bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-11-18: Partial RALBP1 loss depletes DNA repair pathway genes
Authors: Awasthi Sanjay , Bose Chhanda , Jones Catherine , Rahman Rakhshanda , Singhal Sharad S. , Singh Sharda P. 
Published: March 2020

Abstract
TP53 (p53) functions as a stress-responsive, genome protective, tumor suppressor whose functions are lost or altered a majority of breast cancers. TP53 homozygous null mice uniformly die of spontaneous malignancy. The human RALBP1 gene (18p11.22) encodes is a stress-protective, anti-apoptotic mercapturic acid pathway transporter protein (RLIP76 or Rlip) regulated by the Ral/Rac/Rho pathways. In stark contrast to TP53 null mice, RALBP1-null mice are highly cancer resistant, even to the most potent known chemical carcinogens benzo[a]pyrene or dimethylbenzanthracene. We recently reported that pharmacologically or chemically induced haploinsufficiency of Rlip switches off spontaneous carcinogenesis in p53-null mice (Proc. Natl. Acad Sci USA, 2018; 115:3918), indicating an existential role of Rlip in p53-deficient cancer cells and suggesting the possibility that DNA-repair deficient cells could be particularly susceptible to Rlip depletion. Results of present studies demonstrated that RALBP1 depletion by antisense inhibited the growth of the MDA-MB231 cell line in-vitro and in xenografts. Remarkably, Rlip depletion with antisense or upon treatment with an orange-derived flavanone (2-hydroxyflavanone) depleted the expression of PALB2 as well as BRCA1 and BRCA2 in triple negative breast cancer cell lines, and synergistically increased the efficacy of PARP inhibition. These findings suggest that drugs that inhibit or deplete Rlip could be useful in sensitizing DNA-repair sufficient triple negative breast cancer to PARP inhibitors.
Citation Format: Sanjay Awasthi, Chhanda Bose, Catherine Jones, Rakhshanda Rahman, Sharad S. Singhal, Sharda P. Singh. Partial RALBP1 loss depletes DNA repair pathway genes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-18.
Abstract P3-11-23: GDC-0077 is a selective PI3K alpha inhibitor with robust efficacy in PIK3CA mutant hormone-positive breast cancer models
Authors: Edgar Kyle , Hong Rebecca , Song Kyung , Schmidt Steven , Hafner Marc , Arrazate Alfonso , Williams Erin , Cruz Cecile De La , Oeh Jason , Sampath Deepak , Staben Steve , Friedman Lori 
Published: March 2020

Abstract
The phosphatidylinositol 3kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is a major regulator of tumor cell growth, proliferation and survival. Hotspot mutations of PIK3CA are common in all subtypes of breast cancer with a prevalence of approximately 30%. GDC-0077 is a potent ATP-competitive inhibitor of PI3K alpha (IC50 = 0.038 ± 0.003 nM), thereby inhibiting the phosphorylation of membranebound PIP2 to PIP3. Biochemically, GDC-0077 is more than 300fold selective over the other Class I PI3K isoforms, beta, delta, and gamma, and more than 2000-fold more selective over PI3K class II and III family members. Importantly, GDC-0077 is more selective for mutant versus wild-type PI3K alpha in cell-based assays. Mechanism of action studies indicate that GDC-0077 treatment leads to degradation of the mutant PI3K alpha protein in a proteasome dependent fashion, without changing WT PI3K alpha levels. Drug treatment results in sustained reduction of PI3K pathway biomarkers pAkt and pPRAS40, inhibition of cell proliferation, and increased apoptosis in human PIK3CA mutant breast cancer cell lines, to a greater extent than other non-degrading inhibitors such as alpelisib. Combination studies of GDC-0077 with the CDK4/6 inhibitor palbociclib demonstrate a stronger effect in estrogen-depleted HR+ PIK3CA mutant breast cell lines, compared to cells grown in the presence of estrogen. Daily dosing of GDC-0077 in PIK3CA mutant breast cancer patient derived xenograft (PDX) models (n=4) resulted in tumor regressions, induction of apoptosis and a reduction of pAkt, pPRAS40, and pS6RP in a dose-dependent fashion. In vivo combination efficacy studies of GDC-0077 with fulvestrant and palbociclib also indicate the triple combination results in the greatest efficacy. Collectively, our preclinical data support evaluation of GDC-0077 in a triple combination with endocrine therapy and CDK4/6 inhibition in the clinic, in patients with locally advanced or metastatic hormone receptor positive breast cancer whose tumors harbor mutant PIK3CA.
