing primary leiomyosarcoma of the breast warrant a second look for accurate diagnosis and management? [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 PO4-20-12.
Abstract PO4-24-12: Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate
Authors: Nimbalkar Vidya P , VP Snijesh , Rajarajan Savitha , Alexander Annie , Ramesh Rakesh , Srinath B S , Prabhu Jyothi S
Published: May 2024

Background

Breast cancers (BC) in the young women tend to have poor outcomes and higher proportion of aggressive subtypes. Immunotherapy has shown promising results lately, especially for aggressive categories like triple negative breast cancers (TNBC). Success of the immunotherapy is shown to be dependent on the tumor immune microenvironment (TIME) which plays important role in disease progression and response to therapy. Though numerous studies have demonstrated immune hot tumors are associated with better prognosis, mechanism of immunologically hot TIME is not yet deciphered.

Material and methods

Gene expression data derived from RNA sequencing (n=40) of primary BC was used to divide them into immune hot and cold tumors by using 15 gene signature (Wang et al., Sci. Adv. 2021). Average expression of the hot and cold (hot=12 and cold=3) genes was derived for each tumor and median value of their ratio was used to categorize them into immunologically hot and cold tumors. Association of the hot and cold tumors with clinical characteristics was examined. CIBERSORT algorithm was used to identify immune cell subtypes and Kaplan Meier survival analysis was performed to assess the prognostic significance. Similar analysis was replicated in TCGA (n=1083) dataset.

Results

Equal proportion of immune hot and cold tumor was observed in the cohort. Higher proportion of cold tumors were observed in younger and premenopausal (p=0.002) patients. Subtype analysis showed higher proportion of cold tumors in TNBC compared to hormone receptor positive tumors (p< 0.0001). No significant difference was observed in other clinicopathological characteristics between the groups. Further analysis of cold tumors for immune cell subtypes, categorized by the menopausal status showed higher proportion of plasma cells and CD4 memory resting cells and lower proportion of M2 macrophages and B memory cell in premenopausal (n=129, TCGA) compared postmenopausal (n=322, TCGA) tumors. In addition, premenopausal cold tumors were associated with better overall survival compared to postmenopausal group (p=0.001).

Conclusion

Younger premenopausal women with BC are likely to have more immunologically cold tumors. Though circulating levels of sex steroid hormones is the predominant difference between the pre and postmenopausal women, its influence on TIME and therapeutic significance must be explored.

Citation Format: Vidya P Nimbalkar, Snijesh VP, Savitha Rajarajan, Annie Alexander, Rakesh Ramesh, B S Srinath, Jyothi S Prabhu. Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate [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 PO4-24-12.
Abstract PO5-04-06: Enhancing Antitumor Activity of Her2 CAR T cells through TR2BB Co-Expression and Cytokine Signal 3 Incorporation
Authors: Chamorro Diego , Somes Lauren , Madaras Emily , Nalawade Saisha , Shafer Paul , Mosquera Andres , McKenna Mary Kathryn , Hoyos Valentina
Published: May 2024

Chimeric antigen receptor T cells (CARTs) targeting Her2 represent a promising approach for the treatment of patients with Her2 expressing breast cancers (BC). Her2 CARTs confront major challenges within the immune-suppressive tumor microenvironment (TME) of breast cancer, which inhibits sustained T cell proliferation and persistent antitumor activity. To bolster Her2 CARTs' expansion and persistence, we engineered a TNF-related apoptosis-inducing ligand receptor 2 (TR2) specific scFv connected to the endodomain of 4-1BB (TR2BB). TR2BB co-expressing Her2 CARTs exhibited enhanced antitumor potential against BC tumors by triggering myelod derived suppressor cell (MDSC) apoptosis, thereby remodeling the TME and promoting T cell proliferation. Despite better tumor control in mice receiving CAR.TR2BB T cells, recent trials have demonstrated the importance of incorporating a cytokine signal for optimal tumor control in patients with solid tumors. Thus, we hypothesized that we could further augment anti-tumor activity of Her2 CAR.TR2BB T cells against BC by incorporating a cytokine signal 3 through IL-15 or C7R. We engineered the CARTs to (1) ectopically produce IL-15, a crucial T-cell homeostasis and survival cytokine, and (2) express a constitutively active IL-7 receptor (C7R) that triggers IL-7 receptor signaling independently of ligand or the common receptor gamma chain (γc).

