bluuebunny/crossref_metadata_2025 huggingface dataset:
The Value of Breast Ultrasound in BRCA1 and BRCA2 Mutation Carriers.
Authors: Bosse K. , Graeser M. , Rhiem K. , Gossmann A. , Hackenbroch M. , Warm M. , Mallmann P. , Schmutzler R.
Published: December 2010

OBJECTIVE: BRCA1/2 mutations carriers face a lifetime risk for breast cancer of 60 to 80%. Typically, tumor incidence is high at young age and tumor growth rates are significantly elevated. On ultrasound investigation the malignancies often mimic fibroadenomas with round shape, circumscribed margins and a homogeneous internal structure leading to a BIRADS 3 classification. On this background we evaluated the efficacy of ultrasound for the early detection of breast cancer in this high risk group.METHODS: Between 01/1997-07/2008 223 BRCA1/2 mutation carriers participated in a breast cancer screening program which included semi-annual ultrasound (US) and annual mammography (MG) and MR imaging (MRI).Screening procedures started from age 25, MG at age 30. As patients consecutively joint the study women underwent 5 (median) screening rounds with a range of 1 to 22 appointments, totaling 1855 rounds of screening. All three imaging modalities were coded according to the American College of Radiology (BI-RADS classification).RESULTS: We detected 15 primary and 14 secondary contralateral BRCA-associated tumors in 27 patients. Age at diagnosis ranged from 29 to 66 years (median 41 years). BI-RADS classification IV and V enabled the detection of 9 (32%) cancers by mammography, 21 (87,5%) by US and 27 (96%) by MRI scan. Specificity added up to 100%. Three (11%) tumors were detected by the semi-annual ultrasound screen and two patients presented with interval carcinomas (16 and 8 mm in diameter) between two screening appointments. Thus, the proportion of interval cancers was 7%.CONCLUSION: Semi-annual sonography as a supplementary examination enabled us to reveal 3 additional invasive cancers (two stage pT1b, one stage pT1c). Due to the specific tumor morphology and the considerably elevated tumor doubling time mutation carriers may benefit from the addition of semi-annual ultrasound as a highly sensitive and cost-effective method.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4004.
Quality Assurance of an Organised Screening Programme for Breast Cancer in Denmark 1991-2008.
Authors: von Euler-Chelpin M. , Jacobsen K. , Vejborg I.
Published: December 2010

Background: The capital city of Copenhagen, Denmark, has had an organised programme for screening with mammography since 1991. All women resident within the area of uptake and aged 50-69, representing around 45000 women, are invited biennially, unless they actively have asked not to be invited. We have evaluated the programme with regard to the European guidelines for quality assurance in breast cancer screening and diagnosis, to assess performance and impact.Methods: The target population was identified through the national population register, identifying all women meeting the inclusion criteria in terms of age and place of residence, migration and death. The mammography programme supplied data on all invited women, participation and screening test results. Oncological data was retrieved from the National Cancer Register and the Danish Breast Cancer Group. Data was linked using the Danish unique personal identity number.Results: In the first invitation round (1991-1992) the invasive cancer detection rate was 10/1000 and was by the 8th invitation round (2006-2007) 8/1000. The in situ detection rate has been 1/1000 throughout the period. The programme sensitivity is approximately 70%. The detection rate of small tumours (≤ 10mm) was, on average, 39% over the first 4 invitation rounds and 62% by the 8th invitation round. The benign to malign ratio changed from 1:1.6 to 1:11.4, from the first to the 8th invitation round. Recall rates at initial screen dropped from 7% to 4% in the period, and for subsequent screens from 4% to 2%. The false positive rate was 5.5% in the first invitation round and had by the 8th invitation round dropped to 1.3%, with a cumulative risk of 15% over 8 rounds. In the 8th invitation round, there was 82% coverage, a participation rate of 61% and a long term adherence of 50%.Conclusions: The results for the majority of indicators were well within the recommended levels. There had been a significant improvement in the benign to malign ratio, despite that the false positive rate at assessment had decreased. The detection of small tumours had also improved significantly. Participation rates were, however, lower than recommended.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4005.
Does the Additional Prognostic Benefit of Screen Detection in Early Breast Cancer Apply to All Patients?
Authors: Mansell J. , Komolafe O. , Angerson W. , Wilson C. , Doughty J.
Published: December 2010

IntroductionScreen detection may confer prognostic benefit independent of disease stage in EBC leading to suggestions that mode of presentation should be considered when deciding adjuvant therapy. We aim to determine if this additional prognostic benefit is seen in all patients.MethodsData from 3 centres in Glasgow of consecutive women aged between 50-65yrs with EBC diagnosed between 1995 and 2001 were examined. Patients were grouped by mode of presentation into screen detection and symptomatic. Breast cancer specific survival was the endpoint. Multivariate analysis including interaction between mode of presentation and pathology was performed with further subgroup analysis if the interaction was significant.Results1534 women were included with a median follow up of 5.5yrs. Mode of presentation was screening in 1007 (65.6%) women. After adjustment for pathology screen detection had no significant survival benefit: HR 0.73 (0.50-1.08, p = 0.116). Mode of presentation had an independently significant interaction with both nodal status and ER status (p = 0.003 and p = 0.01 respectively). Further analysis demonstrated that screening was an independent predictor of survival in the 1-3 node positive group (HR 0.33 (0.15-0.73), p = 0.006); the ER positive group (HR 0.53 (0.31-0.89), p = 0.017) and in the moderate NPI group only (HR 0.54 (0.31-0.94), p = 0.030).ConclusionsThese results provide evidence of a significant interaction between mode of presentation and pathology. Further research is needed before incorporating mode of presentation into decisions regarding adjuvant therapy.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4007.
Should the Age of Breast Cancer Screening for Ethnic Minorities Be Reduced?
Authors: Soumian S. , Sircar T. , Whisker L. , Skillman J. , Abbott N. , Winter H. , Kaur V. , Kearins O. , Lawrence G.
Published: December 2010

