bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO4-28-06: A Singleminded-2s/Sirtuin interac4on in the regula4on of mitochondrial dynamics across normal mammary development and ER+ BC progression
Authors: Carter Hannah
Published: May 2024

Characterizing the mechanisms underlying the regulation of cellular differentiation and mitochondrial dynamics are critical to understanding normal development and breast cancer in the mammary gland. Our previous studies have highlighted the significance of Singleminded-2s (Sim2s), a member of the bHLH/PAS family, in regulating mitochondrial dynamics during mammary gland development and the progression of estrogen receptor-positive (ER+) breast cancer. Sim2s is temporally regulated, with maximal expression occurring during mid-lactation. Cross-fostered pups nursed by miceover-expressing Sim2s under the mouse mammary tumor virus (MMTV-Sim2s) display significantly higher weights by mid-lactation compared to pups nursed by control dams. Overexpression of Sim2s leads to alterations in mitochondrial morphology and dynamics, characterized by increased OPA1 expression and decreased DRP1 levels, resulting in enhanced mitochondrial fusion and elongation. Furthermore, we have extended our investigations to an ER+ breast cancer cell line (MCF7). We have identified SIM2s as a tumor suppressor expressed in mammary epithelial cells, known to inhibit epithelial-mesenchymal transition (EMT) and metastasis. In our previous studies, we discovered that loss of SIM2s expression in the MCF7 cell line promotes mitochondrial fragmentation, as evidenced by a decrease in OPA1 expression and an increase in DRP1 levels. In conjunction with these findings, literature suggests that sirtuins also play a role in the regulation of mitochondrial dynamics similar to Sim2s. Specifically, there is an upregulation of Sirtuin 1 in cancer when Sim2 is lost, while Sirtuin 3 increases during differentiation and normal development progression. Therefore, our aim is to elucidate the potential interaction between Singleminded-2s and sirtuins, a family of NAD+-dependent deacetylases, in the regulation of mitochondrial dynamics. We hypothesize that Sim2s may modulate mitochondrial function through its association with sirtuins, thereby influencing normal mammary gland development and breast cancer progression.

Citation Format: Hannah Carter. A Singleminded-2s/Sirtuin interac4on in the regula4on of mitochondrial dynamics across normal mammary development and ER+ BC progression [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 PO4-28-06.
Abstract PO5-07-05: Deep learning can diagnose axillary lymph node metastases on optical virtual histologic images in breast cancer patients during surgery
Authors: Zhang Shuwei , Yang Houpu , Zhao Jin , Wang Shu
Published: May 2024

Background: Reliable identification of axillary lymph node (ALN) involvement in patients with breast cancer allows for definitive axillary dissection at the time of the initial surgery, thus avoiding the need for a separate axillary surgery. However, conventional intraoperative ALN diagnostic methods are time-consuming and labor-intensive and can result in tissue destruction. Dynamic full field optical coherence tomography, also called dynamic cell imaging (DCI), has been developed and validated to offer rapid and label-free histologic approximations of metastatic and non-metastatic ALNs. In this study, we aim to optimize the diagnostic pipeline with an automated approach and present the results of using a deep learning (DL) algorithm with DCI to predict ALN status intraoperatively in patients with breast cancer. Methods: Breast cancer patients who required ALN staging were enrolled prospectively in this study. DCI was applied to bisected fresh lymph nodes in a non-destructive manner, and the specimens were subsequently sent for histopathological examination, regarded as the gold standard for comparison. A DL model was trained and fine-tuned on over 80,000 DCI images, and the results were mapped to slide level to predict ALN diagnosis. Results: Total 607 DCI slides of ALNs with 112,852 cropped patches were included in the study. The DL model was trained and validated on a dataset containing 481 slides and tested on an independent testing dataset with 126 slides. In the test set, the DL algorithm yielded accuracy for prediction of ALN status, with sensitivity and specificity of 91.9% and 95.5% and an area under the receiver operating characteristic curve (AUC) of 0.937 (95% confidence interval [CI]: 0.912-0.957) at slide level. Conclusion: These results demonstrate that the integration of DCI with DL is rapid, reduces labor requirements and minimizes tissue destruction. Meanwhile, this algorithm had high classification accuracy to predict the metastatic burden of ALNs for patients with breast cancer.

