bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing Patterns and Present Status of Female Breast Cancer in China over 30 Years.
Authors: Fan L. , Zheng Y. , Yu K. , Liu G. , Shen Z. , Shao Z. 
Published: December 2010

Abstract
Introduction: As a metropolis with rapid social and economic development over the past three decades, Shanghai has a breast cancer incidence that surpasses all other cancer registries in China.Methods: In order to estimate the regular changing patterns of female breast cancer in urban Shanghai, population-based incidence data from 1975 to 2004 were studied. In addition, a one-hospital-based in-patient database of 9709 female breast cancer patients treated surgically between Jan-1990 and Dec-2008 were reviewed, retrospectively.Results: We observed that breast cancer incidence increased dramatically over the past 30 years and documented a peak incidence represented by the middle-age group (45-59 yrs), which emerged in the last 20 years. The incidence peak moved from the 40-44 year group in the previous two decades to the 50-54 year group in the most recent decade. Median age at diagnosis was earlier in Shanghai than in the western countries, although it increased from 47.5-yr in 1990 to 51-yr in 2008. Considerably higher exposure to reproductive risk factors and relatively fewer hormone-dependent cases were observed- only 49.2% of breast cancers were estrogen receptor(ER) positive, 46.1% were progesterone receptor positive. The proportion of asymptomatic cases detected by screening gradually increased, as well as that of early-stage cases (from 78.6% in 1990 to 87.9% in 2008 and carcinoma in situ (14.9% in 2008). Analysis of surgical treatment patterns suggested a trend of less-invasive options.Conclusions: Rapid socioeconomic growth and birth-control policies have revealed some unique risk factors, which pushed the pattern of breast cancer in Shanghai towards that of the western countries. Age of peak incidence as well as median age at diagnosis increase with time, which suggests that increased incidence trending along with increasing age will be observed in the future. The middle-age group born after 1950s would be involved in current birth-control policies and they are also the cohorts related to the incidence boom. Thus specific screening protocols should be refined for the Chinese population, considering not only increasing age but also birth cohorts. Improvements in breast cancer detection provide patients with more opportunities for less invasive treatment options.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2058.
East of England Breast Cancer Survival Close to Best in Europe.
Authors: Wishart G. 
Published: December 2010

Abstract
Background: The Eurocare-4 (2000-2002) period analysis documents a mean European age-adjusted 5-year relative breast cancer survival of 79% with higher individual figures for Finland (85.7%), Norway (84.1% and Sweden (86.3%) (Lancet Oncol 2007; 8: 784-96). The corresponding figure for England was 77.8%. We now compare these predicted survival estimates with actual age-adjusted relative 5-year breast cancer overall survival (Corazziari et al, European Journal of Cancer 2004; 40:15: 2307-2316) for women diagnosed with invasive breast cancer in the East of England from 2000-2002Method: The East of England covers a population of 5.5 million people. 5-year age-adjusted relative breast cancer survival was calculated overall, and in specific age groups, for all women with invasive breast cancer diagnosed from 2000-2002 in the East of England for comparison with the results from the Eurocare-4 study.Results:Age-adjusted 5-year relative breast cancer survival in East of England for period 2000-2002.AGE GROUPRELATIVE SURVIVAL95% CI45-5487.5%86.1-88.9%55-6489.5%88.1-90.9%65-7483.9%81.1-86.1%75+73.3%70.1-76.4%ALL WOMEN82.5%81.4-83.6% Conclusion: These data confirm breast cancer survival rates for East of England that are close to European best figures for women aged 45-64. The age-adjusted survival of 82.5% for all women however is being reduced by worse survival in women aged 65+ and a strategy that ensures optimal breast cancer treatment for women in this age group should allow overall survival to improve even further.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2069.
Evaluation of Cardiac Comorbidities in Patients with Metastatic Breast Cancer Receiving Doxorubicin-Based and Non-Doxorubicin-Based Chemotherapy.
Authors: Lafeuille M. , McKenzie R. , Yameogo N. , Senbetta M. , Vekeman F. , Piech C. , Lefebvre P. 
Published: December 2010