Citation Format: Kyle Edgar, Rebecca Hong, Kyung Song, Steven Schmidt, Marc Hafner, Alfonso Arrazate, Erin Williams, Cecile De La Cruz, Jason Oeh, Deepak Sampath, Steve Staben, Lori Friedman. GDC-0077 is a selective PI3K alpha inhibitor with robust efficacy in PIK3CA mutant hormone-positive breast cancer models [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-23.
Abstract P3-12-02: Anlotinib in pre-treated metastatic HER2-negative breast cancer: A phase II, single-arm clinical study
Authors: Hu Nanlin , Luo Yang , Wang Jiayu , Li Qing , Zhang Pin , Ma Fei , Xu Binghe , yuan Peng 
Published: March 2020

Abstract
Background: There is no standard treatment strategy for patients with locally advanced or metastatic breast cancer suffering progression after one prior chemotherapy with metastasis setting. Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. This study is performed to assessed the efficacy and safety of anlotinib in patients with HER2 negative locally advanced or metastatic breast cancer for whom at least one lines of prior chemotherapy had failed.
Method: This open-label, single arm study enrolled patients with HER2-negative breast cancer, pretreated with anthracycline, taxanes, and who failed in the metastatic setting at least 1 prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients. Anlotinib was administered 12mg d1-d14 for a 21-day cycle. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. The treatment duration is until disease progression or intolerability of anlotinib.
Results: From July 12th in 2018 to July 1st in 2019, 18 eligible patients were enrolled in this, open-label, single arm study and received anlotinib with a median age of 56 years old(range 32 to 74 years). Median follow-up time was 2.8 months(range 1.0 to 9.9 months). Median 18 patients were eligible for efficacy analysis. Median PFS was 4.43 months (95% confidence interval (CI), 3.15m - 5.71 m). ORR was 22.2% (4/18). DCR was 55.6% (10/18). Only 2/18(11.1%) patients was reported dead, so median OS was not reached for now. The most common grade 3/4 treatment-related AEs were hypertension (3/18,16.7%), and the blood pressure got back to grade 1/2 as soon as the antihypertensive drugs were offerd. No other grade 3/4 adverse events were observed. No patients had dose reduction because of adverse events.
Conclusion: Anlotinib exhibited objective efficacy in heavily pretreated, metastatic HER2-negative breast cancer with mild toxicity. Multi-center prospective studies enrolling more patients are needed.
TRIAL REGISTRATION:
ClinicalTrials.gov: NCT04002284
Citation Format: Nanlin Hu, Yang Luo, Jiayu Wang, Qing Li, Pin Zhang, Fei Ma, Binghe Xu, Peng yuan. Anlotinib in pre-treated metastatic HER2-negative breast cancer: A phase II, single-arm clinical study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-12-02.
Abstract P4-01-02: Circulating tumor cells detected after neoadjuvant therapy for inflammatory breast cancer are associated with early relapse despite pCR
Authors: Hall Carolyn , Meas Salyna , Narendran Boomadevi , Sarli Vanessa , Upshaw Joshua , Ueno Naoto , Lim Bora , Valero Vicente , Lucci Anthony 
Published: March 2020

Abstract
Background: IBC is a rare and aggressive subtype of breast cancer. A significant number of IBC patients who achieve pathologic complete response (no residual tumor in breast and axillary nodes, pCR), still relapse after neoadjuvant chemotherapy (NAC). We hypothesized that circulating tumor cells (CTCs) identified in blood after NAC would add additional relapse risk information beyond just PCR alone.
