bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-14-04: Tolerance of Docetaxel: Is Obesity a Risk Factor for Toxicity? A Pilot Study.
Authors: Parent D , Rallet A , Jovenin N , Yazbek G , Cure H , Rey J-B 
Published: June 2012

Abstract
Background Few data are available in the literature regarding chemotherapy dosage adjustment in obese patients. Docetaxel is a lipophilic substance, highly bound to albumin; obesity might result in an accumulation of docetaxel and may lead to a higher rate of toxicity. The objective of this study was to assess the tolerance to docetaxel in obese and non obese patients, according to their body mass index (BMI).
Methods A retrospective study was carried out. Patients were divided according to their BMI, considering a limit of 30 kg/m2. All patients received docetaxel (100 mg/m2) as a part of adjuvant chemotherapy for breast carcinoma. Toxicity of docetaxel such as neutropenia, hand-foot syndrome, mucositis, and neuropathy were assessed in both groups. Patients receiving concomitant therapies leading to similar adverse events were excluded (e.g. cyclophosphamide, 5-FU, …). The included patients received docetaxel alone or in association with trastuzumab or bevacizumab. Qualitative data analysis was performed using Fisher's exact test. Quantitative data were studied using the Student test.
Results Among the 49 patients, 18 (37%) presented with a BMI &gt; 30 kg/m2. The median age was 53 years-old in the group BMI &gt; 30 and 55 years-old in the group BMI &lt; 30 (p = 0.9383). The median dose intensity delivered was 91% (74-100%) in the group BMI&gt; 30 and 97.7% (75-100%) in the group BMI &lt; 30 (p = 0.06). The median value for albumin was 75 g/L (59-86 g/L) in the BMI &gt; 30 and 71 g/L (56-79 g/L) in the BMI &lt; 30 (p = 0.122). Toxicity in both groups was as follows:

No neuropathy was observed in both groups.
Conclusions Obese patients (BMI &gt; 30 kg/m2) presented with more toxicities (p = 0.013). Hypoalbuminemia did not represent a risk factor for toxicity in this study as patients had normal albumin levels. Obesity is a risk factor for toxicity in patients treated with docetaxel. Dosage calculation according to body surface area is not suitable for these patients. Toxicity in the group BMI &lt; 30 seems to demonstrate greater susceptibility to the molecule for these patients.
Further studies will try to identify the different mechanisms of toxicity of docetaxel involved obese patients, including the interaction between docetaxel and fats. Measures have also to be taken to obtain a favorable effectiveness/toxicity balance in obese patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-04.
P4-17-01: Trastuzumab Does Not Increase the Incidence of Central Nervous System (CNS) Relapses in HER2−Positive Early Breast Cancer: The HERA Trial Experience.
Authors: Pestalozzi B , Holmes E , Metzger O , de Azambuja E , Hogge L , Scullion M , Gelber R , Piccart-Gebhart M , Cameron D 
Published: June 2012

Abstract
Background: Retrospective studies of HER2−positive metastatic breast cancer (BC) showed an incidence of CNS metastases of 21% to 34%. We investigated the incidence and clinical aspects of CNS relapse (CNS-R) in patients (pts) enrolled in the HERA trial, a prospectively randomized adjuvant trial in node + or high-risk node - HER2−positive early BC pts.
Methods: 3401 pts were randomized into the 1-year trastuzumab (1yT) or the observation (obs) arms of HERA (Piccart-Gebhart et al, 2005, Gianni et al, 2011). The cumulative incidences of first disease-free survival (DFS) events in the CNS vs other sites were estimated using competing risk analysis. The database of the main study had a clinical cut-off date of 9th June 2008. To obtain additional information regarding CNS-R (including occurrence of CNS-R after first DFS event), a specific CNS-directed questionnaire was sent to investigators of pts who were deceased as of July 2009. Information collected included the date of CNS-R, whether it was symptomatic, the type of CNS-R (brain metastases (BM) or meningeal carcinomatosis (MC)), methods of diagnosis, and treatments at the time of CNS-R. Results: 1yT significantly reduced the risk of other DFS events (p=0.000017, Gray's test), but not of CNS-R (p=0.55) as first event (see table). During the first year of follow up, CNS-R accounted for 15 (14.9%) of the 101 first DFS events in the 1yT arm and 15 (7.7%) of the 194 first DFS events in the obs arm. The analysis of baseline patient and tumor characteristics associated with CNS-R as first event confirmed known risk factors such as young age (&lt;35y), T3 tumor, ≥ 4 + LN, ER neg, and G3.

