bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-10-06: Effect of aging and mTOR inhibition on human mammary stem cells and early breast cancer progression markers
Authors: Broome Larry E , Bouamar Hakim , Lathrop Kate , Jatoi Ismail , Brenner Andrew , Garcia Michael , Nazarullah Alia , Moncada Karla , Kaklamani Virginia , Sun Lu-Zhe 
Published: March 2022

Abstract
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer and is a predecessor to invasive carcinoma development. The origins for early breast cancer have been attributed to aberrant single cells, which may include adult stem and progenitor cells. We performed a window trial with mTOR inhibitor sirolimus in patients with atypical ductal hyperplasia (ADH) or DCIS and investigated the epithelial populations in adjacent normal and ADH/DCIS breast tissues along with their residing stem and progenitor cell activity. Differences associated with age, menopausal status, and treatment by sirolimus have also been explored. While the mammary epithelial populations were seen to be unchanged in aging, we found that age correlates with a decline in stem cell activity. mTOR inhibition was also able to abrogate mammary stem cell activity and decrease luminal progenitor passaging lifespan, particularly in postmenopausal patients. While mTOR inhibition had no effect on myoepithelial populations, it did decrease premenopausal luminal cell populations and reduced prognostic markers associated with breast cancer progression from DCIS to invasive breast cancer. These markers include p16INK4A, COX-2, and Ki67, which were reduced in DCIS breast tissue from patients administered with sirolimus as shown through quantitative analysis of immunohistochemistry. Overall, these findings indicate a link from mTOR signaling to mammary stem cell activity and cancer progression. mTOR inhibitors may have potential for breast cancer prevention.
Citation Format: Larry E Broome, Hakim Bouamar, Kate Lathrop, Ismail Jatoi, Andrew Brenner, Michael Garcia, Alia Nazarullah, Karla Moncada, Virginia Kaklamani, Lu-Zhe Sun. Effect of aging and mTOR inhibition on human mammary stem cells and early breast cancer progression markers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-10-06.
Abstract P1-12-01: Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: Final long-term results of the hellenic cooperative oncology group phase III HE10/05 trial
Authors: Zagouri Flora , Koliou Georgia-Angeliki , Dimitrakopoulos Foteinos , Papadimitriou Christos , Binas Ioannis , Koutras Angelos , Papakostas Pavlos , Markopoulos Christos , Venizelos Vasileios , Xepapadakis Grigorios , Karanikiotis Charisios , Psyrri Amanda , Bafaloukos Dimitrios , Kosmidis Paris , Aravantinos Gerasimos , Res Eleni , Mauri Davide , Koumarianou Anna , Petraki Kalliopi , Tsipoura Anna , Pectasides Dimitrios , Gogas Helen , Fountzilas George 
Published: March 2022

Abstract
Background: Dose-dense sequential chemotherapy based on anthracyclines and taxanes has achieved an 18% reduction of recurrence risk in the adjuvant setting of early breast cancer (BC). However, the optimal chemotherapy schedule and the preferable interval between cycles are still under investigation. Methods: A total of 990 eligible BC patients were randomized to receive either 3 cycles of epirubicin (E,110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by 3 cycles of intensified CMF (Control Arm A, E-T-CMF; 333 patients) or three cycles of epirubicin followed by 3 cycles of CMF followed by 9 consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Experimental Arm B, E-CMF-wD; 331) or 9 consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Experimental Arm C, E-CMF-wT; 326). Trastuzumab was administered for HER2-positive disease. The primary endpoint was disease-free survival (DFS). Results: At a median follow-up of 13.3 years, 330 DFS events (33.3%) had been reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus control arm A either in the entire cohort (HR=0.90, p=0.38 and HR=0.85, p=0.20) or among HER2-positive, trastuzumab-treated patients (HR=0.69, p=0.13 and HR=0.67, p=0.13). Thirty-four patients (3.4%) developed secondary neoplasms. Conclusions: Overall, no significant differences in DFS or OS were found amongst the studied regimens after a long-term observational period. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000151033
Citation Format: Flora Zagouri, Georgia-Angeliki Koliou, Foteinos Dimitrakopoulos, Christos Papadimitriou, Ioannis Binas, Angelos Koutras, Pavlos Papakostas, Christos Markopoulos, Vasileios Venizelos, Grigorios Xepapadakis, Charisios Karanikiotis, Amanda Psyrri, Dimitrios Bafaloukos, Paris Kosmidis, Gerasimos Aravantinos, Eleni Res, Davide Mauri, Anna Koumarianou, Kalliopi Petraki, Anna Tsipoura, Dimitrios Pectasides, Helen Gogas, George Fountzilas. Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: Final long-term results of the hellenic cooperative oncology group phase III HE10/05 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-12-01.
