bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter audit of the incidence of febrile neutropenia and neutropenia associated with docetaxel and cyclophosphamide (TC) chemotherapy for early breast cancer.
Authors: Lakhanpal Roopa , Stuart-Harris Robin , Chan Arlene , Kotasek Dusan , Beith Jane McNeil , Cuff Katharine , Bastick Patricia A. , Lee Clara Inkyung 
Published: March 2020

1079 Background: A 2006 US Oncology trial reported that four cycles of docetaxel and cyclophosphamide (TC) resulted in better disease free and overall survival than four cycles of doxorubicin and cyclophosphamide (AC) in women with early breast cancer (EBC) and TC is now a frequently used adjuvant chemotherapy regimen for EBC. The 2006 trial reported that TC was associated with a 5% incidence of febrile neutropenia (FN), but others have noted a higher incidence of FN. Methods: We have conducted a multicentre retrospective audit of women with EBC treated with TC between January 2010 and July 2011, recruited from seven Australian centres. The primary endpoints of the study were the incidence of FN associated with the use of TC and also the incidence of grade 3 or 4 neutropenia during cycle one of TC. Patients receiving prophylactic granulocyte colony stimulating factor (G–CSF) or prophylactic antibiotics were excluded. Results: Of a total of 368 previously untreated women with EBC who received TC, 300 were evaluable for FN. The median age of the patients was 57 years. Overall, 73 (24.3%) patients developed FN. The highest incidence of FN was seen after cycle one (91.8%) of TC and the incidence of FN appeared higher in women under the age of 65 years. Of 304 patients evaluable for neutropenia during cycle one, eight (2.6%) developed grade 3 neutropenia and 191 (62.8%) developed grade 4 neutropenia. Conclusions: This is the largest study to date which reveals that TC is associated with a high incidence of grade 4 neutropenia and a high incidence of FN. The incidence of FN is above the 20% threshold for the use of G-CSF as primary prophylaxis as recommended by The EORTC and The National Comprehensive Cancer Network. Therefore, we recommend that G-CSF be considered as primary prophylaxis when TC is used as adjuvant chemotherapy for EBC.
Quantitative Ki-67 score as predictive of response to neoadjuvant chemotherapy in breast cancer.
Authors: Brown Jason R. , Lannin Donald R. , Killelea Brigid K. , DiGiovanna Michael , Rimm David 
Published: March 2020

1085 Background: Neoadjuvant chemotherapy is administered prior to surgery for locally advanced tumors but does not confer any additional survival benefit. Measurement of Ki-67, a marker of cell proliferation, has been associated with response to therapy, but methods of measurement are controversial. There is no universal cut-point for association due to subjectivity in threshold for positivity and selection of the field of view. Here we propose that quantitative objective measurement for Ki-67 will provide a reproducible assay for likelihood of response to chemotherapy. Methods: A cohort of 115 consecutive (between 2002 and 2010) invasive breast cancer patients that received neoadjuvant therapy were included if pre-surgical biopsies were obtainable. Ki-67 expression was measured using quantitative immunofluorescence (AQUA) technology using the MIB-1 antibody. Images for each specimen were collected in 5 to 100 fields of view (FOV), and summary scores were obtained corresponding to the average and maximum of all the FOVs. Results: AQUA scoring was comparable to automated calculation of percent positive nuclei for prediction of response to chemotherapy (OR: 2.832 vs. 2.712). Both average and maximum AQUA scores showed Ki-67 expression was directly correlated to pathological complete response (pCR) (Ave p = 0.0002; Max p = 0.0011). Although examining the maximum field of view was more predictive of response to therapy (OR: 3.546 vs. 2.832), averaging all fields provided more sensitivity and specificity (AUC 0.769 vs. 0.732). Ki-67 average (p = 0.0025) and maximum (p = 0.0239) AQUA scores were also significant predictors of pCR in multivariable analysis with tumor size, nuclear grade, nodal status, ER status, and HER2 status considered. Conclusions: Measurement of Ki-67 expression by objective quantitative methods shows increased Ki-67 levels are an independent predictor of response to neoadjuvant chemotherapy. This assay is most sensitive and specific when the average Ki-67 expression from all fields of view is used.
A phase II study evaluating the safety and efficacy of sunitinib with weekly paclitaxel followed by doxorubicin and daily oral cyclophosphamide plus G-CSF as neoadjuvant chemotherapy (NC) for locally advanced (LABC) or inflammatory breast cancer (IBC).
Authors: Specht Jennifer M. , Kurland Brenda F. , Linden Hannah M. , Gralow Julie , Gadi Vijayakrishna K. , Ellis Georgiana Kehr , Rodler Eve T. , Chai Xiaoyu , Eun Jinny , Brown-Glaberman Ursa Abigail , Livingston Robert B. ,   Seattle Cancer Care Alliance Network Investigators
Published: March 2020