Abstract
Background: Some metastatic breast cancer (MBC) treatments are associated with cardiac toxicity. Real-world data regarding baseline cardiac comorbidities in patients with MBC prior to chemotherapy initiation are scarce. Such information would be useful in guiding treatment decisions. This study aims to describe the cardiac comorbidity profile of patients with MBC initiating doxorubicin-based (DOX) versus non-doxorubicin-based (Non-DOX) chemotherapy regimens from a managed-care perspective.Methods: Medical claims from the Ingenix Impact National Managed Care Database between 07/2002 and 06/2008 were analyzed. Patients included were aged ≥ 18 years, and had ≥ 2 diagnoses for breast cancer as well as ≥ 1 diagnosis for metastatic site within 12 months of chemotherapy initiation. Cardiac comorbidities [hypertension (HTN), cardiac arrhythmia (CAr), coronary artery disease (CAD), congestive heart failure (CHF), and myocardial infarction (MI)] were evaluated within 6 months prior to chemotherapy initiation. Patients were categorized based on receipt of DOX vs. Non-DOX-based chemotherapy.Results: A total of 12,345 patients (Non-DOX: 7,023, DOX: 5,322) formed the study population. Compared with the DOX group, the Non-DOX group was slightly older. Both groups reported a significant proportion of patients with cardiac comorbidities prior to chemotherapy, with significantly greater proportions reported in the Non-DOX group. Mean age (SD)HTNCArCADCHFMINon-DOX (n=7,023)56.9 (10.6)35.7%11.8%5.5%3.5%1.3%DOX (n=5,322)52.1 (9.1)30.8%8.1%3.3%2.0%0.5%P-value&lt;.001&lt;.001&lt;.001&lt;.001&lt;.001&lt;.001 Conclusions: Cardiac comorbidities were commonly reported in women with MBC prior to chemotherapy, with significantly greater proportions reported in the Non-DOX group. Such information is useful to healthcare professionals when considering potential interventions for patients with MBC.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2078.
Myelodysplastic Syndrome and Acute Myeloid Leukemia Incidence Following Primary Breast Cancer Treatment.
Authors: Kaplan H. , Malmgren J. , Atwood M. 
Published: December 2010

Abstract
Background: Breast cancer (BC) patients receiving surgery plus radiation and/or adjuvant chemotherapy treatment are routinely monitored for incidence of myelodysplasia (MDS) and leukemia.Methods: A cohort of all breast cancer patients TNM stage 0-III treated with surgery and/or radiation or chemotherapy from 1989 to 2005 at our institution were followed for incidence of blood disorders of any type by our registry system and by linkage to the Surveillance, Epidemiology and End Results registry (SEER) for our area. Cases without surgery (n=111), with stem cell transplantation (n=98), unknown or non-standard chemotherapy regimens (n=23 + 71= 94), lost to follow up (n=66) or cancer status unknown at follow up (n=67) were excluded. The remaining 5790 cases were reviewed for incidence of leukemia including MDS and acute myelogenous leukemia (AML) post breast cancer treatment by chart review including pathology reports, SEER coding for MDS/AML, and death certificates if appropriate. Mean length of follow up was 7.17 years, range 2-18 years.Results: The mean age of MDS/AML patients was 57 years, range 33-76 years. The crude rate of MDS/AML occurrence was .29% (17/5790). 17 cases of MDS/AML (10 MDS/7 AML) occurred during the follow up period as compared with 6.22 (4.03 MDS/2.19 AML) expected on the basis of rates in the general population by age &lt;65, ≥ 65 years calculated from SEER registry data (risk ratio (observed/expected)). The risk of MDS in women &lt;65 was 11.68 times that expected and the risk of AML in women &lt;65 was 9.2 times the expected rate. Risk among women over 65 was not as large (1.38 MDS, ≥ 65, 1.21 AML, ≥ 65). Average time from treatment with radiation or chemotherapy to MDS diagnosis was 5.50 years (range 1.03-12.95) and 3.42 years (range .41-6.84) for AML. The majority of MDS/AML cases occurred in the first five years post treatment (n=10) with 7 more cases observed from 5 to 12.95 years (see figure). Initial treatment of MDS/AML patients was surgery only (n=2), surgery/chemotherapy (n=1), surgery/ radiation (n=7), and surgery/chemotherapy/radiation (n=7). The two MDS patients who had initial treatment of surgery only were subsequently treated with chemotherapy and radiation for recurrence. Fifty percent of MDS patients (5/10) received surgery and radiation treatment without adjuvant chemotherapy treatment.Discussion: The incidence of MDS/AML is very small in this cohort but significantly greater than that expected in the population at large especially among women less than 65 years of age. A significant number of women who received radiation treatment without chemotherapy developed MDS post breast cancer treatment. Average time from treatment to MDS diagnosis exceeded the 2-5 year time period previously reported as an expected interval.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2082.
Brain Metastases in Women with Inflammatory Breast Cancer (IBC): Incidence, Treatment and Outcome.
Authors: Dawood S. , Ueno N. , Valero V. , Andreopoulou E. , Hsu L. , Lara J. , Woodward W. , Buchholz T. , Hortobagyi G. , Cristofanilli M. 
Published: December 2010

