bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between tumor markers and histopathologic and demographic features of patients with breast cancer and their distinctive role in metastatic process.
Authors: Aydin Kubra , Uygur Meliha Melin , Odabas Hatice , Korkmaz Taner , Yasar Nurgul , Dinc Nur , Aydin Dincer , Yuksel Sinemis , Balvan Ozlem , Guven Aslihan , Mayadagi Alparslan , Aliustaoglu Mehmet , Gumus Mahmut 
Published: March 2020

e11540 Background: Tumor marker monitoring is generally performed by the physicians, although in many guidelines, it has not been recommended for breast cancer. In this study, we aimed to research the role of CEA and CA15.3 levels in metastatic process. Methods: In between years 2000 January and 2011 August, the documents of 482 female patients followed by breast cancer diagnosis in Medical Oncology and Radiation Oncology clinics of Kartal Dr. Lutfu Kirdar Education and Research Hospital, were evaluated retrospectively. Results: To determine the role of CEA and CA15.3 levels in evaluation of metastatic process, ROC analysis was performed and its cut-off values were 1.3 ng/ml and 14 U/ml, respectively. Sensitivities of CA15.3 and CEA levels were detected as 83.33% and 87.50%; specificities were 40.80% and 41.14%, respectively. Evaluation of the relationship between CEA and CA15.3 levels and the status of hormone receptors by ROC analysis showed the cut-off values as 26 U/ml and 1,6 ng/ml, respectively. In determination of endocrine sensitivity, the sensitivities of tumor markers elevation were 88.17% and 54.12%, respectively. Their specificities were 26.92% and 73.08%. CEA level elevation in hormone sensitive patients was statistically significant (p: 0.007). When sensitivity and specificity of CA15.3 and CEA levels on detection of c-erbB2 positivity were evaluated by ROC analysis, cut-off values were determined as 17 U/ml and 1,7 ng/ml. Sensitivities of these distinctive cut-off values were found as 58.8% and 71.15% and specificities were 60% and 51.67% (p: 0.017). When the relation between CA15.3 and CEA levels and node involvement was evaluated by ROC analysis, cut-off values were respectively 16 U/ml and 0.9 ng/ml. Their sensitivities were 53.45% and 87.93% and specificities were 55.56% and 51.67%, respectively. Conclusions: The levels of tumor markers have been suggested to have a significant role in prognosis of the disease with respecttothe correlation between different histopathological and clinical features and tumor markers. Randomised controlled prospective studies planned and performed in this issue may clarify this uncertainity.
Biologic subtypes and first relapse pattern in curative surgery performed breast cancer patients: Study of Anatolian Society of Medical Oncology.
Authors: Kaplan Muhammet Ali , Yalçintas Arslan Ülkü , Isikdogan Abdurrahman , Oksuzoglu Berna , Inanc Mevlude , Akman Tulay , Inal Ali , Cankir Havva Yesil , Kucukoner Mehmet , Budakoglu Burcin , Ozkan Metin , Yilmaz Ugur , Baykara Meltem , Yazilitas Dogan , Ersoy Ugur , Bilici Mehmet , Cubukcu Erdem , Yazici Ozan , Suner Ali , Demirci Umut 
Published: March 2020

e11559 Background: Relapse is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in patients with curative surgery performed breast cancer. Methods: We retrospectively evaluated clinical data from 1126 breast cancer patients with relapses after their curative surgery between 1998 and 2012 from referral centers of Turkey. Study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression.Patients were divided into four biological subtypes according to IHC: triple negative (ER negative, PR negative, and HER2 negative), HER2 overexpressing (ER negative, PR negative, and HER2 positive), luminal B (ER and/or PR positive, HER2 positive), and luminal A (ER and/or PR positive, HER2 negative). Results: The proportion of patients with luminal A, Luminal B, HER2-overexpressing, and triple negative breast cancer was 42.0% (n=473), 23.0% (n=259), 13.3% (n=150), and 21,7% (n=244), respectively. Median time to relapse was 26.6 months. 22.5% of the patients (n=253) had multiple relapse sites. The incidence of first distant recurrence site was significantly different among the subtypes. Liver (31.8% vs. 22.4%, p=0.008), bone (42.2% vs 37.0%, p<0.001), and lung metastases (30.9% vs. 22.2%, p=0.019) were increased in HER2 overexpressing, luminal A and triple negative group as first relapse site compared with other groups, respectively. Brain metastasis was increased in HER2 overexpressing and triple negative groups (17.7%), compared with Luminal A and B groups (8.0%, p<0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.
Prognostic value of Ki67LI in HER2-negative luminal (HNL) early breast cancer (EBC): A 14-year single institution experience with long follow-up.
Authors: Ferro Antonella , Russo Lucianna , Eccher Claudio , Caldara Alessia , Triolo Renza , Barbareschi Mattia , Cuorvo Lucia Veronica , DiPasquale MariaChiara , Pellegrini Marco , Bernardi Daniela , Cantaloni Chiara , Maines Francesca , Galligioni Enzo 
Published: March 2020

