bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of three-genomic regions prognostic signature in small node-negative breast carcinomas.
Authors: Gravier E , Pierron G , Vincent-Salomon A , Savignoni A , Gruel N , Raynal V , Pierga J , Fourquet A , Reyal F , Roman-Roman S , Sastre-Garau X , de Rycke Y , Asselain B , Delattre O 
Published: December 2010

Abstract
Abstract #1081
Background: The purpose of this study was to identify a genomic signature of early metastatic recurrence, in order to predict accurately breast carcinomas clinical outcome and to select patients with node negative and small tumor size (&lt;3cm) who would benefit from adjuvant chemotherapy.&#x2028; Patients and methods: Using genome-wide BAC-PAC Genomic Comparative Hybridization (CGH) array (1kb), we analyzed a training set of 78 patients. All patients had invasive ductal carcinomas and were initially treated by surgery and radiotherapy, without chemotherapy. The validation was performed on an independent test set of 90 patients. The training and tests sets were composed of respectively 53 and 58 patients disease-free survivors at 60 months (good prognosis group), and by 25 and 32 patients with distant metastatic recurrence before 48 months (poor prognosis group). In the training set, a signature was established as a logistic multivariate model of regions containing contiguous BAC clones with statistically different ratios and median frequencies of gains and losses between the poor and the good prognosis groups. This signature was then validated using the independent test set to evaluate its accuracy to classify T0T1T2N0 patients according to their outcome.&#x2028; Results: The training test identified a prognostic signature defined by 3 genomic regions, located on the 2p (38.3 to 40.9Mb), 3p (32 to 80.3Mb), and 8q (78.8 to 128.9Mb) chromosomes. In the test set, 90% of patients of favourable outcome were ER +ve and 88% were PR +ve, compared to 62% and 55% in the poor outcome group, respectively. In the test set, our signature was highly informative to identify patients that developed distant metastases before 48 months: the rate of patients well classified was 0.74, CI (95%): [0.64; 0.83], with a specificity of 95%, CI (95%): [86%; 99%]. On Kaplan-Meier analysis, the poor-prognosis genomic signature group of patients had a RR of 3.5 of metastatic relapse (log rank test p&lt;0.001).&#x2028; Conclusions: Our signature, validated on an independent series of small T0T1T2N0 and on a majority of ER/PR positive tumors, may provide a robust and accurate tool to identify, in addition to classical parameters, patients who would benefit from adjuvant medical treatments. The comparison of this genomic signature with RNA based signatures and clinico-pathological parameters, is currently being investigated.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1081.
Triple negative phenotype: not affecting survival in young patients with operable breast cancer.
Authors: Kim E , Han W , Park I , Lee J , Ko E , Yu J , Moon H , Noh D 
Published: December 2010

Abstract
Abstract #1083
Purpose: To investigate the clinicopathological characteristics and outcomes of triple negative breast cancer in young patients.&#x2028; Experimental Design: We analyzed 1,498 patients with primary invasive breast cancer who underwent surgery between January 2000 and December 2003. Patients were divided into those &lt; 40 and ≥ 40 years old and into triple negative and non-triple negative groups.&#x2028; Results: A total of 326 (21.8%) were aged &lt; 40; relative to patients ≥ 40 years old, the younger group showed larger tumor size, higher lymph node positivity, and elevated Ki-67 index. Recurrence-free survival (RFS; P = 0.0002) and overall survival (OS; P = 0.0483) were significantly lower in the younger group. Three hundred seventy four patients (25.0%) had the triple negative phenotype, and of which 93 (24.9%) were &lt; 40 years old. Univariate survival analysis showed that the triple negative phenotype was not a prognostic factor for either RFS or OS in the younger group. In the older group, however, the triple negative phenotype was a significant prognostic factor for both RFS (P = 0.0103) and OS (P = 0.0081) by univariate analysis, and it remained a significant prognostic factor for OS by multivariate analysis (hazard ratio, 1.9; 95% confidence interval, 1.09-3.44; P = 0.025). When the non-triple negative group was subdivided into luminal and HER2 subtypes, the HER2 subtype showed the worst OS in both age groups (P &lt; 0.001), followed by the triple negative group. However, the difference between the HER2 subtype and the triple negative group was significant only in the younger group (P = 0.0064), but not in the older group (P = 0.1446).&#x2028; Conclusions: Triple negative phenotype did not affect survival in patients &lt; 40 years old, because of the markedly poorer survival of non-triple negative tumors of the HER2 subtype in this age group.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1083.
Telephone disclosure of BRCA1/2 test results: a survey of genetic counselors.
Authors: Bradbury AR , Patrick-Miller L , Cummings SA , Fetzer D , Daly M 
Published: December 2010

