bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial heterogeneity of MRI response to first-line hormonal therapy to predict progression-free survival in metastatic breast cancer.
Authors: Kosmin Michael , Makris Andreas , Sokhi Heminder , Thijssen Toon , Padhani Anwar R. 
Published: September 2018

e12544 Background: Whole-body magnetic resonance imaging (WB-MRI) can positively identify response to systemic therapy in metastatic breast cancer (MBC) by the analysis of water diffusivity, cellularity and cell variability. We adapted a novel methodology that captures patient-level, spatial response heterogeneity using the METastasis Response Assessment Diagnostic System (MET-RADS) using WB-MRI. This study evaluated whether spatial heterogeneity seen at the first response assessment is predictive of duration of treatment (i.e. progression-free survival, PFS) in patients on first line hormonal therapy for MBC. Methods: Patients on first line hormonal therapy for MBC had baseline and on-treatment response assessment WB-MRI scans. All patients had a primary breast mass in situ. Patients showing unequivocal disease progression at their first response assessment scans were excluded from further analysis. Criteria for response assessment utilised the methodology described by MET-RADS. A Likert five-point response assessment category (RAC) score (1 = response highly likely, 5 = progression highly likely) was applied to 14 anatomic regions (7 bone & 7 soft tissue). Two scores reflecting the dominant and next most common response per region were recorded, capturing inter- and intra-region response heterogeneity. A novel Response Heterogeneity Index (RHI) summarised the response heterogeneity at the patient level. RHI and depth of response (mean RAC score for all involved regions) and therapy duration were analysed. Results: Twenty-one patients with primary breast mass in situ were analysed. Patients with higher levels of response heterogeneity (defined as RHI > 5; n = 11) had significantly shorter PFS than those with RHI ≤5 (n = 10; median PFS: 11 vs 27 months; log rank test p = 0.011). The depth of response and PFS were unrelated (mean RAC ≤2.5 vs mean RAC > 2.5; median PFS: 21 vs 18 months; log rank test p = 0.46). There were no correlations between RHI score and mean RAC (r2= 0.007). Conclusions: A low spatial heterogeneity of response is predictive of improved PFS in patients receiving first line hormonal therapy for MBC.
A network meta-analysis of fulvestrant vs alternative first-line endocrine therapies for endocrine therapy-naive postmenopausal hormone receptor-positive advanced or metastatic breast cancer.
Authors: Telford Claire , Takyar Shweta , Joshi Parth , Ekman Mattias , Jones Nick 
Published: September 2018

e12545 Background: Fulvestrant (F) is a selective estrogen degrader for hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (LA/MBC). This network meta-analysis examined the efficacy of F (500 mg) vs alternative endocrine therapies (ETs) for first-line treatment of ET-naïve HR+ LA/MBC. Methods: Randomized controlled trials of first-line F, tamoxifen (Tam), anastrozole (A), exemestane (E), letrozole (L), and toremifene (T) for women (≥18 years) with HR+ LA/MBC and no prior ET were identified in a systematic review of MEDLINE, EMBASE, and Cochrane databases from inception to October 2016. Conference proceedings of the American Society of Clinical Oncology, European Society of Medical Oncology, and San Antonio Breast Cancer Symposium from 2013-2016 were hand searched. Trials of targeted combination therapies were excluded. Studies were checked for heterogeneity. A standard fixed-effect Bayesian network meta-analysis was conducted based on hazard ratios (HRs) and assuming proportional hazards for progression-free and overall survival (PFS/OS). Results: Seven eligible studies (1 Phase [Ph] 2, 5 Ph 3, 1 Ph 2/3) were identified. All had PFS data; five had OS data. Two trials compared F vs A; PFS data were available for both trials; sufficiently mature OS data for F were available from Ph 2 only. The proportional hazards assumption was met for PFS only.F had significantly improved PFS vs Tam (HR 0.57, 95% credibility interval [Crl] 0.44-0.73), A (HR 0.75, 95% Crl 0.62-0.91), E (HR 0.65, 95% Crl 0.47-0.91), and T (HR 0.53, 95% Crl 0.37-0.78). Numerically improved PFS was observed for F vs L (HR 0.81, 95% Crl 0.59-1.11). F had significantly improved OS vs Tam (HR 0.63, 95% Crl 0.40-0.98), A (HR 0.63, 95% Crl 0.42-0.94), and E (HR 0.56, 95% Crl 0.33-0.95). OS was numerically improved with F vs L (HR 0.66, 95% Crl 0.41-1.04). Conclusions: This analysis suggests improved PFS and OS for fulvestrant vs tamoxifen, anastrozole, exemestane, and letrozole, and PFS for fulvestrant vs toremifene. Further analysis should be conducted, using non-proportional hazard methods and more mature OS data, to confirm the OS results.
Analysis of real world patient compliance to everolimus-based therapy among post-menopausal women with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC).
Authors: Princic Nicole , Brouillette Matthew , Tang Derek , Lin Chinjune , Lanoue Brad , Barghout Victoria E. 
Published: September 2018

