tbuckley/cabot-search huggingface dataset:
Abstract PS10-08: Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting
Authors: Mikael Eriksson, Marta Román, Axel Gräwingholt, Sylvia Heywang-Köbrunner, Paolo Rossi, Per Hall
Journal: Cancer Research (2024)

Abstract Background: Image-derived AI risk models for breast cancer have shown high discriminatory performances compared with clinical risk models based on family history and lifestyle factors. However, little is known about their generalizability across different screening settings and clinical feasibility. Purpose: To investigate the predictive performance of a clinically used image-derived AI-based breast cancer risk model in multiple European screening populations. Methods: Four European mammographic screening populations in three countries screened between 2009-2020 for women aged 45-69 was used to perform a nested case-control study. In total, 739 women with incident breast cancers were included together with 7,812 controls matched to cases on year of study-entry. Mammographic features (density, microcalcifications, masses, left-right breast asymmetries of these features) for risk assessment were extracted using AI from full-field digital mammograms. Breast cancer occurrence was assessed after two years of follow-up. Absolute risks of breast cancer were predicted using the risk model from negative mammograms at study-entry. Adjusted Area Under the receiver operating characteristic Curves (aAUC) estimated discriminatory performance and, adjusted risk-ratios estimated the stratification performance of women at high/general risk per the clinical guidelines. Results: The overall aAUC of the AI risk model was 0.72 (95%CI 0.70-0.75), range 0.71 (95%CI 0.67-0.75) to 0.74 (95%CI 0.69-0.78) for breast cancers developed in four screening populations. In the 4.6% of women classified at high risk using the NICE guidelines thresholds, cancers were more likely diagnosed after 2 years follow-up, risk-ratio (RR) 6.7 (95%CI 5.6-8.0), compared with the 71% of women classified at general risk by the model. Similar risk-ratios were observed across tertiles of mammographic density. In the high-risk group, 22% of the 2-year future cancers were diagnosed, and 29% of stage 2 and higher cancers, p&amp;lt; 0.01. Conclusions: The AI risk model showed generalizable discriminatory performances across European populations and, captured ~30% of clinically relevant stage 2 and higher breast cancers in ~5% of high-risk women who were sent home with a negative mammogram. Similar results were seen in fatty and dense breasts. An image-derived AI model is feasible for personalized screening to improve screening outcomes. Citation Format: Mikael Eriksson, Marta Román, Axel Gräwingholt, Sylvia Heywang-Köbrunner, Paolo Rossi, Per Hall. Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting [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 PS10-08.
Abstract PO4-13-01: A randomised trial comparing 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early breast cancer (REaCT-ZOL): Quality of life and toxicity outcomes
Authors: Igor Machado, Lucas Clemons, Carol Stober, Gregory Pond, Arif Awan, Henry Conter, Demetrios Simos, Sukhbinder Dhesy-Thind, Mihaela Mates, Vikaash Kumar, John Hilton, Lisa Vandermeer, Mark Clemons
Journal: Cancer Research (2024)

Abstract Background: While adjuvant 6-monthly zoledronate is widely used in patients with early-stage breast cancer (EBC), questions remain around optimal scheduling of adjuvant bisphosphonates. We reviewed quality of life and bisphosphonate-related toxicities observed within a prospective randomised trial. Methods: Patients with EBC were randomised to either a single infusion of adjuvant zoledronate (4mg IV) or to 6-monthly treatment for 3 years. Quality of life was measured using the EQ-5D-5L questionnaire (before and after each infusion and 6-monthly thereafter in the single infusion arm). Acute phase reaction (APRs) data was collected after each infusion and data on other bisphosphonate-related toxicities (hypocalcaemia, renal impairment, ONJ and atypical fractures) was collected 6-monthly for 3 years. Results: Between 21-Nov-2018 and 02-Apr-2020, 211 patients were randomized to either a single infusion (n=107) or 6-monthly (n=104) adjuvant zoledronate. While each zoledronate infusion was associated with a worsening QoL, the overall QoL was the same in the two study arms. APRs occurred in 75% of patients after receiving zoledronate. Other bisphosphonate-related toxicities were uncommon in either arm. Significantly more patients discontinued study treatment in the 6-monthly arm (30/104, 28.8%) compared with the single infusion arm (3/107, 2.8%) (p &amp;lt; 0.001). The most common reason for study discontinuation was the occurrence of APRs, pain and malaise. Disease-free and overall survival rates were not significantly different in the study arms. Discussion: A single infusion of adjuvant zoledronate may offer patients a more convenient and better tolerate regimen than repeat infusions. APRs remain an important toxicity with repeat infusions of zoledronate, leading to increased rates of treatment discontinuation. Larger, definitive, trials comparing a single infusion with repeat treatments are required. Citation Format: Igor Machado, Lucas Clemons, Carol Stober, Gregory Pond, Arif Awan, Henry Conter, Demetrios Simos, Sukhbinder Dhesy-Thind, Mihaela Mates, Vikaash Kumar, John Hilton, Lisa Vandermeer, Mark Clemons. A randomised trial comparing 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early breast cancer (REaCT-ZOL): Quality of life and toxicity 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 PO4-13-01.
Abstract PO5-17-02: Triple-negative breast cancer as an untraceable tumor compared to other immunohistochemical subtypes: a cross-sectional study
Authors: Morgana Silva, Afonso Nazário, Vanessa Sanvido
Journal: Cancer Research (2024)

