bluuebunny/crossref_metadata_2025_split huggingface dataset:
The need for DXA assessment of breast cancer patients following 5 years tamoxifen prior to starting an aromatase inhibitor.
Authors: Brown L , Whannel KJ , McLennan A , Wilson CR , Doughty JC 
Published: December 2010

Abstract
Abstract #6141
Introduction: Aromatase inhibitors are increasingly being used in the adjuvant treatment of post-menopausal women with breast cancer. They are more effective than tamoxifen in terms of disease free survival and have a different side effect profile, all causing loss of bone mineral density. They can be introduced at different points in the adjuvant pathway. It has been postulated that if given in the extended setting, letrozole after 5 yrs tamoxifen, bone health may be less important. Tamoxifen is reported to increase bone mineral density so should make subsequent bone mineral density reduction with letrozole less significant. The aim of this study was to determine whether DXA scanning should be undertaken in women following 5 yrs of tamoxifen prior to starting letrozole.&#x2028; Method: 166 women who had completed 5 years of tamoxifen underwent DXA with assessment of vertebral morphometry and risk factors associated with osteoporosis and fracture rate.&#x2028; Results: Mean age was 63yrs (standard deviation [S.D] 10yrs); 154 women were post menopausal being at least 2 years after their last menstrual period; 12 women were unable to recall when they menopaused. Mean t-score and S.D was calculated at each site; spine -1.26(1.3); femoral neck -1.16(1.1) and total hip -0.91(1.1). Results were categorised by lowest t-score.&#x2028; &#x2028; Conclusion: We have demonstrated that of 166 women following completion of 5 yrs tamoxifen 26.5% have osteoporosis and 35.5% osteopenia. 28% required treatment with bisphosphonates. It cannot be assumed that Tamoxifen will cause a sufficient increase in BMD to render DXA scanning unnecessary. All patients should have DXA scanning following completion of 5 yrs tamoxifen prior to commencing letrozole.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6141.
A pilot study of vascular endothelial growth factor inhibition with bevacizumab in patients with lymphedema following breast cancer treatment.
Authors: Miller KD , Christmon D , Schneider BP , Storniolo A , Clare SE , Sledge GW 
Published: December 2010

Abstract
Abstract #6142
Purpose: Lymphedema is a significant long-term complication of primary therapy for breast cancer but little is known regarding its etiology and persistence other than relation to the number of lymph nodes (LN) removed. We suggest the following model: Mechanical disruption of normal lymphatic drainage leads to increased back pressure on lymphatic vessels producing an increase in interstitial fluid pressure (IFP). The increased in IFP triggers local production of VEGF-C to stimulate compensatory lymphangiogenesis. As VEGF-A (and to a lesser extent –C) also increases vascular permeability, the consequent increase in interstitial fluid and edema predominate. Anecdotally, several patients (pts) with metastatic disease treated with bevacizumab monotherapy noted improvement in long-standing lymphedema. This pilot study was conducted to explore these observations prospectively.&#x2028; Methods: We used an existing biospecimen bank to conduct a case-control study to compare VEGF-A, -C, -D and VEGFR-3 serum concentrations in breast cancer pts with and without lymphedema (matched for age and LN status). In a separate pilot trial, pts with significant unilateral lymphedema receive bevacizumab, 15 mg/kg every 3 weeks. Baseline assessments include arm volume, interstitial fluid pressure (IFP), extracellular fluid volume by lymphometer (ECF), quality of life (QOL) and plasma VEGF-C, -D, and R-3. IFP is measured serially for 24 hours after the first treatment; arm volume, ECF, QOL, and plasma VEGF-C/D/R-3 are assessed at 3 and 6 weeks.&#x2028; Results: Samples were available for 16 pts with chronic lymphedema and 24 matched controls. Median VEGF-C levels were significantly increased in pts with lymphedema (6895 pg/ml vs. 5349 pg/ml, p=0.001). Median VEGF-A levels were slightly higher in pts with lymphedema (375 pg/ml vs.250 pg/ml, p=NS). Eight pts have been enrolled in the pilot trial thus far. Median duration of lymphedema was 4.4 years (2.2-16.6) Median time since surgery was 7.1 years (3.4-17.6); median time since radiation (n=7) was 4.4 years (2.3-7.9). Complete IFP data is available in 5 pts. Baseline IFP was significantly higher in the affected compared to unaffected arm (9.04 vs. -2.07 mmHg; p=0.0017). Median IFP in the affected arm decreased an average of 42.6% 24 hours after bevacizumab infusion (11.1 vs. 6.9 mmHg; p=0.09). Total arm circumference decreased by an average of 2.8 cm three weeks after initial treatment.&#x2028; Conclusions: Preliminary data supports the hypothesis that VEGF plays a central role in the development and persistence of lymphedema after local therapy for breast cancer. Inhibiting VEGF acutely decreases IFP and may be an effective treatment. Treatment and accrual to the pilot trial continues; full data will be available by December 2008.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6142.
