bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-10-02: Comparative Preventive Efficacy of Select Chinese Herbs in Breast Carcinoma Derived Isogenic Cells with Modulated Estrogen Receptor Functions
Authors: Telang NT , Li G , Katdare M , Sepkovic DW , Bradlow HL , Wong GYC 
Published: August 2014

Abstract
Background: Human mammary carcinoma derived estrogen receptor positive (ER+) MCF-7 cells depend on 17β-estradiol (E2) for cellular proliferation in vitro and for tumor development in vivo. Traditionally, ER functions as a ligand activated nuclear transcription factor with E2 as its physiological ligand, and limited availability of E2 modulates ER functions. We have recently demonstrated preventive efficacy of selected Chinese nutritional herbs in this MCF-7 cell culture model. The present study screened additional Chinese nutritional herbs for their preferential preventive efficacy on MCF-7 cells with modulated ER functions.
Methods: MCF-7 cells were maintained in medium supplemented with either 0.7% serum, &lt;1 nM E2, or 0.7% serum+20 nM E2. This approach, while preserving the MCF-7 genotype, provides isogenic cells with either non-functional ER (ER-NF) or functional ER (ER-F) phenotype, and thereby, enables paired comparisons for the preventive efficacy of herbs on the two phenotypes. Anchorage dependent and anchorage independent growth, cell cycle progression, cellular apoptosis, and E2 metabolism represent the quantitative end points.Results: Long-term maintenance of MCF-7 cells in a serum-depleted culture medium (0.7% serum, &lt; 1 nM E2) selects a proliferative sub-population of E2 responsive cells with transiently non-functional ER due to limited availability of E2. The growth inhibitory effects of non-fractionated aqueous extracts from 15 Chinese nutritional herbs were compared in MCF-7 cells selected for either the ER-NF or the ER-F phenotype. Comparative dose response experiments identified IC50 concentrations, and thereby, facilitated rank ordering for growth inhibition. Although all the herbs tested were effective in the present model, two herbs exhibited greater efficacy for the ER-NF phenotype, eight herbs exhibited greater efficacy for the ER-F phenotype, while five herbs exhibited equal efficacy for both the ER-NF and the ER-F phenotypes. Representative herbs at their respective maximum cytostatic concentrations from these three groups, inhibited anchorage independent growth, induced G1 arrest, induced apoptosis, and regulated E2 metabolism in favor of the anti-proliferative metabolites 2-hydroxyestrone and estriol.
Conclusions: Preferential growth inhibition by Chinese nutritional herbs in isogenic ER-NF and ER-F phenotypes of MCF-7 cells and mechanistic efficacy of representative herbs identify possible leads towards their rapid prioritization for planning prevention trials on ER+ and ER− clinical breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-10-02.
Abstract P1-12-03: Low-dose capecitabine monotherapy in HER-2 negative metastatic breast cancer: a retrospective study.
Authors: Ambros T , Zeichner SB , Zaravinos J , Montero AJ , Ahn E , Mani A , Kronish L , Mahtani RL , Vogel CL 
Published: August 2014