IntroductionThe National Health Service Breast Screening Programme (NHSBSP) offers breast screening every three years for all women aged 50 and over in the United Kingdom (UK). Women aged between 50 and 70 are routinely invited. The NHSBSP will extend the age range of women invited for breast screening from ages 47 to 73 in the future. However, the ideal age for screening should take into consideration the relative risk of the population. The UK has a significant population of ethnic minority groups, mainly Asian and Afro-Caribbean, comprising of about 8% of the total population. The ethnic minority groups have remained geographically concentrated in specific regions especially London and West Midlands, where they comprise 30% and 14% of the population respectively. It has been reported that ethnic minorities present with relatively advanced breast cancer at a younger age. These groups could potentially benefit from early screening. We wanted to test this hypothesis by assessing the age and route of presentation of breast cancer across ethnic groups in the West Midlands region.MethodsThe West Midlands Cancer Intelligence Unit (WMCIU), a population based registry, collects prospective data on breast cancer diagnosed and treated in this region. Data on patients treated for breast cancer from 2001 to 2007 was obtained from the WMCIU. The age and route of presentation (screening or symptomatic) of Asian, Afro-Caribbean and Caucasian patients were analysed and compared.Results.A total of 27,444 female patients were diagnosed during this period. Data regarding ethnicity was available for 18,941 Caucasians, 528 Asians and 274 Afro-Caribbean's. Diagnosis through screening was 37%, 26% and 29% for Asian, Afro-Caribbean and the Caucasian population respectively. In the symptomatic group, 26.5% of Asians and 35% of Afro-Caribbeans presented below the age of 47 years compared to 13% of the Caucasian population. Furthermore, 13.5% of Asians, 16.5%of Afro-Caribbeans and 5.9% of Caucasians presented at or below the age of 40 years.ConclusionA significant percentage of breast cancers diagnosed within ethnic groups will still be missed despite revising the screening age to 47 years. Unless the participation of ethnic groups in screening is targeted, the benefits (detecting disease at an earlier stage and potentially reduced mortality) will be lost.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4008.
Diagnostic Work-Up of Contralateral Breast Cancers Has Not Improved over Calendar Period.
Authors: Sandberg M. , Hartman M. , Hall P. , Czene K.
Published: December 2010

Background: Contralateral breast cancer (CBC) is diagnosed in 1-2.6 % of all breast cancer patients directly at diagnosis, after that the risk still remains high (0.7% per year) throughout life of the patient. Breast cancer patients are followed up by palpation and clinical mammography after their diagnosis, partly to be able to diagnose a possible CBC. The aim of this study is to investigate if the diagnostic work-up of patients with breast cancer has improved over the last thirty years and resulted in earlier CBC diagnosis.Materials and Methods: Synchronous contralateral breast cancer is here defined as two cancers occurring maximum 3 months apart, cancers with longer latency time are defined as metachronous. The study population is restricted to patients with maximum three years between the two cancer diagnoses. In this study we used two cohorts; all CBCs in Sweden 1976-2004 (N: 3260), and all CBCs in Stockholm during 1976-2005 (N: 688), the smaller cohort had more detailed information. The study participants were selected from two population-based registers (Sweden Cancer Register and Stockholm Breast Cancer Register). With logistic regression we calculated the odds ratio of being diagnosed synchronously, as compared to metachronously, adjusted for calendar period and age at first diagnosis.Results: The risk of synchronous diagnosis was increased by 27% per each 5-year period, the change was statistically significant. We then investigate if this risk increase by calendar period was due to improved clinical work-up, by including detection mode in the model. We found that the risk estimates for calendar period persisted, thus giving no evidence for improvement of clinical work-up during the study period. This result did not change when stratifying the study population by age at first diagnosis (below/above 55). Next, we instead included adjuvant therapy for the first cancer in the model and the association with calendar period decreased to non-significant levels. We also showed that the proportion of CBCs detected trough clinical work-up has not increased over calendar period (p=0.89), neither when including, nor excluding, screening mammography as part of the work-up. The mean tumour size of the contralateral breast cancer was 16.0 mm and has not decreased over the study period (p:0.62)Discussion: We found an increase in the proportion of synchonous CBCs compared to metachronous over calendar period, this change is not associated with clinical work-up, but with adjuvant therapy. This study gives no indications of any improvement in diagnostic work-up of contralateral breast cancer over the last thirty years. Such an improvement would potentially be very important for survival of the growing population of (first) breast cancer survivors.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4011.
Breast Lesions of Uncertain Malignant Potential: A Challenge for Surgeons.
Authors: Deslauriers N. , Leblanc G. , Sidéris L. , Dubé P. , Leclerc Y. , Dufresne M.
Published: December 2010

