bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-12-13: First analysis of ASTER study AT for 3 cycles followed by CMF for 3 cycles as neo or adjuvant chemotherapy in early stage breast cancer. A single institution experience
Authors: Mariani G , Galli G , Mariani P , Bianchi GV , Capri G , Cresta S , Damian S , De Benedictis E , Valagussa P , Magazzu' D , De Braud FG , Moliterni A 
Published: August 2014

Abstract
Background: The ECTO study demonstrated the efficacy of concurrent doxorubicin and paclitaxel (AT) for 4 cycles followed by cyclophosphamyde/ methotrexate/fluorouracil (CMF) for 4 cycles in the neoadjuvant and adjuvant treatment of operable breast cancer (Gianni L. et al. JCO 2009). With the purpose of ameliorating the tolerability of the regimen, we designed the ASTER study to reduce both the duration and the total dose of treatment with AT followed by CMF. Herein we report on the first data of efficacy of the study and the toxicity.
Methods: A total of 345 patients with operable breast cancer were enrolled between September 2008 and November 2011. Median age was 50 years (range 23-74); 74.5% of patients presented with hormonal receptor positive (HR +) and 23,5% of patients with both hormonal receptor negative (HR-PgR-); 19% of patients presented HER2 over expression/amplification; half patients had Ki67 &gt;14%, almost of patients had pT1 (66%) or pT2 (30%) with 27,5% of pN0. Patients were treated with Adriamycin (60 mg/mq) + Paclitaxel (200 mg/mq) q21 for 3 cycles followed by CMF i.v. 1, 8q28 for 3 cycles (73 as neo-adjuvant and 272 as adjuvant regimen). After chemotherapy in patients with HER2+ trastuzumab was delivered for 1 yr and in patients with HR+ tumors hormonal treatment was recommended for 5 yr. Breast irradiation was mandatory after conserving surgery (64% of cases).
Results: At a median follow-up of 36 months, the relapse free survival (RFS) and overall survival (OS) were 92% and 96% respectively. As expected in patients HR+/HER2- RFS were 95% and OS 99%, in patients HER2+ RFS were 90% and OS 97% and in those HR-/HER2- 83% and 79% respectively.
In the neoadjuvant subset tnpCR, defined as the absence of invasive cells in the primary tumor and in nodes, was obtained in 10% of cases. A tnpCR was achieved in 27% of patients with triple negative cancer and only in 5% of HR positive cancer.
Peripheral neuropathy toxicity was reported in 37% of cases and was essentially mild to moderate. Only 8,7% of patients experienced neutropenia G 3, 4,3% GI toxicity G3 and 2,3% mucositis G3. No cardiotoxicity was documented even in the 65 patients who received postoperative trastuzumab to date.
Conclusions: This results of Aster study AT for 3 cycles followed by CMF for 3 cycles showed similar efficacy and very favorable toxicity compared whit our previous experience of eighth cycle of sequential and non cross resistant chemotherapy in early stage breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-13.
Abstract P3-13-07: A-TaXel: Multicenter phase II combination of bevacizumab (A) with weekly paclitaxel (Ta) and capecitabine (Xel) in first line treatment for patients with triple negative metastatic or locally advanced breast cancer (TNMBC), a GINECO study
Authors: Ferrero J-M , Hardy-Bessard A-C , Capitain O , Lortholary A , Salles B , Follana P , Herve R , Deblock M , Dauba J , Atlassi M , Largillier R 
Published: August 2014

Abstract
Background: Weekly paclitaxel and capecitabine intermittent regimen is a safe and effective combination in first line treatment of MBC including triple negative cancer (Lortholary et al, Breast Cancer Res Treat 2012). In TNMBC, the combination of A with first line Ta or Xel has been shown to improve response rate (RR) and progression-free survival (PFS) (Miller K et al., N Engl J Med 2007, Robert J et al., J Clin Oncol 2011). This phase II study is to evaluate the efficacy and safety of A-TaXel combination in TNMBC.
Methods: Patients (pts) with measurable TNMBC were treated in first line until progression with q28 cycles of Ta (80 mg/m2 D1, 8, 15) + Xel (800 mg/m2 bid D1-5, 8-12, 15-19) + A (10 mg/kg D1, 14). Primary end point was best overall RR; secondary were safety, PFS, response duration and overall survival (OS).
