bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC).
Authors: Paz-Ares Luis , Horn Leora , Borghaei Hossein , Spigel David R. , Steins Martin , Ready Neal , Chow Laura Quan Man , Vokes Everett E. , Felip Enriqueta , Holgado Esther , Barlesi Fabrice , Kohlhaeufl Martin , Rodriguez Oscar , Burgio Marco Angelo , Fayette Jerome , Gettinger Scott N. , Harbison Christopher , Dorange Cécile , Finckenstein Friedrich Graf , Brahmer Julie R. 
Published: February 2017

LBA109 Background: Options for advanced non-SQ NSCLC patients (pts) who progress after platinum-based doublet chemotherapy (PT-DC) are limited, with minimal improvement in overall survival (OS). We report results from a randomized, global phase III study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible. Methods: Pts were randomized to NIVO 3 mg/kg Q2W (n=292) or DOC 75 mg/m2 Q3W (n=290) until progression or discontinuation due to toxicity/other reasons. Primary objective was OS; Secondary objectives were investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression, quality of life, and safety. Results: NIVO demonstrated superior OS (HR=0.73; 96% CI: 0.59, 0.89; P=0.00155) and improved ORR (19.2% vs 12.4%; P=0.0235). HR for PFS was 0.92 (95% CI: 0.77, 1.11; P=0.393). PD-L1 expression was associated with benefit from NIVO (Table). In PD-L1+ pts, NIVO showed improved efficacy across all endpoints at predefined 1%, 5%, and 10% cut- points. Grade 3–5 drug-related AEs occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. No deaths were related to NIVO vs 1 DOC-related death. After discontinuation, 42.1% of NIVO and 49.7% of DOC pts received subsequent systemic therapy. Conclusions: NIVO demonstrated superior OS vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC. The safety profile of NIVO 3 mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase III trials. Clinical trial information: NCT01673867. [Table: see text]
Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: A multicenter, randomized DECOG trial.
Authors: Leiter Ulrike , Stadler Rudolf , Mauch Cornelia , Hohenberger Werner , Brockmeyer Norbert , Berking Carola , Sunderkötter Cord , Kaatz Martin , Schulte Klaus-Werner , Lehmann Percy , Vogt Thomas , Ulrich Jens , Herbst Rudolf , Gehring Wolfgang , Simon Jan-Christoph , Keim Ulrike , Garbe Claus 
Published: February 2017

LBA9002 Background: Complete lymph node dissection (CLND) following positive sentinel node biopsy (SLNB) was evaluated in a randomized phase III trial. Methods: 1,258 patients with cutaneous melanoma of the trunk and extremities and with positive SLNB were evaluated. Of these, 483 (39%) agreed to randomization into the clinical trial. 241 patients underwent observation only, 242 received CLND. Both groups had a subsequent 3-years follow-up. Recurrence-free (RFS), distant metastases free (DMFS) and melanoma specific (MSS) survival were analyzed as endpoints. Results: Patient enrolment was performedfrom January 2006 to December 2014. In the intent to treat analysis, both groups did not differ significantly in distribution of age, gender, localization, ulceration, tumor thickness (median 2,4 mm in both groups), number of positive nodes, or tumor burden in the SN. The mean follow-up time was 34 months (SD ± 22.1). No significant treatment-related difference was seen in the 5-years RFS (P = 0.72), DMFS (P= 0 .76) and MSS (P = 0.86) in the overall study population. Conclusions: In this early analysis of trial results, no survival benefit was achieved by CLND in melanoma patients with positive SLNB. A subsequent analysis three years after inclusion of the last patient is planned.
Breast MRI screening of women at average risk of breast cancer: An observational cohort study.
Authors: Kuhl Christiane K. , Bieling Heribert , Strobel Kevin , Leutner Claudia , Schild Hans H , Schrading Simone 
Published: February 2017