e11569 Background: Several studies have emphasized the biologic and prognostic value of Ki67LI and its role in routine practice, particularly to define prognostic subgroups of luminal tumors. Methods: Ki67LI was identified by immunohistochemical staining in 3760 consecutive EBC pts followed from 1995 to 2008. Median age was 61 y. The relationship with clinic-pathological parameters and the prognostic significance of KI67LI were investigated in all EBCs and in 2380 HER2 negative luminal (HNL) cases, stratified on homogeneous grading (594 G1, 1282 G2, 504 G3). Results: Median Ki67LI values were 22% in all cases, 20% in HNL and 10%, 20% and 35% in HNL- G1,G2,G3 respectively. Ki67LI > 22% (1873 pts) was significantly (p<0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER /PR, positive HER-2, triple negative subtypes. Local and Distant Relapses were 138 (7.3%) and 355 (18.9%) in < or > 22% Ki67LI respectively. Median time to first event was 31.7 ms in > 22% vs 50.1 ms in < 22% Ki67. At a median f-up of 77 months EFS and OS were 91.9 and 92.1% in < 22% vs 78.9% and 81% in > 22% Ki67 respectively (p <0.001). The prognosis was consistently worse for > 22% Ki 67 in all clinical-pathological subsets, except in negative ER group. In multivariate analysis, KI67 maintained an independent prognostic significance for DFS and OS. In HNL, EFS and OS were 93.7 and 92% in < 20% vs 81.7 and 83.3% in >20% Ki67(p <0.001). Using median ki67LI value for different homogenous HNL-GG as cutoffs, we stratified these populations in low and high risk. Results are summarized in the Table. Conclusions: Our study confirms the prognostic value of Ki67LI in EBC,as well as other clinical pathological characteristics such as age, tumor size, histological type, nodal and hormonal receptors status. Cutoffs are different into HNL.They could identify different biological entities in each grading group providing additional prognostic information in outcome prediction. [Table: see text]
Health care utilization and costs among HER2-negative, HR-positive, elderly women with metastatic breast cancer in the United States.
Authors: Pawaskar Manjiri , Karve Sudeep , Dalvi Tapashi , Davis Keith L. , Deeter Robert 
Published: March 2020

e11571 Background: Limited data exist on the cost burden of elderly women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (MBC). We therefore assessed this cost burden in a retrospective analysis of the Surveillance, Epidemiology and End Results-Medicare database (2000-2009). Methods: Women aged ≥65 years diagnosed with MBC or early-stage breast cancer who progressed to MBC with HER2 negative, HR positive status were selected. MBC diagnosis date or date of progression to MBC was the index date. The study included non-HMO patients who had continuous Medicare (Part A and B) enrollment for ≥12 months before index date to death or end of database (2009). All-cause and MBC-related (claims for MBC diagnoses or MBC-related treatments) healthcare utilization and costs were assessed descriptively and then annualized based on follow-up duration. Results: In total, 13,170 women met the inclusion criteria (mean [SD] age 76.7 [7.0] years, 88% white, 77% both ER and PR positive). Mean [SD] post-index follow-up duration was 38.5 [28.1] months. On average, patients had 2.5 hospitalizations (mean length-of-stay: 16 days) and 3 emergency department (ED) visits. Mean [SD] annual all-cause costs (in 2011 $) per patient were $34,264 [$33,429], half of which $16,397 [$18,284] were attributable to MBC. Hospitalizations, hospital outpatient visits, and physician office visits accounted for over three-quarters of total all-cause costs (mean [SD]: $13,804 [$22,589] $4,171 [$6,509], and $8,676 [$11,065], respectively) and 75% of MBC-related costs (mean [SD]: $4,449 [$9,436], $2,844 [$5,383], and $5,799 [$9,945], respectively). Within MBC-related costs, mean [SD] annual costs of chemotherapy, radiation, and hormone therapy were $1,442 [$4,095], $1,872 [$4,086], and $579 [$1,197], respectively. Conclusions: Our findings indicate that HR positive, HER2 negative elderly women with MBC have a substantial economic burden on the Medicare system with primary costs drivers being inpatient, hospital outpatient and physician office visit costs.
Metastatic breast cancer subtypes and central nervous system metastases.
Authors: Aversa Caterina , Geuna Elena , Martinello Rossella , Milani Andrea , Rossi Valentina , Redana Stefania , Valabrega Giorgio , Aglietta Massimo , Montemurro Filippo 
Published: March 2020

