bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-13-01: Differential efficacies of DNA damaging agents in basal-like TNBC subtypes
Authors: Shaffer CV , Robles AJ , Risinger AL , Mooberry SL 
Published: February 2018

Abstract
New approaches are needed to improve long term survival for patients with metastatic triple negative breast cancer (TNBC). Women with metastatic TNBC have a worse 3-year survival compared to women with metastatic HER2+ or ER/PR+ disease.1 Identifying the molecular vulnerabilities of TNBC subtypes could provide for optimal treatment strategies. Gene expression analyses of TNBC patient samples by Lehmann and Bauer, et al. identified 6 subtypes of TNBC.2 Based on the analysis of laser dissected tumor samples, the number of tumor subtypes was reduced from 6 to 4.3 Both analyses identified two types of basal-like cancers, basal-like 1 (BL1) and basal-like 2 (BL2).2,3 The BL1 subtype is defined by the amplified expression of genes involved in cell division and DNA damage response, and RNA polymerase.2 BL2 cancers express high levels of genes involved in growth factor signaling, glycolysis, and gluconeogenesis.2 They show that cell lines representative of the BL1 and BL2 subtypes of TNBC are more sensitive to cisplatin than cell lines representing the other TNBC subtypes. The BL1 or BL2 categorization, however, failed to predict sensitivity to olaparib.2 BL1 and BL2 representative cell lines responded differently when treated with veliparib; BL1 cells were more sensitive than BL2 cells.2 We investigated the response of BL1 and BL2 cells to a variety of DNA damaging agents to determine if the BL1 or BL2 subtype was predictive of sensitivity to a particular drug. DNA damaging agents, including alkylating agents, anti-metabolites, topoisomerase inhibitors, and PARP inhibitors were tested in cells resenting the BL1 and BL2 subtypes. HCC1806 cells (BL2) were found to be selectively sensitive to gemcitabine when compared to HCC1937 cells (BL1). The panel of drugs and cell lines was expanded to further understand the sensitivity of BL1 and BL2 subtypes to a variety of DNA damaging agents. Our goal is to provide preclinical evidence for the informed use of specific DNA damaging agents in the treatment of patients with BL1 or BL2 subtypes of TNBCs.
1. Li, X. et al. Breast Cancer Res. Treat. 161, 279–287 (2017).
2. Lehmann, B. D. et al. J. Clin. Invest. 121, 2750–2767 (2011).
3. Lehmann, B. D. et al. PLoS One 11, e0157368 (2016).
Citation Format: Shaffer CV, Robles AJ, Risinger AL, Mooberry SL. Differential efficacies of DNA damaging agents in basal-like TNBC subtypes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-13-01.
Abstract P3-01-18: Determining the need for axillar lymph node dissection based on pre-neoadjuvant chemotherapy sentinel lymph node biopsy results
Authors: Semiglazov VF , Krivorotko PV , Zhiltsova EK , Dashayan GA , Zernov KU , Bessonov AA , Trufanova ES , Tabagua TT , Ivanova OA , Kanaev SV , Novikov SN , Krzivickiyi PI , Brayanceva ZV , Komayachov AV , Nikolaev KS , Gigolaeva LP 
Published: February 2018

Abstract
An open-label single institution study of sentinel lymph node biopsy prior to neoadjuvant chemotherapy is conducted in the N.N. Petrov research institute of oncology. So far 30 patients with locally advanced breast carcinoma (T2-4N0) were included. Mammography, breast US and SPECT are performed prior to hospitalization so as core biopsy with subsequent IHC staining to determine the levels of ER, PR, KI67 and HER2. Sentinel lymph node biopsy with the use of radiocompound is performed prior to the first cycle of neoadjuvant chemotherapy. Patients receive 4 to 6 cycles with response evaluation after cycles 2, 4 and 6 (same evaluations as at the baseline). Axillary lymph node dissection is later performed along with the definitive surgery of the primary.
Interim analysis showed: 3 of 30 patients with cN0 were node positive after sentinel lymph node biopsy, 27 were node-negative (sn)pN0. All patients with (sn)pN0 completed neoadjuvant chemotherapy with clinical response. No cases of upfront progression were detected. All patients (sn)pN0 underwent axillary dissection upon completion of the neoadjuvant therapy. No cases of nodal involvement were detected (ypN0). All of the patients considered node-positive after sentinel biopsy also underwent lymph node dissection after completion of the neoadjuvant therapy. 2 of them were pN1 and one was pN2.
Conclusion: sentinel lymph node biopsy in cN0 patients prior to neoadjuvant chemotherapy allows to determine a category of patients ((sn)pN0) in whom axillary dissection can be avoided, provided they remain clinically node-negative at the time of definitive surgery.
Citation Format: Semiglazov VF, Krivorotko PV, Zhiltsova EK, Dashayan GA, Zernov KU, Bessonov AA, Trufanova ES, Tabagua TT, Ivanova OA, Kanaev SV, Novikov SN, Krzivickiyi PI, Brayanceva ZV, Komayachov AV, Nikolaev KS, Gigolaeva LP. Determining the need for axillar lymph node dissection based on pre-neoadjuvant chemotherapy sentinel lymph node biopsy results [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-18.
Abstract P3-05-09: Prognostic factors for therapeutic personalized peptide vaccines in patients with metastatic recurrent breast cancer
Authors: Toh U , Saku S , Iwakuma N , Takao Y , Okabe M , Akashi M , Yamada A , Shichijo S , Itoh K , Akagi Y 
Published: February 2018