Abstract P1-13-02: Autophagy inhibition and senolytics to improve the response to fulvestrant + palbociclib in ER positive breast cancer
Authors: Finnegan Ryan Michael 
Published: March 2022

Abstract
While anti-estrogens or aromatase inhibitors in combination with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the current standard of care for estrogen receptor-positive (ER+) Her-2 negative metastatic breast cancer, relapse after remission continues to be a serious limitation to the effectiveness of these therapies. Although these combination therapies prolong progression-free survival compared to endocrine therapy alone, the growth-arrested state of residual tumor cells is clearly transient. Tumor cells that escape what might be considered a dormant or quiescent state and regain proliferative capacity often acquire resistance to further therapies. Our studies are based upon the observation that breast tumor cells arrested by Fulvestrant + Palbociclib enter into a state of autophagy/senescence from which a subpopulation ultimately escapes, potentially contributing to disease recurrence. ER+ MCF-7 breast tumor cells that were induced into autophagy/senescence by Fulvestrant + Palbociclib in vitro were exposed to the autophagy inhibitors, chloroquine and bafilomycin, prior to as well as after growth arrest. However, autophagy inhibition only moderately enhanced the response to therapy and, at best, delayed proliferative recovery. These findings were confirmed by genetic inhibition of autophagy. Despite clear entry into a state of senescence, the Bcl-xl inhibitor and senolytic ABT-263 (navitoclax) failed to promote tumor cell death; this is likely a consequence of high levels of survivin in the MCF-7 breast tumor cell line. However, the BET inhibitor, ARV-825, eliminated a large fraction of the senescent cell population and significantly delayed proliferative recovery. Cell death did not appear to be a consequence of increased apoptosis. Additionally, analysis of three database sets demonstrated that higher breast cancer expression of BRD4, a primary target of ARV-825, correlated with lower recurrence-free survival compared to patients with cancers expressing lower levels of BRD4. These studies indicate that administration of BET inhibitors, which are currently being investigated in multiple clinical trials, may potentially improve standard of care therapy in metastatic ER+ breast cancer patients by prolonging progression-free survival.
Citation Format: Ryan Michael Finnegan. Autophagy inhibition and senolytics to improve the response to fulvestrant + palbociclib in ER positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-02.
