tbuckley/cabot-search huggingface dataset:
Abstract PO2-11-08: Divorce and marital dissolution after Breast Cancer diagnosis in young breast cancer survivors in Mexico
Authors: Saúl Campos-Gomez, Andrea Ovando Trujillo
Journal: Cancer Research (2024)

Abstract Background: The current literature suggests that facing breast cancer can have significant effects on the relationship, for the better or for the worse. The needs of younger women with breast cancer are receiving increased attention, as 23.1% of all newly diagnosed invasive cancer occur in women age 50 or younger. Marital relationships, in particular, may be strained for younger cancer patients as they face health, emotional, and financial stressors from their cancer. The few studies that are available to date have examined the effect of breast cancer diagnosis on marital and relationship Purpose: We examined marital outcomes among young locally advanced breast cancer patients in our institution Methods: Eligible participants were women with diagnosis of breast cancer stage I–III, were at least 6 months post diagnosis, and age 50 or younger at the time of diagnosis. Demographic data collected. Participants reported their marital o relationship status at time of breast cancer diagnosis and after at least 6 moth post diagnosis, whether they were currently married or a member of an unmarried couple, divorced, widowed or separated Other variables examined regarding a possible separation, the reasons for separation, the influence of the cancer on the relationship, the positive or negative perception of the impact of cancer on the relationship, the highest educational attainment and employment status. Descriptive statistics, percentages, frequencies, mean values and standard deviations were calculated. Results: In total, 75 patients were eligible for inclusion with a total of 250 patient with diagnosis of locally advanced breast cancer. The median age was 44 (range 30–48). Most of the patients, stage I or II tumors (55%). The divorce or separation rate was 36%, higher than reported in the literature (14.5%). Among those who were separated, 77% reported that cancer contributed to the separation or divorce. Also, for those who stayed together, 81% reported an impact of the cancer on the relationship, of which 50% reported a negative impact. Of those who had separated, none were in a new relationship. Conclusions: The emotional burdens of cancer may lead to marital stress for younger cancer survivors.; support systems are needed to assist them in the years following diagnosis. Because the marital relationship has multiple dimensions, it is also important to explore and identify those areas of the couple's life that are affected by the experience Citation Format: Saúl Campos-Gomez, Andrea Ovando Trujillo. Divorce and marital dissolution after Breast Cancer diagnosis in young breast cancer survivors in Mexico [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-08.
Abstract ED05-02: When less is more: Patient-friendly radiation courses with WBI and PBI
Authors: I. Meattini
Journal: Cancer Research (2024)

Abstract Over the past few decades, remarkable progress has been made in understanding the biology and pathology of breast cancer. A personalized conservative approach has been currently adopted addressing the patient's individual risk of relapse. After postoperative whole breast irradiation for early-stage breast cancer, a rate of recurrences outside the initial tumour bed lower than 4% at 5 years was observed. Thus, the highest benefits of breast irradiation seem to result from the dose delivered to the tissue neighbouring the tumour bed. Nonetheless, reducing treatment morbidity while maintaining radiation therapy's ability to decrease local recurrences is an important challenge in treating patients with radiation therapy. In this regard, strategies such as partial-breast irradiation and whole breast hypofractionation have been developed to reduce toxicity without compromising oncologic outcomes. According to the national and international published guidelines, clinical oncologists can refer to specific dose/fractionation schedules and eligible criteria. However, there are still some areas of open questions. Breast cancer represents a multidisciplinary paradigm; it should be considered a heterogeneous disease where a "one-treatment-fits-all" approach cannot be considered an appropriate option. A wide overview on the main partial and whole breast irradiation advantages, risks, timings, techniques, and available recommendations is presented, providing practical findings to support clinical decision-making, exploring future perspectives, towards a balance for optimisation of breast cancer. Citation Format: I. Meattini. When less is more: Patient-friendly radiation courses with WBI and PBI [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 ED05-02.
Abstract PO4-05-13: Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis
Authors: Binbin Cong, Jane Lane, Xiaoshan Cao, Tracey Martin, Robert E Mansel, Eleri Davies, Wen Jiang
Journal: Cancer Research (2024)

