bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-16-09: Retrospective analysis of long-term survivors with HER2+ metastatic breast cancer (MBC) treated with trastuzumab in a community setting
Authors: Jones S , Tseng W-Y , Saravanan S , Santos E , Dhanda R , Rembert DS , Yap MA , Lalla D , Brammer M 
Published: August 2014

Abstract
Background: The median survival for patients (pts) receiving trastuzumab (T) in the metastatic setting is approximately 3 years. There are limited data on real world use and outcomes in T treated pts who live longer than 3 years. The objective of this study was to identify and characterize pts with HER2+ MBC who initiated treatment with T (alone or in combination) in a community setting and to determine their treatment patterns and outcomes, including duration of treatment, overall survival (OS) and time to permanent discontinuation of T. Methods: A retrospective observational study was performed using the IKnowMed electronic medical record (EMR) used by the US Oncology Network with the primary time period of 2007 through Dec. 2012. Eligible pts had at least 2 visits at practice locations with full EMR capability. Pts on T when the EMR was implemented had chart review to determine the dates of diagnosis and start of T treatment. Results: The study population included 1856 women with HER2+ MBC who started T (alone or in combination with chemotherapy or hormonal therapy); 873 presented with MBC and 983 developed recurrence following diagnosis of early-stage disease. The median age was 58, range 23 to 96, 59% had ER+ cancer, 64% were postmenopausal and 35% had multiple sites of disease at presentation. Median OS for the entire group was 40.9 months and the median time to permanent discontinuation of T was slightly less, at 39.9 months. Interestingly, the median OS and duration of T use were similar in the recurrent MBC population and in the population who presented with de novo MBC. The proportion of pts receiving T and OS by year are presented (Table). Thirty-two percent of pts are still alive at 6 years, with 17% continuing to receive T.
Outcomes of 1856 Patients Treated with TrastuzumabYear1356Pts still receiving T (%)82%53%27%17%OS (%)84%54%36%32%
Ongoing analysis will evaluate whether there are pt and treatment characteristics that may predict for longer term OS. Conclusions: Using an EMR database we identified 1856 women with HER2+ MBC who initiated treatment with T (alone or in combination) with one third still alive at 5 years and 27% still on T. Future research that focuses on understanding the characteristics of this population can potentially improve care for women with HER2+ MBC with T and newer anti-HER2 agents.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-09.
Abstract P2-16-11: Impact of adjuvant trastuzumab (T) with chemotherapy on breast cancer specific and cardiac outcomes in older women with small, node-negative HER2-positive breast cancer
Authors: Cadoo KA , Morris PG , Patil S , Norton L , Hudis CA , McArthur HL 
Published: August 2014

Abstract
Introduction:
For women with high risk early breast cancer that overexpresses HER2, the role of adjuvant T with chemotherapy is well established. Although the benefits of this approach in women with small, node negative tumors are less well defined, we previously published a retrospective sequential cohort study that suggested that T with chemotherapy is active in this setting. However there are few data about the safety and efficacy of adjuvant T in older women with small, node negative HER2+ breast cancer. Thus, this we conducted a retrospective study of breast cancer specific and cardiac outcomes for this subset.
Methods:
From our previously reported dataset, we identified women &gt; 60y with &lt;2 cm, node-negative HER2+ breast cancer. We identified a “no-T” cohort of 32 women diagnosed Jan ‘02 - May ‘05 and a “T” cohort of 39 patients diagnosed May ‘05 - Dec ‘08. Electronic medical records were reviewed to examine risk factors and incidence of cardiotoxicity as well as patient outcomes including distant disease-free survival (DDFS) and overall survival (OS).
Results:
Women in the two cohorts had similar baseline characteristics including cardiac risk factors (Table 1). There were no cardiac events in the no-T group. In the T group, 3 patients discontinued T due to a cardiac event: 1 with asymptomatic decline in ejection fraction (EF), 1 with atrial fibrillation and dyspnea, and 1 with symptomatic EF decline associated with myocardial infarct and valvular disease. Patients in both cohorts had excellent disease control at a median follow up of 9y and 6y for the no-T and T cohorts respectively. The 3y DDFS numerically favors the T cohort, the confidence intervals are broad and overlapping (Table 1). There were no detectable differences in OS between groups. In our previous report (not selected for age), DDFS at 3yrs was 95% (90-99) and 100% in the no-T (N = 106) and T (N = 155) cohorts respectively.
Conclusion:
In this small retrospective study, older women with small, node negative HER2+ breast cancers had excellent disease control and a low risk of cardiotoxicity. The possible benefits of T in this setting are consistent with prior reports uncontrolled for age.
Table 1 No Trastuzumab N = 32 N (%)Trastuzumab N = 39 N (%)Tumor Size (cm), median (range)1.4 (0.1-2.0)1.3 (0.5-2.0)Multifocal Disease6 (19)4 (10)Grade 324 (75)33 (85)ER Positive20 (63)20 (51)Age, median (range)66 (60-85)65 (60-82)BMI, median (range)24.7 (18.2-34.2)27.3 (18.2-47.1)Chemotherapy16 (50)39 (100)Radiotherapy23 (72)25 (64)Hypercholesterolemia11 (34)18 (46)Hypertension12 (38)13 (33)3yr DDFS (95% CI)91% (74-97)97% (83-100)3yr OS (95% CI)97% (80-100)97% (83-100)
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-11.
Abstract P3-03-07: Combination of eribulin and PI3K inhibitors in triple negative and HER2 expressing breast cancer cell lines results in synergistic growth inhibition and enhanced inhibition of the PI3K pathway
Authors: Luyimbazi D , Luu T , Xing Q , Yan J , Tully D , Han E , Yip RML , Yim JH 
Published: August 2014