413 of the 481 questionnaires (85.9%) were returned. 217 of the 413 deceased pts had a CNS-R diagnosed prior to death (52.5%), with more events occurring in the 1yT arm (see table). By contrast, the incidence of CNS-R as first DFS event was balanced across the arms.

Based on the survey data, CNS-R was symptomatic in 189 pts (87.1%) with no differences between arms. BM were present in 211 pts (97.2%), absent in 5 (2.3%), and missing information in 1 (0.5%). MC was diagnosed in 25 pts (11.5%), absent in 187 (86.2%), missing information in 5 (2.3%). Frequencies for BM and MC were very similar in both arms.
Conclusion: This retrospective analysis of a prospective large study shows more than 50% incidence of clinically diagnosed CNS-R in HER2−positive BC pts who have died. CNS-R was symptomatic in most pts. CNS-R at any time was less frequent in the 1yT arm (88 vs 129). There is no evidence that adjuvant trastuzumab increases the incidence of CNS-R.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-01.
P4-17-09: Comparative Performances of Prognostic Indexes for Breast Cancer Patients Presenting with Brain Metastases.
Authors: Braccini A-L , Azria D , Thezenas S , Ferrero J-M , Romieu G , Jacot W 
Published: June 2012

Abstract
Introduction: Incidence of brain metastases (BM) from breast cancer has increased over the past decade, especially for HER2(+) tumours. Several scores and prognosis systems have been developed in the brain metastases (BM) setting in order to help physicians tailor treatment options depending on patient prognosis and to stratify patients enrolled in clinical studies. The aim of our study was to compare the clinical relevance of the major classifications and existing prognostic scores in a population of breast cancer patients affected by BM.
Methods and Materials: In this retrospective study conducted in Montpellier and Nice Cancer Centres, we retrospectively reviewed the clinical and biological data of 250 patients diagnosed with breast cancer BM between 1995 and 2010. Prognostic value and accuracy of recursive partitioning analysis (RPA), graded prognostic assessment (GPA), basic score for brain metastases (BS-BM) and a clinico-biological score (BS) developed in phase I study and validated in the BM setting were compared.
Results: Median age at BM diagnosis was 55 years-old. Most patients (74%) had good performance status (0-1). Brain was the first metastatic site in one third of patients (33.6%). In 12.4% of cases, no extracerebral metastases were detected at BM diagnosis. Among the 250 patients’ tumors, 43.6% overexpressed HER2 receptor and 25.6% were triple negative (negative estrogen receptor, progesterone receptor and HER2 status). After a median follow up of 4.5 years, median overall survival from BM diagnosis was 8.9 months (CI 95%, 6.9−10.3 months). The four scores were able to discriminate patients according to their survival. Chi2 tests showed a correlation between the different scoring systems. In multivariate analysis, the elimination model identified RPA (p = 0.031; hazard ratio, 0.77; 95% confidence interval, 0.64−0.91) and BS (p = 0.043; hazard ratio, 0.5; 95% confidence interval, 0.31−0.80) as the only two independent predictors of survival. RPA was the most accurate score in order to identify patients with high life expectancy, while RPA and BS were the most accurate scores to classify patients with short life expectancy.
Conclusions: In a general unselected population of breast cancer affected by BM, RPA seems to be the most useful score. Integration of biological parameters in addition of existing clinico-radiological scores is promising in order to improve the prognostic determination accuracy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-09.
P4-17-11: Central Nervous System Involvement and Clinical Outcome, Review of 135 Patients, 9-Year Follow Up.
Authors: Watanabe J , Ogiya A , Tadokoro Y , Tanaka K , Takahashi K , Uematsu T , Mitsuya K 
Published: June 2012