1090 Background: Sunitinib (S) is an oral tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity. The primary objective of this trial was to assess the pathologic complete response rate (pCR) in patients (pts) treated with NC consisting of S with weekly paclitaxel (T) followed by doxorubicin and daily oral cyclophosphamide plus G-CSF (AC+G-CSF). Correlative studies including circulating biomarkers are reported separately. Methods: Pts with HER2 negative LABC or IBC were eligible for this multicenter, phase II trial. Pts received S 25 mg po daily with T 80 mg/m2 IV Qweek (wk) x 12 wks, then AC+G-CSF (doxorubicin 24 mg/m2 IV Qwk + oral cyclophosphamide 60 mg/m2po daily + G-CSF 5 mcg/kg SC days 2-7) x 15 wks. pCR in the breast and axilla was assessed at surgery, and the MDACC CPS+EG score (validated score combining clinical and pathologic results for predicting survival in the neoadjuvant setting) was calculated. Results: 70 pts (ages 33-79) were enrolled; 68 received protocol therapy. 37 (53%) had ER and/or PR positive tumors. 2 patients were unevaluable (hypersensitivity to T, toxicity possibly related to S) and 3 withdrew consent prior to surgery. 61 pts reported any grade AE in S+P period. Among grade 3 or 4 AEs, neutropenia was most common in S+P period occurring in 31/68 (46%). pCR in the breast was observed in 27% (17/63, 95% CI 17%-40%) and breast and axilla in 15/63 (24%). In pts with ER positive tumors, pCR rate in breast was 8/34 (24%) and 9/29 (31%) for pts with ER negative tumors. 18 evaluable pts (29%) had CPS+EG scores ≤2, 40 (63%) had CPS+EG scores of ≥3, and 5 had insufficient information to calculate the CPS+EG score. When response was defined as pCR and/or CPS+EG score ≤ 2, 28 pts (44%) were responders. Conclusions: NC with T+S followed by AC+G-CSF was well tolerated. Using a combined definition of response of pCR and/or CPS+EG score ≤2, 28/63 (44%) pts had response; 19/34 (56%) for ER positive and 9/29 (31%) for ER negative disease. The addition of S to NC may result in promising incremental benefit for pts with ER positive breast cancer. Clinical trial information: NCT00513695.
Randomized phase II trial of gemcitabine versus gemcitabine and imatinib mesylate in patients with previously treated metastatic breast cancer.
Authors: Munshi Pashna Neville , Toppmeyer Deborah , Wong Serena Tsan-Lai , Ganesan Shridar , Tkaczuk Katherine Hanna , Cianfrocca Mary E. , Kaklamani Virginia G. , Gradishar William John , Somer Robert A. , Sharan Kanu , Grana Generosa , Lerma Pauline Marie O. , Pliner Lillian F. , Wieder Robert , Kane Michael P. , Kim Sinae , Tan Antoinette R. 
Published: March 2020

