bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary results from the international neoadjuvant melanoma consortium (INMC).
Authors: Menzies Alexander M. , Rozeman Elisa A. , Amaria Rodabe Navroze , Scolyer Richard A. , Tetzlaff Michael T. , Guminski Alexander , Davies Michael A. , Blank Christian U. , Wargo Jennifer Ann , Long Georgina V. 
Published: September 2018

9581 Background: For several cancers, response to neoadjuvant therapy (NAT) correlates with survival. Targeted and immune therapies achieve high response rates and durable survival in many patients with metastatic melanoma. Their role as NAT for stage III disease is not clear, and whether pathological response following NAT correlates with relapse-free (RFS) or overall survival (OS) in melanoma is unknown. Methods: Pooled clinical data from four ongoing NAT clinical trials (NCT02437279, NCT02231775, NCT02519322, NCT01972347) at three large melanoma centers participating in the INMC were examined. All trials included only patients with surgically resectable clinical stage III melanoma. NAT regimens included dabrafenib/trametinib (DT) and nivolumab (nivo) [single agent or in combination with ipilimumab (ipi/nivo)]. Patients who had undergone surgery prior to 27th January 2017 are included in this preliminary analysis. A pathological complete response (pCR) was defined as no viable melanoma cells in the resected specimen by hematoxylin and eosin evaluations by dedicated dermatopathologists. Results: 58 patients with clinical stage III melanoma (AJCCv7: 18 IIIB, 40 IIIC) have completed NAT and undergone surgery. 18 received neoadjuvant immunotherapy (IT): ipi/nivo x2 doses (N = 10), ipi/nivo x3 doses (N = 4) or nivo x4 doses (N = 4). 40 received neoadjuvant DT, either for two (N = 10) or three months (N = 30). Median age is 55 years (range 22-84). A pCR was observed in 50% of patients, 7 (39%) with IT and 22 (55%) with DT. Median follow-up is 10.2 months (95% CI 8.7-12.5). 14 (24%) patients have recurred (5 local, 8 distant, 1 both), 2 (11%) after IT, 12 (30%) after DT. For those with pCR, 14% have recurred, 0/7 (0%) after IT, 4/22 (18%) after DT. In contrast, for those without pCR, 34% have recurred, 2/11 (18%) after IT and 8/18 (44%) after DT. Two deaths have occurred, both after neoadjuvant TT. Early data suggests improved RFS in those with pCR. Conclusions: Neoadjuvant targeted and immunotherapy are active regimens in clinical stage III melanoma patients and are associated with high pCR rate. Preliminary data suggest pCR correlates with improved RFS. Updated data will be presented. Clinical trial information: NCT02437279, NCT02231775, NCT02519322, NCT01972347.
Outcomes of women with small, early-stage breast cancer in Manitoba from 2006-2011.
Authors: Zhang Hanbo , Lambert Pascal J , Lalani Aly-Khan A. , Fradette Katherine , Ahmed Rashid , Grenier Debjani , Pitz Marshall W. 
Published: September 2018

e12000 Background: The incidence of early-stage breast cancers has increased dramatically over the past decades. Treatment decisions for patients with stage I breast cancers are challenging, as there are significant variations in outcomes based on biologic subtypes. The objectives were to describe the distribution, molecular phenotypes, management, and long-term outcomes of women with early-stage breast cancer (T1mic/T1a/T1b N0 M0) in Manitoba from 2006-2011. Methods: Using the Manitoba Cancer Registry, we created a retrospective cohort of patients with primary breast cancer of ≤1.0 cm, diagnosed between 2006 and 2011. Data included patient demographics, tumour size, treatment modalities (surgery, radiotherapy, chemotherapy and trastuzumab), estrogen-receptor (ER) and progesterone-receptor (PR) status, and human epidermal growth factor receptor 2 (HER2) status. Node-positive cancers were excluded. Patient outcomes were evaluated, including rates of recurrence and overall survival using univariate and multivariable models. Kaplan-Meier curves and cumulative incidence curves were used to illustrate overall survival and recurrence, respectively. Results: Our study included 733 women. Mean age at diagnosis was 62. ER/PR positivity and HER2 positivity (HER2+) were 84% and 8.9%, respectively. Tumours were: T1mic in 14.0%, T1a in 19.1%, and T1b in 66.9%. 98% of patients had surgery, 60% had adjuvant radiation, 3.8% received trastuzumab, and 11% received chemotherapy. The adjusted hazard ratio (HR) for disease recurrence for patients with HER2+ versus HER2- status was 4.31 (95% CI, 2.18 to 8.50; P = 0.0001), and the HR for overall survival was 1.63 (95% CI, 0.72 to 3.67; P = 0.2402). The HR for disease recurrence in HER2+ patients receiving trastuzumab versus HER2+ patients who did not receive trastuzumab was 1.92 (95% CI, 0.61 to 5.97; P = 0.2621). Conclusions: HER2-positivity appears to be an important risk factor for recurrence in small, early-stage breast cancers. In our cohort, trastuzumab did not appear to reduce the risk of recurrence compared to those who did not receive it. This may be due to limited power and selection bias, in which patients with higher risk cancers received trastuzumab.
Outcome analysis of time from diagnosis to treatment in breast cancer patients treated at Edward Comprehensive Cancer Center, Huntington, West Virginia.
Authors: Raufi Ali Mehmood , Srivastava Roma , Jafri Hassaan , Gress Todd W. , Tirona Maria R. B. Tria 
Published: September 2018

