bluuebunny/crossref_metadata_2025_split huggingface dataset:
All-oral combination of oral vinorelbine (NVBo) and capecitabine (X) in HER2-negative metastatic breast cancer (MBC): latest results of a multicenter, international phase II trial with a median follow-up of 37.7 months.
Authors: Tubiana-Mathieu N , Bougnoux P , Becquart D , Chan A , Majois F , Espie M , Morand M , Vaissiere N , Villanova G , Conte P 
Published: December 2010

Abstract
Abstract #6125
Background: Combination chemotherapy regimens are widely considered among the standards in the management of MBC. Oral therapy is an attractive option for many patients. The all-oral regimen of NVBo and X is active with good tolerability in MBC. We report an updated analysis of efficacy and safety from an international phase II study of NVBo plus X.&#x2028; Methods: Main eligibility criteria included: measurable HER2-negative, CT-naive MBC, relapse ≥ 6 months after completing (neo)adjuvant CT, Karnofsky PS ≥ 70%, age ≥ 18 years. Study treatment: 3-weekly cycles of NVBo 80 mg/m2 (after a first cycle at 60) d1 and d8, plus X 1000 (750 if ≥ 65 years) mg/m2 twice-daily d1-14. Treatment was continued until progression or unacceptable toxicity.&#x2028; Results: 55 pts were enrolled and 54 were treated: median age: 58.5 years (41% ≥ 65); prior (neo)adjuvant CT in 63%; type of CT: anthracycline 67%, anthracycline + taxane 18%, CMF 15%; visceral involvement in 78%; &gt; 2 metastatic sites in 46%. Median 7 cycles (range 1-58); median relative dose intensity: NVBo 87%, X 87%; NVBo escalated to the recommended dose of 80 mg/m2 in 91% of pts. G3/4 NCI CTC v2 adverse events: (n=53) neutropenia 49% of pts, (n=54) vomiting 9%, stomatitis 7%, asthenia 7%, febrile neutropenia 6%, infection with G3/4 neutropenia 6%, nausea 4%, diarrhoea 4%, hand-foot syndrome 4%, thrombosis/embolism 4%. Efficacy (n=46 evaluable pts): objective response rate (RECIST) 52% (95% CI [37-67]), CR 2%, PR 50%, SD 28%, PD 20%, disease control (CR+PR+ SD ≥ 6 months) 63% (95% CI [48-77]). Median duration of response was 7.2 months (95% CI [6.0-11.7]). With a median follow-up of 37.7 months, median progression-free survival was 8.4 months (95% CI [5.8-9.7]) and median overall survival was 30.1 months (95% CI [18.2- 40.1]). 21 of the 54 pts treated in the study are still alive.&#x2028; Conclusion: These results show that the all-oral combination of NVBo and X is an effective and well-tolerated first-line poly-chemotherapy regimen for MBC. A retrospective analysis has been made between pts with &lt; or ≥ 65 years (efficacy and safety) and results will be presented during the meeting.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6125.
A comparison of high-dose (HD, 500 mg) fulvestrant vs anastrozole (1 mg) as first-line treatments for advanced breast cancer: results from FIRST.
Authors: Ellis MJ , Llombart A , Rolski J , Feltl D , Macpherson E , Lindemann J , Robertson JF 
Published: December 2010

Abstract
Abstract #6126
Background: The estrogen-receptor (ER) antagonist fulvestrant (Faslodex™) at the approved dose (AD, 250mg) has confirmed efficacy in postmenopausal women with advanced breast cancer following recurrence or progression on an anti-estrogen. However, evidence suggests that higher doses may have greater biological and clinical activity. A recent neoadjuvant study in patients with ER+, locally advanced disease showed significantly greater reductions in Ki67 LI and ER expression for fulvestrant high dose (HD, 500 mg) compared with AD.&#x2028; Methods: FIRST (Fulvestrant fIRst-line Study comparing endocrine Treatments) is a Phase II, randomized, open-label, multicentre study comparing fulvestrant HD (500 mg/month [2×250 mg im injections] plus 500 mg on Day 14 of Month 1) vs anastrozole (1 mg/day) as first-line treatments for postmenopausal women with advanced breast cancer. Eligible patients had no prior treatment for advanced disease and ER+, evaluable disease. Patients received treatment until disease progression or an event necessitating discontinuation. The primary endpoint was clinical benefit rate (CBR), ie the proportion of patients achieving a complete response, a partial response or stable disease for ≥24 weeks. Secondary endpoints included: objective response (OR), time to progression (TTP), duration of response (DoR), duration of clinical benefit (DoCB) and tolerability (adverse events [AEs] and laboratory tests).