bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new design of clinical trial – use of nomograms – illustration with local treatment of T2 tumors in the SEER database.
Authors: Rouzier R , Lesieur B , Coutant C , Uzan S 
Published: December 2010

Abstract
Abstract #4079
Background: Nomograms are more and more used as models in which known prognostic factors are combined and used to predict individuals outcomes. Their use as pivotal tools for conducting clinical trial without randomizing treatment allocation has never been reported. We sought to investigate if the use of a nomogram could mimic a randomized trial. In this report, we designed a study based on the use of nomograms to investigate the prognosis of patients with tumors measuring 2.1 to 5 cm according to local treatment.&#x2028; Methods: The SEER registry provided data from 17 registries. A survival difference is observed according to surgical treatment (p=0.01) in this database. This difference may account for patient and tumor characteristics leading to the choice of local treatment and not to the local treatment itself. To investigate this hypothesis, we developed a nomogram to predict cause-specific survival in patients with T2 tumors treated with breast conservation therapy (BCT). To provide a more flexible model, we represented continuous variables using restricted cubic splines. We then applied this nomogram to patients treated with mastectomy. In this particular application, a nomogram can provide individual predictions of cause-specific survival taking into account several variables and their interaction. Patients treated with mastectomy were then grouped in deciles and predicted survivals for these subgroups were plotted against observed proportions of patients alive (calibration curve).&#x2028; Results: The study population comprised 128,454 patients. The nomogram for predicting cause-specific survival included number of metastatic nodes, tumor size, age, grade, estrogen receptor status of the tumor, and use of radiation. This nomogram was perfectly well calibrated in an internal validation (bootstrap). In patients treated with mastectomy, the calibration curve was almost perfect with a maximal difference of 0.6% between predicted probabilities and observed proportions (figure). Discrimination was very good (area under the ROC curve = 0.73). This result suggests that the apparent survival difference between T2 patients treated with breast conservation and those treated with mastectomy in the SEER database, is related to tumor characteristics leading to the choice of local treatment and not to the local treatment itself.&#x2028; Conclusion: Nomograms may be useful to test a new treatment or therapeutic strategy without randomization. They can provide theoretical individualized outcome with a reference treatment (taking into account multiple variables, and interaction) for patients receiving an alternative treatment. Any difference between predicted probability and observed proportion reflects that alternative treatment modifies outcome.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4079.
Urinary estrogen metabolites in patients at high risk for breast cancer.
Authors: Im A , Vogel V , Ahrendt G , Lloyd S , Garte S , Ragin C , Taioli E 
Published: December 2010

Abstract
Abstract #4080
Background:&#x2028; Variations in estrogen metabolism may be associated with increased breast cancer risk. Women who have preferential metabolism via 16α-hydroxylation are reported to have a higher risk of developing breast cancer compared to women who have preferential metabolism via 2α-hydroxylation. Profiling estrogen metabolites may identify women who are more likely to develop breast cancer within a population of women with known risk factors. Our aim was to evaluate estrogen metabolism in a group of high risk women.&#x2028; Methods:&#x2028; Women were recruited from the Magee-Women's Hospital High Risk Breast Cancer program. Risk factors included first degree family history, atypia, fibrocystic breast disease, BRCA1/2, Ashkenazi Jewish descent. Urine 2:16 OHE ratios were compared among the high risk group, an average risk control group, and a group of women with breast cancer. We also evaluated the relationship between urine 2:16 OHE ratios and epidemiological risk factors including BMI, alcohol use, smoking history and first degree family history.&#x2028; Results:&#x2028; There were 65 high risk patients, 30 breast cancer patients, and 41 controls. The Kruskaul-Wallis rank test and Wilcoxon rank-sum test were used for analysis. There was a significant difference in 2:16 OHE ratios among all three groups, p=0.0001. Urine 2:16 OHE ratios were lower in the high risk group (median 1.15) compared to the control group (2.22), p=0.00, and were lower in the breast cancer group (1.09) compared to the controls, p=0.00. There was a difference in BMI among all three groups, p=0.002. Overall, the 2:16 OHE ratio was positively associated with BMI, p=0.0006, and with alcohol use, p=0.02. Smoking history did not differ among all groups, and there was no association between smoking history and 2:16 OHE ratio. Within the high risk group, family history was not associated with 2:16 OHE ratio.&#x2028; Conclusions:&#x2028; Our research suggests that there is an association between lower urine 2:16 OHE ratios and high risk breast cancer. This association may be linked to specific risk factors such as BMI and alcohol use. This information may help to further elucidate the clinical relevance of using urinary 2:16 OHE ratios as clinical markers and prognostic indicators in this population.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4080.
Mammographic density and breast cancer risk in Chinese women.
Authors: Gao J , Zhao W , Lian R , Liang X 
Published: December 2010