Our repeat weekly tumor challenge assay revealed that CAR.TR2BB.IL15 T cells outperformed CAR.TR2BB.C7R and CAR.TR2BB in T cell proliferation. Both CAR.TR2BB.IL15 and CAR.TR2BB.C7R exhibited improved cytotoxic potential after three weeks of antigen stimulation compared to CAR.TR2BB alone in comparison with CAR.TR2BB alone. Furthermore, in our in vivo xenograft NSG mouse models implanted with Her2 expressing breast cancer cell line and MDSCs, CAR.TR2BB.IL15 T cells showed superior tumor control and improved survival rates.

In summary, the addition of IL15 transgene to our TME targeting Her2 CARTs provides an advantage in terms of T cell persistence, proliferation, and tumor control in in vitro and in vivo models. These promising preclinical results propel us to apply this optimized Her2 targeting CART therapy in a phase I clinical trial for patients with metastatic Her2-expressing breast cancers.

Citation Format: Diego Chamorro, Lauren Somes, Emily Madaras, Saisha Nalawade, Paul Shafer, Andres Mosquera, Mary Kathryn McKenna, Valentina Hoyos. Enhancing Antitumor Activity of Her2 CAR T cells through TR2BB Co-Expression and Cytokine Signal 3 Incorporation [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 PO5-04-06.
Abstract PO5-10-02: Neighborhood deprivation index and time to initiation in patients with metastatic breast cancer
Authors: Rajendran Sneha , Ren Dianxu , Petruzzi Marina , Rosenzweig Margaret
Published: May 2024

Background Cyclin-dependent kinase 4 and 6 inhibitors (CDKi) are first-line therapy for patients with estrogen-positive (ER+) metastatic breast cancer (MBC). The accessibility, usability, and outcomes according to demographic factors have not been well studied in real world practice. Methods Retrospective review of patients with ER+ MBC prescribed first line CDKi therapy at a large NCI-designated cancer center from January 2015 through December 2022. Patient records were abstracted for outcomes including 1) time from CDKi prescription to drug initiation (TTI), 3) time from CDKi initiation to progression, and 3) time from CDKi initiation to death/or 6/30/2022. Patient variables collected were: patient age (continuous), race (patient self-report – Black, White, Other), partner status (Married, Not married), Insurance type (Medicare, Medicaid, Private); Mean BMI; Number of comorbidities (5 categories). Neighborhood deprivation index (NDI) was determined from the patient’s address with higher scores indicating more deprivation. Descriptive, comparative, and correlational statistics were used. Results A total of 173 patients were included in the analysis. Mean age – 63.1, (SD 12.7, range 24-94); race – White n=157, Black n=16; marital status – Married n=102, Not married n=71; mean NDI – 61.0 (SD 23.7, range 6-100); mean BMI – 28.9 (SD 6.9, range 16-48); number of comorbidities – 0 n=35, 1-2 n= 35, 3-4 n = 55, 5-6 n = 20, 7+ n = 28; insurance type – Medicare n = 115, Medicaid n = 21, Private n = 37. TTI: the median TTI was 14 days. There were no statistically significant differences in TTI based on age, race, NDI, or other demographic variables. Time to progression: in the multivariate model, younger age at diagnosis and Medicaid insurance were associated with shorter time to progression. Overall survival: not married, younger age at diagnosis, and Medicaid insurance were associated with shorter overall survival. Discussion Demographic factors are associated with diverse outcomes of MBC therapy, not attributed to delay in CDKi treatment initiation. Personalization of support during MBC illness according to risk factors for worse outcomes may help to equalize incomes.

