bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO4-23-04: Is breast-conserving surgery an optional local therapy for non-inflammatory skin involvement (T4b) breast cancer? A Propensity Score Matching and Inverse Probability Weighting Analysis of SEER Database Results
Authors: Lin Jingyi , Luo Shiping , Zhang Jie , Song Chuangui 
Published: May 2024

Abstract
Introduction: Although breast-conserving surgery (BCS) usage has been widespread in breast cancer treatment, it is still controversial about its application in non-inflammatory skin involvement (T4b) breast cancer. We designed this study to compare the prognosis for BCS versus mastectomy in this population.
Methods: This retrospective cohort study included patients from the SEER database diagnosed with tumor stage T4b breast cancer from 1998 to 2019. To create prognostic factors, balance between BCS+RT and Mastectomy+RT groups, we calculated propensity scores for each patient. The calculation was based on the advance assessment for factors affecting prognosis, with the use of univariable and multivariable Cox proportional hazards models. Based on it, two propensity score-based matchings were conducted, including propensity score matching (PSM) and inverse probability weighting (IPTW). After adjustment, we performed Kaplan-Meier curves and multivariable Cox proportional hazards models to estimate BCSS and OS.
Results: Of 4,680 patients who met the criterion, 588 received BCS+RT, and 4092 received Mastectomy+RT. In the propensity score matching (PSM) cohort, BCS+RT was found to improve breast cancer cause-specific survival (HR, 0.67; 95% CI, 0.53 to 0.85; p=0.001) and overall survival (HR, 0.72; 95% CI, 0.59 to 0.88; p=0.001). Similar results in the analysis of the IPTW-matched cohort confirm this result (BCSS: HR, 0.672; OS: HR, 0.722). Subgroup analysis revealed that those less than 70 years old, grade I+II, 3cm or smaller tumor size, hormone receptor-positive, or received chemotherapy treatment were more likely to benefit from BCS+RT (all p&lt; 0.05).
Conclusions: Locally treatment with BCS usage presented a significantly better survival than with mastectomy for non-inflammatory skin involvement (T4b) breast cancer patients. This finding provided evidence of selection in the local treatment of these patients.
Citation Format: Jingyi Lin, Shiping Luo, Jie Zhang, Chuangui Song. Is breast-conserving surgery an optional local therapy for non-inflammatory skin involvement (T4b) breast cancer? A Propensity Score Matching and Inverse Probability Weighting Analysis of SEER Database 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 PO4-23-04.
Abstract PO4-23-08: Estrogen therapy induces receptor-dependent DNA damage enhanced by PARP inhibition in ER+ breast cancer
Authors: Traphagen Nicole , Schwartz Gary , Tau Steven , Roberts Alyssa , Jiang Amanda , Hosford Sarah , Marotti Jonathan , Goen Abigail , Romo Bianca , Johnson Anneka , Duffy Emily , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon , Kolling Fred , Miller Todd 
Published: May 2024