e12005 Background: Cancer is the second leading cause of death in the USA. In multiple cohorts, adverse outcomes were observed among early breast cancer (BC) patients when time from diagnosis to treatment was 91 days or beyond. Multiple patient and system related factors can lead to delays in treatment initiation.This retrospective study was doneto determine the relationship between diagnosis and time to treatment on OS in BC patients treated at ECCC from 2006 to 2015. Methods: 721 charts of BC patients were retrospectively reviewed. Time interval between diagnosis and initial treatment modality was determined and set at 30 day increments, (0-30 days, 31 to 60 days, and 61 to 90 days and > than 90 days).Time from diagnosis to surgery (TTS) and surgery to adjuvant chemotherapy (TTC) was also calculated. Statistical analysis was done and Kaplan Meier curves were generated to assess the OS. Results: Median age at diagnosis of BC was 58 years. 82% of the BC patients were started on treatment (any modality) within 60 days of diagnosis whereas 35% within 30 days of diagnosis, respectively. Patients who received initial treatment (any modality) > 90 days since diagnosis, had the worst survival outcome (hazard ratio of 2.5, 95% CI 1.315 to 4.91, p value = 0.005). Patients treated after 60 days since diagnosis did show numerical trend towards the worse survival outcome but was not statistically significant. There was a declining trend in survival when TTC was more than 90 days . A similar trend was noted when TTS was > 60 days when adjusted for age, stage and hormone status. Conclusions: The relationship between TTS and BC outcome continues to be a modern health concern. The survival outcome in BC is affected by the length of the interval between diagnosis and treatment. All efforts should be directed towards minimizing them.
Treatment patterns and patient profiles for docetaxel-based adjuvant chemotherapy in early-stage breast cancer in China: A pooled analysis of four observational studies.
Authors: Xu Binghe , Shao Zhimin , Wang Shui , Jiang Zefei , Hu Xichun , Zhang Xiaohua , Li Xi Ru , Liu Jinping , Li Mengquan , Wang Shu 
Published: September 2018

e12017 Background: Adjuvant docetaxel-based chemotherapy is frequently used for operable breast cancer. This study investigated the patterns of use of docetaxel (T) in real-life clinical practice in China. Methods: This retrospective pooled analysis included female Chinese adults (≥18 years) with operable breast cancer treated with docetaxel-based adjuvant chemotherapy enrolled in the Asia-Pacific Breast Initiatives (APBI) I (2006-2008) and II (2009-2011) registries, and two Chinese observational studies; BC STATE (2011-2014) and BC Local Registry (2007-2010). Patients with metastatic disease were excluded. The primary endpoint was assessment of treatment patterns and patient profiles. Patient profiles for treatment regimen selection were investigated using regression analysis. Results: Data from 3020 patients were included. The most commonly used regimen was docetaxel/anthracycline combination (n=1421 [47.1%]; of whom 52.0% received T/epirubicin (E)/cyclophosphamide (C)), followed by docetaxel/other (n=705 [23.3%]; of whom 72.8% received TC), docetaxel/anthracycline sequential (n=447 [14.8%]; of whom 40.9% and 39.6% received 5-Fu/EC-T and EC-T), and ‘Other’ (n=447 [14.8%]; of whom 91.5% received T). Multivariate regression analysis revealed a significant association between selection of docetaxel/anthracycline combination and patient weight, menopausal status, and estrogen receptor and HER-2 status (Table). Conclusions: Data from real clinical practice show docetaxel/anthracycline combination is the most commonly used docetaxel-based adjuvant therapy for operable breast cancer in China; of which TEC is the most popular specific regimen. Several patient profile factors were significantly associated with the selection of docetaxel/anthracycline combination. [Table: see text]
Genomic profiling of metaplastic breast cancer: A single center experience.
Authors: Afkhami Michelle , Amanam Idoroenyi Usua , Aoun Patricia A. , Schmolze Dan , Yost Susan , Frankel Paul Henry , Nguyen Kim , Yu Wai (Kim) Wai , Luu Thehang H. , Yuan Yuan 
Published: September 2018

