bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO4-07-07: The construction and clinical research value of the prediction model of sentinel lymph node metastasis based on indocyanine green fluorescence quantification in breast cancer
Authors: Wu Yang , Zhang Wei , Tang Jinhai
Published: May 2024

Objective: To establish a prediction model of sentinel lymph node metastasis by quantitative indocyanine green fluorescence analysis in breast cancer.

Methods: From May 2023 to June 2023, 20 patients with breast cancer underwent modified radical mastectomy in the General Surgery Department of Jiangsu Provincial People's Hospital were chosen for research and analysis. Sentinel lymph node were taken from all the patients. The sentinel lymph nodes were located by using the double staining method of subcutaneous injection of Methylene blue and intravenous injection of indocyanine green. The postoperative pathology is used as the standard for evaluating the presence or absence of metastatic cancer in lymph nodes. At the same time, the transcutaneous fluorescence of sentinel lymph node was recorded and the peak time of fluorescence intensity curve was plotted. To establish a logistic diagnostic prediction model and fluorescence threshold, the sentinel lymph node was incised during operation and the fluorescence of sentinel lymph node was recorded again. The criteria for ICG positive determination are determined by the Youden index, which was used to judge the lymph nodes above the threshold in the Logistic diagnostic prediction model. Lymph nodes below the threshold determined in the Logistic diagnostic prediction model are the criteria for ICG negative determination. Cases with less than 3 sentinel lymph node were excluded.

Results: 19 cases were ultimately selected. Methylene blue staining data was taking as the judgment standard of sentinel lymph node. Fluorescence imaging was 100% in 14 patients, 66.7% (2/3) in 1 patient, and 125%-150% (5/4-6/4) in 4 patients. Fluorescence quantification values below 2.91 are negative lymph nodes, and values above 4.69 are positive lymph nodes. Moreover, caution is required between 2.91 and 4.69. Combining with the fluorescence dynamic attenuation curve, the positive group has a plateau curve, while the negative group mostly has a decline curve. Combining fluorescence quantification with fluorescence dynamic attenuation curve, the diagnostic rate of positive lymph nodes has a lower false negative rate compared to simple fluorescence quantification and fluorescence dynamic attenuation curve.

Conclusion: The quantitative difference value of indocyanine green fluorescence angiography can be used to predict the positive metastasis of sentinel lymph node in breast cancer, making it an attempt to exempt sentinel lymph node biopsy.

Citation Format: Yang Wu, Wei Zhang, Jinhai Tang. The construction and clinical research value of the prediction model of sentinel lymph node metastasis based on indocyanine green fluorescence quantification 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 PO4-07-07.
Abstract PO4-07-11: FDG-PET is superior to bone scintigraphy for the detection of bone metastases in breast cancer patients
Authors: Kenny Laura , Tin-U Maisher
Published: May 2024

Background: Bone is the commonest site for metastases in breast cancer patients, with up to 44% of patients having bone as their sole site of metastatic disease. Patients are at increased risk of morbidity from skeletal related events (SRE) from bone metastases due to pathological fractures and spinal cord compression. Early diagnosis is crucial so that bone modifying agents can be used to prevent SREs and other agents such as CDK4/6 inhibitors can be considered. Bone scintigraphy is the most widely performed first investigation for patients at high risk or symptomatic from bone metastases.

Methods: We performed a meta-analysis comparing FDG-PET and bone scintigraphy using PubMed, Science Direct, and Embase for the literature search. 1009 patients were included in the study. Data for 2 × 2 contigency tables was selected and QUADAS-2 was used for quality assessment. Diagnostic accuracy was performed using Graph pad Prism 9.5.1 and R studio 2022. Pooled sensitivity and specificity of FDG-PET/CT was 96.6% (95% CI=91.5%-98.7%) and 96.8% (95% CI=82.1%-99.5%) respectively. Respective results for BS were 88.3% (95% CI=79.8%-93.5%) and 81.3% (95% CI=63.1%-91.7%). Sensitivity and specificity of FDG-PET/CT was significantly higher than BS (P=0.0063, P= 0.0068, respectively). The diagnostic odds ratio and area under ROC curve were significantly higher for FDG-PET/CT than BS (654.36 vs 35.24, and 0.980 vs 0.877, respectively).

