bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-06-24: KLF8 Induction of Mammary Epithelial Stem Cell Formation and Tumorigenesis by Regulating EMT-Associated MicroRNAs
Authors: Wang X , Lu H , Li T , Urvalek AM , Yu L , Bennett JA , Zhao J.
Published: April 2011

Although it is well established that the epithelial-mesenchymal transition (EMT) generates cells with properties of stem cells, the molecularmechanisms responsible for this change remain largely undefined. We set out to identify the mechanisms by examining the expression of stem cell markers as well as microRNAs in MCF-10A cells during EMT induction. By immunostaining and FACS analysis, we found that during EMT induction by either TGF-β treatment or overexpression of KLF8, both the expression of CD44high/CD24low and the activity of aldehyde dehydrogenase (ALDH) were dramatically increased. Using microRNA PCR array, we identified a microRNA signature associated with the EMT. Using microRNA inhibitor, We further demonstrated that one of the microRNAs, miR-146a, is upregulated and plays an important role in keeping the stem cell percentage during EMT induced by both TGF-β and KLF8, as revealed by manipulation of miR-146a expression, analysis of the stem cell markers and mammosphere growth. Taken together, these results highlight a novel role for miR-146a in regulating the stem-like cell induction from MCF-10A cells by EMT. Experiments are in progress to investigate the contribution of KLF8-regulated expression of miR146a and its targets to the stem cell induction and transformation. Supported by: NIH, ACS, Komen and NYSTEM grants to J.Z.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-24.
Abstract P4-07-10: Prognostic Significance of Triple Negative Breast Cancer at Tumor Size 1 Cm and Smaller
Authors: Lai H-W , Kuo S-J , Chi C-W , Chen S-T , Chang T-W , Chen D-R.
Published: April 2011

Triple negative breast cancer (TNBC) is an independent biomarker of poor prognosis, and associated with a higher predilection for visceral metastasis and early recurrence. However, the prognostic significance of TNBC with a tumor size ≥1 cm is unclear. Patients with primary operable breast cancer with a tumor size ≥1cm were retrospectively collected at Changhua Christian Hospital and National Cheng-Kung University Hospital in Taiwan. Tumors negative for ER, PR, and HER-2, determined by immunohistochemical stain, were classified as TNBCs and compared with tumors with any receptor positivity (non-TNBC) for disease-free survival (DFS) and cancer-specific survival (CSS). From 1995 to 2006, a total of 377 (13%) patients with tumor size ≥1 cm were enrolled from 2835 primary breast cancer patients. The mean age at diagnosis and follow-up time were 50.86 and 4.04 ± 2.83 years, separately. Compared with non-TNBC patients, TNBC with a tumor size ≥1 cm as a whole or in lymph node-positive subgroup was not associated with a poorer 5-year DFS and CSS. In lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5-year CSS but not DFS than the non-TNBC group. In multivariate Cox regression hazard analysis, lymph node invasion was the most important cause (hazard ratio: 19.89, 95% CI: 2.18-181.89, P=0.0081) of cancer-specific death.

Fig. (a) Disease-free survival (DFS) of TNBC patients versus non-TNBC patients with tumor ≥1 cm. (b) Cancer-specific survival (CSS) of TNBC patients versus non-TNBC patients with tumor ≥1 cm. (c) CSS in node-positive patients with a TNBC versus non-TNBC phenotype. (d) CSS in node-negative patients with TNBC versus non-TNBC. (e) DFS in patients with HR+/ERBB2-, ERBB2+, and TNBC. (f) CSS in patients of HR+/ERBB2- , ERBB2+, and TNBC. (g) CSS in node-positive patients with HR+/ERBB2-, ERBB2+, and TNBC. (h) CSS in node-negative patients with HR+/ERBB2- , ERBB2+, and TNBC.

TNBC is very likely an independent risk factor for CSS in small (≥1 cm) node-negative invasive breast cancer. With tumors 1 cm and smaller, lymph node invasion was the single most important prognostic factor.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-07-10.
Abstract P4-08-08: Cross Reactivity of Clinically Validated Anti-HER2 Antibodies
Authors: Schrohl A-S , Jensen SS , Pedersen HC , Nielsen SL , Brunner N.
Published: April 2011

Background: Human epidermal growth factor receptor (HER-) 2 belongs to the family of epidermal growth factor receptors (EGFRs) with homology to HER1, HER3 and HER4. HER2 is over-expressed in approximately 20% of invasive human breast cancers (Wolff, Hammond et al. 2007). Over-expression of HER2 is associated with a poor prognosis; however, the protein can be targeted by anti-HER2 therapy (trastuzumab, Herceptin®) (Slamon, Leyland-Jones et al. 2001). Trastuzumab therapy is offered only to patients whose tumors over-express HER2 protein and/or show amplification of the HER2 gene. Accordingly, the expression level of HER2 protein and/or amplification of the HER2 gene are determined routinely in all newly diagnosed breast cancers. Essential to this testing of HER2 expression at the protein level is the availability of specific antibody-based test systems.

Aim: The aim of the present study was to investigate the specificity of three clinically approved commercially available anti-HER2 antibodies towards members of the EGFR-family.