&#x2028; Results: In total, 205 women (median age 67 years) were included (fulvestrant HD: n=102; anastrozole: n=103). Median follow-up was 6.5 months. CBR was similar between treatments: fulvestrant HD 72.5%, anastrozole 67.0% (odds ratio 1.3023, 95% confidence interval [CI] 0.7170, 2.3976, p=0.3860). OR rates were: fulvestrant HD 36%, anastrozole 35.5%. Median TTP for anastrozole: 12.5 months; fulvestrant HD: not yet reached, corresponding to a 60% longer TTP for fulvestrant HD (hazard ratio=0.6266, 95% CI 0.3929, 0.9991, p=0.0496). DoR and DoCB were also numerically longer for fulvestrant HD. Both treatments were well tolerated, with no significant differences in the incidence of pre-specified AEs or the small number of withdrawals due to AEs.&#x2028; Discussion: Fulvestrant HD offers CB and OR rates similar to those obtained with anastrozole 1 mg, with a significantly longer TTP. Fulvestrant HD was well tolerated, with no unexpected AEs. The AE profile of fulvestrant HD appears consistent with the known toxicity profile of the AD. These results are encouraging and provide further support for the improved clinical activity anticipated with fulvestrant HD. Confirmation of these findings is awaited from an ongoing Phase III, double-blind comparison of fulvestrant HD and AD (CONFIRM).
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6126.
Decreased expression of EZH2 is associated with ESR1 upregulation and response to anti-estrogens.
Authors: Jansen M , Ruigrok-Ritstier K , van Staveren I , Helleman J , Reijm E , Look M , Meijer-van Gelder M , Sieuwerts A , Sleijfer S , Foekens J , Berns E 
Published: December 2010

Abstract
Abstract #6127
Background: In prostate and breast cancer high levels of Enhancer of Zeste Homolog 2 (EZH2) are associated with tumor progression. EZH2, a histone H3 methyl transferase, is part of the polycomb complex. Together with histone deacetylases (HDACs) EZH2 regulates “genome wide” gene transcription silencing. The aims of this study are a) to correlate EZH2 expression with endocrine therapy response in patients with recurrent disease treated with first-line tamoxifen monotherapy and b) to determine the role of EZH2 in endocrine therapy response using in vitro cell line models.&#x2028; Material and Methods: EZH2 mRNA levels were measured with quantitative real-time PCR (qRT-PCR) in 297 retrospectively collected hormone receptor positive (HR+) primary breast tumor specimens of patients with recurrent disease who did respond (N=110) or were resistant (N=187) to first-line tamoxifen monotherapy. In vitro, EZH2 and estrogen receptor (ESR1) expression was downregulated with siRNAs in the human breast cancer cell line MCF7 and assessed for their sensitivity to the selective estrogen receptor degrader ICI164.384 after 96hrs treatment (N=3). To establish therapy response in vitro, cell number counts were determined. All p-values are two-sided and significant if P&lt;0.05.&#x2028; Results: In 297 HR+ breast tumors, EZH2 as continuous variable, associated significantly with poor response (OR= 0.67 [0.49-0.91]; P=0.001) and a shorter progression-free survival (PFS) (HR=1.28 [1.11-1.47], P&lt;0.001). In the multivariate model with traditional predictive factors, the tertile with highest EZH2 levels was independently related with response (OR= 0.50 [0.26-0.98]; P=0.045) and PFS (HR=1.82 [1.33-2.49], P&lt;0.001).&#x2028; In vitro, EZH2 downregulation in MCF7 with siRNAs showed a significant decrease in cell number compared to the mock silenced cell line (40%). Moreover, ICI treatment of EZH2 silenced MCF7 cells resulted in a 70% cell number decrease versus 23% decrease in the controls (P&lt;0.001). In addition, EZH2 downregulation is associated with a twofold upregulation with ESR1 (P&lt;0.001). Conversely, silencing of ESR1 in MCF7 resulted did not alter EZH2 levels but, as expected, increases HER2 protein levels.&#x2028; Conclusion: In primary breast tumors, high EZH2 mRNA levels are associated with poor outcomes after tamoxifen therapy. These results suggest that EZH2 may identify patients at risk for tamoxifen therapy failure. In vitro studies show that downregulation of EZH2 inhibits cell proliferation and on the other hand results in upregulation of ESR1 levels. The latter may explain the increased sensitivity to ICI164.384 of EZH2 silenced cells.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6127.