Abstract
Background: Capecitabine (CAPE) has clinical activity in metastatic breast cancer (MBC) at an FDA approved dose of 1,250mg/m2 twice daily for 14 days every 21 days (BID Q14). This schedule has been adopted by many United States oncologists, although the starting dose is often reduced. To determine if lower doses of CAPE have comparable clinical activity as the FDA approved dose, we performed a retrospective analysis.
Methods: A retrospective review of records from a large breast cancer oncology practice and from Sylvester Cancer Center Deerfield Beach from 2000–2008 was performed after approval of the University of Miami IRB. Standard practice was CAPE low dose (CAPE-L) 1,000mg BID Q14. Primary outcome was clinical benefit rate (CBR) defined as complete response (CR), partial response (PR) or stable disease (SD) lasting for ≥ 6 months. Response rates (RR) in patients with measurable disease, progression free survival (PFS), overall survival (OS) defined as time period between beginning of CAPE and death, and adverse events (AE) defined according to the NCI CTCAE version 3.0 were secondary endpoints. A literature review was performed for comparison.
Results: Data from 296 patients (pts) with HER-2 negative MBC were reviewed. Of those, 73 received CAPE-L at a starting dose between 303 mg/m2 and 965 mg/m2 (median 614 mg/m2) BID Q14. Median number of prior lines of therapy was 1 (range 0–10); 34/73 (46.6%) of pts received CAPE-L as first line therapy. 23.3% of pts required dose reductions because of palmar-plantar erythrodysesthesia (PPE) (44%), diarrhea (17%), mucositis (11%) or other (28%). RR in 61 patients with measurable disease was 25%. PR occurred in 16/73 (22%), CR (0%), SD ≥ 6 months 21/73 (29%), and PD 31/73 (43%), with a CBR of 37/73 (51%). Median PFS and OS were 6.2 months (95% CI, 4.4 to 8) and 21.4 months (95% CI, 14.4 to 28.6), respectively. AEs are reported in table 2. We recognized 12 trials that used the FDA approved dose in 1,949 patients. Bidimensionally measurable disease was present in 1,630 patients. CBR was reported as 62% in 1,006 patients and RR as 24% in 398. Weighted averages of median PFS and OS were 5.1 months (95% CI, 4.5 to 5.7) and 12 months (95% CI, 9.6 to 14.4), respectively. Detailed toxicity data were available in 11 trials with 1,883 patients. A comparison of current series with literature review at standard dose follows (table 1).
Conclusion: Compared with previously published data, CAPE-L appeared more tolerable with comparable clinical efficacy as package insert doses.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-12-03.
Abstract P1-12-08: Quality of Life in Patients with Locally Advanced or Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes who Received Eribulin Mesylate or Capecitabine in a Phase III, Open-label, Randomized Study
Authors: Cortes Javier , Awada Ahmad , Twelves Christopher , Yelle Louise , Wanders Jantien , Olivo Martin S , Simons W Robert , Dutcus Corina E , Kaufman Peter A 
Published: August 2014

Abstract
Withdrawn by Author.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-12-08.
Abstract P1-13-04: Optimal duration of adjuvant chemotherapy for high risk node negative breast cancer patients: 6-year results of the prospective randomized phase III trial PACS 05.
Authors: Kerbrat P , Coudert B , Asselain B , Levy C , Lortholary A , Marre A , Delva R , Rios M , Viens P , Brain E , Serin D , Edel M , Mauriac L , Campone M , Mouret-Reynier M-A , Bachelot T , Foucher-Goudier M-J , Roca L , Martin A-L , Roche H 
Published: August 2014

Abstract
BACKGROUND: In 2000, the NIH Consensus meeting concluded that 4 to 6 cycles of adjuvant chemotherapy appeared to provide an optimal benefit; So, we underwent a prospective randomized trial comparing 4 and 6 cycles of FEC 100 (JCO 2005; 23: 2686–2693) for high risk node negative breast cancer patients.
METHODS: This study enrolled 18–65 y women with operable breast cancer, without axillary lymph node involvement, or presence of isolated tumor cells, with size superior to 1 cm and another poor prognostic factor: T &gt; 2 cm, HR –, SBR grade II or III, age &lt; 35 y.
After adequate breast surgery and axillary lymph node dissection or sentinel node technique, they were randomized between arm A, 6 cycles of FEC 100, and arm B, 4 cycles, every three weeks. The local regional treatment was completed following usual recommendations. All HR+ patients received hormonal therapy for 5 years. After August 2005, patients with HER2+ tumors were excluded from this study.
The primary end point was PFS at 5 years. This study was powered to detect a 6% difference in favour of 6 cycles.
Between August 2002 and September 2006, 1516 patients were randomized; 1515 are analysed in ITT. Three patients in the B group did not receive any chemotherapy. There is no significant difference between the two arms for tumor and patient characteristics.
RESULTS At a median follow-up of 73 months we observed regarding PFS a low event rate, 197 for the entire population (13%) 91 in arm A median PFS, vs. 106 in arm B median PFS, without any difference between the two groups for DFS, DDFS, local relapse, overall survival. There was no unexpected toxicity. In the arm A we observed more grade III and IV neutropenia, without congestive heart failure.
CONCLUSION At a follow-up of 73 months, we observed a low relapse rate, with no significant difference between the two arms. Duration of FEC100 does not induce different outcomes in this population. Question of length of adjuvant treatment is still open with and without taxanes.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-04.
Abstract P1-13-13: First planned efficacy analysis of the NNBC 3-Europe trial: Addition of docetaxel to anthracycline containing adjuvant chemotherapy in high risk node-negative breast cancer patients.
Authors: Thomssen C , Kantelhardt EJ , Meisner C , Vetter M , Schmidt M , Martin P-M , Veyret C , Augustin D , Hanf V , Paepke D , Meinerz W , Hoffmann G , Wiest W , Sweep FCGJ , Schmitt M , Jaenicke F , von Minckwitz G , Harbeck N ,   the NNBC 3-Europe Study Group
Published: August 2014