Methods: We studied the antibody used in the Herceptest™ (Dako), the PATHWAY® antibody (Ventana Medical Systems, Inc.) and the Oracle™ antibody (Leica Microsystems). Antibody specificity was investigated by manually performed immunohistochemistry (IHC) and in competitive ELISAs. For IHC, Chinese Hamster Ovary (CHO) cells were transiently transfected with the intracellular domain of respectively HER1, HER2, HER3 and HER4 and all three antibodies were applied to sections of formalin-fixed paraffin-embedded (FFPE) transfected cells. In ELISA, cross reactivity towards HER1 and HER4 was tested with peptides corresponding to the C-terminal part of HER1 and HER4.

Results: In IHC experiments, all three antibodies stained cells transfected with HER2. Binding of the antibodies to HER2 was confirmed bycompetitive ELISA. However, in IHC experiments the PATHWAY® and the Oracle™ antibodies also stained cells transfected with HER4. Competitive ELISAs confirmed binding of the PATHWAY® antibody to HER4, whereas binding of the Oracle™ antibody to HER4 could not be confirmed in a competitive ELISA. None of the antibodies cross reacted with HER1 and HER3 homologous to the HER2 binding site of the antibodies.

Conclusions: Two out of three clinically validated anti-HER2 antibodies were shown to cross react with HER4 in FFPE cells. As determination of HER2 over-expression and/or amplification guides therapy with trastuzumab, a valid test result by the use of specific antibodies is crucial to ensure proper personalized therapy with HER2-targeted therapy. These results warrant further investigation of anti-HER2 antibodies and of the procedures for clinical determination of HER2 protein expression. References:

Slamon DJ et al. (2001) J Med 344:783 Wolff AC et al. (2007) J Clin Oncol 25:118

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-08.
Abstract P4-08-09: The Prognostic Importance of “Detection Mode” and “Palpability” in Primary Operable Grade 2 Breast Cancers
Authors: Van Calster B , Zhang X , Vandorpe T , Van Limbergen E , Dieudonné A-S , Leunen K , Smeets A , Amant F , Berteloot P , Weltens C , Janssen H , Peeters S , Wildiers H , Paridaens R , Van Ongeval C , Van Steen A , Vergote I , Moerman P , Christiaens MR , Neven P.
Published: April 2011

Background: Histologic grade 2 breast cancer may benefit most from molecular classification for prognosis. We studied the prognostic value of ‘detection mode’ and ‘palpability’ together with other prognostic variables in a consecutive series of grade 2 lesions.

Patients and methods: We used follow-up data from new diagnosed and primary operable grade 2 breast cancers from UH Leuven (January 2000 - May 2005). Endocrine, chemo-and radiotherapy were given when indicated. The first appearing breast cancer related event (BCRE) was calculated as local (local, regional or contra-lateral) or metastatic (metastatic if both appeared together). These prognostic variables were assessed: age at diagnosis (per decade increase), tumor size (per cm increase), screening (yes/no), palpability (yes/no), lobular type (yes/no), chemotherapy (yes/no), endocrine therapy (yes/no), lymph node status (0, 1, 2-4, >4), combined expression of IHC-measured ER (pos = any expression), PgR (pos if any expression) and HER-2 (positive = IHC2/3+ and FISH pos), architectural, nuclear and mitotic score. Univariable and multivariable proportional hazards Cox regression using the Firth's penalization method to reduce bias in the parameter estimates were used.

Results: Of the 1013 patients in the dataset, 14 had missing values (1.4%). With a median follow-up of 80 months, we observed 116 BCRE (11.6%); 43 local and 73 metastatic. In univariable analysis, screen detected cancers showed better (HR 0.63, 95% CI 0.42-0.93) and palpable cancers worse prognosis (HR 1.96, 95% CI 1.13-3.71) than non-screen detected and non-palpable cases respectively. The beneficial univariable effect of screening weakened in the multivariable analysis (HR 0.83, 95% CI 0.52-1.31) as 582/602 (97%) of non-screen detected cancers were palpable vs 227/397 (57%) for screen-detected cancers. If palpable was omitted from the multivariable model the HR of screening decreased to 0.68 (95% CI 0.44-1.03) thereby approximating its univariable result. Conclusion: Overall, palpability is more strongly related to prognosis, but detection method also has an effect even though we do not have enough events to show this with a convincing level of reliability.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-09.
Abstract P4-09-10: Prevalence of Triple Negative Breast Cancer (TNBC) and Its Management in 3 Large Breast Cancer Centres in Australia: A Retrospective Review
Authors: Chan A , Lewis C , de Boer R.
Published: April 2011

Background:

Triple negative (ER, PR, HER2 negative) breast cancer (TNBC) is a recognised subtype of invasive breast cancer (BC) associated with a worse prognosis. It represents 10-15% of BC and currently there is no tailored therapy in the adjuvant or metastatic setting. Review of outcomes in BC patients (pts) treated by conventional cytotoxics, can provide some understanding as to efficacy of currently used agents and provide an indication of rates of recurrence and disease response to chemotherapy in a non-trial setting. Methods:

The databases of 3 large Australian centres were examined for BC patients with TN tumours defined as: ER and PR negative on immunohistochemistry (IHC) and HER2 negative by either IHC 0 or 1+ or on ISH. Data was entered prospectively and collectively analysed for prevalence, management and outcome of pts with TNBC seen between January 1998 — December 2009. Pt and tumour characteristics were compared to those with non-TNBC. For the TNBC cohort, details on adjuvant chemotherapy given and relative dose intensity (RDI) was assessed. Disease-free survival, breast cancer event rate and systemic treatment given and response in the first-line metastatic setting will be reported. Results:

Over the 12 yr period, 4902 BC pts were seen with 643 (13%) TNBC (98% operable and 2% metastatic at diagnosis). Median age was 51 years (range, 24-90) and 40% were premenopausal at diagnosis. Tumour characteristics for the entire group are shown in Table 1 and adjuvant treatment given to pts with TNBC in Table 2.