e12546 Background: Patient compliance, typically not captured in clinical trials, may have profound effects on treatment effectiveness. As there has been limited real-world data, the objective of this analysis was to examine compliance among HR+/HER2- mBC patients treated with everolimus as a second or later line of therapy in the US across age groups. Methods: In this retrospective cohort study, the MarketScan Commercial and Medicare Supplemental claims databases were used to select post-menopausal HR+/HER2- mBC women who initiated an everolimus-based line of therapy during 1/1/2013- 7/31/2016 study period. The first secondary malignancy diagnosis was the index date. Patients had 6 months of continuous enrollment in their health plans pre- and post- index, and were followed until the earliest of disenrollment, inpatient death, or end of study. Compliance was measured using medication possession ratio (MPR) during a second (2L), third (3L) and fourth (4L) line of therapy. MPR was defined as total days of supply of everolimus during the line of therapy divided by total duration of the line. Results: Of 645 eligible mBC patients treated with everolimus during follow-up, there were 239, 142, and 80 with a 2L, 3L, and 4L of therapy respectively. Mean age overall was 61.1 + 11.7 years and average duration of follow-up was 718.3 + 304.1 days. Across all patients the median MPR ranged during each line from 0.90-0.92 and the majority (93.8%-97.5%) were highly compliant to therapy (defined as MPR>80%). These results were consistent for patients aged <65 and 65+ years across a 2L, 3L, and 4L of therapy (Table). Conclusions: This study shows high compliance for everolimus-based therapy within a 2L, 3L, and 4L of therapy and this is consistent across ages. This real world data suggests good drug manageability and may provide valuable information for clinicians in selecting treatment for mBC. [Table: see text]
Metronomic chemotherapy (mCHT) in HER2-ve advanced breast cancer (ABC) patients (pts): What has changed over the time? Preliminary results of the VICTOR-6 study.
Authors: Cazzaniga Marina Elena , Casadei Virginia , Cagossi Katia , Cavanna Luigi , Cursano Maria Concetta , De Conciliis Enrico Maria Romano , Gebbia Vittorio , Melegari Elisabetta , Pellegrino Benedetta , Pinotti Graziella , Rossello Rosalba , Russo Salvatore , Ortu Salvatore , Saracchini Silvana , Stocchi Lucia , Toniolo Davide , Scognamiglio Giovanni , Valerio Maria Rosaria , Vandone Anna Maria , Clivio Luca ,   On Behalf of The VICTOR-6 Study Group
Published: September 2018