Conclusion: FDG-PET is superior to bone scinitigaphy for the detection of bone metastases in breast cancer.The benefits of replacing BS with FDG-PET/CT are evident. However othere technologies such as DW-MRI should be considered. Large multicentre prospective trials with strict FDG-PET/CT imaging protocols compared to DW-MRI both for disease detection and monitoring of response are required to strengthen the evidence in this field, to help inform imaging guidelines and best practices in the future. Newer technologies such as [18F]estradiol (FES)-PET and [18F]GE-226 for HER2 expression also warrant further investigation in ER positive and HER2 positive breast cancer.

Citation Format: Laura Kenny, Maisher Tin-U. FDG-PET is superior to bone scintigraphy for the detection of bone metastases in breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-11.
Abstract PO4-09-02: Making a Case for Access to Genetic Testing in a Low Resource Country: A review of 313 Cases of MBC
Authors: Alabi Adewumi , Lawal AbdulRazzak , Falowo Tolulope , Fatiregun Olamijulo
Published: May 2024

Background

Breast Cancer is the most common malignancy in Nigerian Women. It is responsible for the highest mortality amongst all malignant conditions.

Breast cancer in Nigerian women typically presents at an earlier age and with a more aggressive tumour with triple negative molecular pattern in Nigerian women.

These are usually some of the criteria for Genetic testing in the NCCN Guidelines.

Due to resource challenges, Genetic testing is not readily available to Nigerian women

We believe that if we can demonstrate that a high proportion of Nigerian women with breast cancer meet the criteria for Genetic Testing for Hereditary Breast and Ovarian Cancers, a case can be made for deploying resources towards Genetic Testing in this population of Women.

Materials and Methods

We collected prospective data about Nigerian Patients with Metastatic Breast Cancer as part of a UICC MBC Grant.

We evaluated these patients for criteria for testing for breast cancer and present the result of our evaluation.

Results

Three hundred and Thirteen patients were recruited for this study. There were 2 male and 311 female. Twelve participants did not know their age, but 146 (40.3%) were younger than 45 years while 175 (55.9%) were older than 45 years. Twenty four (7.7%) had bilateral breast cancer while the 289 (92.3%) had unilateral breast cancer. One hundred and sixty two (54.8%) participants were triple negative, 124 of whom were 60 years or younger.

In total, out of 313 participants, 202 (64.5%) patients were candidates for Genetic testing in a cohort of Metastatic Breast Cancer patients in Nigeria.

Conclusion

Various Indications for Genetic Testing in a cohort of Nigerian patients with breast cancer exists in more than 60% of patients. Considering the importance of PARP inhibitors in the management of breast cancer and implications for family members of these patients. It is important that cost appropriate genetic testing is made available to this group of breast cancer patients.

Table. Risk Factors for Genetic Testing in Nigerian Patients

Citation Format: Adewumi Alabi, AbdulRazzak Lawal, Tolulope Falowo, Olamijulo Fatiregun. Making a Case for Access to Genetic Testing in a Low Resource Country: A review of 313 Cases of MBC [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 PO4-09-02.
Abstract PO4-09-08: Perceptions and Experiences of Black Women on Family History Sharing and Genetic Testing for Hereditary Breast and Ovarian Cancer
Authors: Riggan Kirsten , Yap Jane , Cobran Ewan , Halyard Michele , James Sarah , Kelly Marion , Phillips Daphne , Allyse Megan
Published: May 2024