Abstract P1-24-04: Spatially resolved cell type heterogeneity uncovers the distinct biology of inflammatory breast cancer
Authors: Courtois Elise , Flynn William , Sivajothi Santhosh , Seignon Martine , Luo Diane , Lim Bora , Robson Paul 
Published: March 2022

Abstract
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer due to rapid progression, distinct morbidity due to pain, swelling, infection and eventual death. It accounts for 10% of all breast cancer caused deaths despite being only 2-4% of all breast cancer diagnosis. Histopathologically, scattered tumor emboli and dermal lymphatic invasion are typical histopathological findings of IBC, shown in about 75% of all IBC cases. However, the etiology of this disease remains largely unknown and its diagnostic difficult to establish.Using single cell transcriptomics, we profiled a total of 10 patient-derived needle biopsies from IBC-hormone receptor (IBC-HR), IBC-triple negative breast cancer (IBC-TNBC), TNBC and HR subtypes, and one normal breast sample. After data QC, we obtained a total of 36,000 cells representing immune, epithelial and stromal cell populations. We performed analysis of the spatial cell distribution through a transcriptomics-informed panel using highly multiplex imaging mass cytometry (IMC) on FFPE section obtained from the same patients.While we noted interpatient heterogeneity within cancer cells in our single cell dataset, immune and stromal cells did show similarity across IBC patients. We identified differences across the myeloid compartment between IBC and non-IBC cells, specifically affecting the dendritic cell subpopulations.The interferon gamma pathway was specifically elevated in several cell types across IBC patients, and particularly in immune cells such as T and myeloid cells. We used MX1 as a marker of interferon gamma response as part of the IMC panel and confirmed this signature in IBC samples. There was no alpha and beta interferon transcriptomic signature in the single cells. Through IMC, we were able to identify the cellular composition surrounding the tumor microemboli. Contrary to what has been postulated in the literature, these cells are not lymphatic cells, but appear to be of fibroblastic origin and express the fibroblast marker CD90. As well, we detected a non-overlapping distribution of Collagen 1 positive and CD90 positive fibroblasts throughout the IBC specimens, revealing heterogeneity within the fibroblast population and its organization. Spatial immune cell analysis also revealed the presence of tertiary lymphoid structures in IBC tumors.
Citation Format: Elise Courtois, William Flynn, Santhosh Sivajothi, Martine Seignon, Diane Luo, Bora Lim, Paul Robson. Spatially resolved cell type heterogeneity uncovers the distinct biology of inflammatory breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-24-04.
Abstract P2-08-01: Validation of a 16-gene genomic signature to identify early-stage invasive breast cancer patients who may omit radiotherapy
Authors: Fyles Anthony , Chang S. Laura , Rey-McIntyre Katrina , Shi Wei , Feng Felix , Speers Corey , Pierce Lori , McCready David , Liu Fei-Fei 
Published: March 2022

Abstract
Background While whole breast radiotherapy has been standard of care for invasive breast cancer patients treated with breast conserving surgery, not all women may benefit from radiotherapy. Recently, we demonstrated that a 16-gene signature named Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) could identify breast cancer patients with HR+, HER2- tumors treated with breast conserving surgery alone with a 10-year locoregional recurrence risk of less than 10%. Methods In this study, we apply the signature to patients enrolled in the Princess Margaret Trial, a randomized trial where patients age 50 years or older were randomized to radiotherapy and tamoxifen or tamoxifen alone after breast conserving surgery. Tissue from 132 patients with HR+, HER2- tumors were available for gene expression analysis. Results For women treated with tamoxifen alone after breast conserving surgery, POLAR identified low risk women with a 7% risk of locoregional recurrence at 10 years. Comparison to POLAR-low patients treated with adjuvant radiotherapy did not demonstrate a significant benefit from radiotherapy (HR=1.5[0.14-16], p=0.74). POLAR-high patients not treated with radiotherapy had a 22% risk of locoregional recurrence at 10 years. Comparison to POLAR-high patients treated with adjuvant radiotherapy demonstrated a significant benefit from standard radiotherapy (HR=0.25[0.07-0.92], p=0.038). Conclusions These data suggest that the POLAR genomic signature may be used to identify patients with a low risk of locoregional recurrence without significant benefit from adjuvant radiotherapy. Patients with low POLAR scores may potentially be candidates for radiation therapy omission when treated with breast conserving surgery and tamoxifen.
Citation Format: Anthony Fyles, S. Laura Chang, Katrina Rey-McIntyre, Wei Shi, Felix Feng, Corey Speers, Lori Pierce, David McCready, Fei-Fei Liu. Validation of a 16-gene genomic signature to identify early-stage invasive breast cancer patients who may omit radiotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-01.