Abstract
Although clinical evidence indicates that treatment with estrogens elicits anti-cancer effects in ~30% of patients with advanced endocrine-resistant ER+ breast cancer, the underlying mechanism of action is unclear and this treatment remains under-utilized. ER+ breast cancer cells with acquired resistance to long-term estrogen deprivation (LTED) were used to model resistance to aromatase inhibitors (AIs) seen clinically. Genome-wide CRISPR/Cas9 knockout screening and transcriptomic profiling of LTED cells highlighted DNA Damage Response as a required pathway for therapeutic response to the estrogen 17b-estradiol. Tumor specimens from 2 patients with advanced ER+ breast cancer showed increased DNA damage response upon treatment with 17b-estradiol therapy compared to baseline. LTED cells treated with 17b-estradiol exhibited replication-dependent markers of DNA damage and the DNA damage response prior to apoptosis, while parental cells did not. Such DNA damage was partially driven by the formation of DNA:RNA hybrids (R-loops), and RNase H1-mediated prevention of R-loop formation abrogated 17b-estradiol-induced DNA damage. Pharmacological suppression of the DNA damage response via poly(ADP-ribose) polymerase (PARP) inhibition with olaparib enhanced 17b-estradiol-induced DNA damage. PARP inhibition synergized with 17b-estradiol to suppress growth and prevent tumor recurrence in both BRCA1/2-mutant and BRCA1/2-wild-type cell line and patient-derived xenograft models. We therefore conclude that 17b-estradiol-induced ER activity drives DNA damage and growth inhibition in endocrine-resistant breast cancer cells, and inhibition of the DNA damage response using drugs such as PARP inhibitors can exacerbate transcriptional stress and enhance therapeutic response to 17b-estradiol. This concept is being explored clinically in the PHOEBE trial testing the combination of 17b-estradiol and olaparib (NCT05900895). These findings also warrant further study of other DNA damage response inhibitors in advanced ER+ breast cancer. Moreover, these data indicate that PARP inhibitors may have applications beyond homologous recombination-deficient tumors.
Citation Format: Nicole Traphagen, Gary Schwartz, Steven Tau, Alyssa Roberts, Amanda Jiang, Sarah Hosford, Jonathan Marotti, Abigail Goen, Bianca Romo, Anneka Johnson, Emily Duffy, Eugene Demidenko, Paul Heverly, Yaron Mosesson, Shannon Soucy, Fred Kolling, Todd Miller. Estrogen therapy induces receptor-dependent DNA damage enhanced by PARP inhibition in ER+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-08.
Abstract PO4-26-04: Immunolocalization of cytoplasmic ER in ER-negative breast carcinoma as a potent favorable prognostic predictor
Authors: Ebata Akiko , Suzuki Takashi , Harada-Shoji Narumi , Hamanaka Yohei , Miyashita Minoru , Iwabuchi Erina , Takagi Kiyoshi , Miki Yasuhiro , Tada Hiroshi , Ishida Takanori 
Published: May 2024

Abstract
Background: It is known that estrogen receptor (ER) has extranuclear signaling functions in addition to classical genomic pathway, and estrogenic actions have been reported in ER-negative breast carcinoma cells. However, significance of cytoplasmic-ER immunoreactivity has not been reported in ER-negative breast carcinoma tissues.
Methods: We immunolocalized cytoplasmic ER in 155 ER-negative breast carcinoma tissues and evaluated its clinicopathological significance including the prognosis. As a comparative cohort set, we also used 142 ER-positive breast carcinomas.
Results: Cytoplasmic-ER immunoreactivity was detected in the carcinoma cells, but not in the non-neoplastic mammary epithelium. Cytoplasmic-ER immunoreactivity was positive in the 35 out of 155 (23%) ER-negative breast carcinoma cases, whereas it was detected only in 2 out of 142 (1.4%) ER-positive cases. Cytoplasmic ER status was positively associated with cytoplasmic-PR status, but inversely associated with Ki67 labeling index or distant free-relapse survival rate. Moreover, cytoplasmic-ER status turned out to be an independent good prognostic factor for both distant relapse-free survival and breast cancer specific survival.
Conclusion: These findings suggested that cytoplasmic ER plays important roles in the ER-negative breast carcinoma, and cytoplasmic ER is a potent good prognostic factor.
(accepted in Acta Histochemica et Cytochemica, 2023/Jun/27)
Citation Format: Akiko Ebata, Takashi Suzuki, Narumi Harada-Shoji, Yohei Hamanaka, Minoru Miyashita, Erina Iwabuchi, Kiyoshi Takagi, Yasuhiro Miki, Hiroshi Tada, Takanori Ishida. Immunolocalization of cytoplasmic ER in ER-negative breast carcinoma as a potent favorable prognostic predictor [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 PO4-26-04.
Abstract PO4-27-03: Real-World Evidence: Impact of Margin Involvement on Overall Survival Following Breast Cancer Surgery – A Single-Center Analysis at Charité University Medical Center Berlin
Authors: Beck Maximilian Heinz , Weiler Karoline , Ossmann Sophia , Kiver Verena , Blohmer Jens-Uwe 
Published: May 2024