Citation Format: Sneha Rajendran, Dianxu Ren, Marina Petruzzi, Margaret Rosenzweig. Neighborhood deprivation index and time to initiation 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 PO5-10-02.
Abstract PO5-13-02: BRCA mutational profiles of endocrine-resistant breast cancer
Authors: Karlsson Emelie , Schagerholm Caroline , Robertson Stephanie , Toosi Hosein , Sifakis Emmanouil , Hartman Johan
Published: May 2024

Background

Around 75% of breast cancer (BC) patients have tumors expressing the treatment-predictive biomarker estrogen receptor α (ER) and are consequently offered endocrine therapy. One-third of these patients develop endocrine resistance, a majority with tumors that retain ER expression. For most cases, the resistance mechanism is still unknown, but mutational activity is a suggested mechanism. Germline BRCA mutations are well-known in BC and are found in approximately 23% of patients with triple-negative BC and in 5% of patients with ER+ BC. However, less is certain about the somatic variants, though studies have shown prevalences of around 3% in BC. This study aimed to examine the somatic BRCA mutational profiles of endocrine-resistant paired primary and relapse tumors.

Methods

A retrospective cohort of verified endocrine-resistant BC patients was collected at Karolinska University Hospital in Stockholm, Sweden. Patients diagnosed in 2008-2012 with an ER+ and human epidermal growth factor receptor 2 (HER2) negative primary tumor and a following ER+ and HER2- relapse tumor within five years of ongoing endocrine therapy were included (N=63). DNA was extracted from archived formalin-fixed paraffin-embedded relapse and primary tumor tissue and analyzed by panel sequencing. Tumor-free lymph nodes were used as germline normal samples.

Results

The analysis showed somatic BRCA mutational activity in 38.1% of the patients. Variants were present in 20.3% of primary tumors and 30.4% of relapse tumors. BRCA1 mutations were present in 11.9% of primary tumors and 21.4% of relapse tumors. BRCA2 variations were, in turn, seen in 11.9% of primary tumors and 14.3% of relapse tumors. The frequency of patients that had alterations in both the primary and relapse tumors was 3.2% for BRCA1 and BRCA2 respectively.

Conclusion

This study of a unique endocrine-resistant BC cohort shows a high presence and varying distribution of somatic BRCA mutations in both primary and even higher in relapse tumors. These results suggest that mutational testing for possible further treatment decisions may be relevant for patients exhibiting endocrine resistance, especially in the advanced setting.

Citation Format: Emelie Karlsson, Caroline Schagerholm, Stephanie Robertson, Hosein Toosi, Emmanouil Sifakis, Johan Hartman. BRCA mutational profiles of endocrine-resistant 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 PO5-13-02.
Abstract PO5-13-11: Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast
Authors: Chan Nay Nwe Nyein , Zhan Haiying , Khaimova Revekka , Aung Thazin , Robbins Charles , Gaule Patricia , Rimm David
Published: May 2024