Abstract
Background: Breast cancer infiltrates into central nervous system (CNS) with the incidence of 10–20%. It is commonly accepted CNS screening does not contribute to maintain patients’ survival in metastatic breast cancer (MBC). We review our MBC cases with CNS involvement with the aim of searching prognostic factors and evaluating benefits derived from early detection of CNS lesion. Patients and Methods: From October 2002 to January 2011, 473 MBC patients treated at our hospital were reviewed and assessed. CNS lesion was found in 133 of 473 (28.5%) mostly by magnetic resonance imaging. Receptor statuses in patients with CNS disease were as follows; Estrogen receptor-positive 52.4%, HER2−positive 41.1% and triple-negative 12.7%. Asymptomatic patient at the diagnosis of CNS metastasis, in other words, CNS screening performed case, was 57.8%. Liver metastasis prior to CNS involvement was observed in 51.2% of patients.
Results: Within our 9-year follow-up, 122 patients received irradiation or operation, and 118 died. While major cause of death was lung or liver failure, 23.7% was considered as CNS death. Median overall survival from the diagnosis of primary breast cancer, survival from the MBC development and survival from CNS involvement were 1951, 1027 and 321 days respectively. Patients having HER2−disease showed superior survival after detection of CNS disease than HER2−negative patients. (median 514.0 vs 220.0 days, p=0.001) Asymptomatic patients, excluding underwent best supportive care (BSC), could not receive any survival benefit from early detection of CNS lesion. Liver metastasis prior to CNS involvement did not affect patients’ survival. Nineteen patients (14.1%), 17 of them were asymptomatic, received stereotactic irradiation as an initial treatment for CNS lesion, and showed superior survival after CNS event than patients received whole brain irradiation, surgery or BSC (median 670.0 vs 287.0 days, p=0.01).
Conclusion: Our review disclosed superior survival of HER2−disease with CNS metastasis. Early detection of CNS metastasis is only beneficial to patients when stereotactic irradiation will be suited for.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-11.
P4-17-12: Analysis of Predictive and Prognostic Factors for Metastatic Breast Cancer Patients with Brain Metastasis Treated by Whole Brain Radiotherapy.
Authors: Park IH , Lee KS , Shin KH , Ro J 
Published: June 2012

Abstract
Background We addressed the progression free survival of brain metastasis (PFS_BM) in metastatic breast cancer (MBC) patients treated by whole brain radiotherapy (WBRT) for brain metastasis (BM). In addition, we investigated predictive and prognostic factors for the PFS_BM and OS_BM.
Patients and methods A total of 212 patients with BM, treated by WBRT at the National Cancer Center between January 2000 and December 2010 were reviewed. The PFS_BM was defined as the time interval from the date of start of WBRT to the date of a progression of metastatic lesions in the brain or death or last follow-up.
Results The median age of patients was 45 years (range, 22–72 years) and the median time to brain metastasis was 12.7 months (range, 0.0−72.8 months).

Of all patients, 50 (23.6%) patients were hormone receptor (HR) positive and 104 (49.1%) HER2 positive. Six patients received a surgery or a focal radiotherapy for metastatic lesions prior to WBRT. Seventy one (33.4%) patients had well controlled extracranial systemic disease (CR+PR+SD) when brain metastasis was diagnosed. The median survival after BM (OS_BM) was 5.4 months (95% CI, 4.4−6.4 months) and approximately 14.6% of patients died mainly of progressive brain metastasis. The PFS_BM was significantly affected by poor performance status (PS ≥3) (P&lt;0.001), uncontrolled systemic disease status (P=0.029), disease free interval (DFI) &lt; 2 years (P=0.011), no chemotherapy after BM (P&lt;0.001), and HER2 positivity (P=0.002). Of those, poor PS, no chemotherapy after BM, and uncontrolled systemic disease status were remained important factors on a multivariate analysis. In terms of OS_BM, poor PS (P&lt;0.001), older age (P=0.005), number of systemic metastatic sites &gt;3 (P&lt;0.001), uncontrolled systemic disease status (P&lt;0.001), disease free interval (DFI) &lt; 2 years (P=0.014), no chemotherapy after BM (P&lt;0.001), and visceral involvement (P=0.009) were significant factors. Of those, poor PS (P&lt;0.001), uncontrolled systemic disease status (P&lt;0.001), and no chemotherapy after BM (P&lt;0.001) were important factors for shorter OS_BM when adjusted with other factors.
Conclusions Uncontrolled extracranial systemic disease status, no chemotherapy after BM, and poor PS were significant factors for shorter PFS_BM and overall survival after brain metastasis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-12.
P4-18-03: Basal-Like Phenotype of BRCA Associated Ductal Carcinoma In-Situ.
Authors: Kristjansdottir K , Laprise J , Scalia-Wilbur J , Simon R , Steinhoff M , Legare R 
Published: June 2012