Methods: Blood was assessed for CTCs after NAC in 128 stage III IBC patients as part of an IRB approved study, (LAB04-0698) using the Cell Search® System (Menarini Silicon Biosystems). The presence of ≥ 1 CTC meeting morphological criteria for malignancy was considered a positive result. Fisher exact test was used to evaluate associations between CTC detection and clinicopathologic characteristics, and log-rank test was used to analyze associations between CTC detection after NAC, pCR, and relapse free survival.
Results: Median follow-up was 2.4 years and mean patient age was 53 years. One or more CTC was identified after NAC in 36/128 (28%) of patients. Thirty-six patients (28%) had pCR following NAC. CTC detection was not associated with body mass index, estrogen, progesterone, or human epithelial growth factor receptor-2 (HER2) status, or Ki-67 staining (P= NS). Participants were grouped according to their post NAC CTC and pCR statuses as follows: CTC- and pCR (n = 28), CTC- and no pCR (n = 48), ≥1 CTC and pCR (n = 5) and ≥1 CTC and no pCR (n =18). Difference in recurrence free survival were identified in these groups, with worse relapse-free survival at 2 years identified in those with ≥1 CTCs and no pCR (log-rank p-value = &lt;0.0001).
Conclusions: CTC detection after NAC identified non-metastatic IBC patients who achieved pCR, but remained at risk for relapse. This study warrants larger studies combining both PCR and CTC information in IBC patients to improve risk stratification and to identify patients who could derive benefit from additional adjuvant therapies to reduce their risk for relapse.
Citation Format: Carolyn Hall, Salyna Meas, Boomadevi Narendran, Vanessa Sarli, Joshua Upshaw, Naoto Ueno, Bora Lim, Vicente Valero, Anthony Lucci. Circulating tumor cells detected after neoadjuvant therapy for inflammatory breast cancer are associated with early relapse despite pCR [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-02.
Abstract P4-01-17: Viable circulating ensembles of tumor associated cells persist in patients with no radiologically detectable disease after treatment in breast cancer
Authors: Srinivasan Ajay , Akolkar Dadasaheb , Patil Darshana , Crook Timothy , Sims Cynthe , Patil Revati , Datta Vineet , Ranade Anantbhushan , Fulmali Pradip , Devhare Pradip , Fulmali Pooja , Patel Shoeb , Ainwale Akshay , Puranik Sneha , Datar Rajan 
Published: March 2020

Abstract
Oncological orthodoxy holds that (metastatic) breast cancer is an incurable disease. Response evaluation in metastatic breast cancer is determined by clinical, biochemical and radiological parameters, FDG PET CT being the imaging modality of choice for most types of breast cancer. However, even in cases where FDG PET CT and/or normalisation of serum tumour markers imply complete response to systemic therapy, durable disease-free survival is uncommon. To explore the mechanistic basis underlying persistent disease in spite of apparently effective systemic therapy, we hypothesized that Circulating Metastatic Disease (CMD) in the form of viable tumor cells or clusters might be a feature of persisting breast cancer. To address this, we obtained 15ml of peripheral blood from 927 known and previously treated cases of breast cancers immediately prior to FDG PET CT restaging. Peripheral blood mononuclear cells (PBMCs) were harvested by centrifugation. Circulating Ensembles of Tumor Associated Cells (C-ETACs), which are clusters of heterotypic apoptosis resistant cells of tumorigenic origin were enriched by a novel process using a combination of commercially available stabilizing agents. C-ETACs were characterized by immunostaining for EpCAM, pan-CK and CD45 as well as GCDFP-15 or GATA3. 927 patients underwent FDG PET CT of whom 731 (78.9%) had evidence of FDG avid residual disease. 196 patients (21.1%) had no metabolically active disease, among whom C-ETACs were detected in 171/196 cases (87.2%). The presence of CMD in a high proportion of cases in patients with no evidence of metabolically active disease implies that the majority of patients in whom conventional parameters of disease are negative have residual disease and are not biologically cured.
Citation Format: Ajay Srinivasan, Dadasaheb Akolkar, Darshana Patil, Timothy Crook, Cynthe Sims, Revati Patil, Vineet Datta, Anantbhushan Ranade, Pradip Fulmali, Pradip Devhare, Pooja Fulmali, Shoeb Patel, Akshay Ainwale, Sneha Puranik, Rajan Datar. Viable circulating ensembles of tumor associated cells persist in patients with no radiologically detectable disease after treatment in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-17.