Abstract
Background. Patients with triple negative breast cancer (TNBC) have high levels of pAkt expression and activation of the PI3K-mTOR pathway. Eribulin is a microtubule-targeting agent with benefits in treating taxane and anthracycline refractory breast cancer. Our objective was to evaluate its efficacy in inhibiting PI3K pathway activity and cell growth both alone and in combination with PI3K/MTOR inhibitors BEZ 235 and BKM 120.
Methods. TNBC cell lines MDA468, BT549, HS587T, MDA231, and HER2 expressing breast cancer cell line SKBR3 were used for this study. Both MDA468 and BT549 have PI3K- related mutations. The tetrazolium salt, 3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assays were used to assess growth inhibition after 72 hour treatment with eribulin, BEZ 235 and BKM 120 both alone and in combination. Combination indices (CI) generated by Chou-Talalay plots were used to quantify synergy. Western blots were used to evaluate the expression of phosphorylated Akt (pAkt), S6K1 (pS6K1) and S6 (pS6) from 30 min to 24 hours of treatment at different doses.
Results. Eribulin has IC50 ranging from 60 pM to 300 pM, BEZ 235 has IC50 ranging from 50 nM to 80 nM, and BKM has IC50 ranging from 500 nM or higher. Standard dilutions of eribulin in combination with BEZ 235 resulted in synergistic growth inhibition (CI&lt;1) in both MDA468 and BT549 cells at all doses tested, but required higher concentrations (500 to 2000 nM) for BKM 120. Western blot analysis for all cell lines treated with eribulin showed pAkt inhibition by eribulin alone with doses as low as 1 nM and as early as 4 hours. PI3K inhibitor alone confirmed inhibition of pAkt, pS6K1 and pS6 at early time points with feedback increase in pAkt at 24h. While both BEZ 235 and BKM 120 treatment increased pAkt in a dose dependent fashion at 24 hours, combination treatment with eribulin showed a dose dependent decrease in pAkt.
Conclusion. Our study shows significant synergistic growth inhibition with the combination of eribulin and PI3K inhibitors. This may be related to inhibition by eribulin of the feedback increase in pAkt seen with PI3K inhibitors alone at later time points. These findings point to a potential role for combination therapy of both eribulin and PI3K inhibitors in treating refractory metastatic disease.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-03-07.
Abstract P3-06-24: Decrease of mortality from breast cancer in Brazil: Data from a population-based cancer registry
Authors: Ismael GV , Coradazzi AL , Mattos ÉR , Cantarelli A , Beato CM , Ikoma MV , Veneziano DB , Caldeira JRF , Segalla JGM 
Published: August 2014