Abstract
Background: Brain metastases are an uncommon metastatic recurrence site in breast cancer with a median incidence of approximately 6% in unselected populations. Inflammatory breast cancer (IBC) is an aggressive disease associated with dismal outcome. The purpose of this study was to determine the incidence of and survival following brain metastases among women with IBC.Material and Methods: Two hundred and six women with newly diagnosed stage III or IV IBC diagnosed between the period of between 2003 and 2008 were identified in a prospectively maintained IBC database at the MD Anderson Cancer Center. Cumulative incidence of brain metastases was computed. Cox proportional hazards models were fitted to explore factors that predict for the development of brain metastases. Survival was computed using the Kaplan-Meier product limit method.Results: Median follow-up was 20 months. Eighty three (40.3%) women had de-novo stage IV disease and 123 (59.7%) had stage III disease at diagnosis. Thirty-three (16%) patients developed brain metastases with a cumulative incidence at 1 and 3 years of 2.7% and 22% respectively. Eleven (5.3%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 1 and 3 years of 1.6% and 6.7% respectively. In the multivariable model, no specific factor was observed to be significantly associated with time to brain metastases, including HER-2 status. Median overall survival for the whole cohort was not reached. 3-year overall survival for the whole cohort was 78% (95% CI 69%-86%). Median survival following a diagnosis of brain metastases for all women who developed brain metastases or those who developed brain metastases as the first site of recurrence was 6 months.Conclusion: In this single-institutional study, women with IBC demonstrated a high early incidence of brain metastases associated with poor survival. As such IBC may be an ideal cohort to target screening procedures for brain metastases and/or enrollment of these women in clinical trials evaluating additional adjuvant preventive strategies.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2102.
HOXB13 May Predict Response to Neoadjuvant Letrozole in Patients with Estrogen Receptor-Positive Breast Cancer.
Authors: Ma X. , Bandaru R. , Letzkus M. , Philips P. , Barrett J. , Erlander M. , Goetz M. , Sgroi D. , Gardner H. , Baselga J. 
Published: December 2010