Liposomal doxorubicin is less cardiotoxic than epirubicin in patients with breast cancer: evidence from a randomized clinical trial employing biological, tissue Doppler and standard echocardiographic endpoints.
Authors: Lotrionte M , Palazzoni G , Comerci G , Abbate A , Biondi-Zoccai G 
Published: December 2010

Abstract
Abstract #6145
PURPOSE: Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implications in cancer patients treated with this effective yet potentially toxic therapy. Liposomal anthracyclines (such as liposomal doxorubicin) have the potential for more selective uptake by cancer cells and reduced cardiac toxicity, but early detection at subclinical stage by means of non-invasive tests is pivotal to disclose treatment differences. We thus designed a randomized clinical trial, the Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation (LITE) pilot study to compare the safety of liposomal doxorubicin vs standard epirubicin in terms of clinical and subclinical cardiotoxicity.&#x2028; METHODS: Women with breast cancer and indication to anthracycline chemotherapy were randomized to liposomal doxorubicin or standard epirubicin. Multimodality non-invasive tests, including serial troponin, NT-pro-B-type natriuretic peptide (NT-pro-BNP), standard and tissue Doppler echocardiography were used at baseline and then during follow-up visits to identify subclinical cardiotoxicity.&#x2028; RESULTS: A total of 46 females were enrolled, with a follow-up of 11.0±1.4 months. Use of liposomal doxorubicin instead of epirubicin was associated, at follow-up, with significantly higher left ventricular systolic lateral wall velocities (9.89±2.00 cm/s vs 9.79±2.67 cm/s, P=0.011), and significantly smaller decreases in left ventricular ejection fraction (follow-up LVEF 60.8±4.8% vs 57.1±4.3%, P=0.038). In addition, we found significant correlations between peak NT-pro-BNP values and left ventricular ejection fraction (R=-0.451; P=0.021), and that early changes in diastolic and systolic tissue Doppler parameters could significantly predict much later changes in standard echocardiographic parameters, such as left ventricular ejection fraction (R=0.399; P=0.0035), end-diastolic diameter (R=-0.445; P=0.020), end-systolic diameter (R=-0.427; P=0.010), and deceleration time (R=-0.565; P=0.002).&#x2028; CONCLUSIONS: The present randomized clinical trial, by exploiting tissue Doppler imaging parameters, suggests that a chemotherapy regimen based on liposomal doxorubicin is less cardiotoxic than one based on standard epirubicin in the treatment of patients with breast cancer. Moreover, prolonged follow-up from the overall study cohort shows that NT-pro-BNP values and early changes in tissue Doppler parameters can significantly predict later alterations in standard echocardiographic parameters, thus providing a potential tool for early detection of subclinical cardiotoxicity.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6145.
A comparative analysis of the attitudes of doctors and patients towards adherence behaviour and information provision.