Abstract
Introduction: Limited data is available regarding the impact of margin involvement following surgery for early-stage breast cancer on distant recurrence and overall survival (OS). We therefore conducted a retrospective single-center analysis to provide further real-world evidence of margin status on OS. Methods: We systematically evaluated patients who underwent surgical intervention for early breast cancer or carcinoma in situ at Charité University Medical Center Berlin between 2006 and 2022. Our study cohort included individuals with a minimum follow-up period of 6 months and documented margin status. Patients with secondary tumors were excluded from this comprehensive analysis. Results: In our analysis, we included a total of 3767 patients, with a median follow-up duration of 72.2 months. Among these, 3443 patients underwent surgery for invasive breast cancer, while 324 patients underwent surgery for carcinoma in situ. The median overall survival (OS) for the entire cohort was 63.7 months. Specifically, patients who achieved clear margins after primary surgery exhibited a median OS of 63.5 months (n=3068), and those with free margins after secondary surgery had a median OS of 65.2 months (n=610). Conversely, patients with definitively involved margins experienced a shorter median OS of 58.6 months (n=89). The multivariate analysis revealed a statistical trend toward adverse survival outcomes for patients with definitive involved margins (Hazard Ratio 1.55; 95% CI: 0.93-2.56; p=0.090), with no statistically significant difference observed between clear margins following primary or secondary surgery. Notably, patients who underwent breast-conserving surgery demonstrated a significantly improved OS (HR 0.45; 95% CI 0.37-0.45; p&lt; 0.001). Higher rates of margin involvement were observed in patients with hormone receptor-positive tumors and carcinoma in situ, while lower rates were noted in triple-negative breast cancer and after neoadjuvant chemotherapy. Implication: Our findings suggest that involved margins may be associated with a limited overall survival. Notably, patients who underwent breast-conserving therapy exhibited more favorable outcomes in our analysis, underscoring the oncologic safety of this procedure.
Citation Format: Maximilian Heinz Beck, Karoline Weiler, Sophia Ossmann, Verena Kiver, Jens-Uwe Blohmer. Real-World Evidence: Impact of Margin Involvement on Overall Survival Following Breast Cancer Surgery – A Single-Center Analysis at Charité University Medical Center Berlin [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 PO4-27-03.
Abstract PO4-28-02: Adipocyte Progenitor-Mediated Effects on Mammary Cancer Cells
Authors: Singh Jacqulene Sunder , Joshi Purna , Unger Emma 
Published: May 2024

Abstract
Treatment challenges in breast cancer arise from significant heterogeneity found within breast tumors and the surrounding microenvironment. The tumor microenvironment presents a complex ecosystem which comprises diverse stromal cells including immune, endothelial and fibroblast cell lineages and the extracellular matrix that support tumor progression. Adipocytes represent an abundant cell population in the normal breast and prior studies have reported a crosstalk between adipocytes and mammary cancer cells. De-differentiation of adipocytes into adipocyte progenitor-like cells is linked to a pro-tumorigenic microenvironment in mouse mammary tumors. We have previously demonstrated that adipocyte progenitors in the murine mammary stroma have the capacity to generate epithelial lineages during mammary epithelial growth. The influence of adipocyte progenitors in the mammary tumor microenvironment is not known. In this study, we investigated the effects of adipocyte progenitors on mammary cancer cells and their interactions using the 3T3-L1 adipocyte precursor (AP) cell line and the EO771 syngeneic mammary cancer (MCa) cell line. AP and MCa cell lines were co-cultured, after which MCa cell growth, invasion and migration were assessed using established in vitro assays. MCa cells cultured alone were also exposed to AP-conditioned media to determine whether secreted factors derived from APs could modulate MCa cells. AP cells were found to alter the behavior of MCa cells, affecting their cell proliferation, migration, and cellular phenotype. This work infers the potential of adipocyte progenitors to regulate mammary cancer growth and progression, which warrants further investigation into their fate and role in vivo during mammary tumorigenesis. Keywords: breast cancer, adipocyte progenitors, tumor microenvironment
Citation Format: Jacqulene Sunder Singh, Purna Joshi, Emma Unger. Adipocyte Progenitor-Mediated Effects on Mammary Cancer Cells [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 PO4-28-02.
Abstract PO4-28-05: Prolactin drives labile iron transfer from macrophages to breast cancer cells through CD44
Authors: Farrell Reagan , Pascuzzi Nicholas , Chen Yi-Ling , Torres Miguel , Kim Mary , Gollahon Lauren , Chen Kuan-Hui 
Published: May 2024