Abstract P2-10-07: Prediction of menstruation recovery timing in premenopausal breast cancer patients taking tamoxifen after chemotherapy: An ASTRRA substudy
Authors: Lee Young Joo , Noh Woo C , Nam Seok J , Park Byeong-Woo , Lee Eun S , Im Seock A , Jung Yong S , Yoon Jung H , Kang Sung S , Park Kyong H , Lee Soo-Jung , Lee Min H , Jeong Joon , Kim Sung Y , Kim Hyun-Ah , Han Se-Hwan , Han Wonshik , Hur Min H , Kim Seonok , Ahn Sei-hyun , Kim Hee J 
Published: March 2022

Abstract
Introduction Addition of ovarian function suppression to conventional endocrine therapy alone in premenopausal women provides a survival benefit with moderate to high risk hormone-receptor positive breast cancer, especially who received chemotherapy Prediction of menstruation recovery after chemotherapy is important for deciding subsequent endocrine treatment and addressing fertility issues. Methods In the adding OFS after chemotherapy trial (ASTRRA), patients who resumed ovarian function up to 2 years after chemotherapy were randomized to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. With these 1383 patients, we developed a model that predicts when patients recover menstruation within 3 years after chemotherapy using several variables including age, BMI, chemotherapy regimen and duration, serum E2 and FSH level. Results A total of 1017 patients data were used to develop prediction model and 366 patients data were used for external validation. In development group, 546 (53.6%) patients resumed menstruation during follow up period of 5 years. In multivariable analysis, younger age and AC based regimen without taxane were strong predictive factor for menstruation recovery. However predictive value of chemotherapy regimen was not constant over time. Therefore, we conducted another model with patients (n= 624) who did not recover menstruation within one year. In this patient group, predictive factors for menstruation recovery was age and serum E2 level at 6 months after chemotherapy. We also conducted a simplified scoring system to estimate change of recovery by using risk factors mentioned above. Conclusion Younger age is an important persisting factor predicting menstrual recovery after chemotherapy. Although chemotherapy regimen predicts shor-term menstrual recovery, over time, patient factors have more predictive influence on recovery. Recovery of serum E2 level would be important to predict subsequent menstruation recovery.
Citation Format: Young Joo Lee, Woo C Noh, Seok J Nam, Byeong-Woo Park, Eun S Lee, Seock A Im, Yong S Jung, Jung H Yoon, Sung S Kang, Kyong H Park, Soo-Jung Lee, Min H Lee, Joon Jeong, Sung Y Kim, Hyun-Ah Kim, Se-Hwan Han, Wonshik Han, Min H Hur, Seonok Kim, Sei-hyun Ahn, Hee J Kim. Prediction of menstruation recovery timing in premenopausal breast cancer patients taking tamoxifen after chemotherapy: An ASTRRA substudy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-07.