Citation Format: Shuwei Zhang, Houpu Yang, Jin Zhao, Shu Wang. Deep learning can diagnose axillary lymph node metastases on optical virtual histologic images in breast cancer patients during surgery [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 PO5-07-05.
Abstract PO5-07-09: ACCURACY OF STEREOTACTIC VACCUM-ASSISTED BREAST BIOPSY FOR INVESTIGATING SUSPICIOUS CALCIFICATIONS IN 2,021 PATIENTS A PUBLIC HOSPITAL IN BRAZIL
Authors: Amorim Andressa , Mattar Andre , Antonini Marcelo , Lopes Reginaldo Coelho , Damous Luciana , Gebrim Luiz Henrique , Diogenes Marina , Ramos Marcellus
Published: May 2024

Backgroud: the gold standard for breast biopsy procedures is currently an open excision of the suspected lesion. The cost and morbidity associated with this procedure has prompted many physicians to evaluate less invasive, alternative procedures. More recently, image-guided percutaneous core-needle biopsy has become a frequently used method for diagnosing palpable and non-palpable breast lesions. Although sensitivity rates for core-needle biopsy are high, it has the disadvantage of histological underestimation. Vacuum-assisted stereotactic biopsy (VASB) was developed to overcome some of these negative aspects of core-needle biopsy. Objectives: to evaluate the accuracy of vacuum-assisted stereotactic biopsy (VASB) in the investigation of non palpable suspicious calcifications. Methods: it was a retrospective study from July 2012 to December 2020, in which 2,021 women with suspicious calcifications detected on mammography (BI-RADS 4 and 5) had VASB performed at Hospital Estadual Pérola Byington, São Paulo, Brazil. Fragments were obtained and sent to anatomopathological study; a metal clip was placed on the biopsy site. Four groups were analyzed, based on the biopsy results: benign, precursor lesions, Ductal Carcinoma In Situ (DCIS) and Invasive Ductal Carcinoma (ICD). Results: patients median age was 55y (49-63y). Pathology results on VASB were classified respectively as benign n=1,340 (66.3%), precursor lesions n=84 (4.1%), DCIS n=441 (21.8%) and ICD n=156 (7.7%). The 60 patients with results benign on VASB, because anatomopathological disagreement, surgery was performed, with the following results: benign n=30 (50%), ICD e DCIS n=21 (35%) e precursor lesions n=9 (15%). The sensitivity of the method was 91.7 %, specificity was 97.1%, false negative rate was 3%, positive predictive value was 92.4%, negative predictive value was 96.9%. Conclusion: the VASB method has a good accuracy to distinguish lower and higher risk lesions groups comparing to the gold standard. It has high predictive value in both benign and malignant lesions, guiding therapeutic planning. Keywords: Calcifications; Vacuum-assisted stereotactic biopsy; Breast cancer; Diagnosis.

Citation Format: Andressa Amorim, Andre Mattar, Marcelo Antonini, Reginaldo Coelho Lopes, Luciana Damous, Luiz Henrique Gebrim, Marina Diogenes, Marcellus Ramos. ACCURACY OF STEREOTACTIC VACCUM-ASSISTED BREAST BIOPSY FOR INVESTIGATING SUSPICIOUS CALCIFICATIONS IN 2,021 PATIENTS A PUBLIC HOSPITAL IN BRAZIL [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 PO5-07-09.
Abstract PO5-07-10: CONTRAST MAMMOGRAPHY FOR PREOPERATIVE STAGING OF PATIENTS WITH EARLY BREAST CANCER: PRELIMINARY RESULTS
Authors: Amorim Andressa , Mattar Andre , Bitencourt Almir , Moraes Paula , Finguerman Flora
Published: May 2024

a) Brief description of the objective(s) The aim of this study is to compare contrast-enhanced mammography (CM) with magnetic resonance imaging (MRI) for preoperative locoregional staging of patients with early-stage breast cancer. b) Material(s) and method(s) Prospective, single-center study, approved by the Research Ethics Committee, which included patients with a histological diagnosis of invasive breast carcinoma, candidates for initial medical treatment. Patients treated with neoadjuvant chemotherapy and those in whom the tumor was completely resected in the initial biopsy were excluded. CM and MRI were performed in the week before surgery and the anatomopathological result of the surgical specimen was considered the gold standard. Pearson's modification (r) was used to compare tumor size between different methods. c) Results and discussion Thirty-seven patients were included, with a mean age of 54.5±6.9 years (43-70 years). The mean size of the tumors in pathology was 2.9±1.4 cm (1.1-8.0 cm) and the most common histological type was invasive ductal carcinoma (n=34;87.2%). The clinical stage was IA for 14 patients (37.8%) and IIA for 23 patients (62.2%). The main tumor was identified in 33 cases (89.2%) on conventional mammography and in all cases (100%) on both CM and MRI. There was excellent elasticity between tumor size measured on CM and MRI (r=0.897;p< 0.01). When compared with tumor size in pathology, both methods were adopted in a good way (p< 0.01), however, MRI was functionally superior to CM (r=0.847 vs. 0.683), while mammography conventional showed no therapeutic effect (r=0.222;p=0.21). Multifocal lesions were observed on CM in 2 cases (5.4%) and on MRI in 6 cases (16.2%), with 1 case confirmed as multifocal and the others presenting DCIS associated with the surgical specimen. Suspicious additional lesions were seen in 4 patients (10.8%) on CM and in 3 patients (8.1%) on MRI, of which one was confirmed as malignant in the contralateral breast, which had not been identified in previous exams. d) Conclusions CM showed good adaptability with MRI for assessing tumor size and searching for additional lesions, and may be a cheaper and more accessible alternative for preoperative staging in patients at an early clinical stage.