Abstract
Background: The incidence rates of breast cancer in developed countries increased between 1980 and 1990 due to use of breast cancer screening and lifestyle changes. Since 2000, however, breast cancer incidence has decreased in these areas, which is possibly attributed to less exposure to hormone replacement therapy. Since 1990, the United States, United Kingdom, and France have reported a reduction in breast cancer related deaths, mainly due to improved early detection and more effective therapies. Data considering the trend of incidence and mortality rates in Brazil are scarce. Herein, we have evaluated these trends in a population-based cancer registry.
Methods: We have collected the data from annual rates of breast cancer incidence (BCI) and mortality from breast cancer (MBC) in a population-based cancer registry in Jau (Sao Paulo State, Brazil) and joinpoint regression analysis was used to evaluate the incidence and mortality trends. Annual average percentage change (AAPC) was estimated and increase or decrease in rates was considered when AAPC was statistically significant (p value less than 0.05), otherwise it was considerable stable.
Results: BCI and MBC rates are exposed in Table 1 and 2, respectively.
Table 1. BCI in Jau-SP, from 2000 to 2009.YearNumber of casesBCI (/100,000 women)20003160.9720012944.6520024367.4520033857.6520043143.8820053957.2320062739.2020073744.0320083946.6220093839.33
AAPC for BCI was -3.02% (p = 0.1226) and for MBC was -9,77% (p = 0.0082).
Conclusion: This data from a population-based cancer registry demonstrates that in Jau (Sao Paulo, Brazil), from 2000 to 2009, BCI was stable and MBC has decreased.
Table 2. MBC in Jau-SP, from 2000 to 2009.YearBreast Cancer Related DeathsMBC (/100,000 women)20001320.3620010915.4720021219.8620031216.5620040813.652005067.9520061318.6220070911.312008078.382009076.96
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-24.
Abstract P3-09-03: Final result of randomised controlled phase II study of the efficiency of palonosetron, aprepitant, and dexamethasone for day1 with or without dexamethasone on days2 and 3
Authors: Kosaka Y , Sengoku N , Minatani N , Kikuchi M , Nishimiya H , Waraya M , Enomoto T , Kuranami M , Tanino H , Watanabe M 
Published: August 2014

Abstract
Background: Emesis is one of the major non-hematologic toxicity caused by chemotherapy. The control of Chemotherapy Induced Nausea and Vomiting (CINV) is conducted to a life lengthening. Recently, CINV is controlled by the second generation 5-HT3 receptor blocker (Palonosetron; PALO) and a NK-1 receptor antagonist (Aprepitant; APR). It has been shown that dexamethasone (DEX) with 5-HT3 receptor blocker improves acute / delayed CINV. However, it has not been determined the medication schedule for DEX with PALO and APR. The purpose of this study is evaluated the efficiency of palonosetron, aprepitant and dexamethasone for day1 with or without dexamethasone on days2 and 3. This is final result of current study.
Methods: Breast cancer patients who administered anthracyclin drug regimen have been eligible from April, 2011 to June, 2013. The patients were randomised to group A (PALO/APR/DEX one day) and group B (PALO/APR/DEX three days).
Trial designAprepitant125mg80mg80mg Palonosetron0.75mg dexamethasone9.9mg6.6 mg or placebo6.6 mg or placebo Chemotherapydo days12345
Eighty patients were estimate as study samples. The primary endpoint was a complete response (CR) rate of vomiting, the secondary endpoint was a complete control (CC) rate of vomiting.
Results: Eighty two patients were enrolled in this study. There was not inferiority about CR rate of five days after chemotherapy (81.1% of group A, 82.1% of group B). CC rate of group A (62.2%) was better than that of group B (46.2%). However, CC rate was no significant difference between group A and B. There was no significant difference about any level of nausea between group A and B.
Conclusions: One day of dexamethasone with Palonosetron and Aprepitant treatment is enough to control the emesis of high emetogenic chemotherapeutic agents.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-03.
Abstract P3-09-11: Acupuncture for the treatment of lymphedema in breast cancer patients: A pilot study in Korean women
Authors: Jeong YJ , Kim MS , Jang JI , Bong JG , Park SH , Kwon HJ , Park YS , Kwon OC , Shin IH 
Published: August 2014