HER2 (ERBB2) is an established prognostic and predictive marker for patients with invasive breast cancer and used in HER2-targeted therapy. The clinical and biological significance of expression of HER2 protein in patients with intraductal neoplasms of the breast is not well characterized. In this study, we used our HS-HER2 (High Sensitivity-HER2) which is a CAP/CLIA certified laboratory derived test (LDT) using quantitative immunofluorescence (QIF). We evaluated HER2 expression in DCIS (ductal carcinoma in situ), LCIS (lobular carcinoma in situ) and benign lesions to correlate with their clinicopathologic characteristics. Thirty- eight cases of DCIS, and fourteen cases of LCIS and thirty benign cases were selected from the Yale Pathology department archives and 252 ROIs (regions of interest) were annotated by a board-certified pathologist. DCIS is classified according to the three-tier nuclear grading system: low, intermediate, and high-nuclear grade. LCIS is classified as PLCIS (pleomorphic variant) and CLCIS (classic LCIS) according to the WHO classification of breast tumors. Serial sections of FFPE tumor specimens were used to accurately quantify the HER2 expression by the HS-HER2 assay and the acquisition by QuPath v.04 with Qymia extension. According to the LOD (limit of detection,3 amol/mm2), LOQ (limit of quantification, 9 amol/mm2) and LOL (limit of linearity, 23 amol/mm2) of the optimized HS-HER2 assay as performed in our CLIA lab shows a broad range of HER2 expression in both DCIS and LCIS lesions, ranging from 0.7 amol/mm2 to 111.4 amol/mm2 in DCIS and 3.6 amol/mm2 to 49.9 amol/mm2 in LCIS. High grade DCIS lesions express higher average HER2 levels (111.4 + 0.7 amol/mm2) than combined low and intermediate grade DCIS (77.9 +1.9 amol/mm2) with no significant difference between low/intermediate and high-grade DCIS. CLCIS lesions express higher average HER2 level (49.9 + 3.6 amol/mm2) than PLCIS (35.1 + 5.4amol/mm2) but again this is not statistically significant. HER protein expression is relatively low in benign lesions ranging from 0.8 to 8.4 amol/mm2. Using the HS-HER2 assay, our results show quantitative level HER2 levels in DCIS and LCIS breast lesions. These findings may be important as HER2 targeted therapies that work in gene-unamplified cancer (HER2 conjugated ADCs) gain broader usage in the clinic.

Citation Format: Nay Nwe Nyein Chan, Haiying Zhan, Revekka Khaimova, Thazin Aung, Charles Robbins, Patricia Gaule, David Rimm. Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast [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 PO5-13-11.
Abstract PO5-25-09: rs2242652 POLYMORPHISM OF THE hTERT GENE IN WOMEN WITH BREAST CANCER
Authors: Alvares Miriam , Mascarenhas Elisa , Matos Joao
Published: May 2024

Introduction: Breast cancer is the most common neoplasm in women around the world. There are several risk factors for this cancer: sex, age, body mass index (BMI), hormone therapy, family history, genetic mutations, among several others.

The vast majority of breast tumors are characterized as carcinomas and may originate from ducts or lobules. Immunohistochemistry is related to the expressions of the estrogen receptor (ER) and progesterone receptor (PR), as well as the expression of the human epidermal growth factor receptor 2 (HER2), cell proliferation or the absence of any expression from receptors on the tumor membrane.

The telomeres protect the chromosomes natural endings from suffering DNA loss. Telomerase is a ribonuclear protein complex (RNA and protein) that neutralizes telomeres' shortening.

Recurrent point mutations in the TERT telomerase promoter have been identified in several cancers, and the rs2242652 polymorphism is a single nucleotide change, and has been described as associated with breast cancer risk. Objective: The objective of this study is to analyze the TERT rs2242652 polymorphism in breast cancer women and to test the correlation of such data with the prognosis and various clinical variables. Methods: The study was conducted as an observational clinical study of women with breast cancer. A blood sample was collected from the patient and PCR was performed to extract the DNA and to analyze the telomerase polymorphisms in this population. To ensure a more descriptive analysis, the data was used in the construction of tables and graphs, that were then studied in a qualitative manner. The associations were analyzed through direct correlation tests and were followed by comparisons of categorization groups. Results and discussion: Fifty-four women presented polymorphism of the telomerase hTERT gene rs2242652. They were divided into two groups according to the A or G allele that confer the GA/AA and GG gene variants.

It was found that the GA/AA group had a trend towards more aggressive tumors, presenting 33% triple negative and 22% of tumors with HER2 overexpression, different from the GG group: 19% triple negative and 10% HER2 overexpression. More aggressive T4 tumors, were more expressive in the GA/AA gene variant group representing 20% of the patients, whereas in the GG group they represented only 8%. Conclusion: The data found in this study on the telomerase TERT gene polymorphism rs2242652 with breast cancer refers to a tendency found in tumors that have a more severe prognosis, to associate with the gene variant linked to the A allele of this gene, however a larger sample number is required for statistical confirmation.