With a median follow-up (mfu) of 36 months (m) (0.2-142), 184 BC events occurred in 154/643 pts (25%). First event was CBC 3.5%, local recurrence 6.7%, metastatic 16.4% (Lung 37%, Lymph nodes 34%, Bone 31%, Liver 27%, CNS 9%). The median DFS was 33m with 77% of BC events occurring within 5yrs. Of the 105 pts who died from BC, median time from metastatic diagnosis to death was 10 months (0.1 - 65). Conclusions:

In 3 large oncology institutions, 13% of new pts with BC had TNBC. Despite adequate dose delivery of anthracycline/taxane/combination anthracycline-taxane adjuvant chemotherapy in 78% of these pts, 25% of pts had a BC event at mfu of 3yrs. Despite the majority of pts receiving taxane, capecitabine or anthracyclines in the first-line metastatic setting, median survival was only 10 months, with 75% of pts dying by 2 yrs from metastatic diagnosis. More effective therapies are required in both the adjuvant and metastatic setting for treatment of this aggressive subtype of BC.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-10.
Abstract P4-09-14: Invasive Lobular Carcinoma Is a Prototype of Luminal A Breast Cancer Subtype and Rare in Korea
Authors: Jung S-Y , Kwon Y , Kim E-A , Ko KL , Shin KH , Lee KS , Park IH , Lee S , Kim SW , Kang H-S , Ro J.
Published: April 2011

Purpose Invasive lobular carcinoma (ILC) is known to be the second most frequent histologic subtype, occupying 10% of invasive breast cancer in the Western countries. The present study was designed to assess the clinical characteristics and outcomes of ILC compared to general invasive ductal carcinoma (IDC) and the luminal A subtype (LA-IDC).

Methods The study population included d 2916 patients with invasive breast cancer consecutively diagnosed at the National Cancer Center, Korea between 2001 and 2008. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed.

Results There were 83 pts (2.8%) diagnosed with ILC and 1,088 pts (37.3%) with LA-IDC. Mean age was 48.2 years of all patients, 48.3 years of ILC group and 47.9 years of LA-IDC group. The ILC patients presented with a larger tumor size (≥T2, 59.8% vs. 38.8%, P=0.001), lower histologic grade (HG 1 or 2, 90.4% vs 64.4%, P<0.001), more often estrogen receptor (ER) and progesterone receptor (PgR) positivity (ER+, 90.4% vs. 64.4%, P<0.001; PgR+, 71.1% vs. 50.1%, P<0.001), HER2 negativity (97.5% vs. 74.9%, P<0.001), lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P<0.001), and luminal A subtypes (91.4% vs. 51.2%, P<0.001) compared to the IDC group. Six (7.2%) ILC patients and 359 (12.7%) IDC patients developed disease recurrence with a median follow-up of 56.4 months (range 4.9-136.6 months). Although ILC showed similar prognosis to IDC in general (5-year DFS rate, 91.7% in ILC vs. 87.4% in IDC, P=0.31; 5-year OS rate, 93.6% in ILC vs. 92.5% in IDC, P=0.38), its outcome was closer to LA-IDC, and better than non LA-IDC (LA-IDC (ref); ILC, HR 0.77 in recurrence, 95% CI 0.31-1.90, P=0.57; HR 0.75 in death, 95% CI 0.18-3.09, P=0.70; non LA-IDC, HR 1.69 in recurrence, 95% CI 1.23-2.33, P=0.001; HR 1.50 in death, 95% CI 0.97-2.33, P=0.07) in univariate and multivariate analysis.

Conclusions ILC is a very rare histologic subtype of breast cancer in Korea compared to the Western countries and has distinctive clinicopathological characteristics similar to those of LA-IDC. Acknowledgement: supported by NCC grant #0910320

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-14.
Abstract P4-09-18: Triple Negative Breast (TNBC) Cancer in Hispanic Population: Clinicopathological and Recurrence Features
Authors: Gómez HL , Velarde RG , Neciosup SP , Cruz WR , Mas LA , Suazo JF , Pinto JA , Vigil CE , Vallejos CS.
Published: April 2011

Background: TNBC is characterized by the lack of hormonal receptors and HER2 expression and occurs most frequently in Black and Hispanic than in Caucasian population. We compare clinicopathological and outcome variables between TNBC and non-TNBC Hispanic patients (pts). Methods: We reviewed 1044 cases of operable breast cancer treated at INEN, Lima-Perú (2000 — 2002). Phenotypes were categorized by IHC into TNBC and non-TNBC. Variables in both groups were compared with the X2 test. We used Kaplan-Meier method for comparing disease free survival (DFS), overall survival (OS), post recurrence survival by phenotype (TNBC v non-TNBC) and the hazard rate (HR) for different times. Results: 212 pts (20.3%) were TNBC and 832 non-TNBC (79.7%); median for age was 48 and 49 years (y), for tumor size 3.5 and 2.9cm; TNBC was more likely to have involved nodes (55.7 v 45.6%; P=0.009), tumors > 5cm (14.2 v 8.1%; P=0.011) and histological grade 3 (62.7 v 29.0%; P<0.001). Recurrence rates (RR) were 25.9 v 22.5% (TNBC v non-TNBC). TNBC and non-TNBC present different RR.