Fracture risk in women with breast cancer: can baseline assessment of risk be used to guide treatment?.
Authors: Hadji P , Kalder M , Ziller M , Ziller V , Albert U 
Published: December 2010

Abstract
Abstract #6130
Background: Breast cancer (BC) therapies have been associated with decreases in bone health. Recent studies have shown that BC survivors have a 31% increased fracture risk compared with their peers, elevating the importance of monitoring bone health in women diagnosed with BC. Bone mineral density (BMD) has been the standard used by clinical guidelines (WHO, ASCO) to direct therapeutic decisions. However, emerging guidelines place BMD in the context of several other clinical risk factors that have been correlated with overall fracture risk. This retrospective, case-controlled study uses current and emerging guidelines to estimate the percentage of patients with newly diagnosed breast cancer who may be at increased risk for fracture and who require preventive therapy. Methods: Baseline data from 88 pre- and 402 postmenopausal women (PMW) with BC were compared with data from an equal number of healthy age- and body mass index-matched women. BMD was assessed by 2 methods; dual-energy x-ray absorptiometry (DXA) at the lumbar spine (LS) and total hip, and quantitative ultrasonometry (QUS) at the os calcaneus and phalanges. Baseline BMD measurements were collected at a mean duration of 15 and 242 days after diagnosis of cancer in pre- and PMW, respectively. Results: Baseline LS and total hip BMD was similar between the healthy control groups and patients with BC. Among estrogen receptor-positive (ER+) BC patients, 18.8% of premenopausal women and 36.9% of PMW were osteopenic, and 8.9% of PMW were osteoporotic (according to LS BMD). Among ER+ PMW with BC, 15.9% of patients &gt; 65 years of age, 8.3% of patients 55 to 65 years of age, and 1.4% of patients &lt; 55 years of age had osteoporosis. Only 9% of ER+ PMW with BC would have received bone-protective therapy using the BMD limits (T-score ≤ –2.5) set by ASCO treatment guidelines. Based solely on clinical risk factors (eg, if DXA were not available), 6.5% of patients would have been identified for bone-protective therapy. When clinical risk factors and BMD were both used in the fracture-risk assessment, 28.6% of women would have been eligible for bone-protective therapy. Overall, therapy based on ASCO guidelines was estimated to prevent 18% of fractures, whereas combining risk factors and BMD would prevent more than 45% of fractures. Conclusions: Current treatment thresholds seem to inadequately identify patients who would benefit from bone-protective therapy. The results presented here support the use of overall fracture risk assessment in PMW with breast cancer. Using both BMD and clinical risk factors may more effectively identify patients at risk for fracture, although further studies are needed.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6130.
Pooled cardiac safety analysis of patients with HER2-positive metastatic breast cancer receiving trastuzumab.
Authors: Muehlbauer S , Revil C , Leyland-Jones B , Bell R , Baselga J , Marty M , Jones A , Feyereislova A 
Published: December 2010

Abstract
Abstract #6136
Background: The outlook for women with human epidermal growth factor receptor 2 (HER2)-positive early and advanced breast cancer has been significantly improved by the incorporation of trastuzumab (Herceptin®; H) into therapeutic regimens. H has a proven safety profile observed over 10 years of clinical experience in &gt;500,000 patients (pts); however some concerns remain over cardiac dysfunction. This retrospective study reports detailed new analyses of pooled cardiac safety data from 6 metastatic breast cancer (MBC) trials.&#x2028; Methods: Reports of selected adverse events of symptomatic congestive heart failure (CHF) and cardiac rhythm disturbances (CRDs) as well as left ventricular ejection fraction (LVEF) declines were analysed. As definitions of CHF differed between trials, a detailed manual review of original data was performed, including serious adverse event reports. CRDs were identified based on Medical Dictionary for Regulatory Activities terms. LVEF declines were defined as decreases of ≥15 percentage points (pp) from baseline (BL) or ≥10 pp from BL to an LVEF of ≤50%.&#x2028; Results: In total, 882 MBC pts from 6 trials were evaluable for the pooled analysis: in 2 of the trials H was given as monotherapy (WO16229, MO16982) and in others H was combined with paclitaxel (BO15935), docetaxel (M77001), docetaxel and capecitabine (MO16419), and anastrozole (BO16216). There were 683 pts in the H group and 199 in the control group. Pt characteristics were well balanced between treatment groups. Symptomatic CHF was identified in 11 pts (1.6%) in the H group (including 1 death) and none in the control group. Of the 11 pts with CHF, 9 had received prior anthracyclines. Fifty-five CRDs (6.6%) were reported in 45 pts in the H group, with tachycardia (3.2%), palpitations (2.6%) and arrhythmias (0.6%) being the most frequent. With the exception of a single grade 3 event in each group, all CRDs were grade 1 or 2. Nearly all CRDs resolved with no sequelae (50/55 events; 91%). In the control group 2 pts (0.1%) experienced a CRD. The total number of pts evaluable for LVEF decline was 673 in the H group and 194 in the control group; 74 (11.0%) and 7 pts (3.6%), respectively, experienced a drop of ≥10 pp from BL to ≤50%. Eighty-nine (13.2%) and 9 pts (4.6%), respectively, had an LVEF decline of ≥15 pp from BL.&#x2028; Discussion: This pooled analysis of pts from 6 MBC trials demonstrates that H-based treatment in MBC is associated with a low incidence of symptomatic CHF (1.6%) and LVEF declines (11-13% of pts). Although CRDs were observed with H, the majority were of limited clinical significance.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6136.
