bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of MDA7/IL-24 human breast cancer and the molecular impact.
Authors: Jiang WG , Douglas-Jones A , Mokbel K , Mansel RE 
Published: December 2010

Abstract
Abstract #2060
INTRODUCTION. MDA-7 (melanoma differentiation associated gene-7), also known as IL-24, was initially identified from cancer cells and was found to be up-regulated in melanoma cells. Forced expression of MDA7 in cancer cells was found to be growth inhibitory. MDA7/IL-24 operates in cells via its receptor, MDA7R/IL-24R, which includes at least the IL-20Rα and IL-20Rβ complex and the IL-22R and IL20Rβ complex. The present study investigated the impact of MDA7 on the growth and motility of breast cancer cells and the clinical relevance of MDA7 expression in mammary tumour tissues.&#x2028; MATERIALS AND METHODS. Human breast cancer cell lines MDA MB-231 and MCF-7 were used for in vitro testing. The response of cancer cells to rhMDA7 in growth and cellular motility was determined using growth assay and ECIS (electric cell impedance sensing, and confirmed by wounding assay). Localisation of MDA7 in mammary issues was assessed using conventional immunohistochemical method. Levels of MDA7 transcript in fresh frozen breast tissues were determined using quantitative PCR analysis and analysed against clinical and pathological information.&#x2028; RESULTS. Recombinant human MDA-7 only had a marginal effect on the in vitro growth of the breast cancer cell lines used. However, rhMDA had a significant effect on the migration of breast cancer cells. Cells treated with rhMDA-7 showed a slower rate of migration (electrical resistance 80.1±24.3Ω), when compared with control cells (130±24.3Ω) (p=0.024). Normal mammary epithelial cells showed a good degree of staining of MDA-7, a staining greatly reduced in cancer cells. Using the Nottingham Prognostic Index as a predictor of prognosis, tumours from patients with poor prognosis showed a significantly lower level of MDA-7 transcript compared with tumours from those with good prognosis (p=0.049). A significant difference was seen between tumours from patients who died of breast cancer and tumours from patients who remained disease free (p=0.035), the later showing a higher levels of MDA7 transcript. Using the Kaplan-Meier survival analysis, it was revealed that low levels of MDA-7 were significantly correlated with a shorter disease free survival (mean survival for low level group 121.7 (108.5-134.9) months compared with high levels 140.4 (133.7 – 147.1, 95% CI) months, p=0.0287. ER positive tumours showed a lower but levels of MDA-7 expression compared with ER-negative tumours, although this was not statistically significant (p=0.094).&#x2028; CONCLUSIONS. MDA-7 is a potential regulator of cellular motility of breast cancer cells. The aberrant expression of the molecule is linked to the prognosis and long term survival of patients, indicating the potential clinical implication of MDA-7 in cancer therapies.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2060.
Sentinel lymph node biopsy in pure tubular carcinoma of the breast: a retrospective multicentric study of 234 cases.
Authors: Dejode M , Dravet F , Sagan C , Giard S , Mignotte H , Houvenaeghel G , Ferron G , Leveque J , Tunon de Lara C , Rodier J , Marchal F , Classe J 
Published: December 2010

Abstract
Abstract #207
BACKGROUND. Pure tubular carcinoma (PTC) is a favourable histologic subtype of breast cancer with a low rate of lymph node involvement. This study was initiated to assess the sentinel lymph node (SLN) detection rate and the rate of axillary involvement.&#x2028; METHODS. Inclusion criteria were a PTC (tubular component &gt;90%) core biopsy diagnosed breast cancer smaller than 20 mm, and a homolateral clinically axilla free of nodal involvement. Patients underwent a SLND alone or with an Axillary level I-II Lymphadenectomy (AL). An AL was performed in the case of the learning curve, or in the case of SLN involvement – macrometastases, micrometastases or isolated cells - or in the case of mapping failure.&#x2028; RESULTS. From January 1999 to December 2006, 234 patients were selected from 9 French Comprehensive Cancer Centers. Median tumour size was 9.59 mm (1-22) . The SLN detection rate was 97.9% (229/234). The median number of SLN harvested was 2.15 (range 0-8). Respectively the frequency of macrometastasis - &gt;2mm - was 2.6% (6/229), micrometastasis was 6.5% (15/229) and isolated cells was 0.8% (2/229). There were no false negative cases among the 24 patients with a systematic complementary axillary lymphadenectomy performed in the case of a learning curve. Axillary macrometastasis were found in non sentinel lymph nodes after completed axillary lymphadenectomy in 3 / 6 patients with macrometastasis, in 1/15 patients with micrometastasis and in 0/2 patients with isolated cells. There was no lymph node involvement for tumour size &lt; 10mm. Pathological tumor size &gt;10 mm was statistically correlated to the risk of axillary involvement (p=0.0223).&#x2028; CONCLUSIONS. This study confirms that in the case of PTC ≤ 20mm SLN detection is feasible and the risk of lymph node involvement very low. In the case of PTC&lt;10 mm our series suggests that a surgical axillary evaluation, even with the SLN technique, is not warranted.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 207.
Rapid screening of tissue microarrays for Her-2 FISH testing is a safe, accurate, efficient and economic method enabling provision of an entirely FISH-based Her-2 testing service.
Authors: Faratian D , Graham AD , Rae F , Thomas JS 
Published: December 2010