e11581 Background: The relapse pattern, survival and response to therapy are known to be different between breast cancer (BC) subtypes defined by combining hormone-receptor (HR) and HER2 status. Our aim was to study incidence and predictors of central nervous system metastases (CNS-M) and the outcome after CNS-M according to tumor subtype. Methods: 488 patients (pts) treated with at least one line of chemotherapy for metastatic BC were retrospectively evaluated. According to the combination of HR and HER2 status, tumors were grouped in: Luminal (Lum): HR+/HER2-, Luminal/HER2+ (Lum/HER2+): HR+/HER2+, pure HER2 positive (pHER2+): HR-/HER2+, and triple negative (TN): HR-/HER2-. All HER2+ patients received treatment with Lapatinib or Trastuzumab in addition to chemotherapy for metastatic disease. Median follow up was 34 months. Results: 133 pts (27%) developed CNS-M, with a median time to CNS progression of 43 months. The rate of CNS-M by subtype was: Lum 18%, Lum/HER2+ 37%, pHER2+ 49%, TN 25% (p <0.001). Multivariate analysis confirmed that, compared with Lum tumors, Lum/HER2+ ( HR 2.556, p<0.001), pHER2+ (HR 4.444, p<0.001) and TN (2.249, p=0.011) subtypes were at higher risk of CNS-M. Median overall survival (OS) CNS-M was 8.8 months in the whole series (IC 95% 6.6-11.0). Median OS in months by subtype was: Lum 9, Lum/HER2+ 18, pHER2+ 7, TN 7 (p<0.001). Multivariate analysis revealed that belonging to the Lum/HER2+ subtype (HR 0.528 compared with the Lum subtype, p<0.001) and having isolated CNS (HR 0.398, compared with CNS-M plus systemic progression, p<0.001) predicted significantly reduced risk of death. Conclusions: Among pts with a known increased risk of brain metastases, the Lum/HER2+ subtype appears associated with the longest OS after CNS-M, probably due to different biology and better extracranial disease control by chemotherapy, hormonal therapy and target agents. These results suggest that these patients may benefit from a more aggressive treatment of CNS-M and, possibly, from the screening for asymptomatic CNS lesions.
Assessment of treatment response with fulvestrant (F) 500 mg in standard clinical practice through a retrospective study: NCT01509625.
Authors: Blancas Isabel , Ruiz-Borrego Manuel , Salvador Bofill Javier , Conde Veronica , Carabantes Francisco , Bayo Juan L. , Jaen Ana , Perez Ruiz Elisabeth , Santiago María del Mar , Baena Jose Manuel , Villareal Vicente , Martinez Guisado Antonia , de la Cruz Merino Luis , Rodriguez Pedro , Reyes Evelyn , Cajal Rosana , Delgado Mayte , Gonzalez Flores Encarnacion , Inoriza Angel , Sanchez Rovira Pedro 
Published: March 2020