1 Background: Breast-MRI is currently recommended for screening women at high-risk of breast-cancer only. However, despite decades of mammographic-screening, breast-cancer continues to represent a major cause of cancer-death also for women at average-risk – suggesting a need for improved methods for early diagnosis also for these women. Therefore, we investigated the utility of supplemental MRI-screening of women who carry an average-risk of breast-cancer. Methods: Prospective observational cohort-study conducted in two academic breast-centers on asymptomatic women at average-risk in the usual age range for screening-mammography (40 to 70). Women underwent DCE-breast-MRI in addition to mammography every 12, 24, or 36 months, plus follow-up of 2 years to establish a standard-of-reference. We report on the supplemental-cancer-yield, interval-cancer-rate, diagnostic accuracy of screening-MRI, and biologic profiles of additional, MRI-detected breast-cancers. Results: 2120 women underwent a total 3861 MRI-studies covering 7007 women-years. Breast-cancer was diagnosed in 61/2120 women (DCIS: 20, invasive: 41), and ADH/LIN in another 21. Interval-cancer-rate was 0%, irrespective of screening interval. Forty-eight women were diagnosed with breast-cancer at prevalence-screening by MRI alone (supplemental cancer-detection-rate: 22.6 per 1000); 13 women were diagnosed with breast-cancer in 1741 incidence-screening-rounds collected over 4887 women-years. A total 12 of these 13 incident cancers were diagnosed by screening-MRI alone (supplemental-cancer-detection-rate: 6.9 per 1000), one by MRI and mammography, none by mammography alone. Supplemental-cancer-detection-rate was independent of mammographic breast-density. Invasive cancers were small (mean size: 8mm), node-negative in 93.4%, ER/PR-negative in 32.8%, and de-differentiated in 41.7% at prevalence, and 46.0% at incidence-screening. Specificity of MRI-screening was 97.1%, False-Positive-Rate 2.9%. Conclusions: MRI-screening improves detection of biologically relevant breast-cancer in women at average-risk, and reduces the interval-cancer-rate down to 0%, at a low false-positive rate.
The relationship of magnetic resonance (MR) imaging characteristics with race.
Authors: Chun Jennifer , Schnabel Freya Ruth , Schwartz Shira , Marin Chelsea , Guth Amber Azniv , Axelrod Deborah M. , Shapiro Richard L. , Roses Daniel F. , Moy Linda 
Published: February 2017

10 Background: Research has shown that women of different race have differences in tumor biology. Previous studies have shown that mammographic breast density (BD) and background parenchymal enhancement (BPE) are associated with breast cancer risk. There is data on the relationship of race and BD, but a dearth of information on the relationship of race and MR imaging characteristics such as fibroglandular tissue (FGT) and BPE. The purpose of this study was to evaluate the relationship of race with BD, BPE, and FGT in women with breast cancer. Methods: The institutional Breast Cancer Database was queried for all women with newly diagnosed breast cancer from 2010-2015. Variables included age, race, body mass index (BMI), imaging and tumor characteristics. Statistical analyses included Pearson’s Chi Square Tests. Results: A total of 2,092 women were included in this analysis. The median age was 59 years (range 22-95). Majority of patients had invasive ductal carcinoma (62%), early stage (0, I) tumors (71%), ER-positive (84%), PR-positive (71%), and HER2-negative (86%). However, there was a higher proportion of later stage (p < 0.0001) and triple negative (p = 0.002) disease among blacks. Compared to whites, blacks had higher BMI, lower BD and lower BPE, while Asians had lower BMI <, higher BD, higher FGT and higher BPE (see table). Conclusions: As previously described, we found differences among races with respect to tumor histology. However, the differences in imaging characteristics between races are likely accounted for by differences in BMI and may not be directly related to breast carcinogenesis. [Table: see text]
Factors influencing treatment of inflammatory breast cancer in the United States.
Authors: Lin Heather Y. , Babiera Gildy , Bedrosian Isabelle , Shaitelman Simona Flora , Kuerer Henry Mark , Woodward Wendy A. , Ueno Naoto T. , Shen Yu 
Published: February 2017

118 Background: Guidelines for treating inflammatory breast cancer (IBC) using trimodality (chemotherapy, surgery and radiation) therapy (TT) remain largely unchanged since 2000. However, many such patients did not receive TT. It is unknown how patient-level (PL) and facility-level (FL) factors contribute to TT utilization. Methods: Using the National Cancer Data Base (NCDB), patients who underwent surgical treatment of locoregional IBC from 2003-2011 were identified. We correlated patient, tumor, and treatment data with TT. An observed to expected (O/E) ratio of number of patients treated with TT was calculated for each hospital by adjusting for PL factors. Hierarchical mixed effects models were used to assess the proportion of variation in the use of TT attributable to PL and FL factors, respectively. Results: Among 5,537 patients who met the study criteria, the use of TT fluctuated annually (67.3%-75.7%) and was less likely for patients who were over 70, had a lower income or had an N0 tumor (all p < 0.05). By insurance type, TT use was lowest among Medicare patients. Of the 542 hospitals examined, 55 (10.1%) and 24 (4.4%) were identified as significantly low and high outliers for the use of TT (p < 0.05), respectively. While comprehensive cancer centers represented the majority of high outliers, the TT use by facility type overall was not significantly different demonstrating variability within comprehensive cancer center practice. The percentage of the total variance in the use of TT attributable to facility (11%) was almost triple the variance attributable to the measured PL factors (3.4%). Conclusions: The use of standard of care TT varied widely across facilities with some high volume centers clearly underutilizing TT. To improve clinical outcomes for this rare and aggressive malignancy, it is critical to identify facility level factors impacting the use of TT to ensure the guideline adherence of IBC treatment.
TOX3 as a novel biomarker in luminal B breast cancer.
Authors: Hong Jenny Jimmy , Seksenyan Akop , Yuan Xiaopu , Knudsen Beatrice , Audeh William , Kaye Jonathan 
Published: February 2017