Results: From 04/2010 to 03/2012, 64 pts were accrued including 2 ineligible pts. Patients characteristics were: median age (56.7 yrs), ECOG PS 0 (55%), histological grade III (61%), previous adjuvant chemotherapy (74%), visceral disease (65%), &gt; 1 metastatic sites (74%).
Patients received a median of 6 cycles (1-6), mean 5.1. Grade 3-4 neutropenia, anemia and thrombopenia were 23%, 4% and 16% respectively with febrile neutropenia in 5% of pts. G-CSF support was observed in 7% of cycles. Most frequent non hematologic toxicities were alopecia (gr2 40%), hand-foot syndrome (gr2 27%, gr3 13%), nail toxicity (gr2 40%), hypertension (gr3 35%), neuropathy (gr2 26%, gr3 6%), mucositis (gr2 16%, gr3-4 9%), fatigue (gr3 18%, gr4 2%), nausea (gr2 15%, gr3 2%) and thrombosis (gr2 3%, gr3-4 5%). Treatment interruption due to toxicity was 22%, DPD deficiency in one patient, hospitalization 23%.
RR was 77%, CR 19%, PR 58%, stable disease 14% and progressive disease 9%. Median response duration was 5.6 months. Median PFS was 7.9 months (6.7-9) and OS 19.2 months (17.3-21.1).
Conclusion: A-TaXel is an effective regimen with high RR and manageable toxicity.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-07.
Abstract P3-14-03: Pathological complete response after primary chemotherapy as a surrogate end point of treatment efficacy in breast cancer patients: A trial-based meta-analysis
Authors: Amoroso V , Berruti A , Gallo F , Bertaglia V , Paloja E , Simoncini EL , Generali D , Bottini A , Bruzzi P , Sormani MP 
Published: August 2014

Abstract
Background: The relationship between pathological complete response (pCR) and improved long-term prognosis was first reported in the landmark NSABP B-18 and B-27 trials and then validated in large cohort studies and in meta-analyses. Whether pCR, as surrogate end point, should capture the full effect of neoadjuvant chemotherapy on survival is still unproven. To assess the role of pCR as surrogate of disease-free survival (DFS) and overall survival (OS) at a trial level, we performed a trial-based meta-regression of randomized studies comparing different neoadjuvant therapies with data on both pCR rates and outcome end points.
Methods: The systematic search included electronic databases and proceeding of international meetings. No restriction regarding treatment types was set up except for endocrine therapy trials that were excluded. We did not include studies comparing neoadjuvant versus adjuvant chemotherapy. Relevant data were extracted from each selected trial: patients randomly assigned to treatment and analyzed per arm, tumor stage, type of chemotherapy and targeted therapy, cycles number, additional post-surgical treatments, number of patients achieving pCR and number of outcome events per arm. For each trial, the experimental and the control arm were defined. Treatment effects on DFS and OS were expressed as hazard ratios (HRs) and on pCR as odd ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between the treatment effects on the surrogate outcome and the treatment effects on the clinical outcome.
Results: A final set of 28 trials, 57 arms and 29 contrasts for a total of 13,738 patients was included in the analysis. As one trial had 3 arms, it contributed two contrasts to the analysis. The regression of the logHR for DFS on the logOR for pCR, using the complete set of data, demonstrated a weak but significant association between the two effects (R2 = 0.16, p-value = 0.03). Sixteen% of the variability among the effects on DFS can be explained by the observed effects on pCR. The regression of the logHR for OS on the logOR for pCR demonstrated a weak association between the two effects (R2 = 0.15, p-value = 0.04).
Conclusions: This trial-based meta-regression showed a possible role of pCR as surrogate end point for DFS and OS in breast cancer patients treated with neoadjuvant chemotherapy. The surrogacy of pCR warrants to be further evaluated in more homogeneous subsets of clinical trials in the neoadjuvant chemotherapy-based setting.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-03.