Abstract
Background: Molecular profiling has identified different subtypes of invasive carcinoma. The basal-like tumors represent a subgroup that is known for aggressive behavior. The NCCN guidelines recommend genetic testing for patients with triple negative breast cancer as over 80% of breast cancers in BRCA1 mutation carriers are triple negative tumors, and 70% of those fulfill criteria for basal-like tumors. Ductal carcinoma in-situ (DCIS) is thought to represent a non-obligate precursor to invasive breast cancer. Little is known about basal-like precursor lesions and their association with germline BRCA mutations. The aims of this study were to characterize the immunohistochemical phenotype of BRCA associated DCIS and evaluate the clinical importance of such lesions.
Material and Methods: We identified 32 cases of DCIS from 28 women with a known BRCA1/2 mutation, from our genetics database. Tumor samples were reviewed to identify areas of DCIS for staining. Five micron sections were stained on the Dako Autostainer with antibodies to estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), epidermal growth factor receptor (EGFR), and CK 5/6.
Results: 44% of the DCIS tumors were from BRCA1 mutation carriers and 56% from BRCA2 mutation carriers. 53% of the samples were triple negative (staining negative for ER, PR, HER-2) and 69% of the triple negative tumors were basal-like tumors (staining positive for either EGFR or CK5/6). The basal-like DCIS specimens were all high grade, and they all came from BRCA1 positive patients. 71% of BRCA1 positive DCIS had basal-like features.
Conclusions: DCIS in BRCA1 mutation carriers shows basal-like features that are in line with historical control for invasive carcinomas in the same group, suggesting that DCIS is a precursor lesion for BRCA1 positive cancer. Although further investigation is needed, our data suggest that patients with basal-like DCIS should be offered genetic testing.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-18-03.
P4-19-04: Evaluation of Histopathological Parameters in Male Breast Cancer Reveals Differences Compared with Female Breast Cancer.
Authors: Nilsson C , Johansson I , Ahlin C , Thorstenson S , Bergkvist L , Amin R-M , Holmqvist M , Hedenfalk I , Fjällskog M-L 
Published: June 2012

Abstract
Purpose: To characterize male breast cancer (MBC) by evaluating established histopathological parameters and their prognostic value.
Methods: 197 male patients with invasive breast cancer and available paraffin-embedded tumor tissue were retrospectively assessed. Patient files were reviewed for clinicopathological data. Tumors were re-evaluated for histologic grading on conventional sections. Immunohistochemical (IHC) stainings for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), silver-enhanced in situ hybridization (SISH), Ki-67, CK5/6 and epidermal growth factor receptor (EGFR) were performed on tissue micro arrays. Data on vital status and cause of death were retrieved from the Cause of Death Registry. Cox proportional regression models were used for uni- and multivariate analyses.
Results: ER and PgR positivity was demonstrated in 93 and 78 % of patients, respectively. Nottingham histologic grade III was seen in 41% and HER2 positivity in 11% of all patients. Defining molecular phenotypes using IHC markers revealed luminal (ER+ and/or PgR+, and HER2−) in 83%, luminal/HER2+ (ER+ and/or PgR+, and HER2+) in 11%, basal-like (ER-,PgR-,HER2−,EGFR+ and/or CK5/6 +) in 1%, but no cases of HER2-like or unclassified. Node-positivity (HR 4.6; 95% CI 1.9−11.4), tumor size &gt; 20 mm (HR 2.3; 95% CI 1.1−5.0) and ER-negativity (HR 5.2; 95% CI 1.9−14.2) were significant risk factors for breast cancer death. Grade, HER2 status, Ki-67, or age did not demonstrate independent prognostic information. No difference in breast cancer deaths was demonstrated between luminal and luminal/HER2.
Conclusion: Male breast cancer tumors seem to be of grade III more often than female breast cancer, whereas HER2 expression appears equally common. In our study, the most important predictors for breast cancer death in male breast cancer were lymph nodes, tumor size and ER status. The most common molecular phenotype was luminal.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-04.
P4-20-03: T-Cell Cytokine Production Related to Progression of Breast Cancer Patients.
Authors: Cohen EN , Gao H , Lee B-N , Giordano A , Tin S , Anfossi S , Parker CA , Cristofanilli M , Valero V , Alvarez RH , Hortobagyi GN , Woodward WA , Ueno NT , Reuben JM 
Published: June 2012