Abstract
Abstract #4081
Introduction: Mammographic density has been widely accepted as an important breast cancer risk factor. Women with high mammographic density are believed to have an elevated risk of breast cancer. However, no such association has been shown in native Chinese women so far. We carried out a matched case-control study to evaluate the relationship between mammographic density and the risk of breast cancer among Chinese women in a province of Northern China.&#x2028; Method: Cases included 220 women histologically confirmed with breast cancer at a cancer hospital in Northern China between 2005 and 2007. Each case was matched to a control subject with the similar age (within two years old) who attended the same hospital in the same year and diagnosed as benign breast disease or normal breast. Mammograms were the films used for diagnosis. Breast density was evaluated according to Wolf parenchyma patterns through digitalized normal Medio-Lateral Oblique (MLO) mammography view without knowledge of diagnosis. Risk factor information was obtained from archival database of patient-provided information.&#x2028; Results: Compared to women with low-risk (N1 and P1) mammographic parenchymal patterns, those with high-risk patterns (P2 and DY) had an increased risk of breast cancer (odds ratio = 1.9; 95% confidence interval: 1.1 - 3.2) after adjustment for body mass index, age at menarche, and number of full-term pregnancies. There was no statistically significant difference in this association between premenopausal and postmenopausal women.&#x2028; Conclusion: These results indicate that high mammographic density is associated with the risk of breast cancer in native Chinese women. A larger scale study with the validated computer-assisted mammographic density measurement method is being carried out to further confirm this association.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4081.
Mammographic density and breast cancer risk factors in Chinese women.
Authors: Gao J , Zhao W , Lian R , Liang X 
Published: December 2010

Abstract
Abstract #4082
Background: Past studies have indicated that mammographic density is associated with not only breast cancer risk but also breast cancer risk factors in women living in western nations. However, to data, no such association has been shown among native Chinese women. The aim of this cross-sectional study was to investigate the effects of age, body mass index (BMI), age at menarche, parity, and menopausal status on mammographic patterns in women from a province of Northern China.&#x2028; Methods: Seven hundred and two women's mammograms and information of the breast cancer risk factors were obtained from Shanxi province cancer hospital in Northern China. Mammograms were assessed according to the Wolfe classification.&#x2028; Results: Age, BMI, parity, and menopause were inversely and independently related to high-risk mammographic parenchymal patterns. However, there was no statistically significant association between age at menarche and high mammographic density. Relative to subjects aged less than or equal to 35 years, subjects aged greater than 55 years had reduced 62% (OR = 0.38, 95% CI: 0.14 – 1.00) odds of having a high-risk pattern. In comparison to women whose BMI was less than or equal to 25, there was a 51% and 72% reduction in the odds of having high-risk mammographic patterns for those with BMI 25 to 30 and larger than or equal to 30 respectively (OR = 0.49, 95% CI: 0.32 - 0.74; OR = 0.28, 95% CI: 0.12 - 0.68 respectively). Women with more than three children had decreased 68% risk to have high mammographic density compared to those who were nulliparous (OR = 0.32, 95% CI: 0.1 – 1.0). Premenopausal women were more than four times likely to have a high-risk pattern than postmenopausal women (OR = 4.12, 95% CI: 2.17 – 7.87).&#x2028; Conclusion: Our findings demonstrated that mammographic parenchymal patterns are also associated with some risk factors of breast cancer in native Chinese women. This is consistent with most studies carried out in Western countries. Further studies are needed to determine the relationship between quantitative percentage density and breast cancer risk factors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4082.
Seroma formation after breast cancer surgery and its risk factors.
Authors: Lin Y , Yin W , Zhou L , Lu J , Di G , Wu J , Shen Z , Shao Z 
Published: December 2010