e12552 Background: mCHT is the minimum biologically effective dose of a chemotherapeutic agent, given at regular dosing regimen with no prolonged drug free interval, that leads to anti-tumor activity. Old regimens included Cyclophosphamide-Methotrexate (CM), whereas in the last years new regimens, such as Vinorelbine (VRL) and Capecitabine (CAPE)-based have been developed. Aim of this observational retrospective ongoing study is to describe the use of mCHT in ABC pts across 5 years and the clinical characteristics of the pts together with efficacy of old (CM-like) vs new (VRL/CAPE-based) metronomic regimens in terms of response and disease control. Methods: We retrospectively identified from clinical records those HER2-ve ABC pts who have received any kind of mCHT in the years 2011-2015, alone, or in combination with a non-metronomic drug. Standard statistical approaches were used for describing the sample characteristics. Logistic and non proportional hazard analysis were used to identify factors associated with response, and time to treatment failure and survival, respectively. This preliminary analysis focuses on Response Rate (RR) and Disease Control Rate (DCR). Results: From June 2011 to December 2015, 267 pts have been identified till now and 233 are fully evaluable. Median age at mCHT start was 67 years. 81% was HR+ and 33% had non-visceral metastatic disease. 22% of the pts received CM, 55% VRL-based and 23% mCAPE-based regimens. mCHT use increased over the time from 15.0% (2011) to 30% (2015). As 1st-line treatment, CM was administered in 27% of compared with more than 48% of patients receiving CAPE/VRL-based regimens. Overall Response Rate (ORR) was 28% and Disease Control Rate (DCR) was 79%. Median duration of mCHT was 6.2 months. New generation metronomic regimens produced higher ORR in comparison to old ones (32% vs 13.5%), with similar duration of treatment (6.4 vs 5.4 months, respectively). Conclusions: The use of mCHT in the treatment of HER2-ve ABC pts has deeply changed across the last 5 years, being new generation regimens used in earlier lines of treatment, producing interesting results in terms of objective response and disease control.
Correlation between vitamin D deficiency and metastatic breast carcinoma in a predominantly Hispanic population: A retrospective study.
Authors: Chitnis Saurabh Deepak , Popescu-Martinez Andrea M. 
Published: September 2018

e12553 Background: There have been numerous studies conducted linking Vitamin D deficiency to various cancers, including cancers of the breast. Studies associating Vitamin D deficiency and Breast cancer have shown mixed results in patients with no clear consensus. Recently published in vitro studies have shown that the active form of Vitamin D can inhibit the metastatic capability of breast cancer cell lines to bone. Based on this we aimed to elucidate whether there exists any correlation between Vitamin D deficiency at diagnosis and Metastatic breast cancer. Methods: Retrospective analysis of the EMR for women diagnosed with breast cancer and enrolled in Oncology database seen at NYMC-Metropolitan Hospital Center from 2010-2016 was done. Patients were grouped into either breast cancer with metastases or without metastases and their Vitamin D levels at diagnosis were reviewed. Patients with 25- Hydroxy Vitamin D levels measured within one year of diagnosis of breast cancer were included for the study. Study was planned from 2010-2016 specifically as Vitamin D levels for patients were not monitored as frequently prior to 2010. Results: From total of 102 patients who started follow up with Oncology clinic during the study time period, 2 were referred to our center for further management with diagnosis made prior to 2010 and were not included in the study. Out of the 100 patients considered, 58 patients had Vitamin D levels measured within a year of diagnosis of breast cancer and were included in the study. 70% of the population was Latino/Hispanic. The table represents the results of the study. Odds ratio for a patient with Vit D deficiency to develop metastatic breast cancer was 0.92 and relative risk was calculated to be 0.93. Conclusions: Based on above results, the outcome was similar in both groups. The odd’s ratio and the relative risk imply that there was no difference evidenced between both groups. These findings signify that there was no direct correlation between Metastatic breast cancer and Vitamin D deficiency at time of diagnosis in the population seen at our center. [Table: see text]
Routine clinical use of nab-paclitaxel for advanced / metastatic breast cancer in Germany: Final results of the prospective observational study NABUCCO.
Authors: Schroeder Jan , Potthoff Karin , Salat Christoph , Soeling Ulrike , Hansen Richard , Grebhardt Sina , Harde Johanna , Nusch Arnd , Marschner Norbert 
Published: September 2018