Abstract P2-12-16: Use of ovarian function suppression to preserve fertility during neoadjuvant chemotherapy oncologically safe in women under age 40: An inverse probability weighting adjusted analysis
Authors: Lee Young Joo , Kim Seonok , Kim Hee J 
Published: March 2022

Abstract
Backgrounds Ovarian function suppression by gonadotropin releasing hormone agonist (GnRHa) is used to preserve fertility during neoadjuvant chemotherapy (NCT) in breast cancer especially in young women. Some results showed that patients with hormone-receptor (HR) negative breast cancer treated with NCT concurrent with GnRHa to preserve fertility had better outcome than without GnRHa. Methods From 2011 to 2014, 296 women aged under 40 years old with stage I to IIIA breast cancer, treated with NCT before surgery were analyzed. Primary endpoint was rate of pathologic complete response (pCR). Secondary endpoint was disease free survival (DFS) and overall survival (OS) between two groups categorized by concurrent with GnRHa during NCT to preserve fertility. Subgroup analysis was done with different HR status. Results Ninety-eight patients (33.1%) received concurrent GnRHa with NCT. Baseline characteristic showed no different between two groups except younger age with GnRHa group (p&lt;0.001) and more use of GnRHa in HR+/HER2- subtype (p=0.023). pCR rate was higher with GnRHa group (8.08% vs 20.41%, p=0.002). However there was no significant difference in 5yr DFS between without GnRHa and with GnRHa (HR 1.4 95% CI 0.60 2-3.582) in entire cohort. In HR positive subcohort, 5yr DFS was not different between without GnRHa and with GnRH a group (80.9% and 87.7% respectively,p=0.643). In HR negative subcohort, 5yr DFS was 71.6% vs 70.6% (p=0.931). There were no overall survival difference between two group in entire and subcohort (p&gt;0.05). Multivariable analysis also did not show survival improvement after use of GnRHa in HR- subtype (hazard ratio 2.166, (95% CI 0.746-6.292), p=0.155) and HR+ subtype (hazard ratio 1.231, (95% CI 0.205-7.411), p=0.820). Conclusion Among young women with breast cancer with negative hormone receptor treated with concomitant GnRHa achieved more pCR com compared with no GnRHa during chemotherapy. This result did not reach out to better survival outcome at this point. Trend to better outcome seen in survival curve implies further evaluation in this particular population.
Citation Format: Young Joo Lee, Seonok Kim, Hee J Kim. Use of ovarian function suppression to preserve fertility during neoadjuvant chemotherapy oncologically safe in women under age 40: An inverse probability weighting adjusted analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-16.
Abstract P3-01-13: Comparing portable and clinical ultrasound systems using 3D printed breast phantom inserts
Authors: Valdez Dustin , Fukui Jami , Wolfgruber Thomas , Leong Lambert , Maskarinec Gertraud , Shepherd John 
Published: March 2022

Abstract
Background: Late-stage breast cancer rates in the Pacific where mammography services are limited are exceedingly high. Therefore, alternative accessible breast cancer screening technologies such as portable ultrasound is needed. However, little is known about the performance of portable ultrasound when compared to clinical ultrasound for use in breast cancer screening. By utilizing 3D printing technology, it is possible to design breast phantom inserts to replicate various types of lesions. In this study, we utilized 3D printed breast phantom inserts to compare portable and clinical ultrasound lesion detection performance. Methods: Four different breast inserts were designed using FreeCAD (version 0.19) to replicate different lesion detection properties. The first insert compares lesion shape, the second insert investigates depth and size, the third insert looks at fiber diameter, and the fourth insert looks at clusters. The four inserts were printed using a photopolymer resign (Formlabs Inc Rigid resign, Somerville, MA, USA) and then placed in a gelatin-based breast phantom designed for ultrasound use. Using the portable ultrasound (GE Vscan Extend) and clinical ultrasound (Philips EPIQ 5G), various images were captured of identical angle and orientation for both devices. The number of lesions visualized were counted and presented as a percentage of lesions detected. Results: The portable ultrasound had a 100% lesion detection rate for breast insert 1, 90.3% for breast insert 2, 70% for breast insert 3 and 55.8% for breast insert 4. Clinical ultrasound had 100% lesion detection rate for breast insert 1, 93.1% for breast insert 2, 76.6% for breast insert 3, and 99% for breast insert 4. Conclusion: Portable ultrasound shows comparable lesion detection capabilities to clinical ultrasound in 3 of the 4 breast phantom insert tests. Portable ultrasound may have potential as a capable accessible breast cancer screening device in areas without mammography.
Citation Format: Dustin Valdez, Jami Fukui, Thomas Wolfgruber, Lambert Leong, Gertraud Maskarinec, John Shepherd. Comparing portable and clinical ultrasound systems using 3D printed breast phantom inserts [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-01-13.