Abstract
Background. Third generation aromatase inhibitors (AIs) have been shown to be superior to tamoxifen in multiple randomized clinical trials and become the new standard of treatment for postmenopausal women with early or advanced endocrine-sensitive breast cancer. It is thus important to identify biomarkers predicting resistance to AIs so that alternative therapeutic options can be employed. A two gene expression index, HOXB13:IL17BR, and HOXB13 in particular, has been shown to be a negative predictor of clinical benefit from tamoxifen. It is unclear whether HOXB13:IL17BR or HOXB13 is also predictive of AI therapy.Methods. We performed a retrospective analysis of a phase II randomized neoadjuvant study of everolimus+letrozole vs. placebo+letrozole in patients with estrogen receptor-positive breast cancer. Total RNA was extracted from frozen tissue biopsies taken either prior to treatment or after 15 days of treatment. HOXB13:IL13BR and a molecular grade index (MGI) were measured in 107 pre-treatment samples and 111 samples after 15 days of treatment. Antiproliferative response as defined by a ln[Ki767] &lt;1 at day 15 in the samples analyzed was correlated with these gene expression indices.Results. In the placebo+letrozole treatment arm, the antiproliferative response rate was 30% (14/47). Using a pre-specified cutpoint of 0.06, the response rate was 40% for low HOXB13:IL17BR patients, compared to 12% for high HOXB13:IL17BR patients (p=0.05). In the everolimus+letrozole arm, the antiproliferative response rate in the samples analyzed was 55% (33/60), and the response rates for low and high HOXB13:Il17BR patients were 70% and 37% (p=0.02), respectively. When examined separately, high HOXB13 expression was significantly associated with nonresponse to therapy (everolimus+letrozole arm, p=0.02; placebo+letrozle arm, p=0.03), but IL17BR was not (everolimus+letrozole arm, p=0.6; placebo+letrozle arm, p=0.88). As expected, we observed a significant correlation between MGI and Ki67 staining (Spearman r=0.67, p&lt;0.0001).Conclusions. High HOXB13:IL17BR index and high HOXB13 expression may identify a possible subset of patients with estrogen receptor-positive tumor that could be less responsive to aromatase inhibitors such as letrozole. Furthermore, use of MGI may enable rapid assessment of antiproliferative response by fine needle aspiration.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2120.
Resequencing of the Vascular Endothelial Growth Factor Promoter Reveals Haplotype Structure and Functional Diversity.
Authors: Hancock B. , Radovich M. , Kassem N. , Mi D. , Skaar T. , Schneider B. 
Published: December 2010

Abstract
Our group has previously reported that SNPs in the VEGF promoter are strongly associated with efficacy and toxicity to the anti-VEGF antibody bevacizumab in metastatic breast cancer. In order to better understand the biologic mechanism for our previously reported biomarkers, we embarked on a comprehensive evaluation of the genetic variation in the VEGF promoter coupled with a study of its intrinsic function. By resequencing 96 DNA samples (48 Caucasians, 48 African-Americans) for the VEGF promoter, we elucidated its complete haplotype structure and identified SNPs that were not previously reported in prior resequencing efforts. SNPs that were identified included twenty previously reported SNPs/insertions/deletions, one novel SNP, and one novel deletion. Among these variants, we identified five SNPs (VEGF-3818G/T, -2305G/T, -1210C/A, -1154G/A, & -7C/T) that tag six haplotypes capturing 74% of the genetic variation of the VEGF promoter. Subsequently, we cloned the six major haplotypes into reporter constructs in order to determine the effect of genetic variation on function. The reporter assays were performed in 5 breast cancer cell lines representing all ER and HER-2 statuses along with an inflammatory breast cancer cell line. We demonstrate that there is significant variation in promoter-induced expression among the haplotypes. More importantly, we show that the haplotypes containing the SNPs previously reported to be associated with increased survival with the use of bevacizumab are high-expressing haplotypes, thus lending putative functional evidence to the prior clinical finding. Further, we also report the presence of a low-expressing haplotype predominantly in African-Americans. Altogether, these results set the foundation for future studies elucidating the role of VEGF genetic variation with response to anti-angiogenic therapy and associations with angiogenesis-related diseases.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2122.
PI3K Pathway Activation in Breast Cancer Is Associated with the Basal-Like Phenotype and Cancer-Specific Mortality.
Authors: Lopez-Knowles E. , O'Toole S. , O'Toole S. , McNeil C. , McNeil C. , Millar E. , Millar E. , Millar E. , Qiu M. , Qiu M. , Crea P. , Daly R. , Daly R. , Musgrove E. , Musgrove E. , Sutherland R. , Sutherland R. 
Published: December 2010