Authors: Gavin J , Ung O , Neck P , Everingham S 
Published: December 2010

Abstract
Abstract #6150
Background: Research into adherence to breast cancer therapies has primarily focused upon quantifying adherence rates of patients with an absence of research into the factors affecting adherence behaviour, however, the practitioner-patient relationship is the medium within which the importance of adherence may be discussed and extra support provided. This study is the first to directly compare the attitudes of clinicians and patients towards adherence and information provision using Fishbein's validated model of attitude measurement. Methods: Separate studies completed in 2008 measured attitudes towards adherence and patient information for Australian breast cancer specialists (n=41) and breast cancer patients enrolled in Verve, the Arimidex patient support programme (n=125). These studies were approved by the Southern Cross University Human Research Ethics Committee and survey response rates of 58% for patients and 68% for specialists were achieved. Independent sample t-tests were used to measure differences between clinicians and patients importance and belief strength ratings on the composite variables of disease, product information, lifestyle information, support materials and adherence behaviour. Differences between low and high-risk patient groups were a particular focus of data analysis. Results: Specialists significantly underestimated the importance low and high-risk patients place on many aspects of adherence and patient information. Specialists believe low-risk patients are less likely than high-risk patients to adhere to treatment and understand their condition, product information or lifestyle factors. This view is not supported by the patient data which showed there was no significant difference between patient risk categories in terms of the importance patients placed upon adherence behaviour and the provision of information. Conclusions: There are significant discrepancies between the importance Australian breast cancer specialists and breast cancer patients place on some aspects of their disease management. SpecialistsÂ attitudes towards high-risk patients are more aligned than they are for low-risk patients. Conversely, these data show that a patientÂs breast cancer risk category does not correlate with the importance that patients place upon adherence behaviour and the provision of information. These data suggest that the provision of information should be extended equally to all early breast cancer patients regardless of their risk of recurrence.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6150.
Hormone therapy use before diagnosis and breast cancer survival in the California teachers study.
Authors: Marshall SF , Chang E , Clarke CA , Cress R , Deapen D , Horn-Ross PL , Largent J , Neuhausen S , Reynolds P , Templeman C , Bernstein L 
Published: December 2010

Abstract
Abstract #65
Background: Breast cancer survival appears to be improved by pre-diagnostic use of hormone therapy (HT), but it is unclear from existing studies whether this is attributable to a direct beneficial effect of HT or because HT use encourages the development of certain tumor types with better prognosis. It is therefore important to examine whether the association between HT use and survival still remains after adequate adjustment for tumor characteristics.&#x2028; Methods: The California Teachers Study is an ongoing prospective study of female public school teachers and administrators. These analyses included 2,783 postmenopausal women whose use of HT was known and who were diagnosed with an incident primary invasive breast cancer after joining the cohort in 1995-96 and followed until death or the end of 2005. Incident cancers and tumor characteristics were ascertained through annual linkage with the statewide California Cancer Registry. Deaths were ascertained through annual linkage with the California state mortality files, the Social Security Administration Death Master File and the National Death Index. HT and other covariates were self-reported on the baseline questionnaire. We estimated the relative risk (RR) of breast cancer death stratifying by age in years, and using age in days from breast cancer diagnosis as the time scale (censoring deaths from other causes).&#x2028; Results: During the follow-up period, 159 (5.7%) women died of breast cancer. In unadjusted analysis, former and current HT use, specifically current estrogen-progestin (EP) use (RR=0.37; 0.24-0.57) but also current unopposed estrogen (E) use (RR=0.64; 0.43-0.95), was significantly associated with reduced breast cancer mortality, compared with no HT use. In multivariable analysis, taking into account race, body mass index, smoking history, lifetime physical activity, and co-morbidities, the risk estimates were somewhat attenuated (EP RR=0.40; 0.26-0.63 and E RR=0.67; 0.44-1.00). After additional adjustment for tumor characteristics (stage at diagnosis, estrogen receptor status, number of positive lymph nodes, grade and tumor size) and treatment received (surgery type and radiation) the risk estimates were considerably attenuated (EP RR=0.53; 0.33-0.84 and E RR=0.82; 0.53-1.27).&#x2028; Conclusion: Use of EP before diagnosis was associated with a reduced risk of death due to breast cancer. Use of E was also associated with reduced breast cancer mortality, although the association was not statistically significant after adjustment for indicators of general health, characteristics of the tumor and treatment.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 65.