Recurrence sites and phenotype

Median of follow-up was 7.63 and 7.57y; there was not significant differences for DFS between TNBC and non-TNBC (72.8 v 76.6%;P=0.057), but in OS had differences (73.2 v 79.9%; P=0.014). The HR for recurrence was calculated to 1y (7.9 v 2.7%); 2y (8.8 v 5.8%); 3y (8.0 v 6.5%); 4y (2.7 v 3.3%) and to 5y (3.5 v 3.9%) and the HR for death to 1y (4.3 v 0.8%); 2y (6.7 v 2.6%); 3y (8.4 v 3.8%); 4y (5.5 v 2.8%) and to 5y (2.6 v 4.5%) for TNBC and non-TNBC, respectively. HR for recurrence and death was higher in TNBC until the first 3y and 4y, respectively, then HR were similar for both groups. Post recurrence survival show differences between TNBC and non-TNBC (HR=1.7; 95% IC 1.2 - 2.3; P=0.002). Conclusion: In early breast cancer, TNBC is more aggressive than non-TNBC; present a higher RR in brain, distant nodes and other soft tissues; strongly time-dependent HR for recurrence and death, and a worse Post recurrence survival.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-18.
Abstract P4-09-19: The Naïve-Bayes Decision Tree (NBTree) Classifier — Predicting the Probability of Survival in Breast Cancer
Authors: Al-Allak A , Leonard R , Lewis PD.
Published: April 2011

Introduction

As clinicians we are commonly asked by patients ‘what is my chance of surviving breast cancer?’ A number of methods have been in use in anattempt to provide an answer including the TNM classification and the Nottingham Prognostic index (NPI). With the introduction of new machine learning methods and the vast amount of data available to us the call for new models that can predict survival more accurately. As clinicians we must question the usefulness of methods that only tell us whether a patient will survive ten years or die within that time. You may prefer to make a prognosis and be able to predict the likelihood of survival or death within a chosen time span. Objectives

To develop a new predictive model based on a machine learning method known as the Naïve-Bayes Decision Tree (NBTree) classifier.

Methods

Data set: The Surveillance, Epidemiology, and End Results (SEER) data was used to build a data set of women diagnosed with breast cancer between 1990 and 1997. Inclusion criteria included: all women with a diagnosis of invasive ductal carcinoma, under the age of 70 and with a minimum follow up of ten years. Fields included in the data were tumour size, grade, number of positive lymph nodes, survival time and alive status. Model: NBTree is a classifier that combines a decision tree with a Naïve base classifier to build a model that provides the probabilities of outcome. The model was generated using the freely available statistical package R. The model was built based on tumour size, grade and number of positive lymph nodes. It was then validated using K-fold cross validation and tested on a subset of data.

Results

A total of 50,895 women were included in the analysis. The model was generated a total of 10 times and validated using 10-fold cross validation.

The model was able to correctly classify patients 69.26% of the time. When tested on a sub-group of the data set (2000 cases) the model was able to correctly classify patients in 68% of the instances. Conclusion

The NBTree probablistic - machine learning method provides a robust method of putting a value or probability to ten year survival following the diagnosis of breast cancer. Our future aim is to evaluate the method on European datasets to determine its accuracy for patient management relative to existing validated systems.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-19.
Abstract P4-10-02: Young Age Is Associated with Increased Risk of Local Recurrence Following Breast Conservation Surgery
Authors: Boughey JC , Gullerud RE , Degnim AC , Jakub JW , Lohse CM.
Published: April 2011

Background

Local recurrence after breast conservation surgery (BCS) varies with clinical risk factors. The aim of this study was to evaluate how local recurrence rates vary by patient age at time of BCS.

Methods

With IRB approval, all patients undergoing BCS for primary breast cancer between 1988 and 2001 at Mayo Clinic, Rochester were identified. Patients receiving neoadjuvant chemotherapy were excluded. Local recurrence-free survival rates were estimated using the Kaplan-Meier method. Associations with local recurrence-free survival were evaluated using log-rank tests and Cox proportional hazards regression models.

Results

3,075 patients underwent 3,143 BCS between 1988 and 2001. Mean age at BCS was 61 years (range 21-98). There were 177 (5.6%) patients aged <40, 496 (15.8%) 40-49, 763 (24.3%) 50-59, 803 (25.6%) 60-69, and 904 (28.8%) who were 70+ years old at time of surgery. At last follow-up, 214 patients (6.9%) experienced a local recurrence at a median of 3.4 years following BCS (range 0.1-14.4). Median follow-up for patients who did not experience a local recurrence was 8.7 years (range 0.0-20.2). The 5-year local recurrence-free survival rate was 95.0%. The frequency of local recurrences by age group were as follows: age <40 — 11.9%; age 40-49 — 5.9%; age 50-59 — 5.9%; age 60-69 — 7.6%; age 70 and older — 6.4%. The 5-year local recurrence-free survival rates for these age groups were 90.0%, 95.4%, 95.6%, 95.4%, and 94.7%, respectively (p=0.041; log-rank test).