Citation Format: Miriam Alvares, Elisa Mascarenhas, Joao Matos. rs2242652 POLYMORPHISM OF THE hTERT GENE IN WOMEN 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 PO5-25-09.
Abstract PO5-27-09: Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ breast cancer
Authors: Friedersdorf Matthew , Blake Devon , Thompson Sarah , Marran Krista , Sorrentino Jessica
Published: May 2024

Elevated levels of eukaryotic initiation factor 4E (eIF4E) are found in a broad range of cancers, including breast, and have been associated with aggressive, drug resistant tumors. Furthermore, elevated eIF4E activity is sufficient to cause transformation in various cancers, while inhibition suppresses tumor growth. eIF4E, the main regulator and rate limiting factor of protein synthesis, is the downstream integrator of several important oncogenic signaling pathways (PI3K/AKT/mTOR, Ras/Raf/MEK, and Myc). Activation of eIF4E results in increased protein levels of key proliferation and metabolism proteins such as Cyclin D1 (CCND1) and Ornithine Decarboxylase 1 (ODC1), as well as an overall increase in cellular synthesis machinery, causing cellular growth and proliferation. Here, we describe the development and characterization of novel, potent, and selective eIF4E inhibitors. Compounds from this chemical series have nanomolar activity in multiple biochemical and biophysical m7G cap-competition assays as well as potent inhibition of translation in cellular and biochemical assays. In cells, these compounds rapidly and reversibly decrease protein levels of several oncogenes, including CCND1, leading to a G1 cell cycle arrest. We demonstrate that eIF4E inhibitors cause growth inhibition in a variety of breast cancer cell lines, including ER+ breast cancer. These inhibitors also inhibit growth of breast cancer lines with acquired resistance to Palbociclib with the same potency as the parental cell lines. Additionally, eIF4E inhibition shows an increased sensitivity in resistant cell lines when combined with standard of care (SOC), including Palbociclib. Select analogs from the series demonstrate favorable ADMET/PK properties with good oral bioavailability and low safety risk. Lastly, these compounds have demonstrated near complete tumor growth inhibition in non-breast cancer in vivo models. Ongoing experiments will address in vivo efficacy in ER+ breast cancer in both monotherapy and in combination with SOC.

Citation Format: Matthew Friedersdorf, Devon Blake, Sarah Thompson, Krista Marran, Jessica Sorrentino. Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ 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 PO5-27-09.
Abstract PO5-28-01: Dynamics of Adipocyte Progenitors in the Mammary Gland during Obesity
Authors: Kwende Sharon , Nuthalapati Prashant , Ning Dun , Singh Jacqulene Sunder , Joshi Purna
Published: May 2024

Being overweight or obese is associated with a higher risk of breast cancer (BC) and worse disease-free and overall survival compared to normal-weight BC patients. The underlying biological basis for this association is attributed to alterations in the endocrine and inflammatory milieu of adipose tissue. However, existing chemotherapy and endocrine therapy are not effective in obese BC patients. There is a critical need to pin down adipose tissue cell types that may govern increased BC risk and adverse outcome in obesity. Adipocyte progenitors are immature mesenchymal cells in adipose tissue that have adipocyte differentiation potential and reported to be dysfunctional in obesity. In previous research, we first reported mammary adipocyte progenitors (MAPs) expressing Platelet-Derived Growth Factor Receptor alpha (PDGFRα) in the stromal microenvironment that transition into epithelial lineages during expansion of the murine mammary epithelium. The contribution of MAPs to shaping a pro-tumorigenic mammary tissue milieu in obesity is not known. Here, using diet-induced obesity MAP reporter and lineage tracing mouse models combined with single-cell RNA sequencing, we reveal elevated PDGFRα+ MAPs in the local mammary stroma in obesity. MAPs in the obese mammary gland manifest alterations in proliferation, cell state and molecular mechanisms, generating an inflammatory, cancer-prone tissue microenvironment. Our findings uncover the MAP lineage as a key contributor to forging an aberrant mammary gland in obesity, providing insight into the potential utility of targeting this cell population for eradicating BC risk related to augmented adiposity.