Abstract
Abstract #4085
Background:. Seroma formation is one of the most common complications after breast cancer surgery including modified radical mastectomy and breast conservative surgery. Our study aims to investigate the risk factors of postoperative seroma in Chinese breast cancer patients.&#x2028; Methods: Clinical data of 158 women who underwent surgerical therapy for breast cancer in our hospital were collected prospectively and all patients were followed up. The risk factors for seroma occurrence were compared between the seroma group and control group using X 2 test or t test, as well as the logistic regression was used as multivariate analysis.&#x2028; Results: Univariate analysis showed that the average age of the seroma group was significantly higher than those without seroma formation(58.71vs51.00, P=0.0019), but the total serum protein and albumin content were lower (68.47g/L vs 72.53g/L, P=0.009 and 40.75g/L vs 42.52g/L,P=0.020, respectively). In seroma group, the drainage volume of the first three days, the total and daily drainage volume were all higher (all p values less than 0.01), as well as drainage duration and hospital stay were longer(8.3d vs 14.4d, P=0.000 and 11.5d vs 23.7d, P=0.000, respectively). Logistic regression showed that older patients (OR=1.080, 95%CI 1.016∼1.148, P=0.013), lower total serum protein content(OR=0.814, 95%CI 0.705∼0.940, P=0.005)and higher drainage volume in d1(OR=1.009, 95%CI 1.001∼1.016, P=0.022) and d3 (OR=1.017, 95%CI 1.005∼1.029, P=0.005) were all independent risk factors for subcutaneous seroma. The daily average drainage curve showed a gradually decreasing trend with a highest collections in the first three days. The seroma group had significantly higher average daily drainage volume( P=0.034) and longer duration (P=0.000).&#x2028; Conclusion:The risk factors of seroma formation after breast cancer surgery are complicated. However in order to prevent its occurrence effectively, the factors including age, nutrition status and daily drainage volume should be taken into consideration.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4085.
Comparison of palonosetron (PALO) plus dexamethasone on day 1, with or without dexamethasone on days 2 and 3, in the prevention of chemotherapy induced nausea and vomiting (CINV) in breast cancer patients treated with anthracycline/cyclophosphamide regimens.
Authors: Fabi A , Nole' F , Roila F , Medici M , Steger G , Bachmann C , Roncoroni S , Ballinari G 
Published: December 2010

Abstract
Abstract #4088
BACKGROUND PALO is a selective and potent serotonin antagonist, with a pharmacologically different structure and binding affinity compared to older 5-HT3 receptors antagonists. Multiple studies with PALO have demonstrated better efficacy in preventing emesis throughout the 5 days after moderately and highly emetogenic chemotherapy (CT) compared to ondansetron, dolasetron or granisetron.&#x2028; METHODS This was a phase 4, double-blind, randomized, multicenter, parallel study, in 300 CT naïve patients with breast cancer receiving cyclophosphamide &lt;1500 mg/m2 or anthracycline (epirubicin or doxorubicin) alone or in combination. The study aimed to determine whether the efficacy during the 0-120 hr (overall) period after CT, of a PALO single-dose 0.25mg IV administered 30 minutes before CT plus dexamethasone 8 mg IV approximately 1 hr before CT on day 1 (PALO/DEX/Placebo), was non-inferior to the same day 1 regimen followed by DEX 4 mg orally twice daily on days 2 and 3 (PALO/DEX/DEX). The primary endpoint was complete response (CR), defined as no emesis and no rescue therapy, in the overall phase. Emesis, nausea, use of rescue antiemetics, and functional impact were secondary endpoints. Adverse events (AEs) were documented to monitor safety.&#x2028; RESULTS This study showed non-inferiority in CR rates between the two groups in the overall phase, and in the acute and delayed phases (Table I).&#x2028; &#x2028; There were no significant differences between groups for no emesis and no nausea rates. Rates of AEs were similar in the two groups, with no serious drug-related AEs reported.&#x2028; CONCLUSIONS The comparable results between the two groups support the efficacy of PALO plus DEX administration on day 1 only, with no benefit shown for additional doses of dexamethasone.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4088.
A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis comparing lapatinib plus paclitaxel versus paclitaxel alone for first line metastatic breast cancer (MBC) in HER2+ patients.
Authors: Sherrill B , Dileo A , Amonkar M , Koehler M , Arbushites M 
Published: December 2010