Background: The need for surgical resection of brest lesions of uncertain malignant potential diagnosed at core biopsy is not well established. The aim of our study was to determine the incidence of these lesions on core biopsy and to find the rate of upgrade at surgery and during follow-up.Material and Methods :All breast biopsies at Maisonneuve-Rosemont hospital were prospectively collected from November 1999 to December 2008. We reviewed the records of all patients diagnosed with lobular carcinoma in situ (LCIS), atypical lobular neoplasia (ALH), atypical ductal hyperplasia (ADH) and radial scar during that period. Patients were excluded if there was also presence of invasive carcinoma or ductal carcinoma in situ on the biopsy. An upgrade was defined as the presence of invasive carcinoma or ductal carcinoma in situ on the surgical specimen.Results: During that period, 9325 breast biopsies were done. The women were aged from 37 to 89 years with a mean age of 56 years and were followed for an average of 27 months .There were 20 patients with LCIS (0.2%), 36 ALH (0.4%), 60 radial scars (0.6%) and 110 ADH (1.2%). For lobular neoplasia, 85% of LCIS patients had surgical resection with an upgrade rate of 29% (5/17). On follow-up no patients developed a breast cancer at the site biopsied. 28% of ALH had surgical resection with only one patient presenting an upgrade. For radial scars 58% had surgical resection with an upgrade rate of 3/35 (8%). In all three patients with an upgrade, the biopsy was done on an hypoechogenic lesion. No patients with a radial scar visible only on mammogram presented an upgrade and no patients on follow-up developed a cancer at the site of biopsy. For patients with ADH, 48% had a surgical excision (53/110) with an upgrade rate of 18.9% (9/53). Nine patients of the 49 who did not undergo a surgical excision developed a cancer at the site of biopsy during follow-up (18%). Also, during follow-up, 51% of the patients with ADH who did not have surgery had to be rebiosied around the site of the previous biopsy.Conclusion: The important rate of upgrade in LCIS and ADH mandates a surgical excision when these lesions are found on biopsy results. Also, surgical excision for women with ADH might spare the stress of repeat investigation and biopsy.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4012.
Retrospective Study Assessing the Role of MRI in the Diagnostic Procedures for Early Breast Carcinoma: A Correlation of New Foci in the MRI with Tumor Pathological Features.
Authors: Calvo Plaza I. , Ugidos de la Verga L. , Miró C. , Suarez A. , Perez P. , Quevedo P. , Parras M. , Torres M. , Herrero M. , Buelga P. , García L. , Alonso P. , de la Cruz J. , López Ríos F. , Hidalgo M. , G Estévez L.
Published: December 2010

Purpose: To analyze the role of MRI in the detection of additional disease and the need to perform additional biopsies in early breast carcinoma patients. In addition, to correlate the detection of new foci with tumor pathological features.Methods: Early breast carcinoma patients that had undergone a MRI as well as a mammography as diagnostic procedures were included in the study. The following pathologic features were studied: carcinoma type, histological grade, estrogen (ER)/progesterone (PR) receptors, HER2 and Ki67. HER2 status was established by FISH, while ER, PR and Ki67 status were established by inmunohistochemistry. Univariate analysis was conducted to ascertain significant correlation among detection of new foci and each of the tumor pathological features.Results: To date, data from 98 patients have been analyzed: median age 49 years (range: 35-79); carcinoma type: a) infiltrative ductal carcinoma (n=73, 74%), b) infiltrative lobular cancer (n=13, 13%), c)ductal carcinoma in situ (n= 6, 6%); amplified HER2 (n=18, 18%); grade III (n=33, 33%);Ki67 ≥ 25%(n=33, 33%); positive ER and PR (n=78, 79%); triple negative tumors (n=8, 8%). MRI detected additional disease in 38 cases (39%) that led to an additional biopsy in 20 cases (20%). Thirty-nine patients (39%) underwent mastectomy. A statistically significant correlation was established between the finding of new foci in MRI and high proliferative tumors through the biomarker Ki67 (cutoff ≥ 25%) (p<0.005). No other statistically significant correlation was established with any of the other pathological features analyzed.Conclusion: In patients diagnosed with early breast cancer, MRI detected the presence of additional disease in 39% of the cases, requiring an additional biopsy in 20% of the cases. Tumors with high proliferative index were significantly correlated with the detection of new foci in MRI. An update of the results will be presented at the symposium.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4018.
The Effect of Preoperative MRI on Mastectomy Rates in Breast Cancer Patients.
Authors: Cobain E. , Hong S. , Abe H. , Jansen S. , Jaskowiak N. , Newstead G. , Olopade O.
Published: December 2010