130 Background: A breast cancer (BC)-associated SNP is found in an enhancer region of the TOX3 gene, which encodes a nuclear protein expressed in ER+ mammary epithelial cells but with unknown biological function. As the disease-risk allele reduces TOX3 expression, we proposed that a decrease in TOX3 might favor a progenitor cell state that is more susceptible to tumorigenesis. However, in the context of BC, our data has implicated TOX3 as a tumor promoter. Indeed, high TOX3 gene expression is significantly associated with poor outcome among patients with luminal B (LumB) disease. The Oncotype DX assay predicts likelihood of distant recurrence in ER+ early stage BC, improving patient selection for adjuvant chemotherapy. However, LumB subtypes often have an intermediate recurrence score (RS), where the absolute benefit of chemotherapy is unclear. Thus, we investigated whether TOX3 expression might provide additional discriminatory power. Methods: Tumor specimens were obtained from Cedars-Sinai Medical Center in a retrospective study. Tissue microarrays of 200 histologically-defined LumB breast tumors (ER+Her2-/+ Ki67 > 14%), half of which with associated Oncotype DX data, were stained with an anti-TOX3 monoclonal antibody, to correlate with RS and clinicopathologic outcomes. Results: TOX3 protein was expressed in a significant subset of LumB tumors. Using image analysis to create a histoscore, we found no correlation between TOX3 expression and RS. TOX3 expression was also not associated with frequency of Ki67+ cells, patient age, or tumor size. Further in-depth clinico-pathologic evaluation and prognosis data will be reported. Conclusions: Despite overall efficacy of adjuvant chemotherapy in early stage BC, many patients are exposed to the associated risks without deriving significant benefit. A number of lines of evidence suggest that TOX3 renders tumors more aggressive and metastatic. The lack of correlation of TOX3 expression and RS may suggest a facet of the biology of ER+ aggressive cancers that may not be addressed by the Oncotype DX assay. Thus, prospective studies examining recurrence risk and chemotherapy benefit may need to be expanded to integrate TOX3 expression as an adjunct novel biomarker to guide optimal personalized therapy for BC.
Caveolin-1: Oncogenic role in breast cancer? Clues from molecular profiling.
Authors: Feldman Rebecca , Gatalica Zoran , Reddy Sandeep K. , Castro Michael , Sachdev Jasgit C. 
Published: February 2017

134 Background: Caveolin-1 (CAV1) is the structural component of caveolae, compartments within the plasma membrane that sequester signaling molecules, thus facilitating molecular “hot spots”. The role of CAV1 in breast cancer is an active area of investigation. We sought to understand the clinical and pathological characteristics of CAV1 positive tumors (CAV 1+) through a retrospective analysis of molecularly-profiled breast cancer patients. Methods: 2,728 breast cancer patients molecularly profiled with a commercial assay (Caris Life Sciences) were evaluated retrospectively for expression of various biomarkers by immunohistochemistry (IHC) and in situ hybridization. JMP statistical analysis tool was used to ascertain distributional differences. Results: Using a threshold of 2+ and 30%, 121/2728 (4%) of patients exhibited CAV1 over-expression by IHC. To observe clinicopathologic differences in the CAV1 + and CAV1- tumors, distribution by age, metastatic disease, and triple negative histology (TNBC) were analyzed. Average age for both groups was 55. 39% vs. 54% were metastatic and 74% vs. 26% were TNBC (p = 0.0001) among CAV1+ and CAV1- groups, respectively. To evaluate the potential oncogenic associations of CAV1, we evaluated the relationship between CAV1+ and various oncogenic pathways. Positive EGFR protein expression and presence of EGFR gene amplification, as well as cKIT over-expression associated with CAV1+ (all p-values < 0.001), whereas HER2 expression and amplification were associated with CAV1- (p = 0.001 for both). In addition, higher Ki67, p53 and TOP2A expression by IHC were observed in CAV1+ patients compared to the CAV1- subgroup (90% vs. 66%, 50% vs. 36%, 84% vs. 65% ; all p-values < 0.0001). Biomarker expression differences that did not meet statistical significance: ERCC1, MGMT, PDGFRA, RRM1, SPARC, TS and TOPO1. Conclusions: The majority of CAV1+ breast cancers are comprised of triple negative, higher proliferative tumors, with aberrant p53 expression as well as expression of other growth factor signaling proteins. This data supports the potential role of CAV1 in fostering molecular hubs for signaling and CAV-1 being a potential target for future therapeutic investigation in TNBC.
Primary analysis of a randomized phase II, multicenter trial: Neoadjuvant weekly nab-paclitaxel 100mg/m2 followed by FE100C compared with docetaxel 75mg/m2 followed by FE100C for early breast cancer in Japan.
Authors: Kuwayama Takashi , Yamauchi Hideko , Takano Toshimi , Tsugawa Koichiro , Sato Takanobu , Kitani Akira , Hayashi Naoki , Okuyama Hiromi , Nakamura Seigo 
Published: February 2017