Abstract P4-02-07: Validity of omission of axillary lymph node dissection after neoadjuvant chemotherapy for node-positive primary breast cancer
Authors: Matsumoto Akiko , Umemoto Yasuko , Tsukahara Daisuke , Jinno Hiromitsu 
Published: March 2020

Abstract
Background: Anthracycline and taxane-based neoadjuvant chemotherapy (NAC) has been shown to downstage axillary lymph nodes in approximately 40% of patients. However, the feasibility of sentinel lymph node biopsy (SLNB) following NAC for initially node-positive patients is unclear because of high false-negative rates reported in previous trials. The aim of this study was to evaluate whether axillary lymph node dissection (ALND) could be safely omitted for patients with clinically node-positive breast cancer treated with NAC. Patients and methods: We identified 128 patients with clinically node-positive breast cancer who received NAC from March 2006 to March 2017. A correlation between axillary pathologic response and clinicopathological factors was analyzed. Preoperative clinical assessment of lymph-node status was performed by palpation and diagnostic imaging such as ultrasound and MRI. Lymphatic mapping was performed using a combined method of blue dye and radioisotope. Results: The median age was 56.5 (range: 29-79) years and the mean tumor size was 3.6 ± 2.37cm. Of 128 patients, 72 (56.2%) patients had luminal, 32 (31.3%) had HER2-positive, and 24 (18.8%) had triple-negative disease. Sequential anthracycline and taxane were administered for 115 (89.8%) patients, and 25 (78.1%) patients with HER2-positive disease received concomitant trastuzumab preoperatively. Overall, 53 (41.4%) patients achieved axillary pathologic complete response (ypN0). The ypN0 status was significantly correlated with clinical complete response (cCR) in breast (67.9%, p=0.004), ER-negative disease (59.5%, p=0.004) and HER2-positive disease (56.3%, p=0.049). Multivariate analysis demonstrated that cCR in breast (p=0.015) and ER negativity (p=0.006) were significant predictive factors for ypN0. In 14 ER-negative patients achieving cCR in breast, ypN0 was found in 12 (85.7%) patients. Among 85 patients who converted to clinically node-negative, ALND was omitted in 16 patients (18.8%) after SLNB. Of these 16 patients, irradiation to whole-breast and axilla was performed in 14 (87.5%) and 5 (31.3%) patients, respectively. After a median follow-up of 53.2 months, no axillary recurrence was observed in entire patients and 5-year disease-free survival was not significantly different between patients with or without ALND (85.5% vs. 87.5%, p=0.965). Conclusions: As ER-negativity and cCR were correlated with high eradication rate of initially positive lymph nodes, these patients might be good candidates of omission of ALND after NAC.
Citation Format: Akiko Matsumoto, Yasuko Umemoto, Daisuke Tsukahara, Hiromitsu Jinno. Validity of omission of axillary lymph node dissection after neoadjuvant chemotherapy for node-positive primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-07.
Abstract P4-02-08: What happened to clinically node positive breast cancer patients who showed conversion into pN0 after neoadjuvant chemotherapy?: Single center for 10 years
Authors: Kwak Joo Hwa , Jo Heein , Lee Eun-Gyeong , Song Eun Jin , Han Jai Hong , Jung So-Youn , Kang Han-Sung , Lee Eun Sook , Lee Seeyoun 
Published: March 2020

Abstract
Objective: This study aimed to evaluate the outcomes between sentinel lymph node biopsy (SLNB) and axillar lymph node dissection (ALND) on recurrence and survival in clinically node positive breast cancer patients who showed conversion into pN0 after neoadjuvant chemotherapy (NAC) from 10 years cohort in single center.
Materials & Method: This study enrolled total 225 patients, from January 2006 to December 2015 who underwent breast cancer surgery and axillar lymph node approach in clinically axillar lymph node metastasis with conversion into node negative after neoadjuvant chemotherapy. One hundred patients had only SLNB and 125 patients had ALND finally.
