bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-04-06: Changes of DNA methylation in the development of breast cancer
Authors: He C , Lin N , Shendre A , Jiang G , Lin H , Wan J , Liu Y 
Published: February 2018

Abstract
Aberrant DNA methylation plays an important role in breast cancer initiation and progression via inactivation of tumor suppressor genes and activation of oncogenes. To better understand the changes of DNA methylation in the development of breast cancer, we analyzed genome-wide DNA methylation DNA data in breast tumor, adjacent normal tissue, and normal breast tissue from healthy women. Using the IIILumina MethylationEPIC array, we investigated approximately 850,000 CpG sites. After quality control, 747,803 probes were retained and included the further analysis. To identify DNA methylation markers associated with breast cancer, we performed differential methylation analysis using ChAMP package implemented in Bioconductor. We identified 590 CpG sites that were differentially methylated (P&lt;1X10-4) between tumor and normal, and 637 between tumor and adjacent normal tissue samples. Further pathway analyses revealed that changes in DNA methylation between tumor and normal breast tissue were mainly involved in neurogenesis and neuro differentiation, oxidative stress, insulin secretion and epithelial morphogenesis; while changes in DNA methylation between tumor and adjacent normal tissue were mainly involved in angiogenesis, cell morphogenesis, and cell component movement. We further validated our findings using RNA-seq data. Our results suggested distinct DNA methylation changes involved in different biological pathways, reflecting potential causal and reactive biological mechanisms in the initiation and the progression of breast cancer.
Citation Format: He C, Lin N, Shendre A, Jiang G, Lin H, Wan J, Liu Y. Changes of DNA methylation in the development of 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 P2-04-06.
Abstract P2-10-06: Identifying patients sensitive to anthracycline-containing therapy with quantitative proteomic and genomic profiling
Authors: Schwartz S , Cecchi F , Tian Y , Yau C , Szeto C , Rübner M , Erber R , Beckmann MW , Hartmann A , Benz S , Hembrough T , Fasching P 
Published: February 2018

Abstract
Background: Selecting chemotherapy based on tumor biology can improve response rates and avert toxicity. Studies of the relationship between tumor expression of TOP2A protein and response to anthracycline-based chemotherapy have yielded contradictory results. Here we used mass spectrometry (MS) to evaluate associations between tumor molecular profiles and pathological complete response (pCR) in breast cancer patients treated with neoadjuvant anthracycline-containing therapy.
Methods: Patients were selected from the ERNEST-B (Erlangen Neoadjuvant Study Breast), which is a retrospective cohort study. Archived tumor samples from anthracycline-treated breast cancer patients (n=133) were microdissected and solubilized. In each tumor sample, TOP2A and other target proteins were quantitated with a mass spectrometry assay. Molecular profiling also included RNA sequencing of the tumor and whole genome sequencing of both tumor and matched normal tissue sections. The cohort was dichotomized into high and low expressors of TOP2A using a protein level cutoff of 515 amol/ug of tumor protein. The difference in pCR (ypT0ypN0) rates between high and low expressors of TOP2A was assessed using a z-test for differences in proportion.
Results: TOP2A protein was detected in 84 of 133 (63%) tumor samples from anthracycline-treated patients (range: 178 to 3044 amol/ug). Patients whose tumor expressed TOP2A protein above the cutoff of 515 amol/ug had higher pCR rates than patients with lower TOP2A expression (35.5% vs. 12.1%; odds ratio (OR): 4.48 [95% CI: 1.53-13.28], Fisher' exact test p = 0.004). The difference retained statistical significance in a logistic regression model adjusting for HR and HER2 status (OR: 2.23 [95% CI: 1.15-4.30], p=0.017). In a separate cohort of 19 breast cancer patients who did not receive anthracycline, there was no association between TOP2A protein expression level and pCR rate. Results from a validation cohort as well as the genomic analysis will be presented at the meeting.
Conclusions: In a retrospective analysis of anthracycline-treated breast tumors, TOP2A expression was associated with a higher rate of pCR. Targeted proteomics may predict the response of breast cancer patients to anthracycline-based therapy.