1091 Background: Gemcitabine (GEM) as a standard 30-min infusion has activity as a single-agent in metastatic breast cancer (mbc). Prolonged infusion of GEM at a fixed dose rate (FDR) of 10 mg/m2/min is associated with greater formation of active metabolite and may result in improved antitumor activity. Imatinib mesylate (IM)-mediated inhibition of PDGFR reduces tumor interstitial fluid pressure allowing for improved chemotherapy penetration into tumors. We evaluated the addition of IM to FDR GEM in patients (pts) with previously treated mbc. Methods: This was a randomized phase II trial in mbc pts who progressed after 1 but no more than 2 prior cytotoxic regimens. Eligibility included measurable disease; no prior GEM or IM exposure. Group 1 received FDR GEM IV 1250 mg/m2 at 10 mg/m2/min (over 120 min) on days 3 and 10 every 21 days; Group 2 received the same FDR GEM dose and schedule plus IM 400 mg orally daily on days 1-5 and 8-12 every 21 days. Primary endpoint was time to progression (TTP). Sample size of 40 pts per group was needed to detect an 8 mo increase in TTP with the combination (80% power, α = .05, 2-sided). Secondary endpoints included ORR and safety. Results: Between 5/2006-4/2011, 44 pts were randomized (22 per group). Study closed early due to slow accrual. Median age 54 (31-75); median ECOG PS 1 (0-2); 52% were hormone receptor-positive and HER2-negative; 27% triple-negative, and 20% HER2-positive. Median number of cycles was 2 in Group 1 (range 1-12) and 3.5 in Group 2 (range 1-13). Most common adverse events (%) of any grade, Group 1 vs Group 2 were neutropenia (68 vs. 78), anemia (48 vs. 65), thrombocytopenia (24 vs. 47), nausea (40 vs. 52) and vomiting (24 vs. 21). One gr 4 thrombotic thrombocytopenic purpura occurred in Group 2. Median TTP were 2 mo (95% CI: 1-5 mo) in Group 1 and 2.5 mo (95% CI: 1-5 mo) in Group 2 (p = 0.3 log rank test). ORR was 9.1% in each group (95% CI: 1.6-30.6%), with 2 PRs in each group. Stable disease (≥ 3 mo) was 32% in Group 1 and 41% in Group 2. Conclusions: This study was underpowered to draw any conclusion regarding a difference in TTP between the two groups at the time it was prematurely closed. Combination of IM and FDR GEM showed a trend to increased toxicity compared to FDR GEM alone. Clinical trial information: NCT00323063.
The prognostic and predictive impact of genomic grade index (GGI) versus central grade or molecular class in intermediate-risk breast cancer (BC): Results from the EC-Doc trial.
Authors: Gluz Oleg , Liedtke Cornelia , Peyro Saint Paul Helene P. , Nitz Ulrike , Kates Ronald E. , Huober Jens Bodo , Hartmann Arndt , Kreipe Hans Heinrich , Pelz Enrico , Erber Ramona , Kuhn Walther , Harbeck Nadia 
Published: March 2020

1092 Background: Potential markers for adjuvant taxane-based chemotherapy (CTx) in early, intermediate-risk BC include histologic grade (HG), Ki-67, Genomic Grade (GG) or molecular classification. The randomized EC-Doc trial demonstrated improvements in DFS and OS for EC-Doc vs. FEC in patients with 1-3 positive LN. Methods: Centrally assessed protein expression data by IHC, histology/HG (n=772) and GG (n=476) were obtained. Luminal A/B classes were defined as: ER/PR+/KI-67<20/>20% and/or HER2+. Correlations/concordance of these factors were estimated; impact on DFS and value for predicting taxane-based CTx benefit was assessed. Results: Low, equivocal and high GG (GG-1/-EQ/-3) categories were observed among 54 (11%); 60 (13%); 358 patients (76%) and associated with decreasing 5-yr-DFS rates of 100%, 92% and 82% (p < 0.001).There is only 60% concordance between local (L)/central(C) HG assessments and 63% between GG and C-HG. 37.7% of GG-3 tumors were L- HG3 vs. 72% C-HG3; 79% of C-HG2 and 83% of L-HG2 tumors were re-classified (56-71% to GGI3). Only 5.6-6% of GG1 were HG1 by L/C-HG respectively.GG was prognostic only in L-HG subgroups.In univariate subgroup analyses, EC-Doc was significantly superior to FEC: C-G3 (HR=0.58, 0.39-0.93), high Ki-67 (HR=0.55, 0.32E0.92) and GG-3 (HR=0.58, 0.34-0.99) subgroups. In multivariate analyses of HR+ disease (including age, therapy, GGI category, tumor size, LN status, central/local HG, Ki-67, HER2), either C-HG3 / high Ki-67 (as dichotomous variables) or C-HG3 / GGI (as continuous variable) were identified as independent prognostic factors.In interaction analysis, only C-HG, luminal A subtype and interaction of luminal-B/therapy were significant. If local HG was included instead of C-HG, only GG was as independent prognostic factor. Conclusions: These data support GGI as independent prognostic factor in early HR+ BC and as predictive marker regarding taxane benefit by univariate analysis. There is heterogeneity between L/C-HG and GGI. C-HG and Ki-67 assessment appear similarly informative. A predictive effect regarding benefit of taxane-containing CTx was seen in the IHC-luminal B subtype.
Guidelines for the definitions of time-to-event endpoints in randomized clinical trials: Results of the DATECAN Project for Breast Group.
Authors: Gourgou Sophie , Dabakuyo Tienhan Sandrine , Asselain Bernard , Azria David , Cameron David A. , Cardoso Fatima , Poortmans Philip M. ,   DATECAN Group
Published: March 2020