Abstract Objective: To compare the form of presentation at diagnosis of triple negative breast tumors with other immunohistochemical subtypes, in relation to clinical examination or imaging examination. Methods: This is a cross sectional study that evaluated data related to the presentation of breast carcinomas at diagnosis (clinical examination or screening imaging examination findings), immunohistochemical subtype, histological grade and tumor size, in diagnosed and referred patients. for the Mastology service at Hospital São Paulo – Unifesp, in São Paulo – Brazil, in the period between 2012 and 2021, by analyzing data from the medical records of these patients. Results: Among the 699 invasive carcinomas diagnosed, 246 patients were diagnosed with luminal profile A (35.2%), 257 luminal B (36.8%), 58 luminal B HER-2+ (8.3%), 26 HER-2 enriched (3.7%) and 112 triple negative (16%). Triple negative carcinomas had a higher rate of diagnosis by clinical examination (86.6%), 6.65 times more likely to be diagnosed by clinical examination than luminal A, in addition to having a larger lesion. The triple negative and HER-2 enriched subtypes presented the worst scenarios of clinical stage at diagnosis. Among the tumors diagnosed by screening examination, those belonging to the luminal A were associated with nodules seen on imaging (in 45.1%) and the subtypes luminal B and luminal B HER-2+ with the appearance of microcalcifications. There were no cases of triple negatives involving microcalcifications in our sample. Asymmetries were more common in images of luminal B HER-2+ tumors. In the multivariate analysis, it was observed that only the histological grade and the Ki-67 value are related to the form of diagnosis. Tumors with histological grade 2 or 3 are more likely to be diagnosed by clinical examination and not be traceable in relation to histological grade 1. As for Ki-67, its increase of 1 percentage point leads to an increase of 1.3% in the chance finding on physical examination. There was no correlation of hormone receptors and HER-2 with the chance of the tumor not being screenable. Conclusions: triple negative subtype breast carcinomas present a higher risk of diagnosis by clinical examination compared to other immunohistochemical subtypes and, therefore, tend not to be traceable. Parameters such as high Ki-67 and histological grade correlate with this trend. Citation Format: Morgana Silva, Afonso Nazário, Vanessa Sanvido. Triple-negative breast cancer as an untraceable tumor compared to other immunohistochemical subtypes: a cross-sectional 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 PO5-17-02.
Abstract TC-02: When to do a window trial
Authors: M. Dowsett, S. Hurvitz
Journal: Cancer Research (2024)

Abstract The window of opportunity in the short time between diagnosis and surgery for primary breast cancer has been exploited in trials of many endocrine agents. In these cases the therapeutic effect is antiproliferative and immunohistochemical detection of changes in Ki67 are considered a valid biomarker of likely long term efficacy. Trials have also been extended to assessment of inhibitors of growth factor receptors (eg lapatinib) and COX2 inhibitors. In these circumstances the mode of action is not purely inhibition of proliferation such that while changes in Ki67 may be of interest they should not be taken as necessarily reflecting the presence or absence of efficacy. It is also important to recognise that it may take longer than the time window available to get to a pharmacodynamic steady state. This is reflected by data from studies of tamoxifen and of GnRH analogues in premenopausal women. As well as being a window for assessing the biologic effectiveness of new agents it has been used as a means of assessing the prognosis of patients taking an established drug such as an aromatase inhibitor (AI) in the POETIC and an AI or tamoxifen in the ADAPT trial. Citation Format: M. Dowsett, S. Hurvitz. When to do a window trial [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 TC-02.
Abstract PO5-05-08: LOSS OF SINGLEMINDED 2S RESULTS IN A PI3K SUBUNIT SWITCH WHICH DRIVES THERAPEUTIC RESISTANCE IN ESTROGEN RECEPTOR POSITIVE BREAST CANCER
Authors: Garhett Wyatt, Rachel Steinmetz, Traci Lyons, Weston Porter
Journal: Cancer Research (2024)