Abstract P3-15-02: A prospective, open label, non-comparative trial to determine the incidence of chemotherapy-induced nausea and vomiting associated with the docetaxel-cyclophosphamide regimen in early breast cancer patients. Results from the GEICAM 2009-02 study
Authors: Carañana V , Ramos M , Damau E , García-Saenz JA , González X , Murillo L , Calvo L , Morales S , González-Farré A , Fernández-Morales LA , Carrasco E , Casas MI , Angulo MdM , Cámara MC , García AI , Llombart A , Jara C 
Published: August 2014

Abstract
Background: Docetaxel-Cyclophosphamide (TC) has become a common chemotherapy regimen for moderate-high risk Early Breast Cancer (EBC) patients. The incidence of chemotherapy induced nausea and vomiting (CINV) with TC together with an adequate standard anti-emetic therapy with 5-HT3 antagonist and corticosteroids are unknown. This study investigates the incidence of emesis control (complete response), defined as no vomiting (any grade of NCI CTCAE version 4.0) and no use of rescue treatment within 120 hours after the first cycle of TC. Secondary objective evaluates the efficacy of Aprepitant in non-responding patients.
Methods: EBC patients with no prior moderate-high risk CINV were included. Patients received Docetaxel 75 mg/m2 plus Cyclophosphamide 600 mg/m2 IV every three weeks. Antiemetic treatment consisted of oral Dexamethasone (D) 8 mg (at night) on day 0; oral D 8 mg x 3 (in the morning, 1 hour before chemotherapy and at night) plus 5-HT3 antagonists on day 1; and oral D 8 mg x 2 (in the morning and at night) on days 2 and 3. Non-responding patients (vomiting or need of rescue therapy in the first cycle) were offered participation in the efficacy phase (Aprepitant 125mg day 1 and 80 mg days 2 and 3 added to the standard antiemetic therapy in cycle 2). In addition to the standard NCI-CTCAE adverse event collection, a patient´s diary (from day 1 to 6) and the FLIE (Functional Living Index-Emesis questionnaire) were used. Assuming a 25% (+/- 6%) of patients resistant to standard antiemetic therapy, 212 patients were estimated.
Results: From May-11 to March-13, 212 EBC patients were included. Median age was 57 years (range 34-82), 29.3% were premenopausal. Twenty-seven patients were excluded from the main analysis because of major protocol violations (25) or consent withdrawal (2). Twenty-four patients (13%; IC95%: 8.2 – 17.8) did not respond to standard antiemetics and entered the efficacy phase with Aprepitant. From these 24 patients, 14 (56%; IC95%: 36.5 – 75.5) achieved a complete response on cycle 2. No adverse events related to Aprepitant were observed.
Conclusions: Proper use of standard antiemetic therapy for early breast cancer patients treated with TC provides a high control rate (87%). Among no responding patients, about half of them were rescued with Aprepitant. Identification of the non-responding patients could lead to a better antiemetic control with Aprepitant from the first cycle.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-02.
Abstract P3-15-06: Results of the MARS study on the management of antiangiogenics’ renovascular safety in breast cancer
Authors: Gligorov J , Janus N , Daniel C , Beuzeboc P , Ray-Coquard I , Rey J-B , Jouannaud C , Spano J-P , Thery J-C , Morere J-F , Goldwasser F , Mir O , Scotté F , Oudard S , Azizi M , Dorent R , Deray G , Launay-Vacher V 
Published: August 2014

Abstract
Background:
Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting.
Methods:
This multicentric, prospective, observational study evaluated the renovascular safety of AVD in pts naive from any AVD, conducted in 7 centres in France, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit.
Results:
1124 cancer pts were included; 402 breast cancer (BC) pts received bevacizumab (1st line: 14.4%; median durations of treatment: months)). Median age at inclusion was 55 years (19-65). Visceral, bone and cerebral metastasis frequencies were 74.7, 5.1 and 2.5%, respectively. HTN prevalences: 12.4%. Baseline renal assessment retrieved: Pu 23.9%, Hu 16.2%, mean aMDRD 96.4 ml/min/1.73m2 and 14 pts with aMDRD&lt;60. The incidence of de novo Pu and HTN during f/u was 61.7 and 16.8% (Table). 69.7% of pts with Pu at inclusion improved or remained stable. Among pts with de novo Pu, 75.7% afterwards improved/normalized. No grade 4 Pu has been reported. Renal function remained stable with a mean aMDRD of 96.2 at the end of f/u. 7.4% had grade 2-3 SCr increase (no grade 3-4). No thrombotic micro-angiopathy (TMA) was reported.
Conclusion:
These results on the renovascular safety of bevacizumab in BC pts showed that 1) TMA is rare, 2) Grade 3 Pu developed in 4.6% of pts, with no grade 4, 3) less than 17% developed HTN, and 4) aMDRD was stable. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred.