e12555 Background: nab-Paclitaxel ( nab-P) is approved for treatment of metastatic breast cancer (MBC) on a 3-week schedule based on results from the pivotal trial in which nab-P 260 mg/m2 showed a significant increase of progression-free survival compared with solvent-based paclitaxel. However, numerous studies suggest a weekly schedule might be a more effective and less toxic option (Gradishar 2011). Data beyond clinical trials is limited. Here we report on prospective non-interventional real-world effectiveness and safety data. Methods: The NABUCCO study was designed to collect data on routine treatment of 700 patients (pts) with MBC in Germany. Primary objective was time to progression (TTP), secondary objectives were overall response rate (ORR), overall survival (OS), dosage scheme of nab-P and safety parameters. Descriptive statistics were used to analyze the data. TTP and OS were calculated using the Kaplan-Meier method. Results: Between 4/2012 and 4/2015 697 evaluable pts at 128 sites had been enrolled. Baseline characteristics: Median age 62.3 years (range 29.2-89.3), age ≥ 70 years n = 200 (28.7%), ECOG PS ≥ 2 n = 49 (7.0%), visceral metastases n = 511 (73.3%). The majority of pts received nab-P as 1st-line (n = 280, 40.2%) or 2nd-line (n = 169, 24.2%) chemotherapy. 194 pts (27.8%) received a 3-week schedule, 491 pts (70.4%) a weekly schedule, 12 pts (1.7%) other. In the overall population, median TTP was 5.9 months (95% CI 5.6-6.4), median OS 15.5 months (95 % CI 14.2-17.3). For pts ≥ 70 years median TTP was 6.9 months (95 % CI 5.7-8.5), median OS 14.8 months (95 % CI 12.6-18.8). In the 3-week group median TTP was 5.7 months (95 % CI 5.2-6.9), median OS 15.1 months (95 % CI 12.3-17.5). In the weekly group median TTP was 6.0 months (95 % CI 5.6-6.5), median OS 16.3 months (95 % CI 14.4-18.5). 34.3% of pts developed adverse events grade 3/4 including leukopenia (7.9%), peripheral sensory neuropathy (4.3%) and infections (4.2%). Further subgroup analyses will be presented. Conclusions: nab-P is an effective and safe therapy for pts with MBC in a real world setting. It is as effective in older women as it is in their younger counterparts. A weekly schedule could be a reasonable option.
Metastases from lobular breast cancer as an unusual source of GI bleeding.
Authors: Clarke Emily , George James , Dean Andrew Peter 
Published: September 2018

e12557 Background: With the exception of malignant melanoma, metastases to the GI tract are rare, especially as a first presentation of malignancy. We report a series of patients with GI metastases from lobular breast carcinoma as an unusual source of symptomatic GI bleeding. Methods: We conducted an electronic database search to identify solid tumour patients (excluding melanoma) with metastases to the GI tract. We then analysed the database by tumour type. Results: 3 cases of proven metastasis to the GI tract were identified. All had lobular breast cancer metastases. The database contained 240 patients with breast cancer, identifying 63 with infiltrating lobular carcinoma, 2 with micropapillary and 175 with invasive ductal carcinoma The 1st case had had invasive ductal breast carcinoma 6 years previously and presented with fatigue and shortness of breath from anaemia. Colonoscopy revealed a polyp which was removed. Histopathology showed metastatic lobular breast carcinoma. Further investigation then confirmed an occult breast mass with identical pathology. The 2nd case presented with 18 months of abdominal pain, previous colonoscopy was normal. After onset of anaemia and 25kg weight loss, upper GI endoscopy showed a markedly thickened stomach with evidence of recent bleeding and biopsies confirmed metastatic lobular breast carcinoma. The 3rd case presented with abdominal pain, subsequent blood tests showing a raised CA125 with omental and ovarian masses. Surgical debulking showed metastatic lobular breast carcinoma, though no primary breast lesion was detectable with mammography, ultrasound and MRI. 3 years later, investigation of anaemia with colonoscopy showed a caecal polyp with histology confirming lobular breast carcinoma. Conclusions: Despite all common tumour types being represented in the database it is notable that all 3 cases with mucosal GI metastases had lobular breast cancer. Previous evidence suggests a long latent period from initial diagnosis of breast cancer to development of GI metastases however our report suggests it can occur earlier in the illness. Clinicians should consider this as a rare cause of GI bleeding and further research to understand the mechanism of mucosal metastasis in lobular breast cancer is needed.
Circulating miR-200c-3p as a marker of metastatic disease at diagnosis in breast cancer patients.
Authors: Navarro Manzano Esther , Luengo-Gil Gines , Garcia-Garre Elisa , Fernandez Perez Maria Piedad , Fernandez Sanchez Ana , Ivars Rubio Alejandra , de la Morena Pilar , Zafra Gema Marin , Garcia Martinez Elena , Martínez Alberto , Gonzalez-Billalabeitia Enrique , Ayala Francisco 
Published: September 2018