Abstract
Abstract #2070
Introduction: FISH (fluorescence in situ hybridisation) testing is the gold standard method for Her-2 status assessment in breast cancer yet is only employed in about 30% of tests carried out partly due to cost and labour considerations. Previously we described TMA-based (tissue microarray) testing1 to reducing cost constraints and now describe a rapid screening approach to eliminate unequivocally negative and positive cases and reduce time spent testing.&#x2028; Materials and methods: We examined TMAs (6 cores per case) from 89 cases of invasive breast cancer comparing formal FISH scoring with a rapid screening method using systematic examination of the entire core at x100 magnification without formal counting. Each core was screened by two observers and results recorded for each core as positive (P), equivocal (E) or negative (N). Formal counting and rapid screening methods were timed.&#x2028; Results: The results are given in Table 1. Where both observers agreed that every core in a particular case was negative (43 cases) or positive (10 cases) the predictive value was 100%. The three “Mixed” Groups were constituted as follows: (1) a predominance of positive observations, (2) a predominance of negative observations and (3) a predominance of equivocal observations. Comparison of the FISH scores for the five observational groups using Student's T Test showed significant or highly significant differences (Range: p=0.02-p=0.0001). Screening each 6 TMA core case at x100 magnification took 2 minutes and formal counting of each case took 12 minutes.&#x2028; &#x2028; Conclusion: Using stringent criteria we show that rapid screening of TMAs for routine Her-2 FISH testing provides a safe, economical and time-efficient method for the assessment of Her-2 status in breast cancer. The technique ensures that all patients receive gold standard testing. 65% of Her-2 negative cases can be rapid screened and eliminated from formal counting with 100% confidence. Unanimous positive cases can also be appropriately categorised. The remaining cases require formal counting which takes no longer than is normally the case with whole section techniques. The TMAs also provide a valuable resource for future analyses.&#x2028; Reference: 1. Graham AD, Faratian D, Rae F, Thomas J St J. Tissue microarray technology in the routine assessment of Her-2 status in invasive breast cancer: a prospective study of the use of immunohistochemistry and fluorescence in situ hybridization. Histopathology 2008; 52: 847-855.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2070.
Multicentric/-focal vs. unifocal breast cancer: is the TNM-classification justified.
Authors: Weissenbacher TM , Zschage M , Janni W , Scholz C , Sommer H 
Published: December 2010