Background: Currently, there are two primary surgical options for the treatment of early stage breast cancer: modified radical mastectomy and breast conserving surgery (BCS) with post-surgical radiation. Numerous studies have shown that there is no survival difference between the two surgical treatments, however, in recent years, there is data to suggest that mastectomy rates have been on the rise. While many factors undoubtedly influence surgical management decisions in breast cancer patients, the effect of routine use of preoperative breast MRI may be a contributor to the rise in mastectomy rates. Methods: Breast cancer patients who were treated surgically and received a preoperative MRI were identified using a database from the University of Chicago Department of Radiology, which contains information on over 4200 patients who have received breast MRI since 2002. These patients were cross-referenced with data from the University of Chicago Cancer Registry, which contains information regarding type of surgical treatment, surgeon, stage of cancer at time of diagnosis and surgical stage for all breast cancer patients treated at the University of Chicago Hospitals from 2000-2007. Annual mastectomy rates from 2000-2007 were calculated and compared using Pearson's Chi Square test. Annual mastectomy rates were stratified by mean age at diagnosis and stage of disease. Mastectomy rates prior to routine use of preoperative MRI (2000-2002) and after routine use of preoperative MRI (2005-2007) were calculated for breast cancer patients under 45 and over 45 years of age and rates were compared using Fisher's exact test. Results: A total of 1,404 patients received surgical treatment for a new diagnosis of breast cancer between 2000 and 2007 at the University of Chicago Hospitals. Results to date indicate that mastectomy rates across all years are not significantly different (p = 0.315). Results also indicate that the mean age at diagnosis of patients who receive mastectomy as the initial surgical treatment for their breast cancer is higher than those who receive BCS from 2000-2002, but is lower than those who receive BCS from 2003-2007. In addition, breast cancer patients under the age of 45 have higher rates of mastectomy since the routine use of preoperative MRI which trends toward statistical significance (p = 0.0598). Conclusion: These preliminary results indicate that overall mastectomy rates at the University of Chicago Hospitals are not increasing in concordance with the increased use of preoperative MRI testing, but that younger breast cancer patients may have higher rates of mastectomy in the MRI era.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4019.
Evaluation of Neoadjuvant Chemotherapeutic Effects of Breast Cancer by MRI: Accuracy of MRI in Predicting Pathological Complete Response.
Authors: Fukuda T. , Gomi N. , Miyagi Y. , Tokudome N. , Takahashi S. , Ito Y. , Iwase T. , Akiyama F.
Published: December 2010

Purpose: The importance of the evaluation of pathological complete response (pCR) has been confirmed by the fact that, there is a close correlation between pCR to neoadjuvant chemotherapy (NAC) and prognosis for breast cancer. The objective of our study was to evaluate the accuracy of MRI in predicting CR after NAC.Methods and Materials: 305 women with stage IIB-III palpable solid breast cancer received adriacin(50mg per sqare meter), cyclophosphamide(500mg per sqare meter), plus fluorouracil(500mg per sqare meter) for 6 cycles, followed by 12 cycles of paclitaxel (80mg per sqare meter) or 4 cycles of Docetaxel (75mg per sqare meter) as NAC. They underwent dynamic contrast-enhanced T1WI of the entire breast, before and after NAC. On imaging, complete response (iCR) was defined as no enhanced tumor on all serial images. All patients underwent radical or conservative surgery between Jan. 2005 and Dec.2007, and imaging findings were compared with pathologic findings.Results: 43 out of 305 patients had iCR after NAC. 23 out of the iCR (53%) were identified correctly with pCR (no histological evidence of invasive tumor cells). Yet in 20 out of iCR patients (47% ), MRI underestimated the residual tumor. In 17 out of the 20 patients who were underestimated on MRI, resected specimens showed marked response to chemotherapy and only a small amount of residual tumor was detected. In 3 out of 20 patients who were underestimated on MRI, resected specimens showed mild response to chemotherapy, and considerable amount of residual tumor among fibrotic change was detected.Conclusion: MRI seems to reflects pathological conditions after neoadjuvant chemotherapy effectively, and appears to provide good correlation with pCR.53% of the patients who were evaluated as iCR were pCR.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4026.
Prognostic Utility of HOXB13:IL17BR and Molecular Grade Index for Node-Negative Breast Cancer Patients.
Authors: Habel L. , Erlander M. , Achacoso N. , Ma X. , Sgroi D. , Fehrenbacher L. , Greenberg D. , Quesenberry C.
Published: December 2010

Background: Four studies have reported that a two-gene ratio (HOXB13:IL17BR) may be prognostic and/or predictive of tamoxifen benefit among early stage breast cancer patients. More recently, a 5-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) was reported to predict clinical outcome. We evaluated the performance of these two gene signatures among an independent population of lymph node-negative breast cancer patients from a community hospital setting.Methods: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985-94 and not treated with adjuvant chemotherapy (Habel, 2006). Archived tumor tissues were available on 169 cases (breast cancer deaths) and 335 matched controls and, using RT-PCR, were analyzed for expression levels of the above 7 cancer-related genes and 4 reference genes. Logistic regression methods were used to estimate the 10-year risk and the relative risk (RR) of breast cancer death associated with pre-specified risk categories based on cross-classification of HOXB13:IL17BR and MGI scores.Results: Approximately 50% of patients were classified as low risk by the HOXB13:IL17BR+MGI risk classifier. At 10 years, the risks of breast cancer death for ER+, tamoxifen-treated patients were 3.9% (95% confidence interval (CI) 2.2% - 5.5%), 5.6% (95% CI 2.6% - 8.5%), and 15.6% (95% CI 8.7% - 21.9%) for those in the low, intermediate and high risk groups, respectively. They were 5.9% (95% CI 4.2% - 7.5%), 15.2% (95% CI 8.3% - 21.5%), and 16.5% (95% CI 10.4% - 22.2%) for ER+ patients not treated with tamoxifen. After adjusting for tumor size and grade, the RRs of breast cancer death associated with high vs. low HOXB13:IL17BR+MGI risk categories were attenuated but remained elevated in both treatment groups; the RR continued to be statistically significant in tamoxifen treated patients only.Conclusion: In this population of lymph-node negative patients not treated with adjuvant chemotherapy, the HOXB13:IL17BR+MGI risk classifier was predictive of risk of breast cancer death and appeared to provide risk information beyond standard prognostic factors.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4034.
Polysomy of Chromosome 17 in Breast Cancer.
Authors: Nielsen K. , Ejlertsen B. , Møller S. , Balslev E. , Müller S. , Knoop A. , Mouridsen H.
Published: December 2010