Abstract Introduction: Deleted in Liver Cancer 1 Protein, DLC1, also known as StAR Related Lipid Transfer Domain Containing 12 (StarD12), is a known negative regulator of the Rho GTPases and at the cellular level regulates cell migration. DLC1 gene transcription produces multiple isoforms of the DLC1 protein. The present study examined the clinical and prognostic implications of DLC1 isoforms, DLC1/V1/V2/V3, in relationship with Rho GTPases in human breast cancer. Methods: Expression of three DLC1 isoforms was evaluated in a cohort of breast cancer tissues and against the clinical, pathological and clinical outcome of patients. DLC1 expression was also assessed and compared against Rho GTPases, including Rho and Rho GTP Dissociation Inhibitor (Rho GDI), in the same cohort. Results: DLC1/V3 had a significant impact on the overall survival of patients and high levels were linked to shorter survival (Hazard Ratio=3.551 (95%CI 1.332-9.471, p=0.011), a prediction that was independent of other factors in multivariate analysis. RUC analysis demonstrated a significant predictive value for bone metastasis with DLC1/V3 (RUC=0.714, p=0.020), showing a Hazard ratio of 9.0 (1.8-44.5, p=0.007). Similarly, high DLC1/V2 expression was also linked to a shorter overall survival (p=0.035). DLC1/V2 did not show a significant correlation with bone metastasis. In contrast to V3 and V2 variants, DLC1 had a marginal overall survival benefit for the patients, in that patients with high DLC1 had a longer survival (p=0.056). DLC1/V3 had a contrasting correlation with Rho-A (r=-0.203, p=0.015) and Rho-GDI-G (r=0.194, p=0.019) and the combined expression of DLC1/V3 and RhoA/Rho-GDI-G further identified patients with poorer clinical outcome. Conclusions: DLC1 and its variants have differing impacts on breast cancer; whereas DLC1 appears to be a tumour suppressive molecule, its variant isoform-3 was more oncogenic and a significant negative prognostic factor, together with its regulators Rho and Rho GDI. Citation Format: Binbin Cong, Jane Lane, Xiaoshan Cao, Tracey Martin, Robert E Mansel, Eleri Davies, Wen Jiang. Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis [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 PO4-05-13.
Abstract PO1-04-07: Disitamab vedotin, a clinical stage HER2-directed antibody-drug conjugate, shows potent antitumor activity as a monotherapy and in combination with tucatinib in preclinical breast cancer models
Authors: Kelsi Willis, Renee Hein, Katie Snead, Robert Thurman, Anita Kulukian
Journal: Cancer Research (2024)