Citation Format: Andressa Amorim, Andre Mattar, Almir Bitencourt, Paula Moraes, Flora Finguerman. CONTRAST MAMMOGRAPHY FOR PREOPERATIVE STAGING OF PATIENTS WITH EARLY BREAST CANCER: PRELIMINARY 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 PO5-07-10.
Abstract PO5-09-10: Inflammatory Breast Cancer Patient Profile in a Population of Puerto Rican Women
Authors: Arroyo-Cruz Luz , Martinez-Montemayor Michelle
Published: May 2024

Background: Breast cancer (BC) is the most frequently diagnosed cancer type, as well as the leading cause of cancer death among women in Puerto Rico (PR). Moreover, inflammatory breast cancer (IBC) is a highly aggressive BC subtype. The current study aimed to describe the patient profile and the clinicopathological characteristics of IBC tumors in Hispanic women living in Puerto Rico.

Methods: This is a retrospective, population-based study using the Puerto Rico Central Cancer Registry (PRCCR) database and the Health Insurance Linkage Database (PRCCR-HILD) to identify and describe the patient profile of Puerto Rican women diagnosed with IBC from 2008 to 2018. Variables such as age at diagnosis, staging variables, tumor receptor subtypes, treatment received, and overall survival (OS) were studied. Statistical analysis methods were employed to describe the population, estimate survival curves and examine the risk of dying.

Results: We identified a total of 51 patients. The mean age at diagnosis of IBC in the current study was 59 years old, which is older than the mean age at diagnosis of IBC for women in the mainland US, but younger than the mean age of women that are diagnosed with BC in PR (63 years old). A total of 62.8% of patients had no metastases at diagnosis and 64.7% were diagnosed with stage III disease. Most tumors presented with ER+/PR+/Her2- (21.6%), or a triple-negative (ER-/PR-/Her2-, 15.7%) tumor concordance. The OS during the 12 months post-diagnosis was 66%, whereas at 36 months, OS decreased to 39%. The triple-negative subtype had the worst survival at 36 months (36%). Women with stage IV disease and those with ER-/PR- tumor subtype had a higher risk of dying.

Conclusions: This is the first research to describe the patient profile and characteristics of women diagnosed with IBC in Puerto Rico. Our results suggest that the Puerto Rican IBC patient population presents unique characteristics. This research increases awareness about this lethal disease in PR.

Citation Format: Luz Arroyo-Cruz, Michelle Martinez-Montemayor. Inflammatory Breast Cancer Patient Profile in a Population of Puerto Rican Women [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 PO5-09-10.
Abstract PO5-10-11: BREAST CANCER DIAGNOSIS AND TREATMENT AMONG DISPLACED AND HOST POPULATIONS IN NORTH-WEST SYRIA
Authors: Chagpar Anees , Abbara Aula , Alshemali Alaa , Alahdab Fares , Hamze Moahmed , Attassi Bassel , Alawa Jude , Cech Sydney , Tang Lawrence , Khoshnood Kaveh
Published: May 2024

INTRODUCTION: The protracted Syrian conflict has forcibly displaced more than half the pre-conflict population of 22 million people with 6.7 million IDPs (internally displaced people.) 80% of IDPs are women and children. Given a lack of humanitarian funding for oncology services, NGOs like the Syrian-American Medical Society (SAMS), have used private funding to establish oncology services. We sought to explore differences in breast cancer diagnosis and treatment among IDPs and host populations in SAMS oncology centre in Idlib governorate.

METHODS: Charts of women seen diagnosed with breast cancer at the SAMS Oncology Centre in Idlib governorate between March 2018 and February 2021 were reviewed. Clinicopathologic data was extracted, and non-parametric statistical analyses were performed to compare citizens vs. those who were displaced.

RESULTS: Data for 188 patients were available; for 108/188 (57%) details of IDP versus host status was available. 61/108 (56%) were IDPs, 47 (44%) were host. The median age at diagnosis was similar between citizens and those who were displaced. Further, the clinicopathologic features and treatment between these two groups were similar. The time between onset of symptoms and diagnosis was imilar between the host population and IDPs (median 125.5 days vs. 77 days, respectfully, p=0.255), although there was a trend towards a shorter time from diagnosis to initiation of treatment for IDPs (median 19 days vs. 14 days, p=0.051).

CONCLUSION: From this cohort study, it is notable that there were no significant differences in the tumor size, node positivity or grade at diagnosis. Further, although IDPs are usually considered to have more challenging access to healthcare services compared to host populations, it was notable that there was no significant difference between the time of onset of symptoms to diagnosis between the two groups, and a trend towards a shorter time to treatment. Although this may be related to the relatively small sample size, it may also reflect other commitments of host populations (e.g., employment) that may delay care, or the work of humanitarian organizations in reaching displaced populations. Further, given that in northwest Syria, more than 65% of the 4-4.6 million people in the area are IDPs, access to care between the two groups may be similar. Further work is required to explore this.

Table.