136 Background: Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) is a new solvent free taxane-based anticancer drug. According to CA024 trial, nab-PTX 100mg/m2 demonstrated superior response to docetaxel (DTX) in patients with metastatic breast cancer. Besides, nab-PTX 100mg/m2 was less toxicity. In operable breast cancer, GeparSepto study was reported that the pCR rate were significantly higher with nab-PTX 125/150 mg/m2 compared to paclitaxel. We planned the randomized parallel design phase II trial to evaluate nab-PTX 100mg/m2in early breast cancer. Methods: Stage II-III HER2-negative breast cancer patients were included in this trial and received either 4 cycles of DTX (75 mg/m2 day1) q 3 w or 4 cycles of nab-PTX (100 mg/m2 day1/8/15) q4w followed by 4 cycles of FE100C. The primary end point is pCR (ypT0/is ypN0) rate, and the secondary end points are response rate, histological effect of treatment, breast conservation rate, and toxicity. Results: Between March 2011 to March 2014, 152 eligible patients were enrolled at 6 centers (75 pts were allocated for nab-PTX). Baseline characteristics were well balanced; median age was 51/49 years (DTX/nab-PTX), 61/61% of the patients with ER positive, 38/36% triple negative breast cancer, 57/65% Ki67 > 20%. Clinically response rate was similar to each drug. (53/57%) The pCR rate was 12/17% (p = 0.323). In TNBC group, the pCR rate was 28/30% (p = 0.866). In Ki67 > 20% group, the pCR rate was significantly higher, 16/48% (p = 0.021) with nab-PTX arm. The most common grade3-4 adverse event was neutropenia, which was observed in 40/36% of cases. Non-hematological adverse events of any grade were; 34/32% myalgia (DTX/nab-PTX), 42/35% arthralgia, 55/65% peripheral sensory neuropathy. No Grade3-4 peripheral sensory neuropathy was observed in nab-PTX arm. Infusion reaction of DTX occurred in 1 patient. Conclusions: In this initial effectively analysis, neoadjuvant weekly nab-paclitaxel 100mg/m2 were promising drug in HER2-negative operable breast cancer patients. Larger studies will be needed to evaluate neoadjuvant weekly nab-paclitaxel compared with DTX. Clinical trial information: 000005388.
Safety and efficacy of gemcitabine and trastuzumab in HER2-directed therapy pretreated patients with HER2-positive metastatic breast cancer: SBP-01 study.
Authors: Yoshitomi Seiji , Tsuji Hisashi , Ikeda Masahiko , Ito Mitsuya , Ohtani Shoichiro , Higaki Kenji , Sagawa Teiri , Matsuoka Kinya , Kawai Hiroshi , Takabatake Daisuke , Doihara Hiroyoshi , Shien Tadahiko , Taira Naruto , Ohtawa Yasuyuki , Maruyama Shuichiro , Hikino Hajime , Fujii Sayaka , Yamamoto Yutaka , Ohsumi Shozo , Hara Fumikata 
Published: February 2017