First step in management of weight gain induced by chemotherapy for early breast cancer.
Authors: Meunier A , Roux P , Bachelot T , Gargi T , Perol D , Bachmann P 
Published: December 2010

Abstract
Abstract #6139
Adjuvant therapies for breast cancer are often associated with weight gain (WG). Overweight, obesity and WG have deleterious consequences for quality of life and probably for breast cancer evolution.&#x2028; This french monocentric prospective study aimed to determine the incidence of overweight, obesity and WG during and one year after adjuvant chemotherapy (CT) for early breast cancer. Secondary goals were to examine the observance of national nutritional recommendations for healthy living, to observe their effects on WG prevention and to estimate patients needs for dietetic management.&#x2028; Method : Patients younger than 66 years candidates for adjuvant CT for early breast cancer underwent dietary evaluation at the beginning of CT and were informed of the benefits of WG prevention, healthy diet and living habits. Written recommendations are given. A dietetic follow-up was systematically proposed. Weight, Body Mass Index (BMI) and nutritional habits over the last year before diagnosis, and at 6 and 12 months after chemotherapy were recorded. Statistical analysis is performed to test the association between WG and initial parameters (alpha level 5%).&#x2028; Results: Of 272 consecutive patients recruited from Oct 2004 to Oct 2006, 242 are evaluated at 6 months and 233 after 1 year. The mean age was 51 years ; 44.1% were not menopausal before chemotherapy. TNM classification was as follows: T0: 15%, T1: 41%, T2: 32%, T3: 9%, T4: 3% and N+: 68%. Chemotherapy regimes were based on doxorubicin for 40% of cases, on taxanes for 1.5% and both for 58.5% . Hormonal therapy was provided to 74.85% of the patients. The average weight before chemotherapy was 65.9 kg (44-117); 25.7% of patients were overweight (25&lt;BMI&lt;30) and 15.1% obese (BMI&gt;30). A third experienced WG during the year before diagnosis. Six months after CT, 52.1% patients had gained weight (&lt;5% body weight for 59%, but &gt;10% for 7.1%) and 29.8 % had lost weight. At one year, WG affected 59.7% of the patients. The average of WG is 5.88% of body weight and 14.4% of the patients gained more than 10%. WG before diagnosis seems to be the only factor associated with post CT absence of weight gain (OR 0.542, IC 95% [0.308-0.954], p= 0.0338). Only 43 women (16%) asked for dietetic follow-up, which induced weight loss for 57%. Health recommendations of the national program of nutrition and health (PNNS in France) were observed by 36.1% of the patients at the beginning of treatment, versus 43.5% at 6 months and 52.1% at one year.&#x2028; Discussion and conclusions :&#x2028; This study confirms the high rate of patients gaining weight after chemotherapy. Nutritional information alone is not sufficient, and appropriate healthy program (nutritional follow up and physical activities) must be proposed to limit weight gain and avoid possible consequences on disease free survival and further co morbidities.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6139.
Multi-disciplinary pre-therapeutic consultation significantly improves management of breast cancer patients.