Abstract
Abstract #1098
Disclosure of BRCA1/2 test results has historically been conducted in person by a certified genetic counselor (GC) and/or other health care professional. Due to increasing demand for and access to BRCA1/2 testing, there has been interest in providing genetic counseling services, including disclosure of test results, by telephone and internet. The practice of telephone disclosure among certified genetic counselors has not been described. We conducted semi-structured interviews with GCs to determine current prevalence of, and future interest in, telephone disclosure (TD) of BRCA1/2 test results. Surveys were self-administered and completed via a secure web site. Participants were recruited through the NSGC Cancer Special Interest Group. 195 GCs completed the survey (25% response rate). 23% of respondents have provided pre-test counseling by telephone. 98% reported having provided genetic test results by telephone, although many (48%) conduct TD rarely (&lt;25% of the time). 33% reported TD experiences that had made them question TD as a practice. Comfort with TD varied by test result (37% comfortable with TD for positive test results, 77% for true negative results, 49% for indeterminate results and 33% for VUS results). The majority of GCs do not include a physician (85%) in the TD. Many report encouraging in-person follow-up with a GC (44%) and/or physician (30%). Overall, 42% reported being very interested in TD and 73% felt TD could be an acceptable standard practice. These results suggest many genetic counselors have provided genetic test results by phone and are interested in including telephone disclosure of BRCA1/2 test results in their practice. Given provider interest and the expansion of testing for BRCA1/2 and other hereditary cancer syndromes, further research evaluating the cognitive, affective and behavioral responses to telephone disclosure is warranted. Understanding the impact of telephone disclosure on factors such as, comprehension, risk perception, communication and performance of risk reducing behaviors and their mediators will be critical for the development of telephone disclosure policy and procedures that will optimize adaptive responses to receiving genetic test results via telephone or internet.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1098.
Effects of 5 years of treatment with lasofoxifene on incidence of breast cancer in older women.
Authors: LaCroix AZ , Cummings SR , Delmas P , Eastell R , Ensrud K , Reid DM , Vukicevic S , Armstrong RA , Thompson J , Thompson D , Wolter K , Allred C , Goss P , Osborne KC , Powles TJ 
Published: December 2010

Abstract
Abstract #11
The Postmenopausal Evaluation and Risk-reduction with Lasofoxifene (PEARL) Trial evaluated the effects of 5 years of a new potent SERM on the incidence of estrogen receptor positive (ER+) breast cancer (BC) (co-primary endpoints, invasive alone and invasive plus ductal carcinoma in situ [DCIS] together). 8556 women ages 5980 with femoral neck or spine T-score ≤ –2.5 and &gt; –4.5 were enrolled in 32 countries. Women were randomly assigned to receive 0.25 mg/d or 0.5 mg/d of lasofoxifene (LASO), or placebo (PBO). BC events were ascertained through annual clinical breast exam and mammographic screening and adjudicated by physician oncologists and a BC pathologist blinded to treatment assignment. 77% of women completed 5 years of follow-up and 62–64% remained on study medication until planned trial closure. ITT analyses were conducted using Cox Proportional Hazards models. The protocol-defined primary analysis for all ER+ BCs compared each of the LASO groups to PBO. In the PBO group, 21 women developed invasive or non-invasive ER+ BC (17.3/10,000 person-years (P-Y)) compared to 10 in the LASO 0.25 mg/d group (9.0/10,000 P-Y; HR=0.52, 95%CI 0.25–1.08) and 5 in the 0.5 mg/d LASO group (3.3/10,000 P-Y; HR=0.19, 95% CI 0.07–0.56). For all invasive BCs (ER+ve and ve), 20 women in the PBO group were affected (16.4/10,000) compared to 16 in the LASO 0.25 mg/d group (13.2/10,000 P-Y; HR=0.79, 95%CI 0.41–1.52) and 3 in the 0.5 mg/d LASO group (2.5/10,000 P-Y; HR=0.15, 95% CI 0.04–0.50). For total BC, 24 women in the PBO group were affected (19.8/10,000 P-Y) compared to 20 in the LASO 0.25 mg/d group (16.4/10,000 P-Y; HR=0.82, 95%CI 0.45–1.49) and 5 in the 0.5 mg/d LASO group (4.1/10,000 P-Y; HR=0.21, 95% CI 0.08–0.55). Too few cases of DCIS occurred to determine effects of LASO on noninvasive breast tumors. No significant differences among treatment groups were observed for breast density. LASO also reduced the incidence of vertebral (primary at 3 years) and nonvertebral clinical fractures (co-primary at 5-years). LASO increased risk of venous thromboembolic events, but not stroke, endometrial cancer or endometrial hyperplasia and decreased risk of major coronary events at 0.5 mg/d. Endometrial hypertrophy, uterine polyps, and fibroids were more common with LASO while hypertension and hyperlipidemia was less frequent compared to PBO. We conclude that LASO reduces the incidence of ER+ BC and appears to have a favorable benefit-risk profile for prevention of clinical fractures in postmenopausal women with osteoporosis.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 11.
Sharing BRCA results: are there disparities?.
Authors: Beattie MS , Han PZ , Yu T , Chan S , Wilcox C , Crawford B 
Published: December 2010