Abstract
Abstract #2075
Background:&#x2028; For classification of breast cancer, the TNM-staging is standard since more than fifty years and the prognostic relevance of the T-category is well established. However, tumor size in multicentric and multifocal tumors is assessed by the largest tumor focus only, and does not reflect the cumulative tumor volume. Aim of this study was to compare the prognosis of multicentric/-focal tumors vs unifocal tumors with identical tumor sizes according to TNM-Staging.&#x2028; Methods:&#x2028; Overall, 576 patients between 1963 and 2007 were examined. Based on a consecutive patient cohort (n=5.691 pts), two equivalent groups of 288 early breast cancer patients with multicentric/-focal vs unifocal tumors were selected by matched-paired analysis. Match criterias were tumor size, histopathologic grading as well as hormone receptor status, which were equally distributed in both groups (p=1,0, each). Disease free survival and breast cancer specific survival were evaluated. For the multivariate analysis the Cox regression system was used. The median follow-up was 70 month (5,8 years, range 19 - 312 mts)&#x2028; Results:&#x2028; The Kaplan-Meier estimate for mean breast cancer specific survival was 221.6 mon (206.7 – 236.4 95%CI) in patients with unifocal and 203.3 mon (184.1 – 222.5, 95% CI, p&lt; .0001, log rank test) in patients with multicentric/-focal tumors. Furthermore, in patients with a unifocal tumor the relapse-free survival was 205.9 mon (190.7 – 221.2 95%CI) and 169.6 mon (150.8 – 188.5, 95% CI, p&lt; .0001, log rank test) in patients with multicentric/-focal disease. In multivariate Cox regression analysis, allowing for tumor size, grading and nodal status, multicentricity/-focality was an independent significant predictor for reduced breast cancer specific survival (p&lt; .0001) as well as reduced relapse-free survival.&#x2028; Conclusion:&#x2028; In breast cancer, multicentric/-focal disease is associated with a worse prognosis compared to unifocal disease with identical tumor size. The authors conclude that the tumor biology of multicentric/-focal tumors is not reflected adequately by the current TNM-classification.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2075.
Clinical outcomes of patients with T1N0 breast cancers: how important are biological risk factors?.
Authors: De Boer RH , Chan A 
Published: December 2010

Abstract
Abstract #2078
Background: Tumour size (T) and nodal status (N) have traditionally been regarded as the most important prognostic factors which determine individual recommendations for adjuvant treatment. Early trials of adjuvant systemic therapy relied on nodal status as the key determinant of recurrence risk, with node negative patients (pts) often excluded due to their 'low risk' classification. With greater understanding that predominant growth signalling pathways in a given tumour may be of greater importance than size and nodal spread, current clinical practice places greater emphasis on high risk biological factors. Factors include young age (&lt;35y), HER2 positivity (pos), grade III status, absence of hormone receptors (HR), and triple negative (TN) phenotype. Presence of these features will likely influence systemic treatment recommendations. With this in mind we examined data which has been prospectively collected to determine the outcomes of pts with high risk T1N0 tumours and compared them to pts with lower risk biological profiles.&#x2028; Methods: Data on 2285 pts with early breast cancer were analysed. Comparisons were made between T1N0 high risk pts (defined as having one or more of the following features: age&lt;35, grade III, HER2 pos, or TN) and pts with good biological prognostic features (defined as the absence of all the above factors) in the following subgroups: 1) T1N0, 2) T1N1-2, and 3) T2-3N0. In addition outcomes were specifically assessed in T1N0 pts with Her2 pos vs negative disease; TN vs non-TN.&#x2028; Results: 401 pts with T1N0 high risk tumours were identified (T1N0HR). In the low risk group there were 330 pts with T0 tumours (T1N0LR), 286 pts with T1Npositive tumours (T1NposLR) and 154 pts with T2/T3N0 tumours (T2/3N0LR). There were 137 pts T1N0 Her2 pos (T1N0H2). The median follow up for all pts was 3.4 yrs (0.5-36). Treatment given and clinical outcome for each pt group are shown in the table.&#x2028; &#x2028; The majority of DFS events in the T1N0H2 pts occurred in those not receiving adjuvant trastuzumab (12.4% vs 2.2%). TN tumours were seen in 12.5% of pts studied. Despite the use of systemic therapy in 97.5% of TN pts (vs 64% in non-TN) , there was a higher DFS event and death rate (18% vs 15%; and 13% vs 6% respectively)&#x2028; Conclusions: Outcomes for T1N0HR pts were similar to that of T1N0LR and T2/3N0LR pts, possibly related to the greater use of systemic therapies in the T1N0HR pts (89% vs 50% vs 79%). Despite the high rate of adjuvant systemic therapy, the outcomes for the T1N0HR group were inferior to the outcomes for pts in the T1NposLR group (DFS 15.7% vs 9.8%) supporting the view that biological factors may be a more important determinant of outcome than nodal status. Similarly, even in pts with small tumour size, triple negative phenotype had worse outcome.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2078.
Outcome of breast cancer in young women stratified by age at diagnosis: the younger, the worse? The Korean Breast Cancer Society registry program data.
Authors: Han W 
Published: December 2010