Abstract
Purpose: Lymphedema is a troublesome complication of breast cancer treatment. Recent studies suggest that acupuncture is effective in improving lymphedema in breast cancer patients. The purpose of this study was to assess the feasibility and safety of acupuncture for treatment of lymphedema in Korean breast cancer patients.
Methods: This was a prospective, single-arm, observational study. Participants received 18 sessions of acupuncture, delivered 3 times a week for 6 weeks. Patients were evaluated 1 week before treatment commenced (baseline), once a week during treatment, and 4 weeks after the final acupuncture session. Recruitment was performed from September 2012 through December 2012, and 9 breast cancer patients presenting with lymphedema of the upper limb ipsilateral to surgery were enrolled. The primary outcome measure was severity of lymphedema assessed by stages of lymphedema, visual analogue scale (VAS) and circumferential measurements of the upper extremity. The secondary outcome measure was quality of life assessed by a self-administered questionnaire using the SF-36 Questionnaire.
Results: Acupuncture significantly reduced the severity of lymphedema assessed by VAS (p&lt;0.001) as well as circumferential measurements of upper extremity (p&lt;0.001). Four weeks after the final treatment, symptoms were not aggravated. SF-36 scores remained significant for health status at the end of treatment (p = 0.018). No serious adverse events occurred in 162 treatment sessions and during the 4-week follow-up period.
Conclusions: Our results showed the feasibility and safety of acupuncture for the treatment of lymphedema in Korean breast cancer patients. These findings suggest that acupuncture is a useful complementary and alternative treatment for improvement of lymphedema itself and related symptoms in breast cancer patients. A randomized controlled prospective study with a larger sample size is required to clarify the efficacy of acupuncture for such patients in Korea.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-11.
Abstract P3-15-10: Human neuronal model to study chemotherapeutic-induced peripheral neuropathy
Authors: Dolan ME , Wing C , Komatsu M , Delaney SM , Wheeler HE 
Published: August 2014

Abstract
Chemotherapy-induced peripheral neuropathy is the major dose-limiting toxicity for several anti-cancer drugs including taxanes, platinating agents and microtubule inhibitors. In general, animal models have been used to study neuropathy. Our goals are twofold: 1) to create a human model for study of chemotherapeutic induced neuropathy using iCell Neurons derived from human induced pluripotent stem cells (iPSCs) and; 2) to elucidate the molecular genetic mechanisms underlying chemotherapeutic induced peripheral neuropathy by identifying genetic variants and genes that increase the likelihood of this devastating adverse event. We have used this model system to perform functional studies on candidate targets of interest from clinical studies of chemotherapeutic induced neuropathy. Upon treatment of iCell Neurons with increasing concentrations of paclitaxel (0.001-100 μM) for 72 hours, we identified a reproducible 3-5 μm (12-14%) decrease in cell median neurite process length and a 13-19 μm (10-13%) decrease in cell total neurite outgrowth per order of magnitude increase in drug. The same concentrations of vincristine and cisplatin for 72 hours result in a decrease in cell median neurite process length of 6-18% and 2-4% per order of magnitude increase in drug, respectively. No decrease in neurite length is observed with hydroxyurea, a drug that does not result in neuropathy. Paclitaxel binds to beta-tubulin to exert its cytotoxic effect and genetic variants within the promoter of TUBB2A were shown to be associated with paclitaxel induced neuropathy (Clin Cancer Res, 18(16):4441-8, 2012). As a proof of concept, we have shown that decreased expression of the beta-tubulin isotype TUBB2A by siRNA transfection causes decreased median neurite process length (interaction P = 2.0 × 10-4) and decreased total neurite outgrowth (interaction P = 6.2 × 10-10) of iCell Neurons 48 hours post-paclitaxel treatment. To determine clinical relevance, we have developed a protocol to collect blood of breast and ovarian cancer patients experiencing severe paclitaxel-induced peripheral neuropathy and matched patients without neuropathy following similar paclitaxel regimens to create iPSCs and eventually neurons. We hope to create a resource of these cells for the scientific community.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-10.
Abstract P5-05-03: Progesterone receptor antagonists as inhibitors of breast cancer stem cell activity
Authors: Alferez D , Clarke RB , Cresta C , Mnene S , Howell SJ 
Published: August 2014

