bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-04-01: HER2 Status as Predictor of Mammographic Screening Detection: Comparison of Interval-and Screen-Detected Breast Cancers
Authors: Musolino A , Michiara M , Conti GM , Boggiani D , Bozzani F , Zatelli M , Sgargi P , Ardizzoni A. 
Published: April 2011

Abstract
Background: To determine whether markers of poor prognosis are associated with risk of breast cancer diagnosis in the interval between screening examinations, we estimated the effect of the mode of detection on distribution of breast cancer molecular subtypes using population cancer registry data.
Material and Methods: Subjects (n = 641) comprised all breast cancers systematically collected by the Cancer Registry of Parma Province and diagnosed in women aged 50-69, from 2004 to 2007. These included 370 screen-detected and 271 symptomatic breast cancers (63 women with interval cancers and 208 who had not attended screening). We used logistic regression to determine whether interval cancers were associated with selected clinical and biologic characteristics. We also estimated the relative risk of cause-specific fatality and disease-free survival (DFS) by each resulting predictive factor (screen-detected compared to either symptomatic or interval cancers).
Results: Interval-detected cancers occurred more in younger women and were of more advanced tumor stage than screen-detected cancers. In unconditional logistic regression models adjusted for age and tumor stage, tumors with high histologic grade (odds ratio[OR] = 2.2; 95% CI =1.0-5.4), high proliferation rate (OR =2.7; 95% CI =1.5-4.8), or positive HER2 status (OR =2.6; 95% CI =1.3-5.1) were more likely to surface in the interval between screening examinations. After adjusting for various potential biases, women with screen-detected breast cancer had a substantial survival advantage over those with symptomatic breast cancer. In a multivariate model, positive HER2 status independently predicted poor DFS when the mode of cancer detection was included as covariate in addition to age, histologic grade, proliferation rate, and tumor stage. Conclusions: This is the first population-based cancer registry study demonstrating that HER2-positive tumors account for a substantial proportion of mammographic screening failure to detect breast cancer. Our data indicate that molecular subtype distribution of screen-detected breast cancer differs from that of interval cancers and accounts in part for the better outcome of screen-detected cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-04-01.
Abstract P2-04-02: Increased Risk of Breast Cancer in Women Who Receive False Positive Test Results from Mammography Screening
Authors: von Euler-Chelpin M , Larson Thorsted B , Vejborg I 
Published: April 2011

Abstract
Background: Copenhagen has the longest running organised screening programme for breast cancer in Denmark. The programme started in 1991. One of the possible consequences when screening for breast cancer with mammography is a false positive test result. We assessed the relative risk of developing breast cancer among women who had received false positive test results compared to women who had not.
Method: The mammography programme provided data on participation and test results from 1991 -2005. Oncological data was retrieved from the National Cancer Register. Follow-up ended on 17 April 2008. Data were linked using the Danish unique personal identity number. Relative risks were estimated using Poisson regression, age adjusted. The exposure was categorised as a) false-positive Type1 = negative after further assessment with mammography, ultrasound and fine needle aspiration, and b) Type 2 = negative after surgery.
Results: A total of 59.392 women participated in the mammography programme, representing 650.218 person-years at risk. The relative risk (RR) of breast cancer after any type of false positive (FP) was 1.33 (95% CI, 1.18-1.50), the RR for breast cancer after a Type 1 FP was 1.34 (95% CI, 1.18 — 1.52) and after a Type 2 FP the RR was 1.24 (95% CI, 0.85-1.82). The RR of interval cancer, i.e. breast cancer within the two years following the test result, was 1.73 (95% CI, 1.13-2.66) for women who had received a FP test result as compared to those who had not. Conclusion: Women who have received a false positive test result from mammography screening had a 73% increased risk of developing interval cancer compared to women who had not, and a 33% increased risk of developing breast cancer at any time after a false positive test result. There was an increased risk for both Type 1 (34%) and Type 2 (24%) FP test results, though data was only significant for Type 1 results.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-04-02.
Abstract P2-04-03: Usefulness of Perioperative Screening of Patients with pN0 Invasive Breast Carcinoma: Results on 1058 pN0 Patients of a Population-Based Study of the French Cancer Registry
Authors: Frenel J-S , Leux C , Molinie F , Campone M 
Published: April 2011