Citation Format: Anees Chagpar, Aula Abbara, Alaa Alshemali, Fares Alahdab, Moahmed Hamze, Bassel Attassi, Jude Alawa, Sydney Cech, Lawrence Tang, Kaveh Khoshnood. BREAST CANCER DIAGNOSIS AND TREATMENT AMONG DISPLACED AND HOST POPULATIONS IN NORTH-WEST SYRIA [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 PO5-10-11.
Abstract PO5-22-05: ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY
Authors: Bart Renne , Przybysz Daniel , Ferrari Ramon , Franco Leonardo , Almeida Carlos , Canary Paulo
Published: May 2024

Introduction: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The fast forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published.

Citation Format: Renne Bart, Daniel Przybysz, Ramon Ferrari, Leonardo Franco, Carlos Almeida, Paulo Canary. ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY [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 PO5-22-05.
Abstract PO5-22-11: Radiotherapy-associated Complications in Breast Cancer patients treated with Nipple-Sparing Mastectomy: Results of the Reconstruction-after-Mastectomy AGO R02 Registry
Authors: Peintinger Florentia , Sieghartsleitner Elisa , Pfeifer Bernhard , Pristauz-Telsnigg Gunda , Tsangarakis Georg , Hochstätter Rüdiger , Koller Rupert , Denison Ursula , Hager Christopher , Reitsamer Roland
Published: May 2024

Nipple-Sparing mastectomy (NSM) followed by implant-based breast reconstruction is an oncologically safe procedure increasingly used in patients with breast cancer. A proportion of patients treated with NSM will be receiving adjuvant radiotherapy according to contributing factors indicating radiotherapy use.

Methods

Data from six breast centers in Austria were entered in the AGO R02 Registry from women who underwent breast reconstruction after mastectomy between 2012 and 2022 to evaluate complications associated with surgical techniques and selection of patients. Univariate analysis was used to identify factors that may impact surgical outcome.

Results

The registry included a total of 744 female patients. Of 913 NSMs, 730 NSMs were followed by implant-based reconstruction. Adjuvant radiotherapy was administered in 132/730 patients (18%).

In this group minor complications (infection, hematoma) were observed in 6 patients (4.5%) and major complications requiring additional surgery (wound breakdown, skin and/or nipple necrosis) were observed in 16 patients (12.1%) in a short term follow up of 4 months (mean).

In the group of patients without adjuvant radiotherapy minor complications (infection, hematoma) were observed in 33 patients (4.5%) and major complications (wound breakdown, skin and/or nipple necrosis) were observed in 75 patients (10.3%). In both groups no statistically significant association was observed between complications and age, body mass index, diabetes, preoperative chemotherapy, implant position (pre/subpectoral), use of mesh. Smoking and chemotherapy were the only factors associated with higher proportion of minor complications in patients not receiving radiotherapy.

Conclusions

Women treated with adjuvant radiotherapy after NSM followed by implant-based reconstruction have a higher incidence of major complications requiring additional surgery in comparison with women treated without radiotherapy in a short term follow up. Considering new radiotherapy techniques/volumes and early multidisciplinary planning may optimize multimodal treatment in these patients.

Supported by AGO Österreich

Citation Format: Florentia Peintinger, Elisa Sieghartsleitner, Bernhard Pfeifer, Gunda Pristauz-Telsnigg, Georg Tsangarakis, Rüdiger Hochstätter, Rupert Koller, Ursula Denison, Christopher Hager, Roland Reitsamer. Radiotherapy-associated Complications in Breast Cancer patients treated with Nipple-Sparing Mastectomy: Results of the Reconstruction-after-Mastectomy AGO R02 Registry [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 PO5-22-11.
Abstract PO5-25-02: Microenvironment based co-culture dependence of breast cancer and immune cell interactions on functional outcomes
Authors: Norek Karen , Kennard Jacob , Fuh Kenneth , Shepherd Robert , Rinker Kristina , Kharenko Olesya
Published: May 2024

The tumour microenvironment (TME) includes physical forces from interstitial fluid flow and cell-cell interactions that modulate cancer development and progression through activation of multiple oncogenic pathways leading to tumor growth and metastatic spreading. We previously reported on the role of physical forces on epithelial to mesenchymal transition (EMT) and S100 gene family expression and cell to cell adhesion properties with implications to normal breast development and cancer. Signals from the tumor exit the local tumor environment through interstitial fluid transport and cell migration where they can be found in the blood stream. We developed a whole blood RNA gene expression biomarker panel coupled with proprietary software capable of identifying the presence of an active breast cancer signature at early stages of disease with clinical study results previously reported. Here we report on results from transcriptomic and function studies with cell interaction models. Cancer cells can influence immune cells through direct contact or via secreted molecules causing the immune cells to undergo functional changes. To investigate mechanisms involved in the induction of these alterations in a model system, we performed co-culture studies with human monocytic cells and breast cancer cells. Interaction of human monocytic cells with the breast cancer cells caused significant changes in both behavior and transcriptomes. Moreover, using RNAseq and pathway analysis we demonstrated that the changes induced through the exposure to the more aggressive triple negative (TNBC) phenotype were distinct from the alterations triggered upon contact with an ER+ breast cancer cell line. We also show that cancer-immune crosstalk triggers EMT as well as activation of multiple oncogenic pathways associated with cell migration and invasion, cell chemotaxis and cell-to-cell interactions. As the interplay between cancer and immune cells plays an important role in cancer progression, these findings provide important insight into key mechanisms controlling these outcomes.