Purpose: Polysomy of chromosome 17 is frequently described in breast cancer, but firm definition of polysomy is lacking. We have used normal breast tissue to define the ploidy levels in the truncated nuclei of cut sections based on standard cytogenetic definition of ploidy in whole nuclei. Data from patients with invasive breast cancer enrolled in a randomized clinical trial was used to investigate the effect of polysomy of centromere 17 on patient survival. (Ejlertsen B et al., Eur J Cancer 2007:43:877-84).Material and methods: Fluorescence in situ hybridization (FISH) with TOP2A/CEN-17 was performed on 120 normal breast specimens. Centromere 17 (CEN-17) measurements from matching HER2/CEN-17 and TOP2A/CEN-17 FISH data was available from 649 patients from a previously published biomarker study (Knoop A et. al., J Clin Oncol 2005;23:7483-90).Results: Two thirds of the tumors had an average number of CEN-17 signals below two and 10% had more than three average CEN-17 signals. Monosomy (<1.25 CEN-17/nucleus) of centromere 17 was observed in 8% of the tumors, 60% of the samples were diploid (1.26-2.09 CEN-17/nucleus), 22% triploid (2.10-2.93 CEN-17/nucleus), 5% tetraploid (2.94-3.77 CEN-17/nucleus) and 5% of the tumors had higher ploidy level (>3.78 CEN-17/nucleus). In the aneuploid tumors and especially in the highly polyploidy tumors, amplification is the most frequent event in the HER2 assay whereas deletions increased with the ploidy level in TOP2A assay. Increasing ploidy was associated with decreased overall survival (P=0.0001), but multivariate analysis showed that polyploidy was not an independent prognostic factor neither predictive for treatment outcome.Conclusion: Polysomy 17 is a rare event in tumor samples from patients, but correlate to HER2 amplification and TOP2A deletion. However, inclusion of a reference probe is necessary if deletions are to be revealed and to avoid false positive amplified cases with a high proportion of dividing cells or a doubling of the DNA content. Very high polyploidy is associated with poor survival but is not an independent prognostic factor when other prognostic factor are included in a multivariate analysis. In this large clinical study, polysomy 17 was neither an independent prognostic nor predictive marker.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4035.
Prognostic Factors and Long-Term Survivors in Inflammatory Breast Cancer.
Authors: Woods R. , Huang J. , Livingston R. , Grasso-LeBeau L. , Hendershott K. , Gruessner A. , Mayo J. , Lang J.
Published: December 2010

Background: Inflammatory Breast Cancer (IBC) carries a worse overall survival and demonstrates distinct clinicopathologic qualities which require refinement of prognostic indicators specific to IBC. We hypothesized that given IBC's typically rapid course, nodal status would not be a significant prognostic factor. We also investigated the impact of treatment with radiation and surgery on IBC survival.Material and Methods: Retrospective data from the Surveillance, Epidemiology, and End Results of the National Cancer Institute (SEER 13 and 17 registries) were used to evaluate the prognostic effects of nodal status, surgical resection, and radiation on mortality of patients with IBC. We compared survival between patients with or without positive lymph node status and treatment with radiation, surgery, and those patients treated with both. Data were subjected to multivariate statistical analysis.Results: A total of 3755 IBC patients were diagnosed and reported to SEER between 1995 and 2005. IBC survival appears independent of lymph node status with mean survival times of 34 months for node negative patients and 32 months for node positive patients (figure 1, p= 0.11). We identified 735 cases with adequate local treatment records and follow-up information. In this subset we compared survival between groups that received both surgery and radiation (SR), groups that received one of these therapies independently (S or R respectively), to those without either therapy (NT, no therapy) given positive lymph node status at diagnosis (fig. 2, p<0.001).Discussion: Our data suggests that the prognosis of IBC is not related to lymph node status at the time of diagnosis. Because patients with IBC amenable to surgical intervention or radiation are likely to have more favorable biology then those who progress on chemotherapy, it remains difficult to quantify the impact of local therapies. NCCN guidelines currently recommend first-line chemotherapy before moving to local treatments; therefore one limitation of our study is the assumption that centers reporting data to SEER follow NCCN guidelines. Of special interest is the substantial number of patients that show prolonged survival with local therapies. This supports previous reports that about 30% of patients who complete chemotherapy, surgery and radiation therapy may survive five years or more after IBC diagnosis.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4039.
PI3 Kinase Pathway Analysis in Tissue Microarrays Using Laser Capture Microdissection and Immunohistochemistry.
Authors: Gardner H. , Nuciforo P. , Liu W. , Lee B. , Rheinhardt J. , Barrett C. , Linnartz R. , Dugan M. , Eiermann W. , Pienkowski T. , Martin M. , Robert N. , Forbes J. , Buyse M. , Finn R. , Lindsay M. , Slamon D. , Press M.
Published: December 2010