Abstract
Abstract #2079
Introduction: In the previous studies investigating the relation between age of onset of breast cancer and disease outcome, the age cut-off for very young onset was usually under 35 or under 40. However, these cut-offs were set arbitrarily or empirically without sufficient outcome data on the detailed age strata. Hence we tried to compare breast cancer outcomes of premenopausal women (age ≤50)according to age groups of 5 year interval.&#x2028; Patients and Methods: We analyzed data of 9,885 breast cancer patients aged ≤50 years registered in the Korean Breast Cancer Society Registration Program between 1992 and 2001. The overall survivals were compared between age groups. The median follow-up for this cohort of patients was 74.4 months.&#x2028; Results: 351 patients were aged &lt;30 years (Group I), 1,092 patients were 31-34 (Group II), 2,087 patients were 35-39 (Group III), and 6,354 patients were 40-50 years old (Group IV). Younger patients had significantly higher T-stage, higher lymph-node positivity, and lower hormone-receptor positiviy than older patients. In Univariate analysis, Group I patients showed worse outcome than Group II patients (p=0.03). Also, Group II patients showed worse outcome that Group III patients (p&lt;0.0001). Interestingly, there was no significant difference in survival of Group III and Group IV patients. This survival trend according to age group was found only in hormone receptor positive or unknown patients, and not in hormone receptor negative patients. Multivariate analysis was performed using a Cox regression model including age groups, tumor size (2cm), lymph node involvement, hormone receptor, chemotherapy, and hormone therapy. Compared to the Group IV patients (reference), Group III patients had similar survival (hazard ratio (HR) = 1.06, 95% confidence interval (CI): 0.94-1.20). But, Group II and I patients had significantly worse survival (HR = 1.43 (95%CI: 1.24-1.64), HR = 2.09 (95%CI: 1.69-2.58), respectively). The HR was even higher in patients young than 25 (HR = 2.35, 95%CI: 1.35-4.06).&#x2028; Conclusions: Patients aged 35 to 39 showed similar overall survival compared to patients aged 40 to 50, whereas patients aged &lt;35 showed significantly worse outcome than patients aged 35 to 39. Moreover, patients aged &lt;30 showed significantly worse outcome than patients aged 31 to 34.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2079.
Biology and prognosis by age of primary operable breast cancer.
Authors: Brouckaert O , Camerlynck E , Van Belle V , Van Huffel S , Pintens S , Amant F , Leunen K , Smeets A , Berteloot P , Van Limbergen E , Weltens C , Van den Bogaert W , Paridaens R , Moerman P , Vergote I , Christiaens M , Wildiers H , Neven P 
Published: December 2010

Abstract
Abstract #2082
Introduction Breast cancer (BC) biology and prognosis are age dependent. We studied the effect of age on BC biology, treatment and prognosis.&#x2028; Methods Data from 2059 consecutive patients, primary operated for invasive BC in UZ Leuven (01/01/00–01/06/05), were used. Patients with ≥ 3.5 yrs follow-up were included (n=1064) to study relapse in relation to age (logistic regression).&#x2028; Results Early relapse in BC is age-related, decreasing 3.2% each yr for patients &lt; 60 yrs at diagnosis (p=0.0132, 95% CI OR: 0.943-0.993). This relation is reversed &gt;60 yrs: early relapse increases 5.5% each yr (p=0.0007, 95% CI OR: 1.021-1.082). The positive lymph node status is decreasing 3.5% each yr &lt;65 yrs (p&lt;0.0001, 95% CI OR: 0.950-0.980) and increasing 3.8% each yr ≥65 yrs (p=0.0259, 95% CI OR: 1.004-1.072) (Fig 1). The chance on a positive estrogen receptor (ER) increases with increasing age until 60 yrs (p=0.0071, 95% CI OR=1.009-1.059) with no significant effect &gt;60 years. For the progesterone receptor (PR), this depends quadratically on the age at diagnosis (p=0.0108, 95% CI OR=0.999-1.000), decreasing &lt;50 years and increasing above. With increasing age, the chance on HER-2 positivity decreased (p=0.0414, 95% CI OR: 0.970-0.999). Grade 3 tumors dropped significantly until 50 yrs (p&lt;0.0001 CI OR=0.900 (0.869-0.933) whereafter we observed a non significant upward trend (Fig 2). The chance to receive any adjuvant therapy decreased with age (p=0.0023, 95% CI OR: 0.958-0.991). Above 70 yrs, systemic adjuvant therapy was absent in 12.95% of non-relapsing -, but in 28.95% of relapsing patients. Radiotherapy was not taken into account.&#x2028; Conclusion Early relapse was higher with increasing/decreasing age, starting from age 60. This goes in parallel with the U-shape curve of lymph node involvement (Fig1). Increased relapse and lymph node positivity in elderly might partially be a reflection of the fact that BC is diagnosed in a later stage in elderly patients but might also be related to different biological behavior or to decreased use of adjuvant systemic treatment. HER-2 overexpression decreases with age and age related differences in ER and PR expression as well as tumor grading are observed (Fig 2).&#x2028; &#x2028; &#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2082.
Triple negative breast cancers: comparative study of clinical features and overall survival in an Irish population.
Authors: O'Kane G , Quinn L , Boyle T , Dunne B , Griffin M , Kennedy J , Connolly EM 
Published: December 2010