Abstract
Abstract #1101
Background: BRCA is a unique breast cancer biomarker; it defines risk not only for an individual, but also for a family. Little is known about sharing BRCA results with relatives. This study aims to determine which relatives are told of BRCA results and which relatives pursue BRCA testing. This study also explores whether patient and relative characteristics can account for differences in sharing BRCA results and BRCA testing of relatives.&#x2028; Methods: As part of the UCSF Cancer Risk Program Cohort, all women who receive genetic counseling and BRCA testing at the UCSF/Mt. Zion Comprehensive Cancer Center (CCC) and at San Francisco General Hospital (SFGH) are sent a survey regarding their health habits and their genetic testing experience. Women surveyed are asked: whether they have shared BRCA results; if so, with whom; and whether other family members have pursued BRCA testing. Patient-level variables examined include: cancer status, hospital site, and BRCA results. Relative-level variables examined include: gender and degree of relationship (first- or second-degree).&#x2028; Results: Over 80% of women surveyed have responded to date (n = 151). Overall, 95% report sharing BRCA results with at least one relative, and 41% indicate that other relatives have received BRCA testing. Tables 1 and 2 show rates of telling relatives and of BRCA testing in relatives based on patient and relative characteristics. Although the proportion of BRCA carriers is similar at both sites (22% at the CCC and 20% at SFGH), relatives of SFGH patients are significantly less likely to pursue BRCA testing (p=0.001).&#x2028; &#x2028; &#x2028; &#x2028; Conclusions: After BRCA testing, women are less likely to share results with male and second-degree relatives. The proportion of BRCA carriers is similar at SFGH and at the CCC. Rates of telling relatives of BRCA results are also similar at both sites. A large and significant disparity exists, however, in BRCA testing of relatives of women from SFGH (8% from SFGH vs. 47% from the CCC, p = 0.001). Future research will examine the reasons for low uptake of BRCA testing in this population, barriers to BRCA testing, and potential interventions.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1101.
Enhanced mismatch mutation analysis: a new high throughput screening method for simultaneous detection of point mutation and gross gene rearrangement designed for BRCA1 and BRCA2 genes.
Authors: Gastaldello B , Champ J , Lafon D , Fraud A , Longy M , Viovy J , Weber J , Bonnet F , Sevenet N 
Published: December 2010