Abstract
Abstract #4090
Background: Women with MBC received first line treatment with lapatinib and paclitaxel (L+P) or paclitaxel alone (P) in a phase III randomized, multicenter, double-blind, placebo-controlled study. In a sub-group analysis of HER2+ (ErbB2+) patients, time to tumor progression for L+P was significantly improved, with an emerging trend for survival benefit. The Q-TWiST method was used to examine overall quality-of-life adjusted survival experience comparing the trade-off between treatment toxicities and delayed progression in a subset of the randomized ITT population that overexpressed HER2.&#x2028; Methods: Survival curves for each treatment arm were partitioned into 3 health states: TOX (toxicity) - time with grade 3/4 adverse events (AEs) during progression-free survival time; TWiST (time without toxicity or disease progression) - remaining time prior to progression in which no serious AEs were experienced; REL (relapse) - time until death or end of follow-up following disease progression. The utility-weighted sum of the mean health state durations was derived to calculate a Q-TWiST score and treatment comparisons were made at varying combinations of the utility weights using a threshold utility analysis.&#x2028; Results: The ITT population included 579 subjects ages 23-87 of which 91 were HER2+ (n = 52 L+P, n = 39 P) based on FISH+ or IHC3+ irrespective of FISH (86 patients based on FISH+ or IHC3+ if FISH unknown; n = 49 L+P, n = 37 P). Overall median survival was 96 weeks after randomization based on data through 5FEB07. For the 91 patient cohort, using utility weights of 0.5 for both TOX and REL, i.e. counting 2 days of TOX or REL as 1 day of TWiST, resulted in a 9.4 week difference (p = 0.0459) in quality-adjusted survival favoring L+P. For the 86 patient cohort the difference was 8.5 weeks still favoring L+P (p = 0.1005). Q-TWiST differences between the arms (for 91 patient cohort) ranged from 5-13 weeks across utility weight combinations, with most tests providing a statistically significant advantage of L+P over P alone. Results from the sensitivity analysis using all grade AEs in the TOX state gave similar results.&#x2028; Conclusions: Among HER2+ patients, treatment with L+P resulted in more quality-adjusted survival than with P monotherapy. When utilities for periods of toxicity and relapse were valued at half the utility of TWiST, the Q-TWIST difference was around 9 weeks, approximately 10% of the 96 weeks median overall survival. These findings represent clinically important differences between treatment groups in quality-adjusted survival.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4090.
Response vs. nonresponse to treatment with erythropoiesis stimulating agents among breast cancer patients with anemia: findings from the European anemia cancer treatment study.
Authors: Aapro M , Ludwig H , Bokemeyer C , Soubeyran P , MacDonald K , Albrecht T , Abraham I 
Published: December 2010