Citation Format: Schwartz S, Cecchi F, Tian Y, Yau C, Szeto C, Rübner M, Erber R, Beckmann MW, Hartmann A, Benz S, Hembrough T, Fasching P. Identifying patients sensitive to anthracycline-containing therapy with quantitative proteomic and genomic profiling [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 P2-10-06.
Abstract P2-10-07: A prospective clinical utility study of the impact of the 21-gene recurrence score (RS) assay in the treatment of estrogen receptor positive (ER+), HER2 negative (HER2-), 1-3 node positive (N+) breast cancer (BC)
Authors: Sun J , Fenton D , Baxter S , Chan A , Roberts S , Feng X , Lohrisch C , Gelmon K , Shenkier T , Chia S 
Published: February 2018

Abstract
Background:
The 21-gene RS is routinely used in node negative ER+, HER2- BC to help guide chemotherapy treatment decision making. There is emerging use of the RS in limited N+ BC, though the results from the randomized clinical trial (RxPONDER) is pending. The objective of the study is to determine whether the results of the 21-gene RS will alter physician treatment decisions in ER+ HER2- limited N+ BC.
Methods:
Consenting patients (pts) with ER+, HER2-, 1-3 N+ (microscopic or macroscopic) early stage BC participated in this prospective, multi-center British Columbia Cancer Agency (BCCA) study. Treating physicians completed a questionnaire after an initial visit with the patient to document their treatment recommendation before obtaining the RS assay. At a subsequent visit, the assay result and final treatment recommendations were discussed and physicians completed a second questionnaire on the final treatment plan. The statistical assumption of the study was based upon anticipating an overall treatment decision change rate (from chemo-hormonal therapy to hormone only, or vice-versa) to be at least 30%.
Results:
Out of 84 pts enrolled, 82 went on to have RS testing. 57% of pts had T1 tumors, 40% T2 and 2% T3 tumors. The majority of pts (77%) had N1 macroscopic disease compared to 23% that had microscopic nodal involvement. 63% of cases were grade 2, followed by 23% grade 1 and 14% grade 3. 60% of RS were low (&lt;18), 33% intermediate (18-30) and 7% were high (&gt;30). In 53% of cases there was an altered treatment plan (49% switched from chemo-hormonal therapy to hormone only, and 4% switched from hormone only to chemo-hormonal therapy). Of the 49% that switched to hormone only, 68% had a low RS and 33% had an intermediate RS. All 4% that switched to chemo-hormonal therapy had an intermittent RS.
Conclusions:
This multi-centered Canadian study showed that in 53% of cases, treatment recommendations were changed based on the RS. This suggests that there is clinical utility for the RS in 1-3 N+, ER+, and HER2- breast cancer.
Citation Format: Sun J, Fenton D, Baxter S, Chan A, Roberts S, Feng X, Lohrisch C, Gelmon K, Shenkier T, Chia S. A prospective clinical utility study of the impact of the 21-gene recurrence score (RS) assay in the treatment of estrogen receptor positive (ER+), HER2 negative (HER2-), 1-3 node positive (N+) breast cancer (BC) [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 P2-10-07.
Abstract P2-11-01: Effects of radiotherapy on breast cancer outcomes among stage I, low-Recurrence risk, hormone-Sensitive breast cancer: Pooled analysis of individual data from phase III trials
Authors: Jayasekera JC , Schechter C , Jagsi R , White J , Chapman J-AW , Whelan T , Sparano JA , Anderson SJ , Fyles A , Sauerbrei W , Zellars RC , Li Y , Song J , Julian T , Berry D , Feuer EJ , Luta G , Mandelblatt JS 
Published: February 2018

Abstract
Purpose: Radiotherapy after breast conservation has become the standard of care. Prior meta-analyses of radiotherapy benefits pre-dated availability of gene expression profiling (GEP) to assess recurrence risk and/or did not include all relevant outcomes. This analysis utilized GEP information with individual-level data from seven clinical trials to evaluate the impact of omitting radiotherapy on recurrence and mortality.