Renovascular effects in MARS breast cancer patients treated with bevacizumabRenovascular effectsPrevalence at inclusionIncidence during follow-up (de novo**)Pu* (All grades)23.9%61.7%Pu* (Grade 1)22.2%47.1%Pu* (Grade 2)1.7%10.0%Pu* (Grade 3)0.0%4.6%Pu* (Grade 4)0.0%0.0%Hypertension12.4%16.8%Hu* (All Hu)16.2%42.1%Hu* (Traces/+)11.7%33.2%Hu* (++)2.6%6.3%Hu* (+++)1.9%2.6%SCr increase* (All grades)-80.0%SCr increase* (Grade 1)-68.6%SCr increase* (Grade 2)-7.1%SCr increase* (Grade 3)-0.3%*NCI-CTC v4; **de novo = patients with no event at inclusion and who presented an event during follow-up.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-06.
Abstract P3-15-09: Impact of granulocyte colony-stimulating factors on febrile neutropenia risk during early-stage breast cancer treatment
Authors: Ben Abdallah SS , Letarte N , Messier C , Charpentier D , Yelle L , Younan R , Bestawros A 
Published: August 2014

Abstract
Febrile neutropenia (FN) is a significant cause of both mortality and morbidity in patients undergoing adjuvant or neoadjuvant chemotherapy for early-stage breast cancer (ESBC). The risk of FN varies with respect to the type of chemotherapy used and patient-specific characteristics. Granulocyte colony-stimulating factors (G-CSF) are recommended, but not mandatory, as primary prophylaxis for patients at high-risk of FN. This study aimed to evaluate the impact of filgrastim and pegfilgastrim on the incidence of FN during adjuvant and neoadjuvant chemotherapy for ESBC. Risk factors for FN were also assessed.
We conducted a retrospective cohort study that included 297 consecutive patients undergoing adjuvant or neoadjuvant chemotherapy for ESBC between May 2010 and May 2012. Patients on clinical trials were excluded. 173 patients (58%) received primary G-CSF prophylaxis whereas 124 (42%) did not. In patients receiving G-CSF prophylaxis, filgrastim was more commonly prescribed (59.9%), due to reimbursement reasons in Quebec. In total, 38 patients (12.8%) manifested at least one episode of FN. The incidence of FN was significantly reduced in patients receiving primary prophylaxis with G-CSF (p = 0.012).
The most commonly prescribed chemotherapy protocols were FEC-D (5-Fluorouracil, epirubicin, cyclophosphamide followed by docetaxel), AC-T (Adriamycin, cyclophosphamide followed by paclitaxel), and TC (docetaxel and cyclophosphamide). The use of G-CSF as primary prophylaxis was associated with a decrease in FN incidence in patients receiving FEC-D and TC.
Table 1 Incidence of febrile neutropenia in early-stage breast cancer chemotherapy G-CSF primary prophylaxis N = 173Absence of G-CSF prophylaxis N = 124 N (%)N (%) Febrile neutropenia (all chemotherapy)15 (9)23 (19)p = 0.012*TC4/51 (8)5/11 (45)p = 0.01*FEC-D6/59 (10)8/27 (30)p = 0.023*AC-T3/31 (10)8/63 (13)p = 0.668* denotes statistical significance at p &lt; 0.05
One death occurred in a patient receiving FEC-D who had not received prophylaxis. There was no significant difference in the dosing of filgrastim between patients with FN (mean dose received = 5.289 mcg/kg) and those without FN (mean = 5.167mcg/kg) (p = 0.742). Furthermore, previously described risk factors for FN such as age, comorbidities and decreased baseline albumin were not associated with an increased of FN in our study.
Although this was a retrospective study with inherent limitations, our cohort included, to our knowledge, the largest number of patients in a study of G-CSF use in ESBC. We found a statistically significant reduction of FN in patients receiving primary G-CSF prophylaxis. Primary prophylaxis should be routinely offered to patients undergoing chemotherapy for ESBC and in particular, to those receiving docetaxel-containing regimens.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-09.