Abstract
Abstract #1102
Background : Recent studies showed that large genetic rearrangements (duplication or deletion of one or several exons) are of great importance in genetic diseases. Only few methods such as QMPSF and MLPA fit a routine use for these large deletions and duplications. They have to be performed additionally to a point mutation detection method (usually sequencing or dHPLC), which is labor intensive, time consuming and expensive. We present here a method called Enhanced Mismatch Mutation Analysis (EMMA) based on heteroduplex analysis that offers great sensitivity for point mutation detection and simultaneously detection of gross gene rearrangement by capillary electrophoresis.&#x2028; Material and Methods : EMMA is able to detect point mutations in PCR fragment ranging from 200 bp to 550 bp. It is thus possible to perform size multiplexing and analyze up to 6 fragments in the same run. PCR multiplex fragments of different sizes are prepared by semi-quantitative PCR. Separations are performed in multi-capillary electrophoresis. Poly(acrylamide-g-poly(dimethylacrylamide)) is used as a self coating sieving matrix; this separation matrix contains also additives like free nucleotides for a better sensitivity. One of the fragment is chosen as a reference for peak area normalization.&#x2028; Results : A series of 30 patients has been screened for BRCA1 and BRCA2 genes simultaneously by EMMA and the classical package dHPLC-QMPSF. All mutations and polymorphism detected by dHPLC have been detected by EMMA and new polymorphisms have been characterized for those genes. Furthermore, we will present the whole results of the positive mutation controls of BRCA1 and BRCA2 of the Institut Bergonie molecular genetic lab database screened by EMMA.&#x2028; Discussion : Using a unique condition of capillary electrophoresis separation for a lower number of PCR reaction for each gene (9 for BRCA1 and 15 for BRCA2), EMMA demonstrates a 5 times saving of lab time for technician, and displays a large easiness to use it in a routine way for molecular diagnosis. Finally this technology will benefit of a grant of French Ministry of Industry to be spread in molecular lab of Comprehensive Cancer Centers.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1102.
Characterization of estrogen receptor-positive breast cancers in BRCA1 mutation carriers.
Authors: Wang Y , Collins L , Schnitt S , Garber J , Tung N 
Published: December 2010

Abstract
Abstract #1105
Background: Invasive breast cancers (IBC) in BRCA1 mutation carriers are usually estrogen receptor (ER) negative (-) and more than 80% have a basal-like molecular phenotype. These tumors are typically poorly differentiated invasive ductal carcinomas with a high mitotic rate and frequently show a prominent lymphoid infiltrate, pushing or circumscribed margins, and geographic necrosis or a central fibrotic focus. However, some women with BRCA1 germline mutations develop ER positive (+) cancers; little is known about the characteristics of the ER+ tumors in this group.&#x2028; Design: We identified 41 ER+ IBC that developed in women with BRCA1 germline mutations with available pathologic material for review. The histologic features were analyzed in detail and compared with those of 45 ER- IBC that developed among BRCA1 mutation carriers.&#x2028; Results: Mean patient age was 46y for ER+ and 45y for ER- cases. Ninety percent of the ER+ cases and all the ER- cases were invasive ductal carcinomas or invasive carcinomas with ductal and lobular features. There were 2 mucinous and 2 tubular carcinomas in the ER+ group. The ER+ cancers exhibited a range of histologic grades: 12 (29.3%) were grade I, 10 (24.4%) grade II, and 18 (43.9%) grade III (1 case of microinvasive carcinoma could not be graded). In contrast, 43 of the 45 ER- cancers were grade III (95.6%) and 1 (2.2%) grade II (1 case of microinvasive carcinoma could not be graded). Histologic features commonly seen in association with ER- BRCA1 mutation-associated IBC were compared between the two groups and the results are summarized in the table.&#x2028; &#x2028; Of note, a brisk mitotic rate, pushing margin, and the presence of geographic necrosis/central fibrosis were all significantly more common in ER- than in ER+ tumors.&#x2028; Conclusions: To our knowledge, this study is the first to document in detail the histologic features of the uncommon ER+ IBC occurring in BRCA1 mutation carriers. Our observations suggest that ER+ IBC in BRCA1 mutation carriers represent a morphologically diverse group. This raises the possibility that at least some ER+ IBC that develop in women with germline BRCA1 mutations may be sporadic rather than BRCA1-associated. We are currently analyzing these lesions with a panel of biomarkers and assays for loss of heterozygosity at the BRCA1 mutation sites to further address this important issue.&#x2028; This work was supported by a grant from the Breast Cancer Research Foundation.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1105.
Effects of methyl derivatives of the rexinoid UAB30 on methylnitrosourea (MNU) induced mammary cancers and on various indicators of toxicity.
Authors: Muccio DD , Lubet RA , Atigadda VR , Brouillette WJ , Grubbs CJ 
Published: December 2010