Abstract
Background: Usefulness of baseline routine bone scanning (BS), liver ultrasonography (LUS) and chest radiography (CXR) in asymptomatic women with pN0 Invasive Breast Carcinoma is not evidence-based. Methods: A random sample of 1883 cases of invasive breast cancer diagnosed in 2003 from 10 French counties covered by a cancer registry was analyzed. Clinico-pathological features, staging tests and results were retrospectively collected from the medical record. Results: 1058 pN0 patients were identified. At baseline, CXR, LUS, BS were carried out pre or post-operative in respectively 785 (74%), 782 (74%), and 618 (58%) patients. Data summarizing results with the three imaging techniques are listed in [Table 1]. Initial suspicion was confirmed by other independant tests (bone X-ray, computerized tomography scan). After the initial staging investigation procedures and the further diagnostic procedures if necessary (computerized tomograhy scan or bone X-ray), only 3 (0.3%) patients were diagnosed having metastatic disease. CXR, LUS, BS detected metastasis respectively in 1 (0.13%), 0 (0%), and 2 (0.3%) of patients.
Diagnostic accuracy in the diagnosis of metastatic disease by chest radiography, liver ultrasonography and chest radiography
Conclusion: In asymptomatic pN0 invasive breast cancer, screening for metastases is not warranted because of low frequency of metastases, false positive findings and high cost.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-04-03.
Abstract P2-06-14: Utilizing Human Breast Tissue and Blood to Discern Novel Protective Properties of Early Pregnancy in Reducing Breast Cancer Risk
Authors: Gutierrez CM , Mills DJ , Love S , Lakshmanaswamy R. 
Published: April 2011

Abstract
Introduction: The incidence of breast cancer, the most common cancer in women, is very high in Western Countries and is increasing rapidly in the Third World. Yet, despite better screening, earlier diagnosis, and the development of new therapies, a cure for metastatic breast cancers remains an elusive goal. Since it is difficult to defeat breast cancer after it has occurred, finding new strategies to delay or prevent the development of breast cancer has been an important area for clinical and experimental investigations. Multinational studies have suggested that women who undergo a full-term pregnancy before the age of 20, with or without lactation, have about one half the risk of developing breast cancer compared to women who undergo their first pregnancy after the age of 35 or women who have never undergone a full term pregnancy. Thus, pregnancy at an early age protects against breast cancer development. This universal protective effect of pregnancy serves as a major clue and starting point in the search for new experimental strategies and novel biomarkers related to the prevention of breast cancer.
Methods: Women were recruited who had never been diagnosed with breast cancer and fit in one of the following categories; 1) had their first child ≥25 years of age, 2) had their first child ≥35 years of age, and 3) a control group of women the same age as those in groups 1 and 2 but who have never given birth were recruited and provided a sample of breast tissue and blood simultaneously. These groups were categorized as early parous, late parous, or nulliparous and their RNA was isolated from tissue and whole blood. Human whole genome microarray analysis (Agilent) was performed to identify the genes that were persistently altered in expression due to early pregnancy.
Results: The study of molecular alterations in breast cancer genes has succeeded in identifying some genetic mechanism of breast cancer development. We attempted to elucidate early pregnancy-related changes in genes in breast tissue and blood associated with resistance to breast cancer. Over 2200 genes were up-regulated 2 folds or more in the blood and breast of early parous women than late parous and nulliparous women. Approximately 5000 genes were down-regulated 2 folds or more in the blood and breast of early parous women compared to late parous and nulliparous women.
Conclusion: These studies focused on the analysis of human breast tissue and blood to gain a deeper understanding of changes in parity associated with the protective effect of early pregnancy in women. From these altered gene expressions we have identified a gene signature for early parity. The persistently altered genes will be used as novel biomarkers to predict breast cancer risk and develop strategies to protect the breast from cancer development.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-14.
Abstract P2-06-20: Hormonal Criteria for Assessment of Menopause: Role of Anti-Mullerian Hormone
Authors: Chatterton RT , Khan SA , Heinz RE , Kmiecik T , Scholtens D. 
Published: April 2011