Abstract Estrogen receptor (ER) + breast cancer (BC) comprises over 70% of BC cases and are targeted via ER modulated therapies. Despite this, ER+BC patients can experience recurrence within 20 years and the majority of BC related deaths can be attributed to metastatic ER+BC. These distant metastases are commonly diagnosed as endocrine therapy resistant. Thus, there is an unmet need to identify novel biomarkers for treating ER+ patients with metastases. We have identified a tumor suppressor gene, singleminded 2s (SIM2s), expressed in breast epithelial cells that inhibits epithelial to mesenchymal transition and metastasis, and is downregulated in the progression of breast disease. In ER+BC cell lines, loss of SIM2s results in upregulation of mesenchymal markers and increased PI3K/Akt signaling. Dysregulation of the PI3K/Akt signaling pathway in ER+BC is involved with tumor progression and acquired therapeutic resistance. Our study suggests loss of SIM2s confers resistance in ER+BC through a PI3K subunit switch resulting in upregulation of pro-survival signaling. MCF7 SIM2 knock out cells exhibit increased expression of mesenchymal markers and undergo a phenotypic change compared to wild type cells. Utilizing a migration/invasion assay, MCF7 SIM2 knock out cells exemplify an increase in invasion potential compared to wild type cells. Furthermore, changes in PI3K subunit expression were observed via western blot and real time qPCR analysis. Clonogenic assays revealed an acquired resistance to PI3Kα inhibition, but a susceptibility to PI3Kδ inhibition. This is a significant finding as a current standard of care for patients with ER+ breast cancer recurrence is PI3Kα inhibition. PI3Kδ is an already approved therapeutic target in chronic lymphocytic leukemia, thus PI3Kδ may present a new therapeutically targetable opportunity for ER+BC recurrence. Elucidating the mechanism for acquired therapeutic resistance is an integral avenue for understanding how breast cancer progresses and improving the prognosis of ER+BC patients. Citation Format: Garhett Wyatt, Rachel Steinmetz, Traci Lyons, Weston Porter. LOSS OF SINGLEMINDED 2S RESULTS IN A PI3K SUBUNIT SWITCH WHICH DRIVES THERAPEUTIC RESISTANCE IN ESTROGEN RECEPTOR POSITIVE BREAST CANCER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-08.
Abstract SoA2-02: Implications of therapy induced senescence in breast cancer
Authors: J. Jackson
Journal: Cancer Research (2024)

Abstract The goal of breast cancer treatment is to cause cellular stress sufficient to kill and eliminate the tumor cells. Unfortunately, in many cases cancer cells survive and are not removed by surgery and thus can cause relapse and eventual mortality. Surviving cells have necessarily avoided both intrinsic (e.g., apoptosis) and extrinsic (e.g., immune surveillance) mechanisms of death. Studies over the last 20 years have shown that chemotherapy-treated breast cancer cells can evade cell death by activating programs of cellular senescence mediated by the tumor suppressor p53. While p53 can induce apoptosis in response to stress in some cell types, in breast cancer, p53 preferentially induces cell cycle arrest and senescence in response to chemotherapy. Data show that patients with breast cancers that are wild type for TP53 have a much lower probability of being eradicated by chemotherapy, and have a much shorter survival, compared to patients with TP53 mutant tumors. Human and mouse mammary tumors induce many markers of senescence after chemotherapy treatment, including those associated with cell cycle arrest and the senescence associated secretory phenotype (SASP). These arrested tumors evade death from mitotic catastrophe and can block apoptotic programs via elevated activity of BCL2 family members. More recent studies have addressed how induction of senescence deters immune surveillance. Breast cancer cells exposed to chemotherapy reorganize chromatin structure that amplifies stromal derived signals that stimulate expression of many immune genes, including checkpoint ligands such as PD-L1 and Galectin-9. Further, p53 can directly transactivate other immune modulatory genes such as CD80. Collectively, these properties of senescent cells enable their persistence following treatment and contribute to their potential to drive relapse. These same properties, however, can also be exploited as vulnerabilities to therapeutics such as senolytic drugs that target reliance on BCL2 family members or immunotherapies that target PD-L1 expression. Citation Format: J. Jackson. Implications of therapy induced senescence in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SoA2-02.
Abstract TC-01: Baby-TAM Impact on disease progression
Authors: J. Cuzick, P. Hall
Journal: Cancer Research (2024)