Abstract
Background: We have previously reported the prognostic role of humoral antigen spreading response against prostate-related antigen (PRA) for metastatic recurrent breast cancer (mrBC) patients who received personalized peptide vaccine (PPV) therapy (Toh U, SABCS 2015). The prognostic effect was additionally evaluated by the clinical relevant factors including intrinsic subtype, the regimens of combined chemo-hormonal therapies in present study.
Methods:We analyzed serum IgG responses to all of the peptide candidates included PRAs (PSA, PAP and PMSA) after PPV therapy by the Luminex systemusing peripheral blood samples from 77 vaccinated mrBC patients. The clinical factors and relevant events were statistically evaluated.
Results: After 6 and 12cycles of PPV therapy, the serum IgG of anti-PSA, anti-PAP, and/or anti-PMSA increased significantly in 31 patients (PRA response group), and the median progression free survival (PFS) and median overall survival (OS) were 8.1 and 14.3 months, but were 5.1 and 10.8 months, respectively, in the remaining 46 patients with no anti-PRA IgG response (PRA non-response Group). The anti-PRA IgG level was marginally correlated withPFS (p=0.059) and OS (p=0.082) between these two groups, which was a significant prognostic factor for PFS (Log-rank: 0.009) in estrogen-positive cancer patients (ER+). The statistical analyses showed that the clinical outcome was in favor of &gt; 60 year-old patients, those with longer PPV therapies (&gt;3 months), and those who received combined standard hormonal therapies or bisphosphonate/anti-RANKL therapy.
Conclusions: This study indicated a clinical significance between the pre-and post- PPV therapy measurement of serum anti-PRA IgG in patients with mrBC, which may be a useful prognostic marker for monitoring peptide vaccine treatment outcomes, particularly for patients &gt; 60 years with ER+ breast cancer. These results also suggest that the immunotherapeutic peptide vaccine could be efficiently combined with hormonal therapy, anti-HER2 therapy, and bisphosphonate/anti-RANKL therapy in mrBC patients.
Citation Format: Toh U, Saku S, Iwakuma N, Takao Y, Okabe M, Akashi M, Yamada A, Shichijo S, Itoh K, Akagi Y. Prognostic factors for therapeutic personalized peptide vaccines in patients with metastatic recurrent breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-09.
Abstract P3-06-09: Discovery of novel oridonin-derivatives for the treatment of metastatic breast cancer
Authors: Li D , Zhang Z , Ding Y , Zheng Z , Dong J , Kim H , Xu J , Chen H , Zhou J , Shen Q 
Published: February 2018

Abstract
Metastasis to other organs is the major cause of death from breast cancer. The 5-year survival rate is approximately 99% for localized breast cancer, but sharply drops to approximately 26% for patients with distant metastasis. However, there are currently no effective, targeted therapies available for treating metastatic breast cancer. Oridonin, a complex ent-kaurane diterpenoid isolated from Chinese traditional herb Rabdosia rubescens, has demonstrated great potential in the treatment of various human cancers. However, relatively low aqueous solubility and bioavailability limited its development into clinical applications. Herein, a number of novel nitrogen-enriched heterocyclic oridonin derivatives and dienone analogs such as YD0514, CYD0618, and CYD0686 have been generated from oridonin. These derivative analogs showed improved anti-proliferation effects against breast cancer cells, compared to oridonin. YD0514, CYD0618, and CYD0686 also displayed significant suppression of migration and invasion in MDA-MB-231 cell, a highly metastatic triple-negative breast cancer cell line. Furthermore, YD0514, CYD0618 and CYD0686 also inhibited the endothelial adhesion of GI101 and its derived, highly metastatic sublines, to the endothelium. We next found that YD0514, CYD0618, and CYD0686 can significantly inhibit the expression and phosphorylation of FAK and block the expression of integrin family members in those highly metastatic breast cancer cell lines. Further pathway analysis demonstrated that YD0514, CYD0618, and CYD0686 inhibited cellular motility potentially by decreasing RHOA/ROCK signaling pathway. Our findings suggest that novel oridonin-derivatives, YD0514, CYD0618, and CYD0686 have the great potential to be developed as effective therapeutics for the treatment of metastatic breast cancer. This work was supported by Grants P50 CA097007, and P30DA028821 (JZ) from the NIH, CPRIT (JZ), John Sealy Memorial Endowment Fund (JZ), DFI Grants from MD Anderson Cancer Center (QS), and Holden Family Research Grant in BC Prevention (QS).
Citation Format: Li D, Zhang Z, Ding Y, Zheng Z, Dong J, Kim H, Xu J, Chen H, Zhou J, Shen Q. Discovery of novel oridonin-derivatives for the treatment of metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-06-09.
Abstract P3-10-02: Presence of atypia in ductal lavage and risk of subsequent breast cancer in a prospective study
Authors: De Censi A , Cazzaniga M , Gandini S , Casadio C , Chiapparini L , Guerrieri-Gonzaga A , Macis D , Veronesi P , Bonanni B 
Published: February 2018