e12559 Background: MicroRNAs are involved in cancer biology through their role in regulation of protein expression. The miR-200 family plays a dual role in breast cancer (BC), both regulating epithelial to mesenchymal transition and promoting metastatic colonization. Plasma levels of miR-200 have been previously evaluated as prognostic factors in early and metastatic BC (MBC) but its role as a potential diagnostic marker is less well established. The aim of this study was to determine the potential diagnostic value of miR-200c-3p plasmatic levels in women with locally advanced and metastatic BC. Methods: We included 73 BC patients and 14 controls. Plasma samples were obtained at diagnosis, before treatment. RNA from plasma samples was extracted with NucleoSpin miRNA plasma (Macherey-Nagel). We analyzed expression levels of miR-200c-3p, which were relativized (2-ΔΔCT method) to miR-16. Non-parametric statistical tests were used to determine the association of miR-200c levels with clinical variables. Receiver-operating curves (ROC) were constructed and diagnostic ability evaluated. Kaplan-Meier curves and Cox models were used for survival analyses. Results: 73 BC patients were included: 36 locally advanced BC (LABC) and 37 MBC (7 recurrences and 30 MBC at initial diagnosis [MBCID]). Plasma miR-200c levels were significantly higher in MBC than in controls (p = 0.001) and in LABC (p = 0.001). We found differences neither for age nor for estrogen receptors, HER2, tumor subtype or histology. Overall and disease free survival did not differ by miR-200c levels in any of the groups. Among MBC patients, higher levels were observed in MBCID (p = 0.023). In the group of women with an initial diagnosis of BC (n = 65), high miR-200c levels (over 1st tertile) identified metastatic disease with a sensitivity of 90.0% (95%CI: 72.3-97.4%) and a specificity of 51.4% (95%CI: 34.3-68.3%); negative predictive value: 85.7%; positive predictive value: 61.4%; ROC AUC: 0.79. Conclusions: MiR-200c plasma levels are higher in BC patients with metastatic disease at diagnosis, and might be clinically useful to identify them. Further research on miR200c biological role in MBC and validation in larger populations with sequential samples are warranted.
Long-term responders to first-line bevacizumab-based therapy in metastatic breast cancer (MBC) patients: Results of the observational study LORENA.
Authors: Ramos Vazquez Manuel , Redondo Andres , Manso Luis , Gil Miquel , Garau Isabel , Perez-Carrion Ramon , Garcia-Garre Elisa , Rodriguez Cesar Augusto , Chacon Jose Ignacio , Lopez-Vivanco Guillermo 
Published: September 2018

e12563 Background: Randomized controlled trials in MBC patients evaluating bevacizumab as first-line treatment showed improvements in tumor response and progression-free survival (PFS) when added to chemotherapy. The aim of the LORENA study was to describe the clinical features, prognosis factors and safety of bevacizumab and chemotherapy treatment for MBC in routine practice. Methods: Observational, multicentre, ambispective study conducted in Spain. The study had a retrospective and a prospective phase. Data were obtained from March 2012 to October 2013. In the retrospective phase, eligible patients were women with metastatic or locally-advanced breast cancer, treated with bevacizumab as a first-line therapy, and progression-free survival for ≥ 12 months. In the prospective phase, patients were followed-up and assessed as per routine clinical practice. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. Results: 148 women from 38 centers were included. The mean age was 52 (±11) years. Bone, lung and liver were the most frequent metastasis sites. 138 patients were HER2-neg. on diagnosis (data unknown in 10 patients). The mean exposure to bevacizumab was 18 (±11) months. Most patients had objective response, 23% complete response, and 57% partial response. Median OS was 58.2 months and median PFS was 22.7 months. In multivariate analyses, OS was higher in patients with hormonal maintenance therapy (HMT) (p = 0.009; HR = 2.0) and in patients not treated with taxanes before the metastatic diagnosis (p < 0.0001; HR = 3.3); also, PFS was higher in patients with HMT (p = 0.002; HR = 1.8). No adverse events were observed other than those reported previously. Conclusions: Outcomes of OS and PFS suggest a benefit from bevacizumab maintained therapy. HMT was a PFS prognosis factor. HMT and not having been treated with taxanes before the metastatic diagnosis were two independent OS prognosis factors. Our results could provide further evidence supporting the use of bevacizumab as maintenance therapy for MBC patients.