Abstract Professor Hall will have reviewed his studies on the impact of lower doses of tamoxifen on changes in breast density, an important risk factor. Here I will review the work of Professor Decensi’s team on the ability of 5mg/d of tamoxifen (baby-Tam) on the progression rate of DCIS (69%) and other intraepithelial lesions (11% LCIS, 20% atypical ductal hyperplasia). This trial involved 500 pre- and postmenopausal women randomized equally between baby-Tam and placebo with a 9.7 year median follow up. All breast cancer progression (invasive (77%) and DCIS (23%)) was reduced by 42% (25 vs 41 events, P = 0.03) and contralateral tumours by 64% (6 vs 16 events, P = 0.025). No significant increase was seen in any side effect (Table). I will also briefly discuss their new award for a project to compare baby Tam to baby exemestane in a randomized trial in a similar population as above, initially for side effects, but also subsequently for efficacy. Professor Hall will have reviewed his studies on the impact of lower doses of tamoxifen on changes in breast density, an important risk factor. Here I will review the work of Professor Decensi’s team on the ability of 5mg/d of tamoxifen (baby-Tam) on the progression rate of DCIS (69%) and other intraepithelial lesions (11% LCIS, 20% atypical ductal hyperplasia). This trial involved 500 pre- and postmenopausal women randomized equally between baby-Tam and placebo with a 9.7 year median follow up. All breast cancer progression (invasive (77%) and DCIS (23%)) was reduced by 42% (25 vs 41 events, P = 0.03) and contralateral tumours by 64% (6 vs 16 events, P = 0.025). No significant increase was seen in any side effect (Table). I will also briefly discuss their new award for a project to compare baby Tam to baby exemestane in a randomized trial in a similar population as above, initially for side effects, but also subsequently for efficacy. Citation Format: J. Cuzick, P. Hall. Baby-TAM Impact on disease 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 TC-01.
Abstract PO5-07-10: CONTRAST MAMMOGRAPHY FOR PREOPERATIVE STAGING OF PATIENTS WITH EARLY BREAST CANCER: PRELIMINARY RESULTS
Authors: Andressa Amorim, Andre Mattar, Almir Bitencourt, Paula Moraes, Flora Finguerman
Journal: Cancer Research (2024)

Abstract 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&amp;lt; 0.01). When compared with tumor size in pathology, both methods were adopted in a good way (p&amp;lt; 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 SoA2-01: Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity
Authors: M. Ruscetti
Journal: Cancer Research (2024)

Abstract Cellular senescence is a stress-induced program following aberrant oncogene activation or administration of cancer therapies, including chemotherapeutic agents and CDK4/6 inhibitors commonly used for treating advanced breast cancers, that results in the proliferative arrest of damaged cells and induction of the senescence associated secretory phenotype (SASP). The SASP involves secretion of inflammatory cytokines and chemokines and upregulation of immunomodulatory cell surface molecules on senescent cells that can promote their clearance by the immune system and tumor resolution. However, if left unchecked, the chronic SASP can also lead to immune suppression and further tissue damage that drives tumor dissemination and metastasis. Here we will discuss our efforts to understand how the SASP can promote anti-tumor immunity and immunotherapy activity in some cancer contexts yet in others immune suppression and tumor promotion. Our findings in other solid tumor contexts demonstrate that the tissue microenvironment has a profound impact of the type of SASP program activated and SASP-mediated immune responses produced and suggest further therapeutic interventions to remodel the SASP for immune control of cancer. Moreover, our results in other hormone-driven cancers suggest that CDK inhibitor and chemotherapy regimens produce different SASPs and resulting effects on myeloid cell and lymphocyte phenotypes that could explain their varying effects on anti-tumor immunity and treatment outcomes. Collectively these findings have important implications for breast cancer treatment and pave the path for rationale combination therapies with senescence-inducing agents to achieve immune control in breast and other immunologically “cold” solid tumor malignancies that are generally unresponsive to current immunotherapy regimens. Citation Format: M. Ruscetti. Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity [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 SoA2-01.