Abstract
Abstract #2083
Introduction &#x2028; Triple negative breast cancers (TNBC) are defined by a lack of estrogen, progesterone and Her2 receptors and account for 15% of breast cancers. They present at an earlier age and a higher stage and are associated with a poorer survival compared to non-TNBC's. There is a paucity of information available on outcomes of TNBCs managed with up to date oncology treatment.&#x2028; Aims&#x2028; To investigate TNBCs in an Irish cohort of patients and to compare their clinicopathological features and survival outcomes with non TNBCs.&#x2028; Methods&#x2028; Using a prospectively gathered database all patients treated for invasive breast cancer in our unit between 2001 and 2007 were included. The median age and pathological stage at presentation, histological features and overall survival in the TNBC and non-TNBC groups were compared.&#x2028; Results&#x2028; Between 2001 and 2007 1081 patients were treated for breast cancer at St. James's Hospital. Follow up and full clinical data was available on 934 patients. 121(13%) patients were identified as having TNBCs, 625 (67%) were Her2-ve, hormone receptor +ve and 187 (20%) were Her2 +ve.&#x2028; Age, stage, tumour size and histological grade were similar in the TNBC and the Her2+ groups with the Her2-ve, hormone receptor +ve group having a more favourable pathological profile. Overall survival in TNBC group was significantly worse at 5 yrs compared with the non-TNBC groups.&#x2028; &#x2028; Conclusions:&#x2028; In our patients TNBC's present at a similar age and stage as Her2 + patients. The 5 year survival is worse in the TNBC group. The survival in the Her2+ group is similar to the Her2 – group suggesting that targeted therapy with herceptin is effective. These results highlight the need for a targeted therapy to treat TNBCs.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2083.
Triple negative breast cancer phenotypes: a comparison between symptomatic and screening patients.
Authors: Johnson RK , Winstanley JH , Corcoran F , Pearson M 
Published: December 2010

Abstract
Abstract #2085
Body: Background: Triple-negative breast cancers are defined by a lack of expression of oestrogen, progesterone, and HER-2 receptors. Prognostically, they are associated with a poor clinical outcome. It is uncertain whether during growth and maturation of a breast cancer its phenotype may drift from one which over-expresses ER, PR and HER-2 towards a tumor type that loses this expression. In the UK women are screened for breast cancer between the ages of 50 and 70 years, which provides us with a cohort of patients whose breast cancers are at a much earlier stage than those presenting symptomatically. Thus if phenotypic drift occurred the screening population might have a lower incidence of triple negative tumors compared to those presenting symptomatically.&#x2028; Aim: To compare the incidence of triple negative tumors in a screening and symptomatic population. Materials and Methods: Pathology reports for 2002 to 2004 inclusive were scrutinized for ER PR and HER-2 expression. A list of screening patients was retrieved from our screening database and cross-referenced with pathology reports. Immunohistochemistry (IHC) was used to quantify ER and PR expression, a quick score of 4 or less was negative for over-expression. Similarly IHC was used to quantify HER-2 expression, and a score of 0 or 1+ was negative for over-expression. clinical data, such as patient age, lymphovascular invasion, lymph node status, tumor size, and grade were available for statistical analysis. Results: There were 213 screening patients of which, 31 (14.5%) had triple negative phenotypes and 443 symptomatic patients of which, 73 (16.4%) were triple negative. This difference was not statistically different. Discussion: The incidence of Basal-like breast tumors is similar in the screening group compared to the symptomatic population suggesting that this aspect of tumor biology is determined at a very early stage in the development of tumors and is not subject to phenotypic drift.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2085.