On univariate analysis, patients <40 years old were nearly twice as likely to experience a local recurrence following BCS compared with patients

DCIS was associated with an increased risk of local recurrence compared with T1, T2, T3, or T4 disease (HR 2.25; P<0.001). Factors associated with a decreased risk of local recurrence on univariate analysis included ER positivity (HR 0.46; P<0.001), PR positivity (HR 0.60; p=0.001), adjuvant radiation (HR 0.48; p=0.007) and endocrine therapy (HR 0.65; p=0.012).

Multivariate analysis of patients with complete data (n=2126) demonstrated that age <40 and node positivity were associated with an increased risk of local recurrence, while ER positivity, adjuvant radiation and endocrine therapy were associated with a decreased risk of local recurrence.

Multivariable analysis of local recurrence after BCS

Conclusion

Risk factors for local recurrence after BCS include young age, node positivity, ER and PR negativity and absence of adjuvant radiation and endocrine therapy. Patients under age 40 are at increased risk of local recurrence following BCS for breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-02.
Abstract P4-10-03: Long-Term Follow-Up of SweBCG 91RT, a Randomized Trial of Breast Conservation Surgery with and without Radiotherapy from the Swedish Breast Cancer Group
Authors: Malmström P , Killander F , Anderson H , Holmberg E , Lundstedt D , Mattsson JE , Holmberg L , Karlsson P.
Published: April 2011

Background: Postoperative radiotherapy remains the golden standard after breast conservation surgery. However, national breast screening programmes and increased public awareness of breast cancer have resulted in earlier detection of small tumours with favourable prognosis. The Swedish SweBCG 91RT multicentre study of breast conservation with and without radiotherapy was initiated in 1991. Five year results have been published.(Malmström P et al. Eur J Cancer 39: 1690, 2003). A gene expression signature for radioresistance has also been defined from this patient material. (Niméus-Malmström E et al. Breast Cancer Res 2008, 10:R3(doi10:1186/brc1997). Increasing knowledge of genetically defined subgroups of breast cancer is likely to have an impact on breast conservation treatment. We now present outcome after 15 years of follow-up. Patients and methods: After a standardised radical sector resection 1187 patients with T1-2N0M0 breast cancer were randomised to postoperative radiotherapy or no further treatment. 1178 patients fulfilled the inclusion criteria. The two treatment groups were well balanced with respect to prognostic factors. Median tumour size was 12 mm, and 65 % of cases were detected by mammography screening.

Radiotherapy with tangential MV photons, 48-54 Gy in 24-27 fractions, was administered to the remaining breast parenchyma. CT-based 3-D treatment planning was used. Adjuvant systemic therapy was prescribed according to regional treatment programmes. Nine percent received adjuvant systemic therapy. Patients were followed annually with bilateral mammography for 10 years and thereafter referred to the national Swedish breast screening programme.

Results: With a median follow-up of 15 years, the addition of postoperative radiotherapy did not affect overall survival, 70.8 % with RT vs 68.2 % without RT, p=0.79. This result is based on follow-up for survival until April 2010 for all patients. However, recurrence-free survival, RFS, was significantly improved by radiotherapy, 62,6 % vs 53.7 % after 15 years, P<0.001. The cumulative incidence of local recurrences as first event was significantly lower in the irradiated group 11.8 % after 15 years compared to 24.3 % in the control group, P<0.0001. Results for RFS and local recurrences are based on prolonged follow-up of 85 % of the cases and to 1999 for the remaining. Data with more complete follow-up will be presented at the meeting as will data on treatment efficacy in predefined subgroups.

Conclusions: Postoperative breast radiotherapy is indicated for the majority of patients operated with breast conservation surgery. Analysis of treatment efficacy in subgroups of patients may identify groups for which radiotherapy can be omitted in the future.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-03.
Abstract P4-10-04: Rates of Second Malignancies after Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast
Authors: Shaitelman SF , Grills IS , Kestin LL , Ye H , Nandalur S , Huang J , Vicini FA.
Published: April 2011

Background: We analyzed the risk of developing second malignancies in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) versus surgery alone (S).

Material and Methods: The S+RT cohort consisted of 256 women treated with breast conserving therapy at William Beaumont Hospital. The S cohort consisted of 2,788 women with DCIS in the regional SEER database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 S patients (total of 2048 patients). Matching criteria included age +/− 2 years. The rates of second malignancies were analyzed overall and as contralateral breast versus non-breast cancers and by organ system. Results: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the S cohort. The overall 10-/15-year rate of second malignancies among the S+RT and S cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p=0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the S cohort (p=0.439). The 15- year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the S alone cohort (p=0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and the S cohorts for pulmonary, gastrointestinal, central nervous system, gynecological, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors.

Discussion: Compared with S alone, S +RT was not associated with an overall increased risk of second malignancies in women with DCIS.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-04.
Abstract P4-10-11: Nobel Approach for Breast Conserving Surgery after Primary Systemic Therapy: Real-Time Virtual Navigation
Authors: Suzuki M , Koda K , Yamazaki M , Tezuka T , Kosugi C , Imai K , Hirano A , Nakagawa R , Adachi K , Shirakami R , Yasuda H.
Published: April 2011

Background:

Breast-conserving surgery after primary systemic therapy (PST) has become a widely acceptable procedure for locally advanced breast cancers. Sometimes it is difficult to determine the appropriate resection-line at the time of surgical operation because of tumor size reduction or indistinct boundary of the tumor. Moreover we cannot detect tumors in cases with complete response. That was why we developed a new navigation technique using real-time image reconstruction.