Abstract
Background: Current biological therapies for breast cancer are tailored to steroid hormone (ER, PR) and HER2 receptor status. Understanding the biological basis of resistance to current targeted therapies and the identification of new potential therapeutic targets is an ongoing challenge. The PI3K pathway is altered in a high proportion of breast cancers and may be associated with specific phenotypes and therapeutic resistance. We undertook an integrative study of mutational, copy number and expression analysis of key regulators of the PI3K pathway in a cohort of 292 invasive breast cancer patients with known treatment outcomes.Material and Methods: Mutations in 3 "hotspots" in exons 9 and 20 of the PIK3CA gene were determined by sequencing and PIK3CA gene copy number by qPCR. PTEN loss and Akt activation i.e. pAkt (Ser473) were assessed by immunohistochemistry using tissue microarrays. Cores were scored by 2 independent observers blinded to clinicopathological data and patient outcome and a histoscore calculated by multiplying the percent positive cells and staining intensity in a range 0-3. Standard statistical tests were applied to assess relationship between the measured parameters and patient outcome.Results: Alterations identified included PIK3CA mutations (12/168 i.e. 7%), PIK3CA copy number gain (28/209 i.e. 14%), PTEN loss (73/258 i.e. 28%) and AKT activation (62/258 i.e. 24%). Overall at least one parameter was altered in 72% i.e. 139 of 193 assessable primary breast cancers. PI3K pathway activation was significantly associated with ER negative (P=0.0008) and PR negative (P=0.006) status, high tumor grade (P=0.032) and a "basal-like" phenotype (P=0.01), where 92% (25/27) of tumors had an altered pathway. In univariate analysis PI3K pathway aberrations were associated with death from breast cancer however this relationship was not maintained in multivariate analysis. No association was identified between an activated pathway and outcome in tamoxifen- or chemotherapy-treated patients.Discussion: We conclude that &gt;70% of breast cancers have an alteration in at least one component of the PI3K pathway and this might be exploited to therapeutic advantage especially in "basal-like" cancers.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2123.
Expression Levels of Co-Regulators in Early Breast Cancer.
Authors: Spears M. , Pedraza J. , Thomas J. , Kerr G. , Kerr W. , Campbell F. , McKay L. , Kunkler I. , Cameron D. , Chetty U. , Bartlett J. 
Published: December 2010

Abstract
Introduction: The p160 (SRC) family of estrogen receptor (ER) co-activators have important implications in tamoxifen resistance. The SRC family play a central role in ER mediated transcription. There are three family members; SRC-1, SRC-2 and AIB1. AIB1 is amplified in 5-10% of human breast cancers. SRC-1 expression is associated with HER2 expression, increased risk of recurrence and insensitivity to endocrine treatment. Co-factors interact with the ER and basal transcriptional machine to activate or repress ER-mediated transcription. To investigate the role of ER and its co-factors in breast cancer we have carried out quantitative RT-PCR (qRT-PCR) to measure the relative expression of ERa and its co-factors.Methods: In this study we examined patients which were untreated or treated with chemotherapy or hormonal therapy following breast conservation surgery. RNA was extracted from 340 early breast cancer specimens from the Edinburgh Breast Conserving Surgery cohort (BCS). The BCS is a fully documented consectutive cohort of breast cancers treated by conservation surgery, axillary node sampling or clearance, and whole breast radiotherapy between 1981-1998. Clinico-pathological features and complete follow up (duration &gt;10 years) is available for this cohort. qRT-PCR was carried out using primers for ER, SRC-1, SRC-2, AIB1, NCoR1 and SMRT.Results: This study demonstrated SRC-1 expression to be negatively correlated with both SRC-2 and AIB1 expression. SRC-1 expression was also negatively correlated with the co-repressors NCoR1 and SMRT expression. There was a strong correlation between the co-repressors, NCoR1 and SMRT and the co-activators SRC-2 and AIB1. Relapse-free survival (RFS) was estimated using Kaplan-Meier curves. Patients who had high expression of all three co-activators had reduced relapse-free survival (HR: 2.15 95%C.I. 1.175-3.921, p=0.01). No significant association was noted with overall survival. Exploratory subgroup analysis was under powered and showed no significant association with outcome.Conclusion: In conclusion, our study of expression levels of ER and its cofactors by quantitative RT-PCR in breast cancer samples revealed a correlation between the co-factors and co-repressors. These findings would suggest that ER and cofactors may play a synergistic role in the development and progression of breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2127.