Abstract
Background: Tamoxifen has become the standard of care for premenopausal women with hormone receptor positive breast cancer (BC). However, resistance to Tamoxifen therapy remains a major clinical problem and we have evidence that cancer stem cells (CSCs) may play a role in recurrence in these patients. The progesterone receptor (PR) is a potential therapeutic target in BC but development of steroidal PR antagonists (PRAs) has been halted due to toxicity issues, despite evidence of activity. Recent reports have linked PR activity to the expansion of adult mammary gland stem cells through paracrine effectors such as RANK-L.
Methods: To investigate the effects of PR antagonism on CSCs, we have tested 2 non-steroidal PRAs; onapristone (Schering AG/Arno Therapeutics) and AZPRA (AstraZeneca) in 2 hormone receptor positive BC cell lines (MCF-7 & T47D) and 8 patient-derived samples (PDS; from malignant pleural effusions and ascitic fluid), using a low adherence mammosphere assay. Western and gene expression array analysis of PDS samples were performed to identify predictive biomarkers.
Results: In the presence of 10nM P4 AZPRA inhibited mammosphere forming efficiency (MFE) in MCF-7 cells by 32% (p&lt;0.0001) and in T47D by 21% (p&lt;0.0001). Similar results were seen with onapristone (34% inhibition in MCF-7 (p&lt;0.002) and 34% in T47D cells (p&lt;0.0002). AZPRA or onapristone significantly reduced MFE in 7 of 8 PDS. Tamoxifen affected MFE in 4/6 PDS samples. In 5 of 7 PDS tested additive effects were seen when AZPRA was combined with tamoxifen (&gt;80% reduction in MFE; p&lt;0.001). A similar effect was seen with onapristone (&gt;70% reduction in MFE (p&lt;0.05)). Data from Western analysis of PR A and B isoforms and gene expression analysis of PDS samples will be presented at the conference.
Conclusions: Preliminary data on PR inhibition presented here support the rationale of administration of PRA in the clinic but predictive biomarkers are required to identify which patients are likely to benefit. Combination of PRA with current anti-oestrogen therapies such as Tamoxifen may be a way of overcoming resistance mechanisms by targeting CSCs.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-03.
Abstract S5-04: Primary results of ROSE/TRIO-12, a randomized placebo controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer
Authors: Mackey JR , Ramos-Vazquez M , Lipatov O , McCarthy N , Kraznozhon D , Semiglazov V , Manikhas A , Gelmon K , Konecny G , Webster M , Hegg R , Verma S , Gorbounova V , Abi Gerges D , Thireau F , Fung H , Simms L , Buyse M , Ibrahim A , Martin M 
Published: August 2014

Abstract
Background: To date, anti-angiogenic strategies in metastatic breast cancer have demonstrated benefits confined to modest improvements in progression-free survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab, an anti-VEGF receptor 2 antibody, is a human IgG1 antibody that specifically binds VEGF receptor 2 and blocks ligand stimulated activation. Early phase studies suggested anticancer effects in several solid tumors, and a phase III study demonstrated survival improvements in gastric cancer. The ROSE trial was designed to evaluate ramucirumab in the setting of HER2 negative, unresectable locally recurrent or metastatic breast cancer.
Methods: In this placebo-controlled randomized multinational phase III trial, patients with HER2 negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomized 1:2 to receive docetaxel 75 mg/m2 + placebo IV every three weeks, or to the same chemotherapy + ramucirumab 10 mg/kg IV every three weeks. Treatment was continued with each agent until investigator determined progressive disease using RECIST criteria, or until unacceptable toxicity. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographical region. An independent data monitoring committee oversaw the trial conduct, the efficacy database resides with TRIO, and this analysis was conducted by the TRIO statistical team in collaboration with Eli Lilly and Co. The primary endpoint was investigator-assessed PFS. The sample size was calculated to provide for this event-driven final PFS analysis and interim OS analysis, and a final OS analysis (to be conducted when at least 792 OS events are observed). ROSE also includes evaluation of potential predictive biomarkers.
Results: Between Aug 2008 and Dec 2011, 1144 patients were randomized. At data cut-off (March 31, 2013), median follow-up was 16.2 months. Safety, final PFS and interim OS results will be presented. Anticipated data availability is early November 2013.
Aggregated Patient CharacteristicsAge(years) 24 - 82Prior Taxane Therapy(%)No74 (%)Yes26Visceral Metastasis(%)No29 Yes71Hormonal Receptor(%)Negative/Unknown24 Positive76Geographic Region(%)Americas24 Asia/Middle East/Africa12 Europe/Australia/New Zealand64
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S5-04.