Background. During the performance of the BCIRG trials primary patient tumor samples were obtained from paraffin blocks and assembled into 15 tissue microarrays, including 3000 samples from trial 005 (adjuvant taxol in Her2- node positive patients), 2200 in 006 (adjuvant herceptin in Her2+ high risk patients) and 300 in 007 (addition of platinum in Her2+ first line therapy). This array set was prepared prospectively, in anticipation of molecular epidemiologic studies of a variety of targets in relation to outcome. In order to address the potentially important role of the PIK3CA pathway in modulating outcome in different clinical situations we assessed components of the PIK3CA pathway by various methods.Methods. We analysed the expression of PTEN, Cyclin D1, p53 and Stathmin by immunohistochemistry using standard methods. All markers were scored by histoscore. Phospho S6 240 and phospho Akt 473 were assessed simultaneously by quantum dot immunofluorescence using automated image capture and segmentation. PIK3CA mutations were evaluated using SnaPshot analysis of laser captured TMA spots in a subset of approximately 2000 samples.Results. In the samples analyzed PIK3CA mutation had an incidence of 23%, with 9% being mutations in exon 9 and 13% in exon 20, with 0.5% being mutant in both exons. Initial analysis of the results prior to outcome analysis indicated that Stathmin expression, while being a robust marker with good dynamic range, did not appear to correlate with PTEN loss by IHC or with PIK3CA mutation.Conclusions. PIK3CA mutational analysis is feasible from TMA cores and gives mutation incidences similar to the published literature for archival material. Relationships of markers with outcome will be presented.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4043.
The 70-Gene Profile (MammaPrintTM) Is an Independent Predictor of Breast Cancer Specific Survival for Women 65 Years of Age or Older.
Authors: Bedard P. , Bedard P. , Mook S. , Mook S. , Knauer M. , Knauer M. , Durbecq V. , Bernard-Marty C. , Glas A. , Cardoso F. , Cardoso F. , van 't Veer L. , van 't Veer L.
Published: December 2010

Background: One-half of all new breast cancer diagnoses occur in women age 65 years or older. In this age group, the use of adjuvant chemotherapy is largely influenced by co-morbidity and little is known about the applicability of prognostic multi-gene assays. The 70-gene profile (MammaPrint) is an independent prognostic indicator in early breast cancer, however, its performance in women with breast cancer 65 years or older has not been systematically studied.Methods: Women 65 years or older who were diagnosed at the Jules Bordet Institute and the Netherlands Cancer Institute between 1987 and 2003 with primary breast cancer with 0-3 involved lymph nodes who received either no adjuvant systemic therapy or adjuvant hormonal therapy alone were selected. MammaPrint test results were compared with clinical-pathological risk assessment using Adjuvant!Online.Results: Of 204 women aged 65 years or older (median age 70 years), 129 (63.2%) were classified as genomic low risk and 75 (36.8%) as genomic high risk. After a median follow-up of 8.6 years (range 0.3-17.9), the 5- and 10-year breast cancer specific survival (BCSS) for the genomic low risk group was 96% (SE 2%) and 86% (SE 4%) versus 82% (SE 4%) and 66% (SE 6%) for the genomic high risk group (log-rank p=0.001). In univariate analysis, MammaPrint was prognostic for 5-year BCSS (HR=5.0, 95%CI 1.8-14.1, p=0.002) and 10-year BCSS (HR=3.1, 95%CI 1.6-6.0, p=0.001). In a multivariate model adjusted for 10-year risk predicted by Adjuvant!Online, MammaPrint was independently prognostic for 5-year BCSS (HR=4.4, 95%CI 1.6-12.7, p=0.005) and 10-year BCSS (HR=2.5, 95%CI 1.3-5.0, p=0.009). As in prior validation series, the performance of MammaPrint was time dependent, with improved prognostication for early BCSS (≤5 years).Conclusion: Although a smaller proportion of breast cancers diagnosed in women 65 years or older are classified as high-risk by MammaPrint, it is an independent prognostic indicator that may be useful to select patients that can safely forego adjuvant chemotherapy. Additional data from patients over 70 years of age will be available at the time of the meeting. If these data are confirmatory, the ongoing prospective MINDACT trial will be amended to include older women.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4049.
Serum S100B as a Prognostic Indicator in Patients with Breast Cancer.
Authors: McCartan D. , McIlroy M. , Hill A. , Young L.
Published: December 2010