Black women experience significant disparities in morbidity and mortality related to hereditary breast and ovarian cancer (HBOC). Early identification of women with HBOC is essential for proactive screening and timely diagnosis. However, evidence suggests that Black women receive genetic testing for HBOC at lower rates than their White counterparts. We conducted in-depth qualitative interviews with 107 Black women with a personal or family history of breast or ovarian cancer, to understand their perceptions of their familial risk of HBOC and interest in genetic testing. In phase 1 of this study, participants were recruited from the networks of patient support organizations and historically Black sororities representing mostly highly educated and well insured patients. In phase 2, participants were recruited from a family medicine safety net clinic in Jacksonville, FL for socioeconomic diversity. Participants in both cohorts frequently expressed a lack of awareness about their family cancer history and identified many barriers to family disclosure of a cancer diagnosis. These include a culture of silence around medical issues and a belief that personal difficulties should be kept to oneself. Practical and cultural barriers to family history sharing were magnified among those with lower socioeconomic status. Many participants in both cohorts indicated a strong desire to understand their own risk of HBOC. They also expressed interested in genetic testing to proactively mitigate risk to themselves and future generations. Understanding of the potential relevance of HBOC testing to one’s personal health and post-test actionability was variable across both groups, although perceptions of genetic testing were generally favorable. These findings suggest that culturally tailored educational materials and alternative clinical modalities to collect family health history may be beneficial to improve timely identification of Black women who meet NCCN Guidelines for HBOC testing. Specifically, greater attention should be given to addressing barriers that led to underestimation of HBOC risk among patients experiencing disparities driven by adverse social determinants of health.

Citation Format: Kirsten Riggan, Jane Yap, Ewan Cobran, Michele Halyard, Sarah James, Marion Kelly, Daphne Phillips, Megan Allyse. Perceptions and Experiences of Black Women on Family History Sharing and Genetic Testing for Hereditary Breast and Ovarian 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 PO4-09-08.
Abstract PO4-22-06: Outcomes following Stereotactic Radiotherapy in Oligometastatic Breast Cancer: a single centre retrospective review
Authors: Lynch Sophie , Sukumar Sugeeta , Sawyer Elinor , Smith Daniel , Goldsmith Christy
Published: May 2024

Introduction:

Stereotactic radiotherapy (SABR) is an increasingly used treatment for oligometastatic disease with evidence of survival benefit shown in the SABR-COMET trial. However, the benefit in oligometastatic breast cancer has been brought into question following initial results from the NRG-BR002 trial.

Methods:

A retrospective review of all patients with primary breast cancer treated with stereotactic radiotherapy for oligometastases at our institution was carried out. A total of 31 patients received treatment to 36 lesions between August 2015 and December 2022.

Results:

Neither median overall survival nor progression free survival were reached after median follow up time of 21.5 months. Hormone receptor status as follows: ER+, HER2- (n=25), ER+, HER2+ (n=4,), TNBC (n=2). The majority of lesions treated were bony metastases (92%, of which 17 vertebral and 11 pelvic lesions). The majority had oligometastatic disease at time of SABR (67%), with 33% treated for oligoprogression. Most patients were on systemic anti-cancer therapy (SACT) at the time of SABR, or had a planned start of SACT shortly following treatment. Breakdown of systemic therapy as follows: Endocrine therapy (ET) alone 9 patients (29%), CDK4/6 inhibitor plus ET 13 patients (42%), chemotherapy 3 patients (10%), antibody drug conjugate 2 (6%), anti-HER2 therapy + ET 2 patients (6%), none 2 patients (6%). All patients also received bone-targeted agents (zoledronic acid or denosumab). Local control was achieved in 33 lesions (92%), all of which were bony lesions. Local control was maintained in both patients who were not on SACT: one patient with ER+ HER2- disease developed distant progression after 27 months, the other with TNBC remains disease free after 13 months. Loss of local control was observed in all non-bony sites (lung, IMC node, peri-ureteric soft tissue mass) at a median interval of 10 months (range 7-43 months). 14 patients subsequently developed distant disease progression at median interval of 15 months (range 0-43 months). 12 month progression free survival was 77%. 13 patients received further SACT at median interval of 16 months.