Abstract
Background: Risk assessment in node-negative (N0) breast cancer patients (pts) is routinely performed by established clinico-pathological algorithms (CP) (Schmidt et al. Ann Oncol 2009). ASCO guidelines also recommend invasion markers uPA/PAI-1 (UP; Harris et al. JCO 2007). The prospective randomized multicenter NNBC 3-Europe trial had two questions: 1) Does UP compared to the CP algorithm improve identification of low-risk node-negative breast cancer patients? 2) Does addition of taxanes to adjuvant chemotherapy improve DFS probability in high-risk node-negative breast cancer? Data are mature to report on the second question only.
Methods: Between 2002 and 2009, 4,147 node-negative breast cancer pts were recruited. Risk assessment was performed by CP (43 %) or by UP (57 %). High-risk pts were randomized to receive FE100C*3-Doc*3 (FEC-D) versus FE100C*6 (FEC) as adjuvant chemotherapy. Primary endpoint was disease-free survival probability (DFS). It was planned to accrue 2,572 pts allowing detection of 4% reduction in recurrence probability at 5 years with a power of 80 % at a level of α=0.05 (LogRank) after a minimum observation time of 2.5 years for every recruited patient.
Results: In the intent-to-treat population (ITT, n=2,541), 1,286 high-risk pts received FEC-D, and 1,255 received FEC. In July 2012, 90.8 % of patients had reached the minimum observation time – median follow-up was 43.8, and 44.4 months. Main patients' characteristics were distributed similarly between the two chemotherapy arms: median age was 53 yrs, 37.4 % of pts were premenopausal, median tumor size was 1.90 cm, grade 3 was seen in 53.8 %, hormone receptor status was negative in 30.1 % and HER2 was overexpressed in 20.0 %. Mastectomy was performed in 11 %. All planned courses of FEC-D were given in 84.4 %, of FEC in 91.4 % (p &lt; 0.0001). DFS after 2.5 yrs was for FEC-D 97.5 % (+/− 0.45 %) and for FEC 97.3 % (+/− 0.47 %). Overall-survival probability (OS) after 2.5 yrs was 99.0 % (+/− 0.29 %) for FEC-D and 99.5 % (+/− 0.20 %) for FEC. The survival differences between the two arms were not statistically significant. Per-protocol analysis did not reveal any additional results.
Conclusions: Use of taxanes does not further reduce the rate of early recurrences and led to significantly more treatment discontinuation. Today, with adequate adjuvant chemotherapy even high-risk node-negative breast cancer patients have an excellent prognosis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-13.
Abstract P1-14-04: Long- term outcome after neoadjuvant radiochemotherapy in locally advanced non-inflammatory breast cancer and predictive factors for a pathologic complete remission; results of a multi-variate analysis
Authors: Matuschek C , Boelke E , Roth S , Bojar H , Audretsch W , Janni JW , Nestle-Kraemling C , Sauer R , Speer V , Budach W 
Published: August 2014

Abstract
Background: An earlier published series of neoadjuvant radio-chemotherapy (NRT-CHX) in locally advanced non-inflammatory breast cancer (LABC) has now been updated with a follow up of more than 15 years. Long- term outcome data and predictive factors for pathologic complete response (PCR) were analyzed.
Patients and Methods: 315 LABC patients (cT1-cT4/cN0-N1) were treated during 1991–1998 with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or – in case of breast conservation – an 10-Gy interstitial boost with 192Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time interval between end of RT and surgery were examined in multivariate terms with as endpoint pCR and overall survival.
Results: The total PCR rate after neoadjuvant RT-CHX reached 29.2 % with LABC breast conservation becoming possible in 50.8%. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1,17 [95% CI 1,05-1,31], p &lt; 0,01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80 to 0.99], p = 0.03) could be obtained. Importantly, a pCR was the strongest prognostic factor for long term survival (HR 0.28 [95% CI 0.19–0.56], p &lt; 0.001).
Conclusions: A PCR identifies patients with a significant better prognosis for long-term survival. However, a long time interval to surgery (&gt; 2 months) increases the probability of a pCR after NRT-CHX.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-04.
Abstract P1-14-05: Phase I/II Trial of primary chemotherapy with non-pegylated liposomal doxorubicin, paclitaxel and lapatinib in patients with HER2-positive, early stage breast cancer
Authors: Aktas B , Kümmel S , Krocker J , Elling D , Lantzsch T , Bischoff J , Fersis N , Böhme M , Belau AK , Lampe D , Schmid P 
Published: August 2014