Abstract
Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment would greatly benefit from sampling cellular material from the target tissue. Ductal lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from ductal lavage and BC risk are lacking. We studied the prevalence of atypia in DL in different risk categories and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 years (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model &gt; 1.66% or &gt; 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimen of ductal lavage and in repeated lavage and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia at baseline, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 (21%) in women with atypia versus 11 (10%) in women without atypia (p = 0.02 after adjustment for age). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL predicts subsequent BC in women at increased risk, providing individual risk assessment. The reversal of atypia in DL should be evaluated as a surrogate biomarker of BC therapeutic prevention.
Supported by: Associazione Italiana per la Ricerca sul Cancro (AIRC), Lega Italina per la Lotta contro i Tumori (LILT), AVON Foundation for Women.
Citation Format: De Censi A, Cazzaniga M, Gandini S, Casadio C, Chiapparini L, Guerrieri-Gonzaga A, Macis D, Veronesi P, Bonanni B. Presence of atypia in ductal lavage and risk of subsequent breast cancer in a prospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-02.
Abstract P3-13-02: Withdrawn
Authors: Cottu PH , D'Hondt V , Dureau S , Lerebours F , Desmoulins I , Heudel P , Duhouix F , Levy C , Mouret-Reynier M-A , Dalenc F , Frenel J-S , Jouannaud C , Venat-Bouvet L , Nguyen S , Ferrero J-M , Canon J-L , Grenier J , Vincent-Salomon A , Lemonnier J , Delaloge S 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P4-01-02: Choosing wisely: Radiographic surveillance after breast conservation therapy in HER2+ breast cancer
Authors: Everett A , Wallace AS , De Los Santos JF , Rocgue GB , Parker CS , Keene KS 
Published: February 2018

Abstract
Purpose/Objective(s): ASTRO Choosing Wisely campaign recommends no more than annual mammography after breast conservation therapy (BCT). HER2+ disease portends increased risk of locoregional recurrence in comparison to Luminal A disease. Our previous institutional practice included surveillance imaging every 6 months for the first 2-3 years after BCT. The purpose of this study is to evaluate surveillance imaging intervals as a means of detecting early locoregional recurrence at one institution.
Materials/Methods: Women with HER2+ locoregionally confined invasive breast cancer treated with lumpectomy and radiation as part of breast conservation therapy at one institution were retrospectively identified after IRB approval. Patient demographics, treatment, surveillance, and outcomes data were captured. BRCA+ patients or those without available surveillance follow-up at our institution were excluded. Surveillance period started after the last fraction of radiation was completed.
Results: In 86 women treated from 2008-2016, median age at diagnosis was 57, and 69% were Caucasian. Most patients were treated for Stage I-II invasive ductal carcinoma. All but one were treated with chemotherapy, with similar distribution between adjuvant and neoadjuvant regimens. Receptor status was as follows: ER+ 66%, PR+ 59%, ER+/PR+/HER2+ in 58%, ER-/PR-/HER2+ in 33%. Mammography +/- ultrasound was utilized, with infrequent use of magnetic resonance imaging. Median time from end of radiation to first surveillance imaging was 4 months. All women had 1 post-BCT imaging, with 2nd, 3rd, and 4th available in 91%, 85%, 73% respectively. Interval frequency between first 4 images was 6 months. No patients had expired at the time of analysis. Recurrence were identified in 2 women: 1 identified clinically after negative mammography, and 1 identified on mammography at 27 months.
Conclusion: While overall events are small, discordant biannual mammography did not identify locoregional recurrences in this biologically higher risk group in the first two years post-treatment. This data supports current guideline recommendations limiting surveillance breast imaging in patients undergoing breast conservation to an annual frequency.
Citation Format: Everett A, Wallace AS, De Los Santos JF, Rocgue GB, Parker CS, Keene KS. Choosing wisely: Radiographic surveillance after breast conservation therapy in HER2+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-01-02.
Abstract P4-04-07: Characterization of the effects of estrogen receptor alpha Y537S and D538G mutations on receptor function and pharmacology
Authors: Blake RA , Hartman SJ , Kleinheinz TL , White J , Daly S , Goodwin R , Zhou W , Liang J , Wang X , O'Rourke M , Metcalfe C , Friedman L 
Published: February 2018