e11583 Background: The CONFIRM study showed greater efficacy of F500 as compared to F250.Based on these results a dosage change was authorized in Spain.The aim of this study is to describe the efficacy of F500 (progression free survival(PFS) and clinical benefit rate(CBR) in Spanish patients (P) with estrogen receptor (ER+) Metastatic Breast Cancer (MBC) through a retrospective data collection. Methods: After written informed consent, data collection was recorded from clinical records of P who previously had progressed on hormonal treatment and who received at any time F 500 from 1st January 2010 to 31st October 2011. Results: 102 P in 14 centers were included in the study, 93 P were evaluable.Median age was 65 (39-88). Histology: 80.6% ductal ;15% lobulillar. Hormonal receptors: ER+/ PgR+ 77.4%; ER+/PgR- 21.6 %. HER2 status was documented in 80P, 15% of them were HER2+. 45.4% were Ki67 +. Mean from diagnosis to metastatic disease:3.7 years, 19.3% of P had de novo metastatic disease. 21.5% of P had visceral metastases.82.8% of P had good PS (0-1) when F started.F received as 1st line in 7.5%, as 2nd line in 52.7% and 3rdor more in 39.8% of the P. Average cycles administered: 10(3-48). With a median follow up of 16 months (m) since F treatment (1.4-34.4), median PFS was 10.6 m[8.3-13.0]. CBR was 59.1% (12.9%CR, 12.9 PR and 33.3% SD≥ 24 weeks). Median PFS in P with or without CB was 23.3 m and 5.6 m respectively. Median PFS in P with F in 1 st line was 10.3 m, 11.6 m in 2nd line and 9 m in 3rd line or more. No significant differences in CBR were observed between P with or without visceral metastases (58.9 vs 60%). There was a trend in the CBR between HER –ve and +ve groups (64.7% vs 33.3% p = 0.0565). 1-year survival rate was 86% (77.3-92.3). Median Overall Survival was not calculated because only 20 P had died when data were analyzed. More frequent toxicities were: local injection site pain (11.8%), hot flushes (11.8%) and gastrointestinal disorders (8.6%). Conclusions: F500 in real life setting showed a PFS of 10.6 m and got CB in 2/3 of P with a good toxicity profile, in line with phase III trials. In P who achieve a CB the median PFS was almost two years. P with visceral metastases may benefit from F same as those with non visceral involvement.
Magnetic resonance imaging with concentric shrinkage as a prognostic factor in patients with luminal breast cancer during neoadjuvant chemotherapy.
Authors: Fukada Ippei , Takahashi Shunji , Tanabe Masahiko , Araki Kazuhiro , Kobayashi Takayuki , Kobayashi Kokoro , Gomi Naoya , Horii Rie , Akiyama Futoshi , Iwase Takuji , Ito Yoshinori 
Published: March 2020

e11587 Background: The important characteristics of breast cancer is its tumor heterogeneity and response to neoadjuvant chemotherapy (NAC). We analyzed the patterns of tumor shrinkage as a prognostic indicator after NAC for luminal breast cancer. Methods and Results. Methods: Of 854 patients who had received NAC in the single institute between January 2000 and December 2009, 265 luminal breast cancerwere retrospevively examined. Luminal breast cancer was defined as ER and/or PgR positive in more than 10% of cancer cells and HER2 negative (IHC 0, 1+ or FISH <2.0). Before and after NAC, the primary lesion was evaluated by enhanced MRI in 235 patients. Results: The median follow-up period was 51.4 months. 38 patients(16.2%) experienced recurrence after a median DFI of 49.1 months. The median age was 50 and 232 patients received anthracycline containing chemotherapy and 179 patients received taxane. 120 out of 235 patients exhibited concentric shrinkage pattern. Multivariate analysis for DFS identified Age(49>), strong ER/PgR positivity and concentric shrinkage as significantly favorable, and lymph node metastases as significantly unfavorable prognostic factors. Multivariate analysis for OS identified tumor size as significantly unfavorable prognostic factors(p=0.012). Conclusions: the tumor shrinkage pattern could be an important prognostic factor for luminal breast cancer and this suggests that a concentric shrinkage pattern of response may be infrequently associated with chemotherapy-resistant residual cancer cells.
The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer.
Authors: Inoue Hiroaki , Hirano Akira , Ogura Kaoru , Hattori Akinori , Kamimura Mari , Okubo Fumie , Kinoshita Jun , Kimura Kiyomi , Shimizu Tadao 
Published: March 2020