Patients and Methods: The pooled observational data included women who had undergone breast conservation surgery for stage I, ER+ and/or PR+/HER2- cancers with clinicopathologically estimated 21-Gene Recurrence Scores (RS) of ≤ 18, and did not receive chemotherapy (n= 1,684). The primary endpoint was 10-year invasive or DCIS recurrence free-interval (IRFI-DCIS), including breast cancer death and was estimated using adjusted Cox models. Secondary outcomes were breast-cancer specific and all-cause survival. Covariates included for all models were age, tumor size, grade, hormonal status, type of hormonal therapy, risk score, and trial.
Results: Ten-year IRFI-DCIS was high (96.6% with radiotherapy vs. 91.6% without), for an absolute difference of 5%. Omission of radiotherapy (vs. radiotherapy) was associated with an overall adjusted hazard ratio of 2.6 (95% confidence interval 1.5-4.5) for any first event. There was only a significant increase in risk of loco-regional; not, distant recurrence, breast cancer–specific or overall survival. The effect of radiotherapy varied across subgroups, with lower first event rates for those with estimated RS of &lt;11 (vs. 11-18), and women ages 60+ (vs. &lt;60 years).
Conclusion: Omission of radiotherapy in hormone-sensitive patients with low recurrence risk may lead to a modest absolute increase in loco-regional recurrence, but does not appear to increase risk of distant recurrence or death.
Citation Format: Jayasekera JC, Schechter C, Jagsi R, White J, Chapman J-AW, Whelan T, Sparano JA, Anderson SJ, Fyles A, Sauerbrei W, Zellars RC, Li Y, Song J, Julian T, Berry D, Feuer EJ, Luta G, Mandelblatt JS. Effects of radiotherapy on breast cancer outcomes among stage I, low-Recurrence risk, hormone-Sensitive breast cancer: Pooled analysis of individual data from phase III trials [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 P2-11-01.
Abstract P2-12-09: histopathologic correlation of residual tumor in breast with residual mammographic microcalcification and magnetic resonance imaging after neoadjuvant systemic treatment
Authors: Um E 
Published: February 2018

Abstract
Introduction. In patients with advanced breast cancer, neoadjuvant chemo-therapy is performed to increase breast conserving surgery. Although MRI is known to be accurate in predicting residual cancer after treatment, if calcification remains, the issue of whether to perform surgery based on the residual tumor prediction range in mammography and MRI has not yet been solved. The objective of this study was to estimate the accuracy of residual mammographic (MMG) microcalcification and enhancing lesion in magnetic resonance imaging (MRI) in predicting residual tumor after neoadjuvant systemic treatment (NST).
Method. This is a single-center, retrospective study. We included patients with breast cancer who underwent NST and have microcalcifications in the post NST mammogram and had the surgery from January 2, 2013 to December 30, 2014. All the patients had post NST imaging exams of MMG and MRI. Final pathologic tumor size with histopathology and biomarker status was obtained after surgery. Analysis of correlation between image findings and pathology was evaluated.
Result. Of 151 patients that were included in this study, 125 patients (82.8%) had residual invasive tumor and 26 patients (17.2%) had pathologic complete response. In overall, MRI correlated better than MMG in predicting tumor size (intraclass correlation coefficient [ICC] = 0.769 vs 0.651), but for HR+/HER2- subtype, MMG had higher correlation than MRI (ICC = 0.747 vs 0.575). Specially in HR- subtype, MRI had strong correlation with pathology (ICC for HR-/HER2+ = 0.939 and TN = 0.75), while MMG tend to overestimate the tumor size (ICC for HR-/HER2+ = 0.543 and TN = 0.479).
Discussion. Overall post-NST residual microcalcifications on MMG have lower correlation with residual tumor size than MRI. In other than HR+/HER2- subtype, the extent of calcifications on pre-OP evaluation may not be accurate in evaluating the residual extent of the tumor after NST.
Citation Format: Um E. histopathologic correlation of residual tumor in breast with residual mammographic microcalcification and magnetic resonance imaging after neoadjuvant systemic treatment [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 P2-12-09.