Abstract
Background: Several studies showed that pathologic complete response (pCR) is a surrogate for disease free survival (DFS) and overall survival (OS). Combinations of trastuzumab and anthracyclines in HER2-positive breast cancer are highly active but associated with a high incidence of cardiotoxicity. The risk of cardiac damage can be significantly reduced through liposomal encapsulation of anthracyclines. This phase I/II study was initiated to evaluate the combination of non-pegylated liposomal doxorubicin (NPLD), paclitaxel and lapatinib as primary treatment for patients with early stage, HER2-positive primary breast cancer.
Patients and Methods: Patients with newly diagnosed HER2-positive (IHC 3+ or FISH+) early stage (T1c N1-2 or T2 N0-2) breast cancer were treated with NPLD (60mg/m2; day 1), paclitaxel (175mg/m2, day 1) and lapatinib (750–1500 mg orally daily) in 3-week intervals for up to 6 cycles. The primary endpoints were dose-limiting toxicities (DLT) and pathological complete response (pCR). Secondary endpoints include safety, incidence of cardiac events, and clinical response. Exploratory endpoints include molecular markers for sensitivity or resistance to chemotherapy and/or lapatinib evaluated.
Results: A total of 84 patients have been included. No dose-limiting toxicity were observed and the maximum tolerated doses were NPLD 60mg/m2, paclitaxel 175mg/m2 and lapatinib 1500mg. Recommended phase 2 doses (P2D) were NPLD 60mg/m2, paclitaxel 175mg/m2 and lapatinib 1250mg. The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents. No cardiac event has been observed to date. Preliminary efficacy data confirm a pCR breast rate of 41.7% and pCR rate in breast and lymph nodes of 37.5%, in 32 evaluable patients treated at ≥P2D.
Conclusions: The combination of NPLD, paclitaxel and lapatinib is well tolerated and has high antitumor activity in patients with HER2-positive primary breast cancer. Updated results of all 84 patients will be presented.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-05.
Abstract P1-14-10: Final results of neoadjuvant trial of bevacizumab (B) and trastuzumab (T) in combination with weekly paclitaxel (P) as neoadjuvant treatment in HER2-positive breast cancer: A phase II trial (AVANTHER)
Authors: Fernandez M , Calvo I , Martinez N , Herrero M , Quijano Y , Duran H , Garcia-Aranda M , Suarez A , Lopez-Rios F , Perez D , Perea S , Hidalgo M , Garcia-Estevez L 
Published: August 2014

Abstract
Background: B in combination with T has shown meaningful activity in patients (pts) with metastatic HER2-positive breast cancer. Pathological complete response (pCR) was defined as the absence of invasive disease at the time of histological study and there is a relationship between pCR and disease-free survival (DFS) and overall survival (OS). The complete pathological response rate is between 9 to 34% of patients receiving primary treatment prior to surgery with chemotherapy and when the Herceptin was administrated, a pCR of 39% was reached.
AVANTHER is a Phase II trial of preoperative systemic therapy combining B with T and P in a weekly regimen in HER2 positive breast cancer to assess safety and efficacy of the combination.
Methods: Pts with centrally-confirmed HER2− positive (IHC 3+ or FISH positive) breast cancer (stage II or III including locally advanced) received neoadjuvant chemotherapy (NC) with weekly P (80mg/m2/week) for 12 weeks in combination with weekly T (4mg/kg loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for 4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin plus cyclophosphamide every 3 weeks (4 cycles); primary endpoint was rate of pathological complete response (pCR) in breast and axilla. For all patients, a tissue sample at baseline as well as at surgery was collected for biomarker analyses.
Results: A total of 44 pts have been enrolled. Median tumor size: 3.9 cm. Nine (21%) pts had stage IIA; 19 (45%) stage IIB; 10 (24%) stage IIIA and 4 (10%) stage IIIB. Twenty-nine (69%) pts had estrogen positive receptors.
Data from surgery of 42 patients from a total of 44 patients enrolled were presented in this abstract, but the final results will be present in the symposium. pCR was achieved in 18 (42.9%) pts. Safety and tolerability were good, with rare adverse events of grade 3 [1 (2.4%) episode of severe hypertension, 1 (2,4%) mucosal inflammation].
We presented the results of relationship between magnetic resonance imaging (MRI) and pCR that is one of the secondary objectives of the study.
100% of the patients without pathologic response had stable disease at resonance imaging. Of all patients who had pCR only 55.6% had complete radiological response.
Conclusions: These data show that the combination of P with T and B without an anthracycline for 12 weeks is very effective as NC in HER2 positive breast cancer pts with a high rate of pCR and minimal side effects.
And the MRI is useful for identifying the persistence of residual disease however it only predicts half of the complete pathological responses
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-10.
Abstract P1-14-16: Young age: predicts poor response rate after neoadjuvant chemotherapy in endocrine-responsive breast cancer
Authors: Kim MK , Noh D-Y , Han W , Moon H-G , Ahn S-K , Kim JS , Kim T , Kim JY , Lee JW 
Published: August 2014