e11604 Background: Adjuvant therapy with aromatase inhibitors (AI) is associated with increased bone loss in postmenopausal women. We assessed changes in bone mineral density (BMD) from baseline to 60 months of treatment in patients receiving anastrozole (ANA) as initial adjuvant therapy with/without oral bisphosphonates (Bis). Methods: Postmenopausal women with endocrine responsive breast cancer receiving ANA as adjuvant therapy at our hospital since 2004 were enrolled in this study. BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24, 36, 48 and 60 months. Oral Bis (risedronate or alendronate) treatment was initiated when patients were diagnosed as having osteoporosis with a T-score of -2.5 or lower. Results: Fifty-seven patients were enrolled in the study between 2004 and 2011. Patients’ median age was 65 years (range 50~85) and the median follow-up period was 46.3 months (9.6~83.8). Thirty-five patients were administered Bis (risedronate in 27 patients, alendronate in 8 patients). Within 6 months of hormone therapy, BMD decreased by 0.3% from baseline at the lumbar spine and BMD decreased by 1.2% at the femoral neck. However, BMD increased by 2.8% at the lumbar spine and BMD decreased 0.5% at the femoral neck for 60 months of treatment. In patients treated with upfront Bis (n=24), 4.9% BMD increase from baseline was noted at the lumbar spine whereas in those without Bis (n=20) BMD decreased by 4.6% from baseline within 24 months (p=0.0002). Fractures were observed in 4 patients (7.0%), and 1 patient (1.8%) had fragility fracture. Conclusions: Oral Bis prevented ANA-induced bone loss, and upfront treatment of Bis significantly increased BMD at the lumber spine.
Mediation of HER2 expression-dependent antiproliferative and pro-apoptotic effect of pan-HER2-specific TKIs on breast cancer cells through STAT5 and JNK.
Authors: Gschwantler-Kaulich Daphne 
Published: March 2020

e11606 Background: HER-targeted tyrosine kinase inhibitors (TKIs) have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood. Methods: Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP and immunolabeling for active caspase 3, respectively. Results: All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines, irrespective of their sensitivity against the HER-TKIs. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively. Conclusions: We have shown that HER-TKIs exert a HER2 expression-dependent effect on proliferation and apoptosis in cancer cell lines in vitro, which is at least partially mediated by blockade of JNK and STAT5A/B. Despite slight differences in their specificity towards individual members of the HER family all three inhibitors had comparable antiproliferative and proapoptotic effects in vitro.
Prognosis of pT1a,bN0 breast cancer: Perception from the French oncology community—Results from the EURISTIC survey.
Authors: Spielmann Marc , Azria David , Classe Jean Marc , Dalenc Florence , Dromain Clarisse , Facchini Thomas , Goncalves Anthony , Liegeois Philippe , Namer Moise , Pivot Xavier B. , Pointreau Yoann , Vincent-Salomon Anne , Mahe Mercedeh 
Published: March 2020

e11607 Background: Although most early-stage breast tumors have a favourable outcome, some subgroups carry a higher recurrence risk. The objective of the EURISTIC Survey was to evaluate the perception French physicians have of the prognostic risk associated with the biopathological characteristics of tumors in pT1a,b N0 breast cancer. Methods: This 38 item postal survey was developed by an expert panel. 2,000 physicians involved in breast cancer treatment were contacted. Specialities involved were medical and radiation oncologists, surgeons, radiologists and pathologists. Results: The survey was conducted between September and December 2012. A total of 663 physicians responded (response rate = 33%). They stated treating an average of 50 breast cancer patients per month. 58% of physicians reported that tumour size was not considered a major parameter in this clinical setting. In the absence of an adjuvant treatment, the prognosis of T1a,bN0 carcinoma was perceived better if HR-positive rather than HER2-positive or triple-negative with a "positive" prognosis perception rated by 83%, 21% and 8% of physicians respectively. For pT1a,bN0 tumors, the criteria with the highest perceived prognostic risk were ranked as follows: HER2+ (29%), HR- (20%) elevated tumor grade (20%) and triple negative tumor (14%). The average size threshold for a "negative" prognostic rated tumor was 18 mm. This threshold was scaled up for HR-positive carcinoma (22 mm) and scaled down for HER2-positive (10mm) or triple negative carcinoma (7mm). Between 4 and 17 mm, there was a linear correlation between tumor size and perceived risk of recurrence with HER2-positive tumors always carrying a worse prognostic than HR-positive tumor (Table). Conclusions: French physicians have the perception that HER2-positivity and triple negative tumor biology strongly impact the prognosis of pT1a,b N0 carcinoma, independent of tumor size. [Table: see text]