Citation Format: Sharon Kwende, Prashant Nuthalapati, Dun Ning, Jacqulene Sunder Singh, Purna Joshi. Dynamics of Adipocyte Progenitors in the Mammary Gland during Obesity [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 PO5-28-01.
Abstract PS01-06: The relationship between margin status of <2mm and local recurrence in DCIS patients
Authors: Safi Sarah Al , Yoo Tae-Kyung , Lee Sae Byul , Kim Jisun , Chung Il-Yong , Kim Hee Jeong , Ko Beom Seok , Lee Jong Won , Son Byung Ho , Lee Hee Jin , Gong Gyungyub
Published: May 2024

Background:

There has been controversial evidence regarding adequate margin in breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS). However, the consensus is a surgical margin distance of 2 mm. Moreover, recent recommendations advised on ‘’clinical judgement’’ approach to re-excision in cases of margin distance < 2mm. The ongoing controversy in DCIS margin compared to invasive cancer margin is due to the differences in post operative management. This is important as margin status is one of the modifiable risk factor for local regional recurrence in DCIS. In our study we evaluated margin distance in patient diagnosed with DCIS who underwent BCS on local recurrence

Methods:

Patients who underwent breast conserving surgery between February 2000 and December 2018 at Asan Medical Center were retrospectively reviewed. Patients with involved resection margins were excluded. Kaplan-Meier survival analysis and Cox proportional hazard models were applied to determine the relationship between negative margin width and local recurrence.

Results:

A total of 1,858 patients were included in the study. Almost half of the patients had a tumor size of 1cm or smaller (n=876, 47.1%). Only 98 (5.3%) patients did not undergo radiation therapy. A negative margin width of < 1mm, < 2mm, < 5mm were all not associated with local recurrence (log-rank test p-value 0.1, 0.1, 0.078, respectively). For patients who underwent radiation therapy, a negative margin of any width was not related to local recurrence. Whereas, for patients who did not undergo radiation therapy, those with margins ≤2mm were significantly more likely to develop local recurrence than those with margins < 2mm (10-yr local recurrence rate, 16.4% vs 5.5%, respectively; hazard ratio, 5.709; 95% CI, 1.106-29.46, p=0.038).

Conclusion:

A negative margin is not related to local recurrence in DCIS patients who undergo breast conserving surgery with radiation therapy. Routine additional surgery for wider negative margin may only be needed for patients who do not undergo radiation therapy.

Citation Format: Sarah Al Safi, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Hee Jin Lee, Gyungyub Gong. The relationship between margin status of <2mm and local recurrence in DCIS 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 PS01-06.
Abstract PS03-01: Single cell analysis of paired lymph nodes and primary tumors in breast cancer patients
Authors: Fjørtoft Marit , Rye Inga , Huse Kanutte , Myklebust June , Russnes Hege , Riis Margit , Lingjærde Ole Christian , Garred Øystein , Lande Karin Teien , Bergheim Inger Riise , Schlichting Ellen
Published: May 2024

A sentinel lymph node (SN) is the primary node draining the tumor and is assumed to be affected early in the metastatic process. The sentinel node holds a key position in the immune response against tumor in breast, and represents a unique connection between the tumor and the host immune response. We hypothesize that the immune profile in the primary tumor and the paired lymph node (LN) is different during tumor progression.

3.7 million single cells from paired primary tumor and lymph nodes from 33 breast cancer patients (Oslo2 cohort) was analyzed by single cell mass cytometry (CyTOF) with a 47 antibody immune panel and characterized by a semi-automatic gating approach (FlowSOM).