e12041 Background: Metaplastic breast cancer (MpBC) is a rare malignancy with aggressive clinical presentation and poor prognosis. The goal of this study is to characterize MpBC at the genomic level with targeted exome sequencing and correlate with clinical-pathological characteristics. Methods: We have Identified 23 patients (pts) with a diagnosis of MpBC through the COH Cancer Registry from 1995 to 2013. A next generation sequencing based panel (Onco48) was performed on 21 pts on using the Ion AmpliSeq™ Kit. Molecular testing for two pts was performed at FoundationOne®. Patient’s clinical-pathological characteristics were also captured (age, race, stage, chemotherapy, radiation therapy history, and 5-year relapse free survival (RFS)). Results: Of the 21 specimens tested with COH Onco48, 3 failed to yield results. Of the 20 pts included in the analysis, 1 pt did not have survival information available. The median age at time of diagnosis was 68 years (range 35-93). All of the tumors were TNBC. The subtypes of MpBC were: squamous (35%), spindle (30%), mixed squamous and spindle (15%) and chondroid (20%). A total of 70% of pts received (neo)adjuvant chemotherapy, and 65% received radiation therapy. Median follow-up of alive pts is 63 months. Median RFS and OS have not been reached for entire cohort with a lower 95% of PFS of 22.2 months. The most commonly mutated genes included TP53 (65%), PIK3CA (45%), PTEN (15%).In a univariate analysis, the association of p53, PTEN, PIK3CA mutations and breast cancer specific survival. RFS at 2 years was 33% (0.03-0.64) for those with PIK3CA mutations, and 100% for those without (p<0.01, log-rank). Overall survival was 56% at 2 years in pts with PIK3CA mutations (95% CI 0.23-0.88) compared with 100% in pts without PIK3CA mutations (p<0.02). There are no statistically significant association between P53, PTEN mutation and survival. Conclusions: PIK3CA mutation confers poor prognosis in this small cohort of patients with MpBC. A larger cohort of pts is needed to verify these findings.
Tumor-infiltrating lymphocytes as a prognostic factor in patients with stage I to III breast cancer.
Authors: Richardet Eduardo , Acosta Luciana Paola , Paradelo Martin , Pairola Martin , Di Tada Cecilia , Molina Matias , Dicalbo Luciano Salvador , Villavicencio Rocio Paola , Richardet Martin Eduardo 
Published: September 2018

e12042 Background: Current evidence makes reference to the potential role that tumor-infiltrating lymphocytes (TILs) as a prognostic factor in breast cancer and numerous types of tumors. Different studies have shown that the interaction with the immune response of the host is relevant to the response to chemotherapy. TILs are cell phenotype T CD3 +, which can, in turn, stratify in cytotoxic T lymphocytes (CD8), and regulatory T cells (CD4+ CD25+ FOXP3+).Our aim was to identify whether there was a relationship between TILs and SLE in patients with stage I to III breast cancer who have undergone chemotherapy adjuvant treatment. The secondary endpoint was to analyze the association between subtype infiltrating lymphocytes (CD4 and CD8) and SLE. Methods: Retrospective and analytical study in our institution IONC. Patients with stage I to III breast cancer was analized which had standard risk factors and required adjuvant treatment with chemotherapy. 87 patients completed with the selection criteria. The infiltration degree by H/E was evaluated and CD4 and CD8 by IHQ was marked. SLE was analyzed through the Kaplan-Meier method. Results: 87 samples were analyzed, in 46 patients (52,8 %) evidenced TILs and in 41 patients (47.12%) there were no TILs in their tumor samples. SLE was higher for those patients who had TILs with respect to those patients who did not have any TILs, 45.3 months as opposed to 30.85 months respectively (p: 0,038) and these differences were statistically different. In the TILi analysis, it could observed that 91% patients not revealed infiltrations in their tumor samples.When correlating CD4 and CD8 was carried out, 33% of the patients showed CD4 TILs in their tumor samples and 49.4% evidenced CD8 TILs. There were no SLE differences regarding the presence or the absence of CD4. The high number of CD8 was associated to a higher SLE; 39.06 months as opposed to 37.5 months, but these differences were not statistically different. Conclusions: We could conclude that patients who had showed TILs in their tumor samples had a higher SLE with respect to those who did not show any infiltration and this was statistically significant. There were no differences when samples were analyzed on the presence or absence of CD4 and CD8.
Detection of sentinel lymph node in patients with breast cancer: Application of 3D contrast enhanced ultrasound (3D-CEUS).
Authors: Lu Man , Hu Ziyue , Li Juan 
Published: September 2018