Abstract
Background: Impaired immunosurveillance and immune dysregulation contribute to the pathogenesis and progression of breast cancer (BC). Upon activation, T cells synthesize inflammatory cytokines such as TNF-α that can promote or inhibit tumor growth. We therefore investigated T-cell cytokine syntheses as a predictor of disease progression.
Methods: We recruited 115 BC patients [25 with locally advanced breast cancer (LABC), 21 with metastatic breast cancer (MBC), 25 with non-metastatic inflammatory breast cancer (IBC), and 44 with metastatic IBC (mIBC)] and 31 healthy donors (HD) for this ongoing study. The tumor phenotype consisted of 69 hormone receptor (HR) positive (including 26 patients with HER2 positive disease), 16 HR negative but HER2+, 30 triple negative BC (TNBC). To evaluate T cell function, peripheral blood mononuclear cells from patients and HD were stimulated overnight with immobilized anti-CD3 and soluble anti-CD28 antibodies and assessed for the percentage of T cells that synthesized cytokines by multi-parameter flow cytometry. The associations of T cell cytokine production profile with patient progression free survival (PFS) were analyzed by Kaplan Meier Test.
Results: The median follow-up (FU) of 113 evaluable patients was 14.1 months with a median time to relapse of 10.5 months; 54 patients had stable disease (SD) and 59 patients had progression of disease (PD). In the entire cohort, on univariate analysis, metastasis, IBC, stage, and previous treatment predicted for worse PFS (p&lt; 0.05). In non-metastatic patients (LABC+IBC), absolute count of anti-CD3 activated CD8+ T cells producing IL-17 was significantly higher in the SD patients compared with patient with PD (p=0.038), but it did not predict PFS (p=0.073). Similarly in metastatic patients, anti-CD3 activated CD4+ T cells producing TNF-α were significantly higher in patients with SD (p=0.025) and was predictive of longer PFS (p=0.033). Considering all patients with IBC (IBC + mIBC), although patients with PD had significantly fewer (percent and absolute number) anti-CD3 activated T cells capable of producing cytokines, this immune impairment was mostly related to metastasis and previous treatment. However, the percentage of anti-CD3 activated CD8+ T cells producing TNF-α was an independent positive prognostic indicator of PFS (p=0.002).
Conclusion: Higher than average cytokine syntheses by anti-CD3 activated T cells are significantly associated with longer PFS. These data are consistent with the hypothesis that an adaptive immune response can control disease progression.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-20-03.
P4-20-04: Cytokine Synthesis by Activated Dendritic Cells in Relation to Disease Progression in Inflammatory Breast Cancer (IBC).
Authors: Gao H , Cohen EN , Lee B-N , Giordano A , Tin S , Anfossi S , Parker CA , Cristofanilli M , Valero V , Alvarez RH , Hortobagyi GN , Woodward WA , Ueno NT , Reuben JM 
Published: June 2012

Abstract
Background: Deficiencies in innate and adaptive immune responses by plasmacytoid dendritic cells (pDC) and myeloid DC (mDC) have been linked to poor clinical outcome in breast cancer (BC) (Treilleux, Clin Cancer Res, 2004, PMID 15569976). pDC produce IFN-a and pro-inflammatory cytokines that regulate innate and adaptive immunity in breast cancer. mDC present in blood and secondary lymphoid organs secrete IL-12 and induce inflammatory cytokine production by T cells. Therefore, we studied DC activity in the peripheral blood and assessed their function with clinical outcome in breast cancer patients.
Methods: We recruited 115 BC patients [25 with locally advanced non-IBC (LABC), 25 with IBC, 21 with metastatic breast cancer (MBC), and 44 with metastatic IBC (mIBC)] and 31 healthy donors (HD) for this study. Peripheral blood pDC and mDC were activated through toll-like receptor (TLR)-7 to assess IFN-α and IL-10 production whereas mDC were activated through TLR-8 to assess production of IL-12 and TNF-α by multi-parameter flow cytometry. Associations between cytokine production by TLR-activated pDC and mDC with progression free survival (PFS) and overall survival (OS) of patients were analyzed by Kaplan Meier Test.
Results: The median follow-up (FU) of 113 evaluable patients was 14.1 months with a median time to progression of 10.5 months; 54 patients had stable disease (SD) and 59 had progression of disease (PD). Metastasis, previous treatments, and IBC contributed to shorter PFS and OS. Compared to HD, BC patients had significantly fewer total DC (p=0.008), mDC (p=0.008), and pDC (p=0.003) per μL. In general, the number of TLR-7-activated pDC per μL that produced IFN-a(p=0.023) or IL-10 (p=0.027) and the number of TLR-8-activated mDC per μL that produced IL-12 (p&lt;0.001) or TNF-α (p=0,008) were significantly lower in BC patients than in HD. However, patients with DC that produced these cytokines above the median levels of HD had shorter PFS or OS. In IBC patients, higher numbers of TLR-8-activated mDC that produced TNF-α (p=0.025) or IL-12 (p=0.003) predicted shorter OS. In mIBC patients, a higher number of TLR-7-activated pDC producing IFN-α (p=0.024) or IL-10 (p=0.034) predicted shorter PFS.
Conclusion: BC patients had significantly fewer pDC and mDC in peripheral blood than HD. IBC patients with above average numbers of TLR-activated DC capable of producing proinflammatory cytokines had a significantly shorter PFS or OS. Disease progression in IBC is related to an increased number of activated dendritic cells producing inflammatory cytokines.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-20-04.