Abstract
The frontline therapy for estrogen receptor alpha (ERα) positive Breast Cancer (ER+BC) involves various forms of endocrine therapy, consisting of either Selective Estrogen Receptor Modulators (SERMs) or aromatase inhibitors. An emerging mechanism of ER+BC resistance to endocrine therapy, and consequently disease relapse, has been associated with a set of “hotspot” mutations in and near to helix-12 of the ERα ligand binding domain. Selective Estrogen Receptor Degraders/Down-regulators (SERDs), such as GDC-0810, AZD9496 and GDC-0927, represent a current major pharmacological strategy being applied to develop treatments for such resistant ER+BC. Here, we compare 2 of the most frequent ERα hotspot mutations (Y537S and D538G), with ERα wildtype (WT) and the ability of a set of ERα ligands (including GDC-0810, AZD9496 and GDC-0927) to bind, antagonize and degrade ERα. The concentration of each drug required to bind, antagonize or degrade ERα Y537S or ERα D538G was typically higher than that required for ERα WT. Importantly, ERα Y537S is resistant to estradiol stimulated protein degradation and 4-hydroxy-tamoxifen (a major active metabolite of tamoxifen) stabilizes ERα Y537S protein. This represents a potential mechanism of resistance of ERα Y537S ER+BC to Tamoxifen therapy.
Citation Format: Blake RA, Hartman SJ, Kleinheinz TL, White J, Daly S, Goodwin R, Zhou W, Liang J, Wang X, O'Rourke M, Metcalfe C, Friedman L. Characterization of the effects of estrogen receptor alpha Y537S and D538G mutations on receptor function and pharmacology [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-07.
Abstract P4-13-11: A complication analysis between complete and partial tissue expander coverage using autologous flaps in cases of immediate breast reconstruction
Authors: Kubo K , Hamahata A , Tozuka K , Tsuboi M , Hayashi Y , Takai K , Saito T , Sakurai H , Matsumoto H 
Published: February 2018

Abstract
Background:
To avoid tissue expander exposure following mastectomy flap necrosis, several methods for covering expander by autologous flap in cases of immediate breast reconstruction have been reported. These methods are classified into two groups, complete or partial expander coverage. Two methods have potential risks of postoperative complications following: insufficient lower pole expansion and cranial migration in complete coverage methods, and lateral migration in partial coverage methods. However, the comparisons of complication rates between these two methods have not been reported. This study aims to compare the incidence of expander exposure following mastectomy flap necrosis and expander migration between two methods.
Methods:
A retrospective review of 93 patients (99 breasts) who underwent immediate expander-based breast reconstruction was performed. Patients were divided into two groups, complete or partial expander coverage by autologous flaps. In both groups, expanders were placed into subpectral position. In partial coverage group, the lateral borders of pectralis major muscles were sutured to the mastectomy skin flaps. If the skin flap was too thin to be sutured, the serratus anterior muscro-fascial flap was dissected and sutured to the lateral border of pectralis major muscle to cover the expander completely. Allograft products were not used in both groups. Demographics, intraoperative findings, and postoperative complications were compared between two groups.
Results:
Of the 99 breasts, 56 underwent complete expander coverage and 43 underwent partial coverage. Mastectomy flap necrosis rate was higher in the complete coverage group (Complete 14.3% versus Partial 0%; p=0.0091), however, there was no incidence of expander exposure in both groups. Lateral migration rate was higher in the partial coverage group (Complete 0% versus Partial 9.3%; p=0.033). There was no difference in cranial migration rate between two groups (Complete 12.5% versus Partial 2.3%; p=0.133).
Conclusions:
The thinness of the mastectomy flaps was considered to provide the higher incidence of mastectomy flap necrosis in the complete coverage group. The complete expander coverage reduced lateral migration rate and prevented expander exposure in cases of mastectomy flap necrosis.
Citation Format: Kubo K, Hamahata A, Tozuka K, Tsuboi M, Hayashi Y, Takai K, Saito T, Sakurai H, Matsumoto H. A complication analysis between complete and partial tissue expander coverage using autologous flaps in cases of immediate breast reconstruction [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-11.