e12095 Background: Sentinel lymph node biopsy (SLNB) has became widely accepted as the gold standard procedure for axilla nodal staging .The main methods for the detection of Sentinel lymph nodes (SLNs) are dye-guided and g-probe-guided method.Currently, studies suggest that 2D - Contrast Enhanced Ultrasound(2D-CEUS) may be as good as the accepted techniques for SLNs detection .But the 2D-CEUS can not image the spatial relationship of the lymph vessel and SLNs.The objective of this study was to explore whether three-dimensional contrast enhanced ultrasonography (3D-CEUS) poses higher diagnostic value of in SLNs and lymphatic drainage routes of breast cancer than conventional ultrasonography (US) or 2D-CEUS.To our knowledge, this is the first study to investigate the value of 3D-CEUS in the preoperative diagnosis of SLN metastases in patients with early breast cancer. Methods: By using postoperative pathological results as gold standard, the accuracy and sensitivity of conventional US, 2D-CEUS and 3D-CEUS for SLNs were retrospectively tested in 73 patients with early breast cancer confirmed by pathology between December 2015 and June 2016, all patients underwent US, 2D-CEUS and 3D-CEUS before operation. Injection of the Blue dye was performed half an hour before the operation. Results: According to the postoperative pathology, 25 of 73 patients were with lymphatic metastasis. The lymph nodes detection rate of 2D-US,2D-CEUS and 3D-CEUS was 35.2%, 73.4%, 79.4% ,respectively.The correct rate of 2D-US,2D-CEUS and 3D-CEUS was 74%,90.4%,91.8%, respectively(p<0.05).The lymph drainage route of SLNs are divided into 7 types by 3D-CEUS and the enhancement modes of the lymphatic vessels and the lymph nodes are divided into six categories by 2D-CEUS. Conclusions: The 2D-CEUS and 3D-CEUS can clearly display the SLNs and the lymph drainage routes. 3D-CEUS possesses advantages over 2D-CEUS in displaying lesions with spatial relationship which is informative to preoperative assessment of the stage, the operative type and surgical prognosis in patients with breast cancer, and can contribute greatly to the easy detection of SLNs during SLNB. Clinical trial information: Approval NO,SCPPHEC-D-2015-75.
TARGIT E(lderly): Prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer—3 year local control and overall survival.
Authors: Wenz Frederik K. ,   TARGIT E Trialists
Published: September 2018

e12105 Background: To investigate the efficacy of a single intraoperative radiotherapy treatment within elderly low risk patients with breast cancer (≥ 70 years, <3.5cm, cN0, cM0, invasive-ductal histology) which is followed by whole breast radiotherapy (WBRT) only when risk factors are present. This prospective, multicentric single arm phase II study (NCT01299987) is based on the experimental arm of the randomized protocol of the international TARGIT A study. Here we present 3 year data on local control and overall survival after a median follow-up of 24 months. Methods: 541 patients from 28 international centers were recruited between February 2011 and September 2014. Sixty-three patients were excluded from the analysis because of screening failure, drop-out or loss to follow-up. During breast conserving surgery a single dose of 20 Gy of intraoperative radiotherapy was given using the INTRABEAM system (Carl Zeiss Meditec, Germany). Additional postoperative WBRT (46 – 50 Gy) was prescribed only in patients with risk factors (larger size, other histology, small free margin, lymphvessel invasion, positive nodes, multifocality/multicentricity, extensive intraductal component (EIC)). Systemic therapy was given according to international standards. The primary outcome was local relapse. Overall survival was a secondary outcome. Discontinuation of the trial was scheduled if rates of local relapse rates rise to 3/4/6% after 2.5/5/7.5 years. Results: After a median follow-up of 24.0 months (120 pts with 3 year f/u), one ipsilateral in-breast recurrence and nine deaths were observed resulting in an actuarial local relapse free survival of 99.7% and actuarial overall survival of 96.6% after 3 years. Conclusions: The results of the prospective TARGIT E trial consolidate earlier reports from the randomized TARGIT A trial supporting the use of accelerated partial breast radiotherapy (APBI) in selected patients. The observed local relapse rate after 3 years is well below the prospectively defined stopping rules (Neumaier et al. BMC Cancer 2012). Further follow-up will be performed. Clinical trial information: NCT01299987.
The first report of multicenter validation study on curebest 95GC breast, a multi-gene assay to predict prognosis of node negative and ER positive breast cancer patients.
Authors: Ito Ken-ichi , Oba Takaaki , Aogi Kenjiro , Ohsumi Shozo , Takahashi Mina , Shiroma Noriyuki , Oda Miyo , Arihiro Koji , Tsukamoto Fumine , Shiino Sho , Yoshida Masayuki , Kishi Kazuki , Kinoshita Takayuki 
Published: September 2018