Citation Format: Karen Norek, Jacob Kennard, Kenneth Fuh, Robert Shepherd, Kristina Rinker, Olesya Kharenko. Microenvironment based co-culture dependence of breast cancer and immune cell interactions on functional outcomes [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 PO5-25-02.
Abstract PO5-27-05: Computational design and validation of a novel peptide-drug conjugate for treatment of triple negative breast cancer
Authors: Liu Francine , Zhai Andrew , Yoluk Ozge , Broom Aron , Stone Tracy , Butterfoss Glenn , Popa Serban , Li Tianyu , Siow Lucas , Ing Christopher , White David
Published: May 2024

Sortilin (SORT1) is a member of the vacuolar protein sorting 10 protein (Vps10p) family that functions as a receptor regulating peptide and protein trafficking between the plasma membrane, lysosomes, and trans-golgi network. As a cell surface receptor, SORT1 is able to mediate efficient endocytosis of extracellular ligands to the lysosomal compartment. Numerous reports have identified enriched SORT1 expression in a variety of tumor types, including triple-negative breast cancer (TNBC), a subtype of breast cancer associated with aggressive clinical behavior and poor disease outcomes. We sought to exploit SORT1-dependent internalization of peptides as a platform for rapid and specific chemotherapy delivery into TNBC cells. Using ProteinStudio (our proprietary computation-enabled design capabilities), we generated high-affinity SORT1 targeting peptides that exhibit efficient receptor dependent internalization and lysosomal localization. Alternative computational approaches such as AlphaFold2 failed to recapitulate the peptide design. Peptide drug conjugates (PDCs) were generated via a linkage strategy that combines our designed peptides to the antimitotic agent monomethyl auristatin E (MMAE). Our PDC molecules exhibit potent tumor regression in a MDA-MB-231 TNBC cell derived xenograft model, thereby highlighting the potential of SORT1-engaging PDCs as an efficacious targeted chemotherapeutic delivery strategy.

Citation Format: Francine Liu, Andrew Zhai, Ozge Yoluk, Aron Broom, Tracy Stone, Glenn Butterfoss, Serban Popa, Tianyu Li, Lucas Siow, Christopher Ing, David White. Computational design and validation of a novel peptide-drug conjugate for treatment of triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-05.
Abstract SoA3-01: SERMs versus SERDs for targeting ESR1 mutations
Authors: Greene G.
Published: May 2024

Estrogen receptor positive (ER+) breast cancers are effectively treated with adjuvant endocrine therapies, with or without the addition of CDK4/6 inhibitors. However, many patients develop resistance and progress to ER+ metastatic disease (MBC). Acquired mutations in ESR1, which encodes estrogen receptor alpha (ERa), contribute to 20-40% of endocrine therapy resistant MBC. An emerging, unanswered and controversial question is the best choice of ER-targeted therapy for ET-resistant mutant ER+ MBC, recognizing that for most patients, a balance between compliance, effectiveness and quality of life are competing issues. To partially address some of these issues, we have tested and compared a relatively nontoxic SERM, lasofoxifene, to a complete estrogen receptor antagonist (CERAN), OP1250, in a mutant ERa (MCF-7 Y537S ERa) MBC endocrine therapy resistant xenograft tumor model (MIND = Mammary intraductal) to examine the efficacy of both drugs in a metastatic context in which a frequently observed, aggressive mutant ERa is expressed. As single agents, both Lasofoxifene and OP1250 inhibited primary tumor growth as well as metastasis to the lung, liver, brain and bone, with greater effect at higher doses of each drug, and both were substantially more effective than fulvestrant, the current gold standard for treating progressive disease. When combined with palbociclib, an additional decrease in metastasis was observed, compared to lasofoxifene, OP1250 or palbociclib as single agents. In total, these results demonstrate that lasofoxifene, a SERM, is as effective as OP-1250, a complete ER antagonist and SERD in a xenograft MIND model of mutant ER+ metastatic breast cancer. The potential use of lasofoxifene or OP1250, both alone and in combination with CDK4/6 inhibitors, to reduce tumor growth and metastasis in patients with ET-resistant metastatic breast cancer, is being tested in clinical trials to determine whether either drug is a preferred therapy versus current standard of care for mutant ER+ MCB.