Abstract
Abstract #1108
UAB30 is a RXR selective retinoid that has shown excellent activity in preventing chemically-induced mammary cancers with minimal toxicity (specifically not increasing serum triglycerides), and is currently undergoing a Phase I clinical trial. Several methyl analogs were synthesized in an attempt to obtain a more active preventive agent and to better understand the mechanisms of activity/toxicity of this class of agents. The retinoids included 4-methyl-UAB30, 5-methyl-UAB30, 6-methyl-UAB30, 7-methyl-UAB30, and 8-methyl-UAB30. The compounds were evaluated in the MNU-induced mammary cancer model using female Sprague-Dawley rats. MNU (75 mg/kg BW) was administered at 50 days of age and the animals observed for 120 days afterward for the development of ER+ mammary cancers. The retinoids were given at a dose of 200 mg/kg diet, except 7-methyl-UAB30 (given at 100 mg/kg diet). 4-Methyl-UAB30 and 7-methyl-UAB30 were highly active; reducing mammary cancer multiplicity by 74 and 61%, respectively. The retinoids 5-methyl-UAB30, 6-methyl-UAB30, and 8-methyl-UAB30 did not have chemopreventive activity in this model. The 8-methyl-UAB30 derivative actually caused a 108% increase in growth of the mammary cancers. As we have previously shown (Carcinogenesis 27, 1232-1239, 2006), serum triglycerides correlated with cancer preventive activity; i.e., high levels were observed with active retinoids. 4-methyl-UAB30 caused an initial large increase in body weight gain of the rats. Of interest, serum levels of 6-methyl-UAB30 and 7-methyl-UAB30 were high, while the other agents were low or could not be detected. All methyl derivatives caused varying decreases in liver retinyl palmitate levels. Structure-activity relationships are also being evaluated using crystallography of RXR/UAB-rexinoid complexes as a guide. Structure-based and dynamic-based approaches are used to facilitate the design of new rexinoids that fit into the LBD of RXRs. For example, 4-methyl-UAB30 had a 5-fold greater binding affinity to hRXR alpha LBD than 9-cis-retinoic-acid. These studies emphasize that minor modifications of a retinoid molecule can drastically change its absorption, metabolism, toxicity, binding affinities to receptors, and activity in preventing mammary cancers. (Supported by NCI Breast SPORE CA089019 and contract HHSN261200433001C).
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1108.
A potential role of EGFR-inhibitors for the prevention of BRCA1-related breast cancer.
Authors: Burga LN , Tung N , Troyan SL , Lee BT , Houlihan M , Pories SE , Staradub V , Tobias A , Come SE , Coffey K , Wulf GM 
Published: December 2010

Abstract
Abstract #1110
Background: The majority of women who develop a BRCA1-related breast cancer develop an ER-/PR-/HER2- breast cancer. Endocrine prophylaxis does not prevent these ER- breast cancers. Therefore, there is a need to develop novel chemoprevention agents in this population. 67% of BRCA1-associated ER- breast cancers also overexpress epidermal growth factor receptor (EGFR). We therefore examined EGFR as a potential target for chemoprevention&#x2028; Methods: We isolated primary mammary epithelial cells (HMECs) from women with a germline BRCA1 mutation who underwent prophylactic mastectomies and from age-matched controls without a mutation who underwent reduction mammoplasties. We used a three-dimensional matrigel-based colony formation assay to assess clonality and proliferative capacity of these cells as well as their response to EGFR-inhibition. Flow cytometry was used to determine the number of EGF binding sites per cell. As a corresponding mouse model we used conditional MMTV-Cre BRCA1-/-p53+/- mice. Results: HMECs from BRCA1 mutation carriers and from controls express EGFR to a similar extent as HCC1937 BRCA1-associated triple-negative breast cancer cells (5x103 binding sites/cell). In ex vivo 3D-cultures we observed that HMECs derived from BRCA1 mutation carriers showed greater clonal and proliferative capacity when compared to normal controls. However while the HMECs derived from BRCA1 mutation carriers and normal controls were equally sensitive to the growth-inhibitory effect of Erlotinib at concentrations as low as 0.2 μM, the ID50 for HCC1937 breast cancer cells was &gt; 10 μM. Similar findings were observed in murine MECs derived from normal control mice as well as BRCA1-/-p53+/- mice which develop breast cancer at the age of 7 to 8 months. Both groups of murine MECs were equally sensitive to Erlotinib growth inhibition. Conclusion: MECs derived from breast tissue of women and mice with a germline BRCA1 mutation express EGFR and are highly sensitive to growth inhibition with the EGFR inhibitor Erlotinib. In contrast, BRCA1-associated HCC 1937 breast cancer cells are more resistant to Erlotinib inhibition despite EGFR expression. We are now studying whether Erlotinib given via oral gavage daily has the potential to delay or prevent breast cancer in this mouse model of BRCA1-related breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1110.