Abstract Disitamab vedotin (DV, RC48-ADC) is an antibody-drug conjugate (ADC) that targets cancers expressing HER2. DV consists of an anti-HER2 monoclonal antibody, disitamab, conjugated with the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a cleavable vedotin linker. DV has multimodal antitumor mechanisms of action that include direct cytotoxicity of HER2-expressing cancer cells and bystander effect-based cytotoxicity of neighboring cells, both of which are mediated by the intracellular release of MMAE. Released MMAE can also induce immunogenic cell death, which promotes immune cell recruitment to the tumor. In addition, DV stimulates Fc-gamma receptor mediated antibody-dependent cellular cytotoxicity, which can lead to target cell death. DV also inhibits HER2-activated downstream signaling pathways, further blocking cell growth, survival, and proliferation. Previously, we showed the cytotoxic activity of DV against a panel of breast cancer cell lines with varying levels of HER2 expression, including the HER2-low range. Here, we sought to further characterize the preclinical antitumor activity of DV in patient-derived 3D models and patient-derived xenographs (PDX). In cultured breast cancer cells, DV was more potent and internalized to a greater magnitude than the HER2-directed ADCs trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). In patient-derived 3D models, DV had superior activity compared to T-DXd. We further explored whether dual HER2 targeting with DV in combination with the HER2-selective oral TKI tucatinib improved the antitumor outcomes. In PDX models with varying HER2 IHC levels and models refractory to T-DXd, DV as a monotherapy and in combination with tucatinib showed significant tumor growth inhibition. This result is consistent with previous in vitro results that showed increased cytotoxicity of the combination of DV and tucatinib in cell lines with a wide range of HER2 expression, which may be mechanistically attributed to elevated HER2 cell surface levels upon treatment with tucatinib. Overall, these findings provide scientific rationale to explore DV in HER2-positive and HER2-low breast cancer patients as a monotherapy or in combination with tucatinib. Citation Format: Kelsi Willis, Renee Hein, Katie Snead, Robert Thurman, Anita Kulukian. Disitamab vedotin, a clinical stage HER2-directed antibody-drug conjugate, shows potent antitumor activity as a monotherapy and in combination with tucatinib in preclinical breast cancer models [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-07.
Abstract PO5-08-04: Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center
Authors: Ujjwal Karki, Tara Rangarajan, Dana Zakalik
Journal: Cancer Research (2024)

Abstract Background: Pathogenic variants (PVs) in ATM are associated with an increased risk of breast, pancreas, and other cancers. The clinical and pathological characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing between December 2012 and May 2023 and were identified to harbor ATM PVs were included in the study. We analyzed demographics, germline findings, histopathology, genomic recurrence score, and management of ATM PV carriers with breast cancer. Results: A total of 222 individuals were identified to have PVs in ATM, of whom 184 (83%) were female. The majority were Caucasian (n = 179, 81%) and of those, 22 (12%) had Ashkenazi Jewish ancestry. The median age at genetic testing was 52y, with a range of 20-90y. A total of 111 patients (50%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 70; 63%). The median age at breast cancer diagnosis was 53y, with a range of 25-84y. The most common histopathology was invasive ductal carcinoma (74%), followed by DCIS (21%), and invasive lobular carcinoma (5%). The majority of patients had breast tumors with stage 2 or 3 (78%), grade 2 or 3 (92%), ER and/or PR positive (92%) and HER2 negative (70%). One patient had triple-negative breast cancer. Forty-four percent of breast cancers were less than two centimeters, 23% were lymph node-positive, and 29% had lymphovascular invasion. Thirty-eight percent of patients underwent bilateral mastectomy, 54% received radiation therapy, 40% received adjuvant chemotherapy, 24% received neoadjuvant chemotherapy, and 70% received hormonal therapy. Of the 15 breast cancers with known 21-gene recurrence scores, 47% were intermediate (11-26), 33% were high (&amp;gt;=26) and 20% were low (&amp;lt; =10). Other notable cancers observed were pancreas (n = 9), colorectal (n = 6), prostate (n = 5), uterine (n = 4), melanoma (n = 4), and thyroid (n = 4). Conclusion: Our study outlines the clinical and pathological characteristics of ATM-associated breast cancer in a large academic center. The majority of breast cancers were invasive ductal type, early stage, intermediate or high grade, and hormone receptor-positive with an intermediate or high recurrence score. Despite the early stage, a significant proportion of patients underwent bilateral mastectomy. Further studies are needed to better elucidate the unique characteristics of breast cancer in ATM PV carriers in order to provide tailored management guidelines for this population. Citation Format: Ujjwal Karki, Tara Rangarajan, Dana Zakalik. Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center [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 PO5-08-04.
Abstract PO3-15-11: Soluble sFas, sFasL, sPD1, and sPD-L1 analyses in the blood peripheral of locally advanced breast cancer women before and after neoadjuvant chemotherapy
Authors: Carolina Vasconcelos, Marcelo Salgado, Carlos Eduardo Anunciação, Denise Viana, Leuridan Torres, Nathália Valois Montarroyos de Moraes
Journal: Cancer Research (2024)