Abstract P4-01-02: The role of FLT PET early assessment of response to endocrine therapy for early stage breast cancer
Authors: Linden HM , Kurland BF , Link JM , Novakova A , Chai X , Gadi VK , Specht JM , Hills D , Gralow JR , Schubert EK , Korde L , Peterson LM , Doot R , Eary J , Shields A , Krohn KA , Mankoff DA 
Published: August 2014

Abstract
Background: In estrogen receptor positive (ER+) tumors, a low proliferative index (Ki-67) two weeks into endocrine therapy predicts response. FLT PET non-invasively measures tumor proliferation in vivo. The pre-operative window is an opportunity to assess impact of systemic therapies. We tested associations between FLT PET qualitative and quantitative measures and Ki-67 following two weeks of aromatase inhibitor (AI) therapy.
Methods: Women with clinical stage I-II ER+ HER2– breast cancer underwent “run-in” of AI monotherapy prior to definitive surgery. Premenopausal women were given GNRH agonist treatment 2 W prior to AI therapy. FLT PET was performed before AI therapy, and 1-7 days before surgery. Ki-67 was measured in baseline core biopsy and surgical specimens.
Results: Fourteen patients (8 postmenopausal, 6 premenopausal) have been enrolled. All have undergone baseline FLT PET imaging; 11 have completed imaging and surgery, including one premenopausal patient with no residual invasive carcinoma following 26 days of AI therapy. The majority harbored ductal carcinomas (n = 9, 5 with lobular histology) with the majority histologic grade ≥ 2 (n = 11). The median number of days exposed to AI was 19 (range, 9-42). Baseline SUVmax ranged from 1.2 to 3.9 (median 2.2), and post run-in SUV (6-64 days later) ranged from 1.2 to 2.8 (median 1.8). Baseline Ki-67 ranged from 6-26.2, median 11.6; surgical Ki-67 post AI therapy ranged from 0- 20.3 median 3.7, with seven below 5%. SUV and flux declined in most patients, as did Ki-67.
Quantitative FLT flux correlated with tumor response assessed by proliferative index (Ki-67) before the “run-in” period, with a stronger correlation at surgery, Pearson correlation coefficients = 0.41 and 0.82, respectively. FLT SUV and qualitative changes were not strongly associated with Ki-67.
Conclusions: Both pre and postmenopausal women with early stage breast cancer showed imaging and tissue response to endocrine therapy. Quantitative, but not qualitative FLT is a promising tool to assess tumor proliferation and response to therapy. Accrual is ongoing and updated results will be reported.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-02.
Abstract P4-01-06: High resolution breast PET for monitoring response of breast cancer to neoadjuvant chemotherapy
Authors: Nelson JC , Lehde NL , Green CJ , Villanueva-Meyer J 
Published: August 2014

Abstract
Purpose:
To evaluate the sensitivity and accuracy of high resolution breast PET for monitoring the response of breast cancer to neoadjuvant chemotherapy.
Patients and Methods:
High resolution breast PET imaging was performed in 29 women before and following the completion of neoadjuvant chemotherapy in this retrospective patient review study. Tumors were divided into three receptor subtype categories: triple negative, human epidermal growth factor receptor 2 (HER2) positive, and estrogen receptor (ER) positive/HER2 negative. Breast PET was used to characterize lesion morphology, size and maximum FDG uptake. Lesion FDG uptake to background glandular FDG uptake (LTB) was used to allow comparison between imaging studies. Tumor response was assessed dichotomously (i.e. presence or abscence of residual tumor in the surgical specimen) and results were compared to breast PET findings. For discrepant findings, retrospective re-review of the breast PET images was completed with full LTB ratio and Grey/Red evaluation.
Results:
The average age of the patients was 52.6 years (range 24 - 72 years). Pathology found residual tumor in 66% (19/29). Breast PET images correctly identified residual disease in 17/19 patients and correctly predicted a complete pathological response in 9/10 patients for an overall accuracy of 90% (26/29). One tumor was missed due to poor positioning and a second (&lt;1mm in size) was not identified. One breast PET showed residual uptake which was found to be sclerosis on pathology. The cancer subtype with the highest FDG uptake before chemotherapy was the triple negatives with a LTB ratio of 17.4, next highest was the HER2+ at 16.7 while the HER2 negative group showed the lowest metabolic activity at 11.1. One patient with two tumors in the same breast showed total response of one tumor to neoadjuvant chemotherapy while the second tumor grew in size.
Conclusion:
High resolution breast PET was highly accurate in identifying tumor response to neoadjuvant chemotherapy.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-06.