Authors: Ciobotariu N , Fioretta G , Rapiti E , Neyroud I , Balmer-Majno S , Sappino A , Schaefer P , Bouchardy C , Vlastos G 
Published: December 2010

Abstract
Abstract #6151
Introduction&#x2028; Modern therapeutic management of breast cancer requires a multidisciplinary approach. Since 2001, the Geneva University Hospitals has set up a pre-therapeutic consultation (COSP) involving gynaecologists, medical oncologists, radiation therapists, as well as radiologists, pathologists, plastic surgeons, and nurses. The COSP team discusses and provides therapeutic recommendations for newly diagnosed breast cancer patients seen in our institution. This study evaluates the impact of COSP on patient's management.&#x2028; Patients and methods&#x2028; Between 2001-2005, 1771 patients had breast cancer diagnosis among the resident population: 750 patients were referred to the COSP and 1021 were not. We compared patients and tumours characteristics between these two groups by logistic regression. We compared concordance between initial proposed therapeutic option and final COSP treatment recommendation by heterogeneity test. Changes in treatment were considered as major if they concerned type of surgery, or the addition of systemic neo-adjuvant treatments. Other changes were coded as minor. Trend tests were calculated to evaluate management changes over time.&#x2028; Results&#x2028; Patients referred to the COSP were significantly younger, more often of low socio-economic status, foreigners, divorced, and treated in public sector. They were less frequently diagnosed through screening, and had more advanced stage at diagnosis. Complete initial treatment recommendation was available for 654 patients. For 109 (17%) patients, COSP dramatically changed the initial therapeutic propositions. For 169 (26%) patients, COSP proposed only minor changes. Among patients referred to the COSP, we observed a significant increase of immediate reconstructive surgery (p&lt;0.001) and an increase of standard treatment options for women aged 80 years or more (p&lt;0.001). Similar changes were absent among patients not referred to the COSP.&#x2028; Conclusion&#x2028; The multi-disciplinary pre-therapeutic consultation provides important changes in initial treatment options in routine health care practice. In particular it improves reconstruction and generalisation of good practices in elderly patients. This approach should become a gold-standard in the management of all breast cancer patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6151.
Significant increased recurrence rates among breast cancer patients with HER2-positive, T1a,bN0M0 tumors.
Authors: Rakkhit R , Broglio K , Peintinger F , Cardoso F , Hanrahan EO , Litton JK , Sahin A , Larsimont D , Meric-Bernstam F , Buchholz TA , Valero V , Theriault RL , Piccart M , Ravdin P , Hortobagyi GN , Gonzalez-Angulo AM 
Published: December 2010

Abstract
Abstract #701
Background: Controversy surrounds the prognosis of breast cancer patients with T1a,bN0M0 tumors following locoregional therapy and the need for adjuvant systemic therapy, especially for HER2+ disease. The purposes of the study were to determine the recurrence-free survival (RFS), and distant recurrence-free survival (DRFS) in small HER2+ tumors compared with hormone receptor ( HR)+ and triple receptor- (TN) tumors.&#x2028; Methods: Stage T1a,bN0M0 breast cancers diagnosed between 1973-2003 were reviewed by dedicated breast pathologists. HER2+ tumors were defined as 3+ by IHC or gene amplification. Patients were categorized into 3 groups:TN (ER-, PR-and HER2-), HER2+ (regardless of HR status) and HR+ (HER2-). RFS and DRFS were estimated by the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were fit to determine the association of each group with the risk of recurrence after adjustment for other characteristics.&#x2028; Results: Of the 1796 patients, 427 were excluded from the analysis due to being male (2), lack of receptor information (249), and adjuvant chemotherapy (176) leaving 1369 pts for analysis. Median age was 57 years,(range, 26-88). There were 381(28%) T1a and 988(72%) T1b tumors; HR+ 68%, TN 23%, HER2+ 9%. Patients who had HER2+ breast cancer tended to be younger,(p=0.001); have more T1a tumors, (p=0.001); and have higher nuclear grade,(p&lt;0.001). At a median follow-up of 74 months(range 1-350), there were 160 recurrences and 77 distant metastases. Five and 10-year RFS and DRFS are summarized in the table. After adjustment for other characteristics, patients with HER2+ breast cancer had a significantly worse RFS (HR: 5.19, 95% CI: 3.21-8.39, p&lt;0.0001) and DRFS (HR: 4.66, 95% CI: 2.47-8.80, p&lt;0.0001) compared to patients with HR-positive breast cancer.&#x2028; Conclusions: Breast cancer patients with HER2+ T1a,bN0M0 tumors have a significant risk of relapse and should be considered candidates for adjuvant systemic therapy including anti-HER2 agents.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 701.