Tumor cells were found in 11 LN. When analyzing the leucocytes from LN we identified a significant difference in immune cell type skewing towards higher abundance of memory CD4 and CD8 T cells expressing an exhausted phenotype in LN with metastasis. In addition, a higher abundance of activated Tregs and significantly lower abundance of resting Tregs was found in the metastatic LNs compared to the sentinel lymph nodes. The change in immune composition and exhaustion was correlated to the metastatic tumor burden. The skewing towards an exhausted immune profile was also found in larger primary tumors compared to smaller primary tumors.

We further analyzed tumor cells from 8 patients with paired primary tumor and LN. No differences were identified in the primary tumor when stratified by LN status, but LNs with smaller metastasis expressed lower levels of epithelial markers essential in the Epithelial-to-Mesenchymal Transition such as E-cadherin, Pan Cytokeratin and EpCAM – this in contrast to the LN with manifested metastasis in the axilla which expressed higher levels of epithelial markers and lower levels of mesenchymal markers such as Vimentin and CD44.

We identified a skewing in the immune profile from a naive phenotype towards a memory and exhausted phenotype in CD8 and CD4 T cell population in LN with manifested metastasis, as well as in larger primary tumors. We also identified that tumor cells in smaller metastatic tumors resembled a “mesenchymal like” phenotype compared to in the larger manifested tumors. These results suggest that the immune suppression is correlated with the tumor burden.

Citation Format: Marit Fjørtoft, Inga Rye, Kanutte Huse, June Myklebust, Hege Russnes, Margit Riis, Ole Christian Lingjærde, Øystein Garred, Karin Teien Lande, Inger Riise Bergheim, Ellen Schlichting. Single cell analysis of paired lymph nodes and primary tumors 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 PS03-01.
Figure S3 from Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids
Authors: Desai Ridhdhi , Huang Ling , Gonzalez Raul S. , Muthuswamy Senthil K.
Published: May 2024

Muc2 staining and KT5720 treatment in R201C-expressing stable organoids
Supplementary Table 6 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 6. LuCaP Proteome GSEA Hallmark
Supplementary Table 4 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 4. LuCaP Proteome VSN ROTS NE vs AdCa
Supplementary Figure 8 from Coregulation of NDC80 Complex Subunits Determines the Fidelity of the Spindle-Assembly Checkpoint and Mitosis
Authors: Kim Sehong , Lau Thomas T.Y. , Liao Man Kit , Ma Hoi Tang , Poon Randy Y.C.
Published: May 2024

Figure S8. Downregulation of NDC80C enhances sensitivity to antimitotic drugs.
Supplementary Figure 7 from Coregulation of NDC80 Complex Subunits Determines the Fidelity of the Spindle-Assembly Checkpoint and Mitosis
Authors: Kim Sehong , Lau Thomas T.Y. , Liao Man Kit , Ma Hoi Tang , Poon Randy Y.C.
Published: May 2024

Figure S7. SPC24–SPC25 subcomplex cannot prevent mitotic arrest and slippage in the absence of NDC80 and NUF2.
Supplementary Figure 6 from Coregulation of NDC80 Complex Subunits Determines the Fidelity of the Spindle-Assembly Checkpoint and Mitosis
Authors: Kim Sehong , Lau Thomas T.Y. , Liao Man Kit , Ma Hoi Tang , Poon Randy Y.C.
Published: May 2024

Figure S6. Co-regulation of NDC80C subunits is not caused by cell cycle effects.
Supplementary Table 22 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 22. LuCaP Phosphoproteome VSN Normalized Differential Expression ROTS AdCa vs NE
Supplementary Figure 4 from Coregulation of NDC80 Complex Subunits Determines the Fidelity of the Spindle-Assembly Checkpoint and Mitosis
Authors: Kim Sehong , Lau Thomas T.Y. , Liao Man Kit , Ma Hoi Tang , Poon Randy Y.C.
Published: May 2024