Abstract
Introduction: The difficulty in establishing the time of menopause poses a problem in many breast cancer research studies. We sought to determine the value of adding anti-mullerian hormone (AMH) to the accuracy of designating hormonal signs of menopause in 179 women who were recruited for a case-control study of nipple aspirate fluid (NAF) biomarkers.
Methods: A questionnaire was administered to obtain medical and reproductive history, self-reported menstrual cycle length, last menstrual period and age. Serum estradiol, progesterone, FSH, and AMH were measured in a blood sample obtained on the day of the study encounter. Criteria for premenopause were: serum FSH &lt;30 mIU/ml, AMH &gt;0.08 ng/ml, estradiol (E2) &gt;30 pg/ml, and menstrual periods of 25 to 35 days. For postmenopause the inverse of the hormone levels and no menstrual periods for &gt;12 mo and age &gt;52 years was used. Serum progesterone (P4) concentration of &lt;3 ng/ml provided confirmation of postmenopause. Results: The age range was from 35 to 69 years (median 51). By self-report (amenorrhea &gt;12 mo and age) 76 subjects were premenopausal; 70 were postmenopausal and 33 subjects were perimenopausal. Table: Designation of menopausal state based on hormonal criteria: Concordance of individual measures with the designation based on all criteria (percentages).
Table
FSH was found to be discordant in 1 (1.1%) of premenopausal subjects and in 5 (5.3%) of postmenopausal subjects. AMH was found to be discordant in 21 (24.7%) of premenopausal subjects and 6 (6.4%) of postmenopausal subjects. Estradiol was discordant in 13 (15.3%) of premenopausal subjects and in 7 (7.4%) of postmenopausal subjects. Progesterone was &lt;3 ng/ml in all of the postmenopausal subjects. The combination of FSH and AMH predicted 100% of the grouping based on all measures; FSH and E2 predicted 99.9%. The absence of progesterone is a certain criterion for postmenopause but adds nothing to the designation of premenopause. Comment: An accurate determination of the hormonal and reproductive status of women is critically important in studies relating hormones to breast cancer risk. The loss of ovarian hormones has long-term implications, and the menopausal status at the time of sampling determines the recent and current hormonal exposure. Using the hormonal criteria, all women in this study could be classified as pre-or postmenopausal. Adding AMH to the usual hormones did not improve the designation based on the other criteria.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-20.
Abstract P2-06-22: The Modulation of CXCL9 Release by Prostaglandin E2 and Cyclooxygenase Inhibitors in Human Breast Cancer
Authors: Bronger H , Kräft S , Stöckel A , Welk A , Kiechle M , Schmitt M , Schwarz-Boeger U. 
Published: April 2011