Conclusions:

SABR for bony metastases from breast cancer has excellent local control rates in combination with systemic treatment but may also give patients significant time off treatment. Questions remain regarding the ideal sequencing and combination of SABR and SACT, particularly in hormone receptor positive patients where there are a number of lines of effective SACT.

Citation Format: Sophie Lynch, Sugeeta Sukumar, Elinor Sawyer, Daniel Smith, Christy Goldsmith. Outcomes following Stereotactic Radiotherapy in Oligometastatic Breast Cancer: a single centre retrospective review [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 PO4-22-06.
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

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< 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

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

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

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< 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

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

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

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 < 0.001) and a higher hormone receptor positivity (97.4% vs. 79.3%, p < 0.001). Additionally, the presence of lymphovascular emboli was lower in ILC (8.0% vs. 24.6%, p < 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

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 PO5-12-08: QTc prolongation as Adverse Effect of CDK4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials
Authors: Carvalho Bruno , Reis Pedro Cotta Abrahão , Marinho Alice , Comini Ana Carolina , Xavier Debora , Pessoa Beatriz Mella S. , Batalini Felipe
Published: May 2024

Introduction: CDK4/6 inhibitors (CDK4/6i), such as abemaciclib, ribociclib, and palbociclib, have significantly improved outcomes for patients with ER+/HER2− breast cancer. Nevertheless, they differ among each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. Ribociclib causes concentration-dependent increases in the QTc interval, particularly in combination with tamoxifen. However, the pathogenesis of ribociclib-induced QTc prolongation remains unclear. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only.

Methods: We performed a systematic review and meta-analysis of randomized clinical trials (RCTs) to compare QTc prolongation in patients using CDK4/6i in combination with hormonal agents to patients that did not use CDK4/6i, including neoadjuvant, adjuvant, or metastatic scenarios in breast cancer. We searched Embase, PubMed and Cochrane Library databases from inception to June 2023. The outcomes evaluated were QTc prolongation of all grades. Statistical analysis was performed with R software version 2023.03.0+386.

Results: We included 14 RCTs comprising 16,013 patients in the quantitative analysis, of whom 8,585 underwent therapy with CDK4/6i, and one more paper was included only in the qualitative analysis due to not reporting the exact number of events of QTc prolongation. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR 2.32; 95% CI 1.67–3.23; p=0.000001; I²=46%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a risk ratio of 3.07 (RR 3.07; 95% CI 2.17-4.36; p< 0.000001; I² = 21%) while the palbociclib subgroup had a risk ratio of 1.52 (RR 1.51; 95% CI 1.05-2.16; p=0.025, I²=0%).

Conclusion: Our findings suggest that QTc prolongation may be a common adverse effect of CDK4/6i, with ribociclib carrying greater risk. These results are important for guiding clinical decision-making, and further investigation is warranted to better understand the mechanisms and clinical implications of CDK4/6 i-induced QTc prolongation.

Citation Format: Bruno Carvalho, Pedro Cotta Abrahão Reis, Alice Marinho, Ana Carolina Comini, Debora Xavier, Beatriz Mella S. Pessoa, Felipe Batalini. QTc prolongation as Adverse Effect of CDK4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials [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 PO5-12-08.
Abstract PO5-16-06: Prophylactic Neurokinin-1 Receptor Antagonist Use Pre- and Post- Choosing Wisely Initiative among Women with Breast Cancer
Authors: Kamat Shweta , Brown Britny , Cohen Steven , Vyas Ami
Published: May 2024

Objective: In April 2012, the American Society of Clinical Oncology (ASCO) issued recommendations as a part of the Choosing Wisely (CW) campaign with the aim to identify the areas of low-value utilization. One of the CW recommendations is not to use expensive antiemetics, specifically Neurokinin-1 Receptor Antagonist (NK1-RA) for patients initiating low or moderate emetic risk chemotherapy. The purpose of this study was to determine the impact of CW on prophylactic NK1-RA use among women with breast cancer.