BackgroundThe nuclear receptor co-activator SRC-1 has recently been implicated as an important mediator of breast cancer metastasis in vitro. These findings are in keeping with previous reports from our group reporting significantly reduced disease free survival in patients who express SRC-1 when compared to those who do not. We identified the developmental protein HOXc11 as interacting with SRC-1 in tamoxifen resistant breast cancer cells. Dysregulation of homeobox genes has been reported in a wide variety of both solid organ and haematological malignancies. The putative target gene of HOXc11, S100B is a secreted protein, known to be of prognostic significance in malignant melanoma. The aim of this work was to examine the relationship between HOXc11, SRC-1 and S100B and their relevance to disease progression in breast cancer.Materials and MethodsAll chromatin immunoprecipitation (ChIP) and proliferation assays were performed in tamoxifen resistant breast cancer cells derived from MCF7s. Immunohistochemistry was performed for S100B, HOXc11 and SRC-1 on a tissue microarray of 560 patients with invasive breast cancer with a median follow up of 6.5 years. S100B was assessed using an ELISA based technique (Diasorin, USA) on serum samples of a prospective cohort of patients with breast cancer prior to any treatment.ResultsChIP assays confirmed recruitment of both HOXc11 and SRC-1 to the promoter region of S100B after treatment with tamoxifen at both 45 minutes and 2 hours when compared to control. Treatment of tamoxifen resistant cells with HOXc11 siRNA resensitised the cells to the anti-proliferative effects of tamoxifen. Immunohistochemistry revealed S100B to be a strong predictor of reduced disease free survival in patients receiving adjuvant endocrine treatment (Hazard ratio 5.82; p<0.0001). Tumour expression of S100B was associated with expression of both HOXc11 and SRC-1 providing translational evidence for a relationship between these proteins. Elevated serum levels (>0.15ug/l) of S100B were found in 10.5% of patients with breast cancer prior to treatment. Elevated S100B correlated with HER2 positivity (Fisher's exact: p=0.005) but not with any of the other standard clinico-pathological factors examined. From a cohort of 80 patients with known medium to long term follow up, elevated serum S100B showed a strong positive correlation with disease recurrence (p=0.017, odds ratio 9.38).DiscussionOur investigations into the prognostic significance of S100B in breast cancer have shown considerable promise. Given it's accessibility as a serum protein, quantifiable by ELISA, it offers potential as a marker for disease recurrence in patients with breast cancer.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4052.
A Prospective Comparison of Switches in Biomarker Status between Primary and Recurrent Breast Cancer: The Breast Recurrence in Tissues Study (BRITS).
Authors: Jordan LB. , Purdie CA. , Quinlan PR. , Anderson E. , Thompson AM.
Published: December 2010

IntroductionDisease recurrence and metastasis results in morbidity and mortality from breast cancer. In deciding the best therapeutic approaches at the time of recurrence, the molecular phenotype of the original (primary) cancer is often used. However, it is unclear whether the phenotype of the recurrent cancer is unchanged or has evolved from the original primary. Following several retrospective studies, the Breast Recurrence In Tissues Study (BRITS) is the first prospective study to address this clinically important question.MethodsTo detect a clinically significant switch in biomarker status 137 matched primary and recurrent breast cancer tissue samples were prospectively collected (to an estimated 95% confidence with a precision of 5% to detect a switch) from consenting patients and successfully constructed into tissue microarrays (TMA). Central laboratory analysis of ER (clone 6F11, 1:200) PR (clone 16, 1:800) and HER2 (CB11, 1:1200) was performed by two specialist breast pathologists. ER and PR were scored using the Allred method and HER2 status confirmed by FISH for HER2 2+ (primary or metastasis).Results137 women, mean age 62.6 years (range 27-87 years), 83/137 (60.6%) of whom were postmenopausal were successfully examined. For the original primaries, 96/137 (70.1%) were invasive ductal cancer, 17 (12.4%) grade 1, 66 (48.2%) grade 2 and 43 (31.4%) grade 3, mean size of original primary 23.96mm (range 2.0-134.0mm) and 27 (19.7%) multicentric. Lymphovascular invasion was identified in 76/137 (55.5%) and a margin not clear in 18 (13.1%).Time from the original primary to the recurrence biopsy was a median 92.2 months (range 5-327 months), and occurred as locoregional recurrence in 101 (73.7%). The recurrent biopsy was excisional tissue in 100 (73%) and core biopsy in 37 (27%).Central laboratory analysis of the original primary was ER positive in 109 (79.6%), PR positive in 85 (62.0%) and HER2 positive in 14 (10.2%); the recurrent disease was ER positive in 101 (73.7%), PR positive in 75 (54.7%) and HER2 positive in 16 (11.7%). A switch in receptor status, in either direction, was identified for ER in 14 patients (10.2%; p=0.983 Wilcoxon sign rank test), PR in 34 (24.8%; p=0.003 Wilcoxon sign rank test) and HER2 in 4 (2.9%; p=0.074 Wilcoxon sign rank test). In the judgement of the investigators the switch led to a change in the subsequent treatment in 24 patients (17.5%).ConclusionThis prospective study has demonstrated that the management of locally recurrent or metastatic breast cancer should include tissue sampling, since switches of ER, PR or HER2 status in the breast cancer recurrence may change the planned treatment for one in six patients.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4053.
The Clinicopathologic Characteristics and Clinical Outcomes of Estrogen Receptor-Negative and Progesterone Receptor-Positive Breast Cancer.
Authors: Kang S. , Jeon Y. , Kim C. , Cho Y. , Lee S.
Published: December 2010