Abstract
Introduction
IFN γ inducible chemokine CXCL9 impairs tumor growth and metastasis formation through recruitment of natural killer (NK) cells and tumor suppressive T lymphocytes in murine breast cancer models. In human breast cancer CXCL9 mRNA expression correlates with response to different chemotherapeutic regimens and tumor infiltrating lymphocytes, indicating that enhancing intratumoral CXCL9 is a feasible therapeutic way to improve tumor suppressive immune infiltration. However, little is known about the regulation of CXCL9 in human breast cancer. Since overexpression of cyclooxygenases (COX) correlates with impaired NK cell infiltration as shown before, this system is a conceivable candidate for modulating intratumoral CXCL9 concentration. Material and Methods
For regulation studies, MCF 7 and MDA MB 231 breast cancer cells were stimulated with IFN γ with or without prostaglandin E2 (PGE2) or COX inhibitors (indomethacin, aspirin, celecoxib). CXCL9 was localized in human breast cancer samples by immunohistochemistry. Its release was measured by ELISA. Expression of CXCL9 and cyclooxygenases in 60 breast cancer samples was determined by ELISA and western blot, respectively.
Results
Within the tumor microenvironment, the cancer cells are the major source of CXCL9, thus making them the appropriate cell type to study CXCL9 regulation. PGE2 significantly reduces IFN γ mediated CXCL9 release from MCF 7 and MDA MB 231 cells, and inhibition of endogenous cyclooxygenases by indomethacin or aspirin correspondingly augments this secretion. However, the COX 2 specific antagonist celecoxib has PGE2-agonistic effects and impairs CXCL9 release, probably via COX independent mechanisms.
Conclusion
Suppressing endogenous PGE2 by cyclooxygenase inhibition increases CXCL9 release from breast cancer cells and is therefore a feasible way to enhance intratumoral immune infiltration. However, due to possible COX independent mechanisms the choice of the appropriate COX inhibitor seems to be crucial. The predictive value of CXCL9 as a novel biomarker and its correlation with COX overexpression in human breast cancer is discussed.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-22.
Abstract P2-06-23: A New Way To Determine Multifocality: The Use of Molecular Markers?
Authors: Werkoff G , Antoine M , Rodenas A , Gligorov J , Chopier J , Uzan S , Rouzier R. 
Published: April 2011

Abstract
AIM: Multifocality in breast cancer has a great on treatment options. However, the prevalence of multifocality is currently underestimated at the time of diagnosis because of the lack of sensitivity of clinical examination and imaging. Our aim was to develop a tool for predicting multifocality based on clinical and immunohistochemical criteria. METHOD: This study was conducted at Tenon Hospital with samples from patients operated on between 2002 and 2009. We constructed a tissue micro-array (TMA) from 100 breast specimens: 50 multifocal tumors and 50 unifocal unifocal tumors. Unifocal tumors were matched with multifocal tumors by size of largest focus, hormonal receptor status and SBR grade. These unifocal controls had either a mastectomy or a pre-operative MRI to rule out occult multifocality. We studied the expression of ten different antibodies (HER2, KI67, CK 5/6, CK 14, CK18, Vimentine, C-kit, EGFR, p53, and p63). From the results of this analysis we developed a prediction model based on a multivariate logistic regression. RESULTS : For the proteins tested, the concordance of immunohistochemical staining of foci from multifocal tumors ranged from 72% to 100%. In the univariate analysis, only c-kit expression was significantly associated with multifocality (P&lt;0.05). The discrimination (area under the ROC curve) of a multivariate model based on clinical, pathological, and immunohistochemical variable was good (0.72) but lacked robustness when tested by internal validation.
CONCLUSION: We report the first clinico-biological predictor of multifocality. New markers are currently tested to improve the performance of the multivariate model.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-23.
Abstract P2-07-01: Simvastatin Prevents Breast Cancer Skeletal Metastasis by Increasing p53 Levels To Increase PTEN and Inhibit CD44 Expression
Authors: Mandal CC , Ghosh-Choudhury N , Yoneda T , Choudhury GG , Ghosh-Choudhury N. 
Published: April 2011