Abstract P2-12-11: Does conservative surgery treatment for locally advanced breast cancer safe after neoadjuvant treatment?
Authors: Boufelli G , Mota BS , Franca FC , Doria MT , Maesaka JY , Ricci MD , Piato JRM , Rocha FBC , Giribela AHG , Gonçalves R , Masili-Oku S , Mano MS , Chala LF , Thompson BM , Baracat EC , Filassi JR 
Published: February 2018

Abstract
BACKGROUND:
The aim of this study was to assess the oncological efficacy of breast conserving surgery (BCS) after neoadjuvant chemotherapy in patients with local advanced breast cancer.
PATIENTS AND METHODS:
A retrospective cohort study was conducted with locally advanced breast cancer invasive (Stage IIb to III) treated at ICESP, an oncologic referral center between 2008 and 2016. Endpoints were disease free survival (DFS), local disease free survival (LDFS) and overall survival (OS). Multivariable analyses were performed using Cox proportional hazards models.
RESULTS:
530 patients were included, 26% (138) were stage IIB, 41.9% (222) IIIA, 29.6% (157) IIIB and 2.5% (13) IIIA. 88.8% (470) were invasive ductal carcinoma. The mean age was 51.5(23-95). 95.5% and 4.5% were submitted Neoadjuvant Chemotherapy and Hormone therapy, respectively. The BCS were performed in 24.5% (130) patients versus 75.5% (400) of mastectomies. The mean follow up was 36.4(0.16-80.2) months. There were no differences in local disease free-survival 59 (95%CI 58-61) versus 60 (95%CI 57-60); p=0.4 and overall survival 56.2 (95%CI 52-60) versus 59.3(95%CI 53-65); p= 0.24 for mastectomy and BCS. The disease free survival was lower at mastectomy group 51.4 (95%CI 49-53) versus 56,8 (95%CI 53-59); p=0.01. Logistic regression models were significant only for cancer stage both patterns, although the results were better for masses, particularly when kinetic assessments were included (LR 12.8; p = 0.005)
CONCLUSION:
In our population, the BCS does not affect the overall and local disease-free survival rates, which seems to be safe to perform in patients who desire to conserve the breast after neoadjuvant treatment.
Citation Format: Boufelli G, Mota BS, Franca FC, Doria MT, Maesaka JY, Ricci MD, Piato JRM, Rocha FBC, Giribela AHG, Gonçalves R, Masili-Oku S, Mano MS, Chala LF, Thompson BM, Baracat EC, Filassi JR. Does conservative surgery treatment for locally advanced breast cancer safe after neoadjuvant treatment? [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 P2-12-11.
Abstract P3-03-02: ER dependent breast cancer phenotype in BRCA
1/2 carriers
Authors: Peretz TY , Zick A , Luna K , Grinshpun A , Sonneblick A , Iziely B , Hamburger TG , Cohen S , Granit AM , Dvir M , Rosenberg S 
Published: February 2018

Abstract
Background: Hereditary breast cancer (HBC) comprises more than 10% of all breast cancers (BC). Mutations in the BRCA1/2 genes are found in approximately half of HBC patients. The majority of BRCA1 associated tumors are ER, PR and HER2 negative with basal-like expression pattern. BRCA2 associated tumors are mostly ER positive (ER+). In the present study we aim to further explore clinical and molecular characteristics of BRCA associated BC in 3 different cohorts.
Methods: Three different BC databases (DB) were evaluated: (i) Hadassah oncogenetic BC DB (n=4429); (ii) Nick-Zainal et al. BC DB (n=560), and (iii) METABRIC BC DB (n= 1980). We tested for differences in age at diagnosis between BRCA positive (BRCA+) and BRCA negative (BRCA-) patients with either ER+ or ER negative (ER-) tumors. Point mutation analysis was performed in cohorts ii & iii and mRNA differential expression (DEA) and pathway analysis were performed in cohort iii, using Ingenuity Pathway Analysis (IPA).