Materials and methods: Multi-detector row computed tomography (MD-CT) has been performed for all breast cancer patients in our institute. DICOM images of MD-CT were analyzed by image processing software ‘OsiriX'. OsiriX is an open source software which anyone can download from website (http://www. osirix-viewer.com). OsiriX has been specifically designed for navigation and visualization of multimodality and multidimensional images. We used 3D volume rendering images. At the time of surgery, pre-PST volume rendering images ware superimposed directly on the patients’ skin from projector which was connected to a personal computer in the operating room.

Results: We could see ‘real-time’ rendering images (from skin to organ by layer to layer) on the patient's body. By using pre-PST imaging data, we could recognize precise tumor area and could perform breast conserving surgery safer and easier than before.

Conclusion: Using 3D reconstruction MD-CT images which were obtained before PST, ‘real-time’ virtual navigation was helpful to determine the resection-line for clear surgical margin in breast-conserving surgery after PST. This new technique does not need some expensive equipments and easily performed by surgeon. Ordinary personal computer and projector make it possible to demonstrate a new environment in surgical operation.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-11.
Abstract P4-11-09: Evidence of Better Cosmetic Outcome after Intra-Operative Radiotherapy with the TARGIT Technique Compared with External Beam Radiotherapy for Early Breast Cancer: Objective Assessment of Patients Enrolled in a Randomised Controlled Trial
Authors: Keshtgar MR , Williams NR , Corica T , Saunders C , Joseph DJ
Published: April 2011

Background: The international randomised TARGIT Trial started accrual in 2000 to determine if there is non-inferiority between the novel technique of TARGIT [intra-operative radiotherapy with Intrabeam® (Carl Zeiss, Germany)] and conventional external beam radiotherapy (EBRT) in women with early breast cancer, with the main outcome measure of risk of local relapse within the treated breast. We report here the data from a sub-protocol assessing cosmesis in a sub-set of patients over 50 years old participating in the TARGIT Trial from one centre (Perth, Australia). Materials and methods: Frontal digital photographs from 114 patients (59 TARGIT, 55 EBRT) taken at baseline and 1, 2 and 3 years after completion of breast conserving surgery were assessed blinded to allocated treatment using specialist software (BCCT.core 2.0, INESC Porto, Portugal) which produces a composite score (Excellent, Good, Fair, Poor) based on asymmetry, colour and scar.

Results: Median age at randomisation was 61 (IQR 56-67) years; all patients were free from recurrence. The categories Excellent and Good;

Fair and Poor; were combined to form EG and FP, respectively. Results are shown in Figure 1. On average patients in the TARGIT group attained EG significantly sooner than those in the EBRT group; a higher cumulative proportion of patients in the TARGIT group had attained EG by each of the three annual examinations post surgery, Log Rank test p=0.0244. By 1 year post surgery 74.6% (SE 5.7%) and 56.4% (SE 6.7%) had achieved EG cosmesis in the TARGIT and EBRT groups respectively. Discussion: These results indicate that the cosmetic effects of targeted radiotherapy using Intrabeam® are better than those obtained with conventional EBRT, with the largest difference one year after surgery.

Figure 1. Cosmetic outcome by randomised treatment

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-09.
Abstract P4-11-12: Neurocognitive Function and Quality of Life of Patients Treated within a Prospective Randomised Clinical Trial Testing the Role of Prophylactic Cranial Radiotherapy (PCI) in Patients Treated with Trastuzumab (Herceptin®) for Metastatic Breast Cancer. The Anglo Celtic VII Trial
Authors: Canney PA , Paul J , Murray E , Lewsley L-A.
Published: April 2011

Background. Various authors have reported a relatively high incidence of CNS metastases in patients with HER2 positive tumours receiving Trastuzumab based therapy for metastatic breast cancer. There has been concern with regard to the possible neuropsychological sequelae of PCI, although data from two prospective randomised trials assessing toxicity and quality of life after PCI for small cell lung cancer (UK02 and PCI 85) have failed to confirm this.

Methods. The HER-PCI trial was a prospective randomised trial of PCI in patients with HER2 positive breast cancer who had progressive systemic disease and had Trastuzumab therapy + chemotherapy as planned treatment. Patients had a screening MRI or CT of the brain after randomisation with a view to excluding those with sub-clinical CNS disease. Neurocognitive function was assessed at baseline, 3,6 and 9 months from randomisation using EORTC QLQC30, EORTC neurological sub-scale BN20, Hospital anxiety and depression score (HADS) and the Addenbrookes Cognitive Examination (ACE-R). Patients were randomised 1:1 to no PCI or PCI delivered at around 6 weeks after the start of their systemic treatment for metastatic disease. The PCI dose was 30Gy in 10 fractions, a fraction deferred if due on a day of planned chemotherapy.

Results. 51 patients entered the randomisation between March 2007 and March 2010. 25 received PCI and 26 did not. 46 (90%) of patients received Trastuzumab + chemotherapy and 5 patients single agent Trastuzumab. The mean age was 54 years. Results of the neurcognitive testing and QOL will be presented

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-12.
Abstract P4-12-01: A New Resource To Accelerate Research into the Cause and Prevention of Breast Cancer: The Love/Avon Army of Women
Authors: Love SM. Dr
Published: April 2011

Background: It is well established that there is a need for more research into the cause and prevention of breast cancer. While many studies are done in cell lines and laboratory animals, translation of findings to women often falters due to perceived difficulty in recruiting women for research. The Dr. Susan Love Research Foundation received a grant from the Avon Foundation to form the Love/Avon Army of Women (AOW); an online recruitment resource designed to partner women with the research community in an effort to accelerate breast cancer research.