Abstract
Bone represents one of the main sites of metastatic spread of breast cancer. The prognosis for the breast cancer patients with bone metastasis is very poor with severely compromised life style associated with extreme bone pain and fracture prevalence. We used heart injection model to test the effect of simvastatin on breast cancer bone metastasis. Simvastatin prevented osteolytic lesions in mice injected with MDA-MB-231 (MDA) human breast cancer cells, indicating that statin attenuates breast cancer metastasis to bone. To investigate the mechanism, MDA cells were used in an in vitro wound-healing assay. Simvastatin significantly inhibited the migration of MDA cells. Transwell invasion assay using collagen-coated discs confirmed the inhibitory effect of simvastatin on breast cancer cell invasion. We have recently shown that simvastatin inhibits primary tumor growth in mice by upregulating the tumor suppressor PTEN. Overexpression of PTEN in MDA cells significantly blocked their ability to migrate and invade. To determine the mechanism of PTEN upregulation, we considered the tumor suppressor protein p53, which is known to regulate PTEN expression. Simvastatin-treated mice tumors showed significantly increased levels of p53. Similarly, simvastatin enhanced the expression of p53 in MDA cells. Additionally, simvastatin increased transcription of the reporter plasmids containing the consensus p53-binding element (p53-Luc) or the PTEN promoter (PTEN-Luc). Cotransfection of p53 with these reporter constructs resulted in similar increase in transcription, indicating a role of p53 in PTEN expression by simvastatin. Recent reports indicate a direct correlation between expression of CD44 in breast cancer and their metastasis to other organs including bone. Levels of CD44 were significantly reduced in the tumors of mice treated with simvastatin. In MDA cells, simvastatin decreased the expression of CD44 protein and its transcription, as determined by CD44 promoter-driven luciferase construct (CD44-Luc). p53 acts as transcriptional activator or transcriptional repressor in a cell-type and context-dependent manner. Presence of non-canonical p53-binding elements has been reported in the CD44 promoter. Cotransfection of p53 with CD44-Luc significantly suppressed the transcription of CD44. Furthermore, expression of p53 markedly reduced the expression of CD44 protein. Finally, downregulation of endogenous CD44 by specific shRNA decreased migration of MDA cells. Together these results uncover a novel action of simvastatin, which targets p53 expression to simultaneously increase PTEN and decrease CD44 thus blocking migration and preventing bone metastasis of the human breast cancer cells.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-07-01.
Abstract P2-07-02: Low-LET γ-Radiation Induced Protein S-Nitrosylation Regulates Tumor Invasion and Metastatic Transcriptional Response
Authors: Veeraraghavan J , Natarajan M , Herman TS , Aravindan N. 
Published: April 2011

Abstract
Local-regional radiotherapy is one of the major therapeutic means in the management of breast cancer. However, besides the therapeutic effect, studies have shown that irradiation promotes malignant behavior of cancer cells both in vitro and in vivo by activating several tumor invasion and metastatic molecules. In this regard, ascertaining the molecular alterations contributing to this radiation-induced response is imperative. Accordingly, we investigated the role of radiation-induced NO-dependent nitrosylation in the transcription of invasion and metastatic genes in human breast adenocarcinoma cells. Human MCF-7 cells either mock irradiated, exposed to 2Gy (IR), treated with L-NAME (NOS inhibition) or BAY-11-7082 (phosphorylation inhibition) and then exposed to 2Gy, were examined for modulations in the transcriptional response of 93 tumor invasion and metastasis signaling genes. Cells treated with β-estradiol and mock-irradiated MDA-MB-231 cells were used as positive controls. Compared to mock irradiated cells, real time QPCR profiling revealed that 20 of 29 IR-induced genes including Birc3, Casp8, Ctgf, Ctsk, Htatip2, Kras, Map2k7, Mgat5, Mta2, Nme1, Nme2, Nme4, Pax5, Pten, Runx1, Serpinb5, Syk, Timp1, Timp2 and Timp4 were completely suppressed with NOS inhibition. Conversely, as opposed to NOS inhibition, IR-induced phosphorylation inhibition either failed to suppress or further induced the expression of these IR-induced genes. Furthermore, β-estradiol treatment revealed upregulation of 16 of these 20 IR-induced nitrosylation-dependent molecules and serves as a positive control for the study. More importantly, the highly metastatic, MDA-MB-231 cell line showed a robust induction in the expression of 15 of these 20 IR-induced nitrosylation-dependent genes. Taken together, these data imply that IR induces the expression of tumor invasion and metastatic genes and more importantly, may regulate the radiation-activated invasion and metastatic phenotype in breast adenocarcinoma cells.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-07-02.