Influence of anthracycline- and taxane-based neoadjuvant chemotherapy on tumor HER2 protein expression in locally advanced breast cancers: results from the I-SPY TRIAL (CALGB 150007/150012 & ACRIN 6657).
Authors: Livasy C , Carey L , DeMichele A , Cowan D , Markey J , Little D , Investigators I-SPY Clinical , Dressler L 
Published: December 2010

Abstract
Abstract #703
Background: The I-SPY trial is a multi-institutional study of locally advanced breast cancers in which serial biopsies of breast tumors are performed at multiple timepoints, allowing comparison of tumor biomarker status before, during, and after therapy. Tumor HER2 status has an important role in predicting response to chemotherapy and targeted therapy in breast cancer. The aim of this study was to determine if the administration of neoadjuvant chemotherapy was associated with changes in tumor HER2 protein expression.&#x2028; Methods: Eligible patients had biopsy-confirmed primary breast cancer measuring at least 3 cm. Required initial treatment was an anthracycline based neoadjuvant chemotherapy regimen: AC followed by T (91%), AC without T (6%), and chemotherapy beyond AC +/- T 2%. Serial core biopsies were performed at baseline (T1), after one cycle of AC (T2), intra-regimen (T3), and pre-surgery (T4). Immunohistochemistry (IHC) for HER2 was performed centrally on core samples at T1 and T2 and on post-surgery (PS) excision/mastectomy specimens (for patients with residual tumor). HER2 results were classified as negative, indeterminate, or overexpressed using conventional scoring criteria. Tumor HER2 status was compared between timepoints T1 and T2, T2 and PS, and T1 and PS. Patients receiving Herceptin therapy were excluded from this analysis. Additional molecular analysis is being performed and the IHC results will be compared with gene expression and phospho-HER2 results.&#x2028; Results: 221 patients were enrolled and completed therapy. The median age was 49 years, with a range of 27-69. Median tumor size was 6 cm; 58% had clinically positive nodes. HER2 results were obtained centrally at baseline on 178 (80%) patients. 41 of 178 (23%) tumors were positive for HER2 overexpression. The overall pCR rate in HER2 positive patients was 52% compared to 19% for HER2 negative patients (p&lt;0.001). Patient HER2 results were compared at T1 and T2 (n=154), T2 and PS (n=81), and T1 and PS (n=89). Nine of the 32 (28%) HER2 positive patients with multiple timepoint HER2 results were excluded due to receiving Herceptin therapy. The tumor HER2 status between timepoints is summarized in the table below.&#x2028; &#x2028; Conclusions: Tumor HER2 protein expression levels appear stable in patients undergoing neoadjuvant chemotherapy with anthracycline- and taxane-based regimens. Rare tumors (2-3%) showed a change from a HER2 positive result to a HER2 negative result during chemotherapy; these findings may be related to tumor heterogeneity rather than a true treatment-induced change in HER2 status.&#x2028; Support: CALGB CA31964 and CA33601, ACRIN U01 CA079778 and CA080098, NCI SPORE CA58207.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 703.
Multiplexed AQUA-based assessment of SWOG 9313 shows prognostic value of continuous ER, PR and HER2 assessment.