Methods: The AOW was launched in 2008 with the goal of recruiting one million women interested in participating in breast cancer research, and of encouraging researchers to submit studies for recruitment. Researchers interested in having the AOW recruit for their studies submit a proposal that will be reviewed by the AOW Scientific Advisory Committee, comprised of nominees from AACR and NBCC. If a study is accepted, a mass e-mail describing the study procedures and inclusion/exclusion criteria is sent to the entire AOW database. Women sign up at www.armyofwomen.org to join the AOW. Women aren't committing to participating in a particular study, but agree to receive AOW e-mails about breast cancer research studies. Women self select based on interest and study criteria, and undergoa secondary on-line screening before contact information is passed on to the researcher for the enrollment process.

Results: Over 334,000 women have signed up, including survivors and healthy women, ranging from ages 18 to 100, representing all 50 US states and 47 countries. To date, the AOW has recruited for 31 studies, both regional and national, that vary from biomarker and circadian rhythm research to psycho-social and quality of life studies. With over 41,000 AOW members having participated in the research process, this method of recruitment has been found to be effective and efficient. The diversity of the AOW members has proved beneficial for many studies such as those needing to enroll African American women, women of varying sexual orientations, or young survivors.

Many studies were closed to enrollment within the first 48 hours after accruing all subjects while others were very quickly over-enrolled by 5-10%. This overwhelming response has led many researchers to seek additional funding to increase their statistical significance and accommodate all eligible subjects.

Conclusions: The Love/Avon Army of Women is a novel resource for scientists to accelerate accrual, expand the number and diversity of their subject population and to obtain exactly the type of specimens they need when they need it. This new partnership between women and scientists can revolutionize research and accelerate efforts to eradicate breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-12-01.
Abstract P5-01-03: MRI vs Breast Specific Gamma Imaging (BSGI) in Newly Diagnosed Breast Cancer: A Prospective Head-to-Head Trial
Authors: Kirstein LJ , Fulop T , McPartland L , Cohen I , Boolbol SK.
Published: April 2011

Introduction: Functional breast imaging is emerging as an adjunct to mammography and ultrasound in newly diagnosed breast cancer patients. Magnetic resonance Imaging (MRI) is the modality most widely employed. However, it is expensive, uncomfortable for certain patients, and interpretation is variable, depending upon a radiologist's expertise. Breast Specific Gamma Imaging (BSGI) has emerged as an alternative functional imaging study. While MRI evaluates differential enhancement of benign versus malignant lesions, BSGI evaluates the metabolic activity of normal versus abnormal cells by tagging mitochondria with Technecium99. In retrospective analyses, BSGI has been found to have similar sensitivity to MRI, but to date there has not been a prospective trial comparing these modalities in newly diagnosed breast cancer patients. We sought to prospectively compare BSGI to MRI in newly diagnosed breast cancer patients, to determine if this newer functional imaging study is as sensitive to MRI in detecting index lesions.

Methods: Patients with newly diagnosed invasive breast cancer from June 1, 2009 through May 31, 2010 were consented for an IRB approved protocol in which they underwent both breast MRI and BSGI. Each imaging study was read by a dedicated breast radiologist, with one radiologist reading all MRI, and another reading all BSGI studies. All subsequent biopsies were performed percutaneously, using image guidance. Patients were excluded if excisional biopsy was performed for diagnosis, or their MRI was performed at an outside facility. Patients with DCIS were also excluded. The sensitivity for each modality was calculated. Results: There were 53 patients enrolled in the study that had both MRI and BSGI for newly diagnosed invasive breast cancer. The sensitivity for MRI was 96% and for BSGI was 91% (Table 1) (P>0.5, ns). There was one index tumor not seen on either MRI or BSGI. It was a 2mm invasive ductal carcinoma diagnosed by calcifications on mammogram. The other index tumor not seen on MRI was visualized on BSGI. Two of the remaining four index tumors not visualized on BSGI were located in the posterior breast. Two studies were false negative. These four lesions were visualized on MRI.

Discussion: In this prospective study comparing BSGI to MRI for newly diagnosed invasive breast cancer, BSGI was found to be as sensitive as MRI at detecting index lesions. Of the four false negative BSGI, two tumors were located near the chest wall, a known limitation of this technology. Larger prospective studies need to be performed to determine the true sensitivity and specificity of BSGI.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-03.
Abstract P5-01-08: Preoperative Positron Emission Tomography/Computed Tomography (PET/CT) and 18F-Fluorodeoxyglucose (18F-FDG) Compared with Conventional Assessment in Patients with Early Primary Breast Cancer: Preliminary Results of a Prospective Study
Authors: Petersen MB , Berthelsen AK , Timmermans-Wielenga V , Kroman N , Binderup T , Tange UB , Andersson M , Kjaer A , Loft A , Graff J.
Published: April 2011

Background: The prognosis and clinical management of patients with newly diagnosed breast cancer depends on the extent of disease. The aim of this study was to compare the diagnostic and therapeutic impact of preoperative PET/CT, using 18F-FDG in the initial extra-axillary staging of patients with early breast cancer, to the results of conventional assessment. One hundred patients are planned enrolled. We here report the results of the first fifty consecutive patients.