Abstract
Cancer cells are “ferrophilic” and exhibit great dependence on iron. While iron metabolism is closely related to tumor development, the source of iron and the mechanisms cancer cells adopt to actively acquire iron is not well understood. In the present study, we discovered a novel function of the lactating hormone, prolactin, in the regulation of iron transport. In breast cancer cells using mouse triple negative breast cancer cell lines EO771 and Py230 for demonstration, prolactin stimulation increased intracellular labile iron pool. Analyses of gene expression involved in iron transport revealed dramatic induction of CD44, a surface receptor for iron bound hyaluronan. Other genes involved in iron uptake including transferrin receptor (TFRC), CD163 and divalent metal transporter 1 (DMT1) were not changed. The utilization of neutralizing antibodies against CD44 significantly blocked prolactin mediated labile iron pool accumulation in breast cancer cells. In contrast to what was found in breast cancer cells, prolactin had the opposite impact on immune macrophages. Prolactin treatment increased ferroportin (FPN I, iron exporter) but had no influence on all iron uptake transporters leading to net iron release by macrophages. To further determine if the iron released by macrophages can be a direct source of iron utilized by breast cancer cells, we conducted co-culture work of macrophages with pre-stained labile iron pool and breast cancer cells without any iron staining and found a gradual increase of fluorescent iron pool developed in breast cancer cells over time. In conclusion, our work presents a multidisciplinary regulation of iron transport among prolactin, macrophages, and cancer cells. The novel regulatory role of prolactin to drive iron flow can provide new information on fine-tuning immune responses in tumor microenvironment and potentially benefit the development of novel therapeutics.
Citation Format: Reagan Farrell, Nicholas Pascuzzi, Yi-Ling Chen, Miguel Torres, Mary Kim, Lauren Gollahon, Kuan-Hui Chen. Prolactin drives labile iron transfer from macrophages to breast cancer cells through CD44 [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 PO4-28-05.
Abstract PO5-02-13: Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma
Authors: Shin Ik Beom , Kang Eunhye , Jung Ji-Jung , Lee Hawjeong , Byeon Jin Young , Choi Yunhee , Lim Changjin , Cheun Jong-Ho , Kim Hong-Kyu , Lee Han-Byoel , Han Wonshik , Moon Hyeong-Gon 
Published: May 2024

Abstract
Purpose
Invasive lobular carcinoma (ILC) is the second common types of breast cancer and its clinicopathological feature and outcomes differ from invasive ductal carcinoma (IDC). However, in terms of survival outcomes, there are conflicting data on the prognostic implication of the ILC when compared to that of IDC. This study aims to evaluate the survival outcomes of patients diagnosed with ILC at single center and compared them with those of IDC.
Methods
We reviewed the data of the 13,034 IDC patients and 935 ILC patients who were treated between January 2005 and December 2022 at Seoul National University Hospital. We investigated the overall treatment outcomes of two histologic types with a special focus on the tumor size and lymph nodes.
Result
ILC exhibited distinct characteristics compared to IDC, including a larger tumor size (2.6 ± 1.8 vs. 1.9 ± 1.1 cm, p &lt; 0.001) and a higher hormone receptor positivity (97.4% vs. 79.3%, p &lt; 0.001). Additionally, the presence of lymphovascular emboli was lower in ILC (8.0% vs. 24.6%, p &lt; 0.001). While IDC patients showed slightly better overall survival (OS) than ILC (10-year OS, ILC 89.9% vs. IDC 91.1%, the difference was not statistically significant (p = 0.85). However, distant metastasis-free survival (DMFS) was significantly higher in ILC (10-year DMFS, ILC 93.2% vs. IDC 89.9%, p = 0.001). Age at diagnosis, tumor size, presence of lymphovascular emboli, high expression of Ki-67, and higher pathologic N stage were poor prognostic markers for ILC. Multivariate analysis for DMFS showed that age, high expression of Ki-67 and higher pathologic N stage were poor prognostic markers for ILC. Tumor size was not an independent prognostic factor for DMFS (HR: 0.92, 95% CI: 0.72-1.17, p = 0.491) and for OS (HR: 1.18, 95% CI: 0.99-1.41, p = 0.060) in ILC.
Conclusion
Our data suggest that the tumor size, which is a well-known prognostic factor in IDC, carries distinctly different prognostic implication in ILC. These observation indicate that adjuvant treatment decisions based on tumor size can be tailored to different histologic subtypes of breast cancer.
Citation Format: Ik Beom Shin, Eunhye Kang, Ji-Jung Jung, Hawjeong Lee, Jin Young Byeon, Yunhee Choi, Changjin Lim, Jong-Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma [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 PO5-02-13.
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: Wyatt Garhett , Steinmetz Rachel , Lyons Traci , Porter Weston 
Published: May 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.