e12107 Background: Curebest™ 95GC Breast (95GC) is one of the multi-gene assays to predict prognosis of node negative and estrogen receptor (ER) - positive breast cancer patients, developed using 95 gene-set without overlap with that used in Oncotype DXⓇ(ref 1). It has been shown to have the capability to classify the “intermediate” patients determined using Recurrence Online (microarray-based simulation model for Oncotype DXⓇ) but was validated only using the data from single institute and public database. Here we report the result of the first multi-center validation study for this multi-gene assay. Methods: ER-positive and T1-2/N0/M0 breast cancer patients who received adjuvant hormonal therapy were enrolled retrospectively. Fresh frozen tissues were applied to the assay, resulting classification into “L” and “H”, which was used for the validation on 5 year recurrence free survival (5Y-RFS) data of each patient. Results: 73 cases out of 150 enrolled cases were eligible and analyzed. 46 patients were classified as “L” whose 5Y-RFS was 96.5% (95%CI:89.5-98.9) while 27 patients were classified as “H” whose 5Y-RFS was 79.0% (95%CI:63.6-88.5). There was a statistically significant difference between RFS of “L” and “H” group by Log-Rank test (p = 0.0016). Significant association with 95GC were seen in histological grade (p = 0.0012), Recurrence Online (p < 0.001) and PAM50 (p < 0.001). The assay could classify the patients of histological grade 2, intermediate group by Recurrence Online (RS > 17, RS < 31) and Luminal B patients into “L” and “H”. Conclusions: Curebest™ 95GC Breast was well validated by this first multi-centered retrospective study on 5Y-RFS of the ER positive, node-negative patients who received only hormonal therapy in adjuvant setting. This result indicates the usefulness of 95GC as a novel multi-gene assay, as it can classify target patients into 2 groups, “H” and “L” according to predicted prognosis of 5Y-RFS. Reference: 1. Naoi et al. Breast Cancer Res Treat (2011) 128:632-641
Exercise training during anthracycline-based chemotherapy for breast cancer.
Authors: Fraser Steve , Bigaran Ashley , Selig Steve , LaGerche Andre 
Published: September 2018

e12110 Background: Breast Cancer is the most common female malignancy in Australia and worldwide. Medical advancements in breast cancer detection, diagnosis, and treatment have increased the 5 year-survival rate to 90%, so a focus on non-breast cancer related causes of morbidity and mortality have emerged. Anthracycline-chemotherapy has had considerable success in reducing tumour size, cancer recurrence and improving survival rates but significant adverse effects including reductions in VO2peak and cardiac function. Exercise training may provide a treatment option to reduce the cardiotoxic and fitness declines seen in women treated with anthracycline-based chemotherapy. Therefore this study aims to investigate the effects of exercise training for women recently diagnosed with breast cancer undergoing anthracycline chemotherapy Methods: 20 women recently diagnosed with breast cancer were evenly split into either usual care (UC, n = 10, age 49.2 ± 13.4yrs, Ht 164 ± 0.09cm, Wt 77.4 ± 19.7kg, BMI 23.5 ± 5.4) or three months of AEP led aerobic and resistance training designed to reduce the adverse effects of chemotherapy treatment (Ex, n = 10, age 50.9 ± 7.4 yrs, Ht 161 ± 0.09cm, Wt 70.7 ± 23kg, BMI 21.9 ± 6.9). Key measures including cardiac function, VO2peak, strength and cancer related fatigue were assessed pre and post intervention. Results: Baseline VO2peak (UC 22 ± 6.6 ml/kg/min, Ex UC 26.3 ± 6.7 ml/kg/min were below predicted values. Breast cancer patients tolerated exercise training during chemotherapy treatment and preliminary result suggest a decline in VO2peak and cardiac function during chemotherapy treatment and that exercise training was able to ameliorate this. More complete data will be presented at the conference. Conclusions: An Exercise Physiologist led aerobic and resistance training program was well tolerated in women recently diagnosed with breast cancer. The program appears to minimise some of the adverse effects of treatment, notably fitness declines and cardiotoxicity and should be considered in the oncology setting. Clinical trial information: ACTRN1261600160241.