Citation Format: G. Greene. SERMs versus SERDs for targeting ESR1 mutations [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 SoA3-01.
Abstract Wrk2-04: Virtual screening of ultra-large chemical spaces for novel chemotype discovery
Authors: Irwin J.
Published: May 2024

Recently, 'tangible' virtual libraries have made billions of molecules readily available. Prioritizing these molecules for synthesis and testing demands computational approaches, such as docking. We will present recent results in which protein structure is interrogated using molecular docking, resulting in new high-affinity compounds that exhibit new biology in animal models. Singh I, Seth A, Billesbølle CB, Braz J, Rodriguiz RM, Roy K, Bekele B, Craik V, Huang XP, Boytsov D, Pogorelov VM, Lak P, O'Donnell H, Sandtner W, Irwin JJ, Roth BL, Basbaum AI, Wetsel WC, Manglik A, Shoichet BK, Rudnick G. Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Cell. 2023 May 11;186(10):2160-2175.e17. doi: 10.1016/j.cell.2023.04.010. Epub 2023 May 2. PMID: 37137306; PMCID: PMC10306110. Fink EA, Xu J, Hübner H, Braz JM, Seemann P, Avet C, Craik V, Weikert D, Schmidt MF, Webb CM, Tolmachova NA, Moroz YS, Huang XP, Kalyanaraman C, Gahbauer S, Chen G, Liu Z, Jacobson MP, Irwin JJ, Bouvier M, Du Y, Shoichet BK, Basbaum AI, Gmeiner P. Structure-based discovery of nonopioid analgesics acting through the α2A-adrenergic receptor. Science. 2022 Sep 30;377(6614):eabn7065. doi: 10.1126/science.abn7065. Epub 2022 Sep 30. PMID: 36173843; PMCID: PMC10360211. Kaplan AL, Confair DN, Kim K, Barros-Álvarez X, Rodriguiz RM, Yang Y, Kweon OS, Che T, McCorvy JD, Kamber DN, Phelan JP, Martins LC, Pogorelov VM, DiBerto JF, Slocum ST, Huang XP, Kumar JM, Robertson MJ, Panova O, Seven AB, Wetsel AQ, Wetsel WC, Irwin JJ, Skiniotis G, Shoichet BK, Roth BL, Ellman JA. Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity. Nature. 2022 Oct;610(7932):582-591. doi: 10.1038/s41586-022-05258-z. Epub 2022 Sep 28. PMID: 36171289; PMCID: PMC9996387.

Citation Format: J. Irwin. Virtual screening of ultra-large chemical spaces for novel chemotype discovery [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 Wrk2-04.
Supplementary Figure 6 from ROR2/Wnt5a Signaling Regulates Directional Cell Migration and Early Tumor Cell Invasion in Ovarian Cancer
Authors: Grither Whitney R. , Baker Breanna , Morikis Vasilios A. , Ilagan Ma. Xenia G. , Fuh Katherine C. , Longmore Gregory D.
Published: May 2024

Additional ID8 ROR2-/- data
Supplementary Table 25 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 25. LuCaP Proteome VSN Normalized Differential Expression ROTS AdCa vs NE
Supplementary Table 24 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 24. LuCaP Phosphoproteome VSN Normalized Differential Expression ROTS AdCa CR vs NE
Supplementary Table 13 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 13. LuCaP Phosphoproteome GSEA Hallmarks
Supplementary Table 11 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 11. LuCaP Phosphoproteome Kinase Substrate Enrichment Analysis of NE vs AdCa
Supplementary Table S3 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 S3: Goodness of fit of study sample and cohort.
Supplementary Table S2 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 S2: Sample size by Quarter
Supplementary Table 1 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 1: Summary of occupational exposures and modifying chronic health conditions in the MPC patient cohort
Data 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

Abstract
Continuous tobacco use in patients with cancer is linked to substantial healthcare costs due to increased risks and complications, whereas quitting smoking leads to improved treatment outcomes and cost reductions. Addressing the need for empirical evidence on the economic impact of smoking cessation, this study examined the association between smoking cessation and healthcare cost utilization among a sample of 930 patients with cancer treated at The University of Texas MD Anderson Cancer Center's Tobacco Research and Treatment Program (TRTP). Applying conditional quantile regression and propensity scores to address confounding, our findings revealed that abstinence achieved through the TRTP significantly reduced the median cost during a 3-month period post-quitting by $1,095 [β = −$1,095, P = 0.007, 95% confidence interval (CI), = (−$1,886 to −$304)]. Sensitivity analysis corroborated these conclusions, showing a pronounced cost reduction when outlier data were excluded. The long-term accrued cost savings from smoking cessation could potentially offset the cost of participation in the TRTP program, underscoring its cost effectiveness. An important implication of this study is that by reducing smoking rates, healthcare systems can more efficiently allocate resources, enhance patient health outcomes, and lessen the overall cancer burden.
Prevention Relevance:
This study emphasizes the dual impact of smoking cessation programs in patients with cancer: quitting smoking and reducing healthcare costs. It highlights the importance of integrating cessation programs into cancer prevention strategies, ensuring both individual health benefits and broader, system-wide economic efficiencies.