Methods: Using Optum’s de-identified Clinformatics® Data Mart Database for 2010 to 2018, a retrospective cohort study was conducted for women aged ≥18 years with breast cancer with at least one newly initiated claim for low/minimal/moderate emetic risk chemotherapy (n = 25,549). All approved antiemetics - aprepitant, fosaprepitant, rolapitant, and netupitant/palonosetron) were included. An interrupted time series using a segmented regression model was used to assess the effect of CW on the prophylactic NK1-RA use.

Results: The prophylactic use of NK1-RAs among patients with breast cancer receiving low/minimal/moderate emetic risk chemotherapy decreased from 11.1% pre-CW to 7.7% post-CW. Segmented regression analysis showed that there was a significant increase of 0.11 per 100 patients per quarter in the use of prophylactic NK1-RAs prior to CW recommendation. However, immediately after the CW (occurred in Q42013), there was a significant decline in prophylactic NK1-RA use by 1.03 per 100 patients in Q22014. For the time after intervention, there was a significant decline in NK1-RA use by 0.37 per 100 patients per quarter in the post-CW period compared to the pre-CW period (p< 0.05).

Conclusion: This study highlights a significant but modest decline in the inappropriate use of prophylactic NK1-RAs after the implementation of CW antiemetic recommendation. Continued statewide or local educational efforts for dissemination of CW recommendations are needed to facilitate appropriate prophylactic use of NK1-RAs.

Table. Adjusted* Interrupted Time Series Segmented Regression Analysis of Prophylactic NK1-RA use among women with breast cancer before and after the Choosing Wisely initiative *Adjusted for insurance, health plan type, age, comorbidity, and emetic risk

Citation Format: Shweta Kamat, Britny Brown, Steven Cohen, Ami Vyas. Prophylactic Neurokinin-1 Receptor Antagonist Use Pre- and Post- Choosing Wisely Initiative among Women with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-06.
Abstract PO5-17-02: Triple-negative breast cancer as an untraceable tumor compared to other immunohistochemical subtypes: a cross-sectional study
Authors: Silva Morgana , Nazário Afonso , Sanvido Vanessa
Published: May 2024

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 PO5-18-06: On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy
Authors: Tkaczuk Katherine , Rosenblatt Paula , Mehra Ranee , Scilla Katherine , Tait Nancy , Yue Binbin , Serrero Ginette
Published: May 2024

Progranulin (PGRN/GP88) is an 88 kDa glycoprotein characterized by seven and a half double cysteine rich repeats which is the largest member of the granulin-epithelin protein family. PGRN/GP88 has been demonstrated as a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC), lung prostate, ovarian and digestive cancers. PGRN/GP88 tissue expression is an independent prognostic factor of recurrence in breast, lung cancers while elevated serum PGRN/GP88 level in metastatic breast, lung, ovarian and prostate cancer patients. Elevated PGRN/GP88 levels are associated with poor outcomes such as progression and shortened survival. An anti-human PGRN/GP88 monoclonal antibody able to inhibit the the in vitro and in vivo action of human PGRN/GP88 has been developed, chimerized and expressed in CHO cells. All IND enabling activities including pharmacology, GMP manufacturing, formulation and GLP toxicology studies have been conducted. The IND application has been filed and cleared by the Food and Drug Administration. A first-in-human, first-in-class phase 1 safety and efficacy clinical study of AG01 in patients with solid tumors and advanced disease with special focus on patients with breast, lung and ovarian cancers has been initiated and is on-going at the University of Maryland Greenebaum Cancer Center. The trial is registered as NCT05627960 to clinicaltrials.gov site. The presentation will provide an update on the number of patients enrolled in this on-going phase 1A trial.

Supported by grants R44CA162629 and R44CA224718 from the National Cancer Institute to GS.

Citation Format: Katherine Tkaczuk, Paula Rosenblatt, Ranee Mehra, Katherine Scilla, Nancy Tait, Binbin Yue, Ginette Serrero. On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy [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 PO5-18-06.