Abstract
Background: Breast cancer rarely occurs in very young women(age&lt;35years), its diagnosis and management could sometimes be difficult. Especially, the patients with positive hormone receptors have significantly lower overall and disease-free survival rates in very young age group than in the older age group. In the previous study, adjuvant tamoxifen therapy might provide less survival benefit when added to chemotherapy in very young breast cancer patients. This study was to compare the response to neoadjuvant chemotherapy for HR-positive breast cancer patients according to the age.
Patients and Methods: A total of 551 consecutive patients were evaluated, received preoperative chemotherapy and referred to surgery at the Seoul National University Hospital from January 2001 to December 2010. The clinicopathologic factors and the response to neoadjuvant chemotherapy between the very young age group and the older age group were retrospectively compared. A pCR was defined as the absence of residual invasive carcinoma in the breast.
Results: Among the 551 patients who received neoadjuvant chemotherapy, 297 patients revealed HR-positive. The median age of all patients was 42 (range, 24∼67)years and very young age group accounted for 17.2%(51/297). Of 297 patients, 262 (88.2%) received taxane-containing regimen pre-operatively, and there's no difference of chemotherapeutic regimen between two age groups. There were no differences noted between two age groups about clinicopathologic characteristics. The univariate and multivariate analysis of variables related to ORR(CR+PR vs SD+PD) to neoadjuvant chemotherapy showed that very young age at diagnosis was independent predictive factor for poor neoadjuvant chemotherapeutic response.(p = 0.043, OR = 0.528) And this tendency was observed more significantly in age under 30.(p = 0.001, OR = 0.147) Only thirteen patients(4.4%) achieved pCR, which is relatively lower rate, reflective poor chemotherapeutic response in HR-positive group, and there was no relations between pCR rate and the two age groups(p = 0.861) in this study. Taxane-containing regimen(p = 0.004) and Ki67 level(p = 0.005) were related to pCR statistically significantly. Breast conservation rate is not significantly different between two age groups.(age&lt;35: age&gt;35= 51.2% vs 41.3%, p = 0.150)
Conclusions: The very young age group showed lower ORR(CR+PR) to neoadjuvant chemotherapy, although there was no significant difference in pCR rate between the two age groups in HR-positive breast cancer patients. We might have to consider and revalue the chemotherapeutic role as neoadjuvant therapy in very young age, HR-positive group, since they had lower survival rate than others.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-16.
Abstract P1-14-20: Meta-analysis Results from the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC)
Authors: Cortazar Patricia , Zhang Lijun , Untch Michael , Mehta Keyur , Costantino Joseph , Wolmark Norman , Bonnefoi Hervé , Cameron David , Gianni Luca , Valagussa Pinuccia , Zujewski Jo Anne , Justice Robert , Loibl Sibylle , Wickerham Lawrence , Bogaerts Jan , Baselga Jose , Perou Charles , Blumenthal Gideon , Blohmer Jens , Mamounas Eleftherios , Bergh Jonas , Semiglazov Vladimir , Prowell Tatiana , Eidtmann Holger , Paik Soonmyung , Piccart Martine , Sridhara Rajeshwari , Fasching Peter , Swain Sandra M , Slaets Leen , Tang Shenghui , Gerber Bernd , Geyer Charles , Pazdur Richard , Ditsch Nina , Rastogi Priya , Eiermann Wolfgang , von Mincwitz Gunter 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-20.