142 Background: Prognosis of HER2-positive metastatic breast cancer (MBC) has been dramatically improved by trastuzumab (Tmab). More recently, newer anti-HER2 agents such as lapatinib, pertuzumab and T-DM1 have prolonged survival. Despite the efficacy of these drugs, most patients develop progressive disease during or after treatment, and alternative anti-HER2 agents plus chemotherapies are required in subsequent lines of treatment. However, there are few evidence on efficacy of Tmab-containing regimens after disease progression. Gemcitabine (GEM) is non-cross resistant to anthracycline and taxane. Preclinical studies have shown that the combination of Tmab and GEM has synergistic effect against HER2-positive breast cancer cell lines. SBP-01 study assessed the efficacy and safety of the combination of Tamb and GEM in patients with HER2-positive MBC previously treated with anti-HER2 therapy. Methods: SBP-01 study included patients treated with one or more anti-HER2 directed regimens for MBC. Patients were administered with GEM 1250 mg/m2 on days 1 and 8 of each 21-day cycle and Tmab 4mg/kg loading dose and then 2mg/kg weekly. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival, and safety. Results: Between June 2011 and June 2014, 35 patients were enrolled. Patients had ER positive tumor (37.1%), a median of 2 metastatic organ sites, visceral metastasis (80.0%), prior (neo) adjuvant Tmab (22.9%) and a median of 2 prior chemotherapy regimens for MBC. Previous HER2-directed drugs included Tmab (94.3%), lapatinib (37.1%), T-DM1 (8.6%) and pertuzumab (2.9%). ORR was 22.9% (95% CI, 8.6%-36.8%). Median PFS was 146 days. Patients with stable disease response received a median of 7 cycles (6-28 cycles) of treatment. Grade3/4 leukopenia (20.0%) and neutropenia (48.6%) were observed. All non-hematological toxicities were less than grade3. Conclusions: The Combination Tmab and GEM is effective and well-tolerated regimen for patients previously treated with HER2-directed therapy, and appears to make disease stable for long time period. Clinical trial information: UMIN000005881.
Review of trends in adjuvant chemotherapy regimens in breast cancer over 10 year period at Yale New Haven Hospital (YNHH).
Authors: Gnanajothy Rosana , Chung Gina G. , DiGiovanna Michael , Abu-Khalaf Maysa M. , Lannin Donald R. , Harris Lyndsay 
Published: February 2017

144 Background: Adjuvant chemotherapy for breast cancer has undergone many changes over the past 10 yrs. The objective of the study was to review prescribing trends in adjuvant chemotherapy regimens for early stage breast cancer in a single institution, over a decade. Methods: A retrospective chart review was conducted of patients (pts) with early stage breast cancer treated at YNHH from 2002 to 2011.Total charts analyzed was 1097 and 308 pts had complete data. Results: The HER 2 positive group accounted for 64 pts. The most commonly used regimen was ACTH (doxorubicin and cyclophosphamide 4-14 d cycles, paclitaxel and trastuzumab weekly for 12 weeks, and trastuzumab for 1 yr). This regimen was utilized in 35% of pts and was most likely to be used in node positive (N+ve) pts compared to node negative (N-ve) pts (OR 2.9 (95 % CI 0.97-9.1)).TCH (docetaxel, carboplatin, trastuzumab,6-21 d cycles and trastuzumab for 1 year) was the second most common regimen used in 21% of pts and predominantly in N-ve pts(OR 12.4 (95% CI 02.45-63.2)). Majority of the study group (184 pts) were ER+PR+ and HER 2- .The predominant chemo regimen was DD AC T (dose dense AC followed by paclitaxel in 4 -14d cycles each) in 50% of pts, and TC (Docetaxel, cyclophosphamide4-21d cycles) utilized in 48 pts (26.09 %). Majority of the N-ve pts were treated with TC (OR 12.4(95% CI 2.4-63.27) whereas N+ve pts were predominately treated with DDACT (OR 2.98(95% CI 0.97-9.16). The Triple negative group included a total of 57 pts .The most frequent chemo regimen through the years was DDACT (54.39% of pts) followed by TC (21.05% of pts). N+ve pts were more likely to be treated with DDACT (OR 8.91(95% CI (2.65-29.94)) whereas N-ve pts mostly received TC (OR 8.75(95% CI (1.70-45.00)) The methotrexate and 5 fluorouracil based regimens were utilized more frequently in earlier years of study and less frequently in later years. Conclusions: Anthracycline and taxane based regimens have gained precedence over older regimens. HER 2 +ve pts were most commonly treated with ACTH, and TCH. N+ve HER 2+ pts were most likely to be treated with ACTH and N-ve HER2+ pts with TCH. In Her 2 negative and triple negative pts, DDACT was more utilized in N+ve pts whereas, TC regimen in the N-ve pts.