Authors: Rimm DL , Barlow WE , Harigopal M , Tedeschi G , Peggy PL , Yeh I , Haskell C , Livingston R , Hortobagyi GN , Hayes DF 
Published: December 2010

Abstract
Abstract #704
Introduction: HER2 is expressed at high levels due to gene amplification in about 15% of breast cancer cases and it has been shown to be a poor prognostic marker. However, HER2 is also expressed in normal breast duct tissue, albeit a much lower levels. We hypothesized that continuous analysis of expression using AQUA will provide prognostic information beyond that attainable with conventional methods.&#x2028; Methods: A tissue microarray was made from 2123 cases of the 3122 patients accrued to SWOG 9313, in which sequential doxorubicin and cyclophosphamide (A-C) was compared to combination AC. A multiplexed assessment of HER2 and estrogen receptor (ER) was performed on the same slide using the immunofluoresence-based AQUA® method of automated quantitative analysis. Reproducibility and fidelity of multiplexing were determined for each marker by regression analysis.&#x2028; Results: As expected, both ER and PR were significantly predictive of disease-free survival (DFS) when both are tested as continuous variables, both adjusted for node status, tumor size, treatment and menopausal status (p-values 0.005 and &lt;0.001, respectively). HER2, measured as a continuous variable showed a bi-phasic effect. It has been previously reported (Camp et al, Cancer Research 2003, 63;1445) that both the high and low expressers of HER2 have worse outcome (low levels are equivalent to that seen in normal breast ducts). Splitting the SWOG cohort by deciles shows that both the top and bottom decile have worse DFS than the middle 80% (log rank p=0.012). Also, modeling the hazard ratio as a function of concentration shows a U-shape relationship showing both high and low HER2 expression is associated with poorer DFS.&#x2028; Conclusions: The AQUA method provides a reproducible method of continuous measurement of ER, and HER2 on the same slide. In this cohort both ER and PR as continuous variable are highly prognostic, as expected, but multiplexing with HER2 did not affect outcome. Quantitative analysis demonstrated that both low and high levels of HER2 expression were associated with poor outcome. Studies are ongoing to determine the significance of this observation with respect to biological classifications of breast cancer and relationships with breast cancer therapies.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 704.
HER2 status and efficay of taxane-based adjuvant therapy of early breast cancer (EBC): a metanalysis of randomized trials involving 7,831 patients.
Authors: De Laurentiis M , Criscitiello C , Giordano A , Giuliano M , Lauria R , Forestieri V , Montanino A , De Placido S 
Published: December 2010

Abstract
Abstract #707
Background. Taxanes have recently been introduced in the adjuvant treatment of EBC yielding on average an improvement of disease-free-survival (DFS) and overall survival (OS) as compared to anthracycline-based regimens (De Laurentiis et al., JCO 2008). It has been questioned, however, that this average benefit may be driven largely by improved outcome in a restricted subset of patients. Particularly, it has been suggested that only patients with HER2+ tumors may derive benefits from taxane administration (Pritchard et al. JCO 2008). We performed a meta-analysis on the interaction between HER2 status and the efficacy of adjuvant taxane-based therapy by pooling subsets data of the available randomized trials.&#x2028; Methods. We searched the Pubmed database to identify randomized trials that compared taxane-based with non-taxane-based adjuvant chemotherapy regimens for EBC and reported efficacy data according to HER2 status. We also searched the proceedings of major international conferences to identify relevant trials with subset analyses. Hazard Hatios (HRs) for DFS were pooled across the studies according to HER2 status by inverse variance weighting. A pooled test for treatment by HER2 status interaction was performed by weighted linear meta-regression. All statistical tests were two-sided.&#x2028; Results. Six studies were eligible for this analysis, accounting for 11,631 patients, of whom 7,831 had HER2 status information available. Overall, taxanes were superior to non-taxane-based regimens in terms of DFS with a pooled HR = 0.85 (95%CI: 0.77-0.93). At pooled subgroup analysis taxanes yielded a statistically significant DFS improvement both in HER2+ disease (n = 1,730), with a pooled HR = 0.78 (95% CI: 0.67 to 0.92; p= 0.004), and in HER2- disease (n = 6,101), with a pooled HR = 0.88 (95% CI = 0.79 to 0.98; p= 0.02). A test for interaction showed that there is no statistically-significant difference in the efficacy of taxane-based chemotherapy according to HER2 status (p=0.27).&#x2028; &#x2028; Discussion. There is no evidence of interaction between HER2 status and taxane efficacy in EBC. HER2 status should not be used to decide which patients are candidate to adjuvant taxane-based therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 707.