Figure S4. Co-regulation of NDC80C subunits.
Supplementary Table 20 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 20. LuCaP Proteome VSN Normalized Differential Expression ROTS AdCa CR vs AdCa NCR
Supplementary Table 17 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 17. LuCaP NE Functional Proteome
Supplementary Table 12 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 12. LuCaP Phosphoproteome GSEA Pathways
Supplementary Figure 4 from An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression
Authors: Prasad Hari , Mandal Susmita , Mathew John Kandam Kulathu , Cherukunnath Aparna , Duddu Atchuta Srinivas , Banerjee Mallar , Ramani Harini , Bhat Ramray , Jolly Mohit Kumar , Visweswariah Sandhya S.
Published: May 2024

Supplementary Figure 4 shows how NHE9 affects cell apoptosis and cell cycle progression in colorectal cancer cells.
Supplementary Table S4 from Examining the Association between Abstinence from Smoking and Healthcare Costs among Patients with Cancer
Authors: Kypriotakis George , Kim Seokhun , Karam-Hage Maher , Robinson Jason D. , Minnix Jennifer A. , Blalock Janice A. , Cui Yong , Beneventi Diane , Kim Bumyang , Pan I.-Wen , Shih Ya-Chen Tina , Cinciripini Paul M.
Published: May 2024

Supplementary Table S4: Covariate balance before and after applying inverse probability of treatment weights (IPTW) with the threshold of standardized mean difference (SD) being 0.1
Supplementary Table S2 from Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma
Authors: Shen Yajing , Chen Jiajun , Wu Jinyu , Li Tiandong , Yi Chuncheng , Wang Keyan , Wang Peng , Sun Changqing , Ye Hua
Published: May 2024

Supplementary Table S2: RNA sequencing data (GSE22058, GSE121248, and GSE55092) from the Gene Expression Omnibus (GEO) database were downloaded for analyses. These three datasets derived from two microarray platforms (Rosetta/Merck Human RSTA Custom Affymetrix 1.0 microarray and Affymetrix Human Genome U133 Plus 2.0 Array). The GEO query software package was used to download datasets and to collect clinical information. The sample sizes for these three datasets are shown in Supplementary Table S2.
Supplementary Table 2 from Triple Primary Cancers: An Analysis of Genetic and Environmental Factors
Authors: Borja Nicholas A. , Silva-Smith Rachel , Calfa Carmen , Sussman Daniel A. , Tekin Mustafa
Published: May 2024

Supplementary Table 2: Summary of patients with pathogenic variants identified in the MPC cohort
On the Hunt for the Missed Genetic Causes of Multiple Primary Tumors
Authors: Chan-Pak-Choon Fiona , Foulkes William D.
Published: May 2024

Improved cancer screening and treatment programs have led to an increased survivorship of patients with cancer, but consequently also to the rise in number of individuals with multiple primary tumors (MPT). Germline testing is the first approach investigating the cause of MPT, as a positive result provides a diagnosis and proper clinical management to the affected individual and their family. Negative or inconclusive genetic results could suggest non-genetic causes, but are negative genetic results truly negative? Herein, we discuss the potential sources of missed genetic causes and highlight the trove of knowledge MPT can provide.

See related article by Borja et al., p. 209
Figure S7 from High-Dimensional Analyses Reveal IL15 Enhances Activation of Sipuleucel-T Lymphocyte Subsets and Reverses Immunoresistance
Authors: Saeed Muhammad A. , Peng Bo , Kim Kevin , Rawat Kavita , Kuehm Lindsey M. , Siegel Zoe R. , Borkowski Ariel , Habib Nabih , Van Tine Brian , Sheikh Nadeem , Tuyen Vu , Thorek Daniel L.J. , Fehniger Todd A. , Pachynski Russell K.
Published: May 2024

IL-15 significantly improves activation of sip-T in peripheral blood in vivo