See related Spotlight, p. 197
Figure S9 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 does not alter CD54 expression in sip-T in vivo
Figure S4 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 treatment of sip-T significantly improves their cytotoxicity (determined by incucyte) against prostate tumors
Figure S2 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

CyTOF analysis of various immune checkpoint molecules in sip-T subsets
Figure S3 from Tsyn-Seq: a T-cell Synapse–Based Antigen Identification Platform
Authors: Jin Yimei , Miyama Takahiko , Brown Alexandria , Hayase Tomo , Song Xingzhi , Singh Anand K. , Huang Licai , Flores Ivonne I. , McDaniel Lauren K. , Glover Israel , Halsey Taylor M. , Prasad Rishika , Chapa Valerie , Ahmed Saira , Zhang Jianhua , Rai Kunal , Peterson Christine B. , Lizee Gregory , Karmouch Jennifer , Hayase Eiko , Molldrem Jeffrey J. , Chang Chia-Chi , Tsai Wen-Bin , Jenq Robert R.
Published: May 2024

Tsyn-seq system spike-in assay.
Supplementary Methods, Tables, and Figure Legends from ILT2 and ILT4 Drive Myeloid Suppression via Both Overlapping and Distinct Mechanisms
Authors: Tian Jane , Ashique Amir M. , Weeks Sabrina , Lan Tian , Yang Hong , Chen Hung-I Harry , Song Christina , Koyano Kikuye , Mondal Kalyani , Tsai Daniel , Cheung Isla , Moshrefi Mehrdad , Kekatpure Avantika , Fan Bin , Li Betty , Qurashi Samir , Rocha Lauren , Aguayo Jonathan , Rodgers Col , Meza Marchelle , Heeke Darren , Medfisch Sara M. , Chu Chun , Starck Shelley , Basak Nandini Pal , Sankaran Satish , Malhotra Mohit , Crawley Suzanne , Tran Thomas-Toan , Duey Dana Y. , Ho Carmence , Mikaelian Igor , Liu Wenhui , Rivera Lee B. , Huang Jiawei , Paavola Kevin J. , O'Hollaren Kyle , Blum Lisa K. , Lin Vicky Y. , Chen Peirong , Iyer Anjushree , He Sisi , Roda Julie M. , Wang Yan , Sissons James , Kutach Alan K. , Kaplan Daniel D. , Stone Geoffrey W.
Published: May 2024

Supplementary Methods, Tables, and Figure Legends
Supplementary Table S1 from Machine Learning Links T-cell Function and Spatial Localization to Neoadjuvant Immunotherapy and Clinical Outcome in Pancreatic Cancer
Authors: Blise Katie E. , Sivagnanam Shamilene , Betts Courtney B. , Betre Konjit , Kirchberger Nell , Tate Benjamin J. , Furth Emma E. , Dias Costa Andressa , Nowak Jonathan A. , Wolpin Brian M. , Vonderheide Robert H. , Goecks Jeremy , Coussens Lisa M. , Byrne Katelyn T.
Published: May 2024

Supplementary Table S1. Statistical comparison between the Liudahl et al. original PDAC cohort and the selected subset used as Cohort 1 in this study. Mean value and standard error of the mean (SEM) shown for each variable. P-values computed using Fisher’s exact test for categorical variables,
Wilcoxon rank-sum test for continuous variables, and log rank test for overall survival.
Supplementary Figure S4 from Machine Learning Links T-cell Function and Spatial Localization to Neoadjuvant Immunotherapy and Clinical Outcome in Pancreatic Cancer
Authors: Blise Katie E. , Sivagnanam Shamilene , Betts Courtney B. , Betre Konjit , Kirchberger Nell , Tate Benjamin J. , Furth Emma E. , Dias Costa Andressa , Nowak Jonathan A. , Wolpin Brian M. , Vonderheide Robert H. , Goecks Jeremy , Coussens Lisa M. , Byrne Katelyn T.
Published: May 2024

Supplementary Figure S4. A. Elbow plot showing optimal number of RCNs (k=7) for grouping cellular
neighborhoods. B. Bar chart showing the number of cells assigned to each of the seven RCNs across all αCD40
IA regions. C. Bar chart showing the percentage (out of 100) of cells assigned to each of the seven RCNs across
all αCD40 IA regions. D. Stacked bar chart showing fraction (out of 1.0) of RCNs present per αCD40 IA region.
E. Stacked bar chart showing average proportion (out of 1.0) of RCNs present in IA regions for eachαCD40-treated patient. F. Scatterplot reconstructions for each αCD40 IA region. Each dot represents a cell present in the IA, and each cell is colored by its original cell state phenotype (top scatterplot) or RCN assignment
(bottom scatterplot).
Supplementary Figure S1 from Machine Learning Links T-cell Function and Spatial Localization to Neoadjuvant Immunotherapy and Clinical Outcome in Pancreatic Cancer
Authors: Blise Katie E. , Sivagnanam Shamilene , Betts Courtney B. , Betre Konjit , Kirchberger Nell , Tate Benjamin J. , Furth Emma E. , Dias Costa Andressa , Nowak Jonathan A. , Wolpin Brian M. , Vonderheide Robert H. , Goecks Jeremy , Coussens Lisa M. , Byrne Katelyn T.
Published: May 2024