Abstract Assess soluble sFAS, sFASL, sPD1, and sPD-L1 levels in patients with HER2 or triple-negative (TN) breast cancer submitted to neoadjuvant chemotherapy. A prospective cohort study was performed with TN and HER2+ breast cancer patients between 2015 and 2018. Soluble levels of sFasL, sFas, sPD-L1, and sPD1 were collected before and after neoadjuvant chemotherapy (NAC). NAC regimens included a dense dose of Adriablastin and cyclophosphamide during four cycles, followed by Paclitaxel for 12 weeks. No clinical evidence of tumor in the breast and axillary lymph nodes was defined as a pathological complete response (pCR). Twenty-one women with TN (56,7%) and 16 (43,3%) HER2+ breast cancer were included. Twenty-one women (56.7%) presented complete pathological response (pCR) after neoadjuvant chemotherapy (NAC), defined as the absence of invasive disease in the breast and lymph nodes. High sPD1 and sFas levels in the TN and HER2+ patients compared to the control group (P&amp;lt; 0.05). In paired analysis, statistical differences of sFas and sFasL levels in TN and HER2+ patients before and after NAC (P&amp;lt; 0.05). Low levels of sPDL1 in HER2+ patients with pCR compared to non-pCR (P&amp;lt; 0.05). High sFasL levels in TN patients with pCR compared to the non-pCR group (P&amp;lt; 0.05). Conclusion: soluble sFas, sFas-L, sPD1, and sPD-L1 levels were apoptosis-related markers with potential predictive value of neoadjuvant chemotherapy response in TN and HER2+ breast cancer. Keywords: breast cancer; FAS receptor; Programmed death 1, HER2+, Triple negative Citation Format: Carolina Vasconcelos, Marcelo Salgado, Carlos Eduardo Anunciação, Denise Viana, Leuridan Torres, Nathália Valois Montarroyos de Moraes. Soluble sFas, sFasL, sPD1, and sPD-L1 analyses in the blood peripheral of locally advanced breast cancer women before and after neoadjuvant chemotherapy [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 PO3-15-11.
Abstract PO1-13-11: ZNF689 promotes homologous recombination via NBS1 ubiquitination and its loss confers sensitivity to PARP inhibition in triple-negative breast cancer
Authors: Li-Ping Ge, Zi-Yu Wang, Xi Jin, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: Cancer Research (2024)

Abstract Background: Triple-negative breast cancer (TNBC) poses significant clinical challenges due to the lack of targeted therapies and poor prognosis. Homologous recombination (HR) deficiency is a defining characteristic of TNBC and renders tumors susceptible to Poly (ADP-ribose) polymerase (PARP) inhibitors. However, not all TNBC patients respond to PARP inhibitors, highlighting the need to identify novel biomarkers to predict therapeutic response and improve treatment strategies. Methods: In this study, we investigated the role of zinc finger protein 689 (ZNF689) in DNA damage response (DDR) and its impact on PARP inhibitor sensitivity in TNBC. Using a comprehensive set of molecular and cellular techniques, including immunoprecipitation, in vitro and in vivo ubiquitination assays, protein expression analysis, and functional assays using TNBC cell lines, patient-derived organoids (PDOs), patient-derived xenograft (PDX) models, and cell line xenograft models, we elucidated the mechanistic role of ZNF689 in HR and PARP inhibitor response. Results: Our findings revealed ZNF689 as a novel player in DDR. ZNF689 is activated by ATM-mediated phosphorylation and recruited to DNA damage sites in an ATM-dependent manner. At the DNA double-strand break sites, ZNF689 collaborates directly with NBS1 to facilitate K63-linked ubiquitination of NBS1 via the E3 ligase SKP2. Furthermore, ZNF689-mediated NBS1 ubiquitination stabilizes the MRE11-RAD50-NBS1 (MRN) complex and feedbacks activation of ATM, therefore accelerating HR repair. Loss of ZNF689 results in HR deficiency, leading to increased sensitivity of TNBC cells to PARP inhibitors in both in vitro and in vivo models. Additionally, the combination of PARP inhibitors and paclitaxel demonstrated potential for improved efficacy in treating ZNF689-deficient TNBC. In our clinical analysis, we observed a positive correlation between ZNF689 expression and the levels of NBS1 and phosphorylated ATM in TNBC patient samples. Importantly, low ZNF689 expression was associated with a favorable response to PARP inhibitors in TNBC patients. Conclusions: Our study highlights the significant role of ZNF689 in HR and its impact on the response to PARP inhibitors in TNBC. These findings suggest ZNF689 as a promising therapeutic target for enhancing the effectiveness of PARP inhibitors in TNBC patients. Working Modle Citation Format: Li-Ping Ge, Zi-Yu Wang, Xi Jin, Yi-Zhou Jiang, Zhi-Ming Shao. ZNF689 promotes homologous recombination via NBS1 ubiquitination and its loss confers sensitivity to PARP inhibition in 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 PO1-13-11.
Abstract ED11-03: Approaches to radiation therapy for inflammatory breast cancer
Authors: J. Bellon
Journal: Cancer Research (2024)