Patients and methods: Fifty consecutive patients with newly diagnosed early operable breast cancer with tumors ≥2 cm were examined preoperatively with conventional assessment (mammography, breast/axilla ultrasound, chest x-ray and blood samples) and PET/CT. Conventional assessment and PET/CT were evaluated independently with no prior knowledge of the other. Distant metastases/new primary cancers found on PET/CT were confirmed histologically, by other imaging modalities or with at least 1 year of follow-up.

Results: The mean age was 56 ± 11 years. PET/CT identified primary tumor in all but two patients (96%). Nine cases of extra-axillary lymph node involvement were solely revealed by PET/CT in the internal mammary chain (n=7) and the supraclavicular region (n=2). Additionally, PET/CT solely detected distant metastasis (ovary, bone) in two patients and new primary cancers (ovary, lung) in another two patients. Two patients (4%) had non-malignant focal uptake of 18F-FDG confirmed with histologic biopsies (schwannoma, colon adenoma).

In 12 patients (24%) extra-axillary malignancy was detected by PET/CT only, leading to an upgrade of initial staging in 20% (10/50) of patients and ultimately a modification of planned treatment in 4 (8%) patients. No patient was down staged by PET/CT.

Conclusion: PET/CT is a valuable tool to provide information on extra-axillary lymph node involvement, distant metastases and other occult primary cancers. Preoperative 18F-FDG-PET/CT has a substantially impact on initial staging and on clinical management in patients with early stage breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-08.
Abstract P5-03-05: Triple Negative Breast Cancer: Prognosis Dependent on Presenting Stage Rather Than Receptor Status
Authors: Hamm CM , Poliquin G , Poliquin V , El-masri M.
Published: April 2011

Purpose: To investigate the differences in survival and prognostic factors such as age at diagnosis, stage, size of tumor, mode of identification, treatment and family history between patients that have triple negative breast cancer (TNBC) and those who are not (at least one positive marker).

Methods: a retrospective chart review was conducted on 1018 eligible breast cancer patients who were diagnosed between 2000 and 2005 in Essex, Kent, and Lambton counties in Ontario.

Results: Our demographic findings supported those of previous publications whereby age at diagnosis was younger for TNBC patients (53.2 vs 60.9 respectively; p < 0.001). The frequency of stage III cancer was higher among TNBC patients than that of other cancer patients (16.2% and

6.3%, respectively; p > 0.001). Frequency of self detection was higher among TNBC patients compared to patients with other cancers (76.8% and 56.4%, respectively; p <.001). Perhaps most importantly, while TNBC had had HR of 2.29 (95%CI = 1.33 - 2.93), the adjusted survival analysis suggested that there was no significant difference in the overall survival between the two groups (HR = 1.22; 95%CI = .63 - 2.39). The significant predictors of survival in the adjusted analysis were; age, stage of cancer, and size of cancer.

Conclusions: We believe that this is the first indication that patients with TNBC do as well as their non-TNBC cohorts when matched for stage at presentation. Future studies need to focus on identification of patients who are at increased risk of TNBC so appropriate screening tests can be obtained.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-03-05.
Abstract P5-03-09: Ovarian Hormones Promote Mammary Carcinogenesis by Altering Growth Factor Receptor Signaling
Authors: Arumugam A , Parada J , Gamez M , Boopalan T , Delgado A , Agullo P , Lakshmanaswamy R.
Published: April 2011

Study of carcinogenesis in rat models plays an important role in understanding the nature of neoplastic transformation. Identification of biological, cellular and molecular alterations involved in the carcinogen induced preneoplastic transformation has vital importance in mammary cancer development. Copenhagen rats are resistant to the carcinogen, N-methyl-N-nitrosourea (MNU) induced mammary carcinogenesis. Our previous studies indicate that MNU induced preneoplastic lesions were promoted to mammary cancer by the hormones estrogen and progesterone. The purpose of this study is to delineate the molecular mechanisms of hormonal promotion of mammary carcinogenesis. Seven week old female Copenhagen rats were administered a single dose of 50 mg/kg body weight MNU intraperitoneally. Four weeks post carcinogen administration, rats were divided into 4 groups, 1) Control, 2) rats treated with 30 mg estradiol, 3) rats treated with 30 mg progesterone, 4) rats treated with 30 mg estradiol plus 30 mg of progesterone. Two weeks after the implantation rats were killed and mammary glands were excised and used for further experiments. Quantitative RT-PCR experiments showed up-regulation of growth factor receptors such as Igf-1r, Egfr and growth factor signaling members Grb2, Pi3k and Ras mRNA expression. Immuno histochemical studies showed strong staining to growth factor receptors and western blotting studies showed increased protein levels of growth factor receptors such as IGF-1R and EGFR and active form of proliferative signaling molecules Akt and SAPK/JNK were up-regulated in combination of estradiol and progesterone treated rats. Phosphorylated p38 was reduced in the combination of hormones treated rat preneoplastic lesions when compared to control. Combination of ovarian hormones treatment provided enhanced growth factor signaling environment and promoted the mammary lesions through activation of SAPK/JNK and growth factor signaling pathways.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-03-09.