Results: Age (years) at diagnosis for cohorts i, ii,&iii respectively, for ER+ PT:BRCA1-44, NA, 60; for BRCA2-49, 48, 64; for BN – 53, 56, 63. For ER-: BRCA1-42, 42, 47; for BRCA2-48, 52, 49; for BN-49, 54, 56. For cohorts ii&iii, higher frequencies of TP53 and PIK3Ca mutations were found among BRCA+&BRCA-, respectively. DEA was performed between BRCA+&BRCA- in ER- tumors: the major activated pathways involved cancer related processes and were highly significant (up to p=1e-7.5, FDR=1e-4.5). Surprisingly - the most significant pathway was Estrogen Mediated S-phase Entry and the most activated upstream regulator was ERBB2. Similar evaluation in ER+ showed mostly differences in immune related pathways (differences not statistically significant).
Conclusions: Younger age at presentation was observed in BRCA1 vs. BRCA2 patients. No age differences were observed between ER+&ER- PT in cohort i&ii, in cohort iii ER- BRCA+ Patients were younger than ER+ BRCA+ (similar age as ER+ BRCA-). BRCA+ show different mutational profile than BRCA-. ER+ BRCA+ and BRCA- show similar genomic characteristics. By contrast, for ER- BRCA+ differs markedly from BRCA-. This might imply that BRCA+ associated tumors consist of two genomically distinct subtypes: (i) ER-, and (ii) ER+. The results may shed light on possible somatic factors which affect the development of BC BRCA+ and carry preventive and therapeutic implications.
Citation Format: Peretz TY, Zick A, Luna K, Grinshpun A, Sonneblick A, Iziely B, Hamburger TG, Cohen S, Granit AM, Dvir M, Rosenberg S. ER dependent breast cancer phenotype in BRCA 1/2 carriers [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 P3-03-02.
Abstract P3-05-15: PD-1 expression and its correlation with tumour infiltrating lymphocytes and Ki67 in patients with breast cancer
Authors: Vos H , Lambein K , Floris G , Nevelsteen I , Smeets A 
Published: February 2018

Abstract
Introduction: Immunotherapy targeting the programmed death-1 (PD-1) checkpoint has resulted in good outcomes in patients with melanoma, non-small cell lung cancer and head and neck cancer. Recent data have showed that patients with ER/PR negative breast cancer might benefit from immunotherapy as well. We investigated PD-1 expression on tumour infiltrating lymphocytes (TILs), the presence of TILs and Ki67. Furthermore, the association of PD-1, TILs and Ki67 with time to metastasis was statistically determined.
Methods: Resection specimens of 284 patients with an ER/PR negative invasive ductal adenocarcinoma of at least 2 cm were analysed. Haematoxylin-eosin staining was performed to determine the percentage of TILs. Subsequently these percentages were divided into three groups: less than 10%, 10%-30% and more than 30% which matches with respectively 30%, 50% and 20% of the patients. PD-1 expression on the TILs of 116 patients and Ki67 expression of 185 patients were assessed using immunohistochemistry.
Results: An increase in the fraction of TILs was significantly associated with a lower risk of metastasis (hazard ratio [HR] = 0.7, 95% CI = 0.6-0.9). PD-1 expression on TILs was observed in 97% of the patients. Three patients had no expression of PD-1, this lack of PD-1 expression significantly increased the risk of metastasis (HR = 5.541, 95% CI = 1.2-25.0). No association could be noted between PD-1 expression and the amount of TILs or Ki67 (p-values of respectively 0.272 and 0.637). Similarly, no association could be noted between Ki67 and the amount of TILs (p-value = 0.1954)
Conclusion: PD-1 was expressed on TILs in patients with breast cancer. Surprisingly, no correlation was found between PD-1 expression and TILs or Ki67. However, an increased amount of TILs was significantly associated with a lower risk of metastasis.
Citation Format: Vos H, Lambein K, Floris G, Nevelsteen I, Smeets A. PD-1 expression and its correlation with tumour infiltrating lymphocytes and Ki67 in patients with 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 P3-05-15.