Abstract Inflammatory breasst cancer ((BC) is an uncommon and highly agressive form of breast cancer, with a predilection for both distant metastases and local regional recurrence. In this talk we will review challenges in radiation therapy planning and execution unique to IBC. These include staging studies and photographs to define the full extent of disease prior to systemic therapy, as well as current thoughts on dose and fractionation. We will also discuss pros and cons of local therapy in patients with metastatic disease, as well as ongoing research studying ways to optimize local regional control with concurrent systemic therapy and radiation. Citation Format: J. Bellon. Approaches to radiation therapy for inflammatory 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 ED11-03.
Abstract PO1-18-02: Histologic grade is a better predictor of specific survival than Ki67 in localized ER+/HER2- breast cancer: a real-world study
Authors: Cesar SÁNCHEZ, Cataldo Alejandro, Benjamin Walbaum, FRANCISCO ACEVEDO, Christine Constabel, Antoine Saure, Pablo Rey
Journal: Cancer Research (2024)

Abstract Introduction: Breast cancer (BC) is the most common cancer in women. The determination of prognostic factors is relevant for the decision of systemic therapy. Objective: To determine, in the real world, the prognostic role of Ki67 and histologic grade (HG) in patients with non-metastatic BC in two cancer centers; an academic and a community hospital. Methodology: Retrospective analysis of a longitudinal BC patients registry. Clinicopathological characteristics and disease specific survival (DSS) of women diagnosed in stages I/II/III between the years 2012-2021 were analyzed. Results: We evaluated 3,969 cases that met the inclusion criteria. In the univariate analysis, prognostic factors significantly associated with DSS were: reason for consultation (screening vs symptoms), stage, hormone receptor status, HG and Ki67. On multivariate analysis, stage III, Ki67 ≥20%, and GH3 were significantly associated with a risk of death of 4.41, 2.52, and 1.92; respectively, regardless of the treatment center and BC subtype. However, in the hormone receptor positive (HR+)/HER2 + group the HG presented greater discriminatory power than Ki67. Hazard ratio 2.0 for both, but not statistically significant for Ki67. The ROC-AUC curves for Ki67 indicated that the best cut-off point for DSS was 20%, for the entire cohort and also for the HR+/HER2- group. Conclusions: The behavior of the prognostic variables was expected and coincided with the literature. HG seems to be a better predictor of specific mortality in HR+ BC. Ki67 showed a cut-off value consistent with that suggested by expert consensus. Citation Format: Cesar SÁNCHEZ, Cataldo Alejandro, Benjamin Walbaum, FRANCISCO ACEVEDO, Christine Constabel, Antoine Saure, Pablo Rey. Histologic grade is a better predictor of specific survival than Ki67 in localized ER+/HER2- breast cancer: a real-world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-02.