1094 Background: With the necessity of reducing randomized clinical trial (RCT) duration, cost and number of patients, surrogate endpoints of overall survival (OS) are increasingly being used in cancer RCTs. However, most of these endpoints currently lack of standardized definition enabling a comparison of RCT results. Some recommendations have been proposed for specific cancer sites but they do not rely on a formal consensus methodology. The objective of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide guidelines to standardize definitions of time-to-event endpoints in RCTs for different cancer sites. Here, we present results for BREAST cancer. Methods: We relied on the modified Delphi consensus method, a validated formalized consensus process for the development of practice guidelines. International experts with various backgrounds and expertises were involved. First, the coordinating committee, a group of statisticians and epidemiologists involved in the design and conduct of RCTs, led a comprehensive literature review to identify time-to-event endpoints, events of interest and the existence of guidelines in adjuvant and metastatic settings. The steering committee, which included additional medical experts, validated the list and prepared the questionnaire sent for rating to an independent expert committee. Results: The consensus process involved 2 rounds of scoring (31 experts) and 1 in-person meeting (in parallel to ASCO'12). Each expert had to rate on a 1-9 scale if s/he agreed or not for including events (e.g. death from breast cancer) in the definition of time-to-event endpoints (e.g. progression-free survival). 150 events had to be scored for the 11 selected endpoints. Consensus was reached for 57% of the events after the 2 rounds of scoring. After the in-person meeting, consensus was reached for all the remaining events except one. Conclusions: The DATECAN guidelines should help standardizing definitions of commonly used endpoints. This process should (i) facilitate the comparison of RCTs and (ii) improve the quality of future RCTs by providing better estimation of sample size and treatment effect.
Improved outcome and selection bias in primary breast surgery for patients with metastatic breast cancer.
Authors: Hadzikadic Gusic Lejla , Falcone John , McGuire Kandace P. , Soran Atilla , Diego Emilia , Thomas Christine R. , McAuliffe Priscilla F. , Bonaventura Marguerite , Johnson Ronald , Ahrendt Gretchen M. 
Published: March 2020

1098 Background: Retrospective studies showing improved survival in patients with metastatic breast cancer (MBC) who undergo surgical treatment of the primary tumor have been criticized for bias in favor of younger, healthier women with lower disease burden. We attempted to identify these biases in our population. Methods: Our institutional cancer registry was queried for patients with MBC from 1994-2010. Demographics, clinical, radiologic and pathologic staging, as well as treatments and outcomes were recorded. Surgical and non-surgical groups were compared for differences in overall survival (OS) and clinicopathologic variables, including comorbidities, using uni- and multivariate analysis. Results: Ninety-one patients with metastatic disease identified within 3 months of initial diagnosis were eligible. 53% (48 pts) had primary breast surgery and 47% (43 pts) did not undergo surgery. Patients in the surgery group were younger on univariate analysis (mean age 53 vs. 62, p<0.01). Neither BMI (mean 30 vs. 29 kg/m²) nor Charlson comorbidity score (mean 6 in both groups) were significantly different, p=NS. Bone metastases were more common in the surgery group (48 vs. 26%) and multiple metastases in the non-surgery group (35 vs. 17%), p<0.05. Patients in the non-surgery group had ≥ 1 visceral metastasis when compared to the surgery group (62 vs. 35%), p<0.05. Higher OS was demonstrated in the surgery group both with Kaplan Meier curves (p<0.05) and univariate analysis (mean 3 vs. 2 yrs, 95% CI 2.6, 3.7), p<0.05. Survival was higher in the surgery group (p<0.01), at 1 year, but this difference did not persist at 3 and 5 years. On multivariate analysis, only difference in age remained significant (p<0.01). Conclusions: Our study supports existing data that women with MBC who have surgical treatment of the primary tumor have an improved survivorship. However, it also suggests a bias towards increased use of surgery in patients who are younger with smaller burden of metastatic disease. We did not find a bias in favor of healthier patients. Further study to determine the mechanism and magnitude of benefit of primary tumor extirpation is still needed.
Neoadjuvant bevacizumab: Surgical complications of mastectomy with and without reconstruction.
Authors: Kansal Kari Joanne , Dominici Laura Stewart , Tolaney Sara M. , Isakoff Steven J. , Krop Ian E. , Smith Barbara L. , Jiang Wei , Potler Hannah , Brock Jane E. , Winer Eric P. , Golshan Mehra 
Published: March 2020