Supplementary Figure S1. A. Stacked bar chart showing percent tissue area (out of 100) sampled per resection from each patient. Bars are colored by histopathologic site of the regions sampled. B. Representative IHC staining of each antibody used in sequence in the panel. Scale bar = 50 μm. C. Two representative regions stained with CD3, CD8, and CD4 antibodies. For each region, top images show gates for CD8 on CD3+ population (left) and CD4 on CD3+ CD8- population (right), and bottom row shows pseudo-colored mIHC images.
D. Hierarchical gating template used to phenotype cells using image gating cytometry in FCS Image Cytometry
RUO.
Data from Tsyn-Seq: a T-cell Synapse–Based Antigen Identification Platform
Authors: Jin Yimei , Miyama Takahiko , Brown Alexandria , Hayase Tomo , Song Xingzhi , Singh Anand K. , Huang Licai , Flores Ivonne I. , McDaniel Lauren K. , Glover Israel , Halsey Taylor M. , Prasad Rishika , Chapa Valerie , Ahmed Saira , Zhang Jianhua , Rai Kunal , Peterson Christine B. , Lizee Gregory , Karmouch Jennifer , Hayase Eiko , Molldrem Jeffrey J. , Chang Chia-Chi , Tsai Wen-Bin , Jenq Robert R.
Published: May 2024

Abstract
Tools for genome-wide rapid identification of peptide–major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell–APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen derived from human papillomavirus type 16 (HPV16), Tsyn-seq successfully enriched the correct cognate antigen from a cDNA library derived from an HPV16-positive cervical cancer cell line. Tsyn-seq provides a method for rapidly identifying antigens recognized by TCRs of interest from a tumor cDNA library.

See related Spotlight by Makani and Joglekar, p. 515.
Data from ANXA3-Rich Exosomes Derived from Tumor-Associated Macrophages Regulate Ferroptosis and Lymphatic Metastasis of Laryngeal Squamous Cell Carcinoma
Authors: Xu Licheng , Li Wenjing , Liu Danxi , Cao Jing , Ge Jingchun , Liu Xinyu , Wang Yue , Teng Yujian , Liu Pengyan , Guo Xinyue , He Chen , Liu Ming , Tian Linli
Published: May 2024

Abstract
Tumor-associated macrophages (TAM) induce immunosuppression in laryngeal squamous cell carcinoma (LSCC). The interaction between LSCC cells and TAMs affects the progression of laryngeal cancer through exosomes, but the underlying molecular mechanism remains unclear. Proteomics analysis of TAMs isolated from human laryngeal tumor tissues obtained from patients with confirmed lymphatic metastasis revealed an upregulation of annexin A3 (ANXA3). In TAMs, ANXA3 promoted macrophages to polarize to an M2-like phenotype by activating the AKT–GSK3β–β-catenin pathway. In addition, ANXA3-rich exosomes derived from TAMs inhibited ferroptosis in laryngeal cancer cells through an ATF2–CHAC1 axis, and this process was associated with lymphatic metastasis. Mechanistically, ANXA3 in exosomes inhibited the ubiquitination of ATF2, whereas ATF2 acted as a transcription factor to regulate the expression of CHAC1, thus inhibiting ferroptosis in LSCC cells. These data indicate that abnormal ANXA3 expression can drive TAM reprogramming and promote an immunosuppressive microenvironment in LSCC. Meanwhile, ANXA3-rich exosomes inhibit ferroptosis of LSCC cells and promote lymphatic metastasis, thus promoting tumor progression.
T-Cell Expression of CXCL13 is Associated with Immunotherapy Response in a Sex-Dependent Manner in Patients with Lung Cancer
Authors: Brennan Michelle , DeBruin David , Nwokolo Chinye , Hunt Katey S. , Piening Alexander , Donlin Maureen J. , Ferris Stephen T. , Teague Ryan M. , DiPaolo Richard J. , Alspach Elise
Published: May 2024

Emerging evidence in preclinical models demonstrates that antitumor immunity is not equivalent between males and females. However, more investigation in patients and across a wider range of cancer types is needed to fully understand sex as a variable in tumor immune responses. We investigated differences in T-cell responses between male and female patients with lung cancer by performing sex-based analysis of single cell transcriptomic datasets. We found that the transcript encoding CXC motif chemokine ligand 13 (CXCL13), which has recently been shown to correlate with T-cell tumor specificity, is expressed at greater levels in T cells isolated from female compared with male patients. Furthermore, increased CXCL13 expression was associated with response to PD1–targeting immunotherapy in female but not male patients. These findings suggest that there are sex-based differences in T-cell function required for response to anti–PD1 therapy in lung cancer that may need to be considered during patient treatment decisions.

See related Spotlight by Cruz-Hinojoza and Stromnes, p. 952