Backgrounds: Invasive breast cancer patients with estrogen receptor positive (ER+) or progesterone receptor positive (PR+) tumors are treated by similar treatment strategies. Yet the prognosis of ER-PR+ tumor is currently controversial. The aims of this study were to evaluate the clinicopathologic characteristics and the prognosis of patients with ER-PR+ breast cancer.Materials and Methods: 1570 patients who underwent an operation for stage I-III breast cancer from January 1995 to December 2005 were included in this study. The patients were stratified according to the ER/PR phenotype and our study focused on the ER-PR+ phenotype. The clinicopathologic characteristics and the prognosis of patients with the ER-PR+ phenotype were compared with those of the patients with ER+ (ER+PR- or ER+PR+) breast cancer.Results: The mean age at diagnosis was 47.1 years (age range: 20-88) and the mean follow-up was 65.2 months. The hormone receptor phenotype was “ER-PR+” in 75 cases (4.8%) and “ER+ (ER+PR+ or ER+PR-) in 917 cases (58.4%). A patient age < 35 (p=0.002), a high histologic grade (p=0.004) and C-cerbB2 over-expression (p=0.006) were more frequent for the patients with the ER-PR+ tumors. There was a significant difference between the two groups for the mean age (p<0.001), but there was no difference in the nodal status, the tumor size and the presence of vascular invasion. The 5 year and 10 year disease-free survival (DFS) rates of the ER-PR+ group were 67.2% and 55.3%, respectively, and those of the ER+ group were 84.9% and 73.1%, respectively (p <0.001). The 5 year and 10 year overall survival (OS) of the ER-PR+ group were 82.4% and 62.6%, respectively, and those of the ER+ group were 93.4% and 83.3%, respectively. There was significant difference between the two groups for the OS (p =0.001).Conclusion: ER-PR+ tumors have more aggressive clinicopathologic features than ER+ tumors for the patient age, the tumor grade and the presence of C-erbB2 overexpression. Furthermore, ER-PR+ tumors showed a worse prognosis than did the ER+ tumors. Consequently, the treatment modality and the prognosis of the patients with ER-PR+ tumors probably need to be altered from those of the patients with ER+ tumors.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4054.
Young Age as a Prognostic Factor for Operable Breast Cancer: Significance of Molecular Subtype in Recurrence-Free Survival.
Authors: Kim E. , Han W. , Noh D.
Published: December 2010

Background: Breast cancer is uncommon in young women. Biology of the disease in this age group is poorly understood and the prognostic significance of young age at diagnosis remains controversial. We investigated the clinicopathological characteristics and outcomes of younger breast cancer patients (≤35 years of age), and assessed the prognostic significance of young age according to molecular subtype.Methods: We analyzed 2,474 primary invasive breast cancer patients who underwent surgery between 2000 and 2005. The younger age group consisted of patients aged ≤35 years. Subtypes were defined by expression of hormone receptor (HR) and HER2: luminal (HR+ irrespective of HER2 status), triple-negative (HR- and HER2-) and HER2 (HR- and HER2+).Results: A total of 229 (9.3%) patients were aged ≤35 years. Breast cancers in this age group were associated with larger size, higher lymph node positivity, higher nuclear and histological grades, and elevated Ki-67 index, compared with tumors in older patients. Younger patients had a greater probability of recurrence than older patients (P<0.001). By multivariate analysis, young age remained a significant predictor of recurrence (hazard ratio, 1.54; 95% confidence interval, 1.15-2.06; P=0.004). When the cancer subtypes were considered, young age was a significant predictor of recurrence in patients with both luminal and HER2 subtypes. In patients with the triple-negative subtype, however, young age was not a predictor of recurrence.Conclusions: Young age (≤35 years) was an independent predictor of recurrence for operable breast cancer patients with the luminal and HER2 subtypes, but not for those with the triple-negative subtype.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4063.
Clinicopathologic Signature of TNBC Patients with Good Prognosis.
Authors: Kim K. , Lee E. , Lee J. , Bae J. , Korea Breast Cancer Society .
Published: December 2010

Objectives We analyzed the molecular breast cancer subtypes using Korean Breast Cancer Society Registration Program data during 1993-2006 to compare the clinical feature and prognosis for "triple-negative" breast cancer with other types of breast cancer.We also compared patients expired from breast cancer within 3 years of diagnosis with the others in triple-negative breast cancer patients to find clinicopathologic variables influencing prognosis.Patients and methods We studied a cohort of 38,356 breast cancer patients, with assessable data for ER, PR, and Her-2/neu status. Patients were divided in four groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+ HER2+), triple-negative (ER-, PR-, HER2-), and Her-2/neu (ER-,PR-, HER2+). The median follow-up time was 75.6 months. Age, nodal status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival were evaluated.Results The luminal A(15,605patints, 40.7%) subtype was the largest in our study sample compared with luminal B(3,646patients, 9.5%), triple-negative(6,438 patients,16.8%), and Her-2/neu(4,035patients, 10.5%) subtype.Compared with breast cancer-specific survival of the luminal A subtype and luminal B, the triple-negative(OR=2.38) subtype and Her-2/neu(OR=2.65) subtype had shorter overall survival. Triple-negative subtype was correlated with more advanced stage(P < 0.0001), higher histological grade(P < 0.0001), and more frequent p53 overexpression(P < 0.0001).Those with triple-negative breast cancer had an increased likelihood of mortality within 5 years of diagnosis(P < 0.0001). But, thereafter, the risk of death declined rapidly. In luminal A and luminal B group, the risk of death was constant over 7 years of follow-up. Overall, the triple-negative group had a “good” long-term prognosis.There were annual improvement in 3 year survival rates for other hormone-positive breast cancer patients from 1998 to 2004(mean rate=0.67%/year). But, triple-negative breast cancer group had no survival improvement in the same period.2831 triple-negative breast cancer patients had assessable follow up data over 3 years. 283 patients(10.0%) expired from breast cancer within 3 years of diagnosis. Tumor size, nodal status, histological grade were correlated with breast cancer specific mortality, in univariate analysis with triple-negative breast cancer patients. Histological grade was the only factor to have correlation with breast cancer specific mortality in multivariate analysis.Conclusion Triple-negative breast cancer has more aggressive clinical course than other forms of breast cancer. It is necessary to develop new prognostic marker and effective therapeutic strategy.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4065.