1100 Background: Neoadjuvant therapy is commonly used in operable breast cancer. We prospectively evaluated the surgical complications in a cohort of patients who underwent mastectomy following neoadjuvant doxorubucin hydrochloride/cyclophosphamide/paclitaxel (AC/T) plus bevacizumab and compared the rate of complications to a matched cohort of neoadjuvant AC/T without bevacizumab. Methods: One hundred patients with HER2-negative breast cancer enrolled in a single-arm trial of neoadjuvant AC/T plus bevacizumab (cohort 1), 60 of these patients underwent mastectomy and were matched with 59 patients who received standard neoadjuvant AC/T (cohort 2) over a similar time period in the same healthcare system. All patients underwent mastectomy with or without reconstruction. Fisher’s exact tests were used to compare complication rates, with a p<0.05 was considered significant. Results: Patients were matched well in terms of demographics. The overall complication rate was 33% in cohort 1 and 31% in cohort 2 (P-value=0.84; Table). In cohort 1, 7 of 23 (30%) patients who underwent immediate expander/implant reconstruction had complications, including 2 patients who had explantation of their reconstructions. In cohort 2, 0 of 8 (0%) had complications (p value=0.15). Conclusions: Nearly a third of patients undergoing neoadjuvant therapy with AC/T with or without bevacizumab developed a postoperative complication after mastectomy. The use of bevacizumab was not associated with a significant increase in surgical complications, although this is a non-randomized data with a small sample size. As larger data sets become available with the use of neoadjuvant bevacizumab with mastectomy, further refinement may be necessary. [Table: see text]
Acute and late side effects after intraoperative electron radiotherapy during breast conserving surgery of breast cancer.
Authors: Matuschek Christiane , Boelke Edwin , Janni Wolfgang , Zwiefel Karin , Simiantonakis Ioannis , Njanang Freddy-Joel , Budach Wilfried , Alessandro Marina 
Published: March 2020

1101 Background: Intraoperative boost irradiation as part of breast-conserving therapy is a perfect method to adequately capture the high risk tumor relapse area. The most homogeneous dose distribution is achieved with electrons. Intraoperative electron radiotherapy (IOERT) as a boost for breast cancer releases a high single dose of radiation to the breast tissue; therefore acute toxicity is of particular attention. To date there is only inadequate information available on breast cancer patients treated with IORT using electrons applied as a boost. We therefore analyzed the acute toxicity and late side effects after radiotherapy with 10 Gy as a boost with a minimum follow-up of 3 months. Methods: A total of 385 patients treated with IOERT (10 Gy with 5, 7 and 9 MeV electrons) with a dedicated robotic linac (NOVAC 7, New Radiant Technology, Aprilia, Italy) to the tumor bed during breast-conserving surgery as a boost followed by whole-breast radiotherapy (WBRT,50- 50.4 Gy; 1.8-2 Gy per fraction) were included in this study. All patients underwent a retrospective follow-up regarding acute and late side effects. Toxicities were documented using the common toxicity criteria (CTC 4.0 of the European Organization for Research and Treatment of Cancer) and normal tissues subjective, objective, management and analytic scales (LENT-SOMA). Results: The IOERT was well tolerated and the cosmetic results were good. As a side effect there were five patients with seroma. Two patients developed a secondary wound healing. Two patients developed chronic pain in the irradiated breast. Ten patients developed a grade 2 fibrosis. The remaining patients did not develop any grade 3 or 4 side effects. The observed toxicity rates were not influenced by age, tubus size, electron energy or systemic therapy. 80 patients had a follow up longer than 5 years. Three of them developed distant metastasis and one patient died. Conclusions: After IOERT of the breast using electrons we did not find any unexpected acute and late toxicity rates.