Abstract
Abstract #4095
Background. More cancer patients (pts) with anemia are being treated with erythropoiesis stimulating agents (ESA) in Europe than 7 years ago, but treatment response patterns remain poorly documented. The use of ESAs in breast cancer (BCA) is under debate and knowledge about response rates may benefit clinical risk-benefit analysis. We conducted a subgroup analysis of the A.C.T. study to estimate the proportions of responders vs. nonresponders to ESA treatment (Rx) among breast cancer pts with anemia (Hb≤11g/dL) using five commonly used measures of treatment response.&#x2028; Methods. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA Rx. 148 centers in 12 European countries contributed 415 BCA pts who were on chemotherapy, anemic, and treated with an ESA (18.9% of total study sample). Patient demographics, clinical status, treatment patterns, and hemoglobin (Hb) and performance outcomes are reported by Aapro et al. (2008 SABCS). Five measures of treatment response were estimated: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0-12.9g/dL achieved by visit 3.&#x2028; Results. Types of ESA prescribed included epoetin alfa (22.9%), epoetin beta (39.3%), darbepoetin (37.6%), and other (0.2%) at a median standardized dose of 30000 IU/wk. 33.0% of patients received iron supplementation; of these 11.9% received IV iron. Mean Hb increased from 9.9±0.8g/dL to 11.1±1.3g/dL from visits 1 to 3, indicating a positive treatment response across all patients. Table 1 presents the percentages of responders versus nonresponders according to the 5 measures.&#x2028; &#x2028; Conclusions. An increase in Hb of ≥1g/dL over the course of treatment is an attainable goal in approximately three-quarters of BCA pts with anemia. Adding time constraints, increasing the threshold level to ≥2g/dL, and/or setting an evidence-based target range of 12-12.9g/dL is associated with lower response rates. In BCA pts, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4095.
Functional assessment of the arm following breast cancer treatment using the DASH survey.
Authors: Jacobs LK , Kelley KA , Detrani ME , Tsangaris TN , Chang DC 
Published: December 2010

Abstract
Abstract #4096
Treatment of the axilla with surgery and radiation therapy (RT) has a risk of lymphedema and diminished function of the arm. The purpose of this study is to evaluate the Disability of the Arm, Shoulder and Hand survey (DASH) as a potential functional assessment tool post breast cancer treatment by comparing it to the Lymphedema and Breast Cancer Questionnaire (LBCQ), a lymphedema-specific questionnaire, the SF12, and functional arm measurements.&#x2028; A series of patients presenting to the Johns Hopkins Hospital Avon Foundation Breast Center for follow-up of breast cancer were collected. Inclusion criteria are patients &gt; eighteen years receiving either a sentinel lymph node biopsy (SLNB) or axillary node dissection (ALND) at Johns Hopkins Hospital. Exclusion criteria were individuals who reported mental illness, prior deficits of the arm, or any bilateral procedure for treatment of breast cancer. Dependent variables are the DASH, LBCQ, and SF12 scores. Independent measures are arm circumferences and range-of-motion measurements of both arms.&#x2028; The study population included 41 female individuals presenting either prior to or following surgical procedures in the axilla. See Table 1 for demographics. Of those undergoing lumpectomy, 95.24% had RT, none received axillary RT, and 31.58% of the mastectomy patients had RT to the axillary basin. Subjects receiving RT (65.85%) either had whole breast RT (74.07%) or axillary RT (25.93%), others received chemotherapy (53.66%), and a small percentage received herceptin (7.32%).&#x2028; Internal validation of the quality of life surveys were highly correlated to each other. (Table 2). External validity was determined by comparing the quality of life surveys to the physiologic measures. The physical component of the SF-12 was significantly correlated to moderate lymphedema (p=0.019), which is defined as a difference in arm circumference of 2.0 to 3.0 cm. The patient sample included 11 patients with lymphedema, therefore the sample size was insufficient to assess the correlations between arm circumference and range of motion with the DASH and LBCQ.&#x2028; The DASH, LBCQ, and SF-12 are appropriate and valid measures of post-operative quality of life in the patient population post breast cancer treatment. Further patient recruitment is necessary to adequately determine the external validity of the DASH as a measure of the quality of life of patients with lymphedema.&#x2028; &#x2028; &#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4096.