Results: The median follow-up time was 58 months (range, 12-147 months) in only SLNB group and 103 months (range 9-174 months) in ALND group and the median number of retrieved SLNs was 2 (range, 1-6) and 11 (2-31).
The 5 years overall survival rate of SLNB and ALND group is 94%, 95.7% (P=0.786), disease free survival rate 91.9%, 91.6%, (p=0.753) which was not statistically significant. Three patients (3%) and 6 patients (4.8%) showed loco-regional recurrence respectively. All they showed ipsilateral axillary lymph node recurrence. Seven patients (7%) and 6 patients (4.8%) in SLNB group and ALND group showed distant metastasis. However, there were more complications in the ALND group than in the SLNB group. Among them, ALND group showed the higher rate of shoulder stiffness than SLNB group (7% vs 10.4%, p=0.384, respectively). Especially, the incidence of lymphedema was 6 times higher in ALND group. (4 patients (4%) vs 29 patients (23.2%), p=0.271)
Conclusion: We found the SLNB only group did not increase the recurrence or metastatic rate from the patients, but reduced the incidence of complications such as lymphedema from the 10 years single center cohort. Therefore, we suggest SLNB can be considered as a reliable as an alternative to ALND when the complete response is achieved by re-staging with imaging study after neoadjuvant chemotherapy.
Keyword: neoadjuvant chemotherapy, sentinel lymph node biopsy, axillar lymph node dissection
Citation Format: Joo Hwa Kwak, Heein Jo, Eun-Gyeong Lee, Eun Jin Song, Jai Hong Han, So-Youn Jung, Han-Sung Kang, Eun Sook Lee, Seeyoun Lee. What happened to clinically node positive breast cancer patients who showed conversion into pN0 after neoadjuvant chemotherapy?: Single center for 10 years [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-08.
Abstract P4-02-19: First reported use of the Faxitron LOCalizer™ Radiofrequency Identification (RFID) system in the axilla- A pilot trial in targeted axillary dissection (TAD)
Authors: Malter Wolfram , Eichler Christian , Puppe Julian , Thangarajah Fabishy , Mallmann Peter , Krug Barbara , Warm Mathias , Holtschmidt Johannes 
Published: March 2020

Abstract
Introduction: Adequately marking suspicious lymph nodes before neoadjuvant chemotherapy in breast cancer patients is commonly done by introducing a titanium clip followed by stereotactic hook wire location. However, clip dislocation and/or wire dislocation are common problems. Furthermore, locating a clip within the axilla is problematic since stereotactic location may be anatomically challenging. An ideal solution would be a clip which can be easily found without the use of a stereotactic intervention. This pilot trial proves the concept of using radiofrequency identification devices (RFID) in targeted axillary dissection (TAD).Methods: This pilot trial represents a single center, consecutively recruited, evaluation (n=10) for targeted axillary dissection using the Faxitron LOCalizer™ radiofrequency identification chip system. Patients were given the choice between wire guided TAD vs. LOCalizer™ TAD. Primary endpoints were: percentage of successful location /failure to locate. Secondary endpoints were major and minor complication rates as well as surgeon evaluated outcome.Results: Primary endpoints showed a 100% location rate of the suspicious lymph nodes at a 0% major complication (revision surgery) rate. Additional guided wire marking was not necessary for lymph node location. Surgeons evaluated the new system as being safe to use and only slightly more difficult to place than a standard clip or a wire system.Conclusion: This pilot trial proved the concept of TAD via a RFID system. When using this system, preoperative stereotactic lymph node marking is no longer required, thus patients may be spared additional x-ray exposure. Using the LOCalizer™ system should therefore be considered for any TAD.
Citation Format: Wolfram Malter, Christian Eichler, Julian Puppe, Fabishy Thangarajah, Peter Mallmann, Barbara Krug, Mathias Warm, Johannes Holtschmidt. First reported use of the Faxitron LOCalizer™ Radiofrequency Identification (RFID) system in the axilla- A pilot trial in targeted axillary dissection (TAD) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-19.