bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-10-31: Epithelial Proliferation (Ki67) Is Not an Independent Variable for Breast Cancer Relapse in Symptomatic or Screen Detected Breast Cancers (SDBC)
Authors: Bundred NJ , Knox WF , Cramer A , Wilson M , Prasad R , Morris J 
Published: April 2011

Abstract
Background: UK screen detected breast cancers (SDBC) (aged 50-65 years) have an overall 97.2% 5 year relative survival compared to 77.6% for symptomatic cancers. Epithelial proliferation has been used to determine therapy in the St. Gallen guidelines (Ki67 ≥30% indicates the need for chemotherapy).
Methods: To determine the value of Ki67 in post-menopausal breast cancer in women aged 50-65 years, we have studied Ki67 in 1270 women aged 50-65 years (mean 57 years) with either symptomatic cancers (n=412) or SDBC (n=858) with a 10 year follow up.
Results: Ki67 predicted relapse and death in both symptomatic and SDBC. Mode of detection, size, grade, node status and oestrogen receptor (ER) were independently predictive of breast cancer mortality and Ki67 was not an independent variable. In small size ≤15mm ER positive SDBC (n=248) or symptomatic cancers (n=146), Ki67 was not prognostic (p=0.13 and 0.59 respectively). Twelve per cent of symptomatic and 2% of SDBC had died within 5 years. Mean Ki67 in SDBC was 21.4 (SD 10.3) and 34.2 (SD 16.2) in symptomatic cancers (p=≤0.001). ER positive cancers had lower Ki67 levels (p=0.002). For each 10 unit increase in Ki67, increases in distant relapse occurred (RR 1.43:95%CI;1.32-1.55).
Ten Year Survival According to Ki67 and Mode of Presentation
Discussion: Epithelial proliferation is prognostic in breast cancer but its value is predominantly in large size (≥15mm) symptomatic tumours and Ki67 alone cannot be used to determine therapy.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-31.
Abstract P3-10-37: Molecular Analysis of Single Circulating Tumor Cells for Characterization of the Targets of Systemic Breast Cancer Therapy as Chance to Individualize Therapy
Authors: Carl S , Camara O , Plaschke-Schluetter A , Kroll T , Pachmann K. 
Published: April 2011

Abstract
Background: In breast cancer therapy predictive and prognostic markers are derived from the primary tumor but systemic therapy aims at eliminating the remnant tumor cells left in the body after surgery which the cells circulating in peripheral blood are part of. For individualized therapy, therefore, it would be advantageous to better characterize this remnant disease for more targeted therapeutic approaches. Materials and Methods: 10 to 20 single live epithelial antigen positive cells were isolated from peripheral blood of 50 newly diagnosed breast cancer patients using the automated capillary cell isolation system of the MMI CellEctor and individually deposited under visual control onto Ampli Grid slides (Advalytics). The mRNA was the reverse transcribed and amplified using primers for 6 different tumor associated targets among them EpCAM and Her2/neu.
Results: Expression profiling could be successfully performed from more than 80% of all individually deposited isolated cells demonstrating the epithelial nature of these cells but also heterogeneity among the cells of in individual patients with respect to other genes. Thus we show that circulating epithelial cells from breast cancer patients can be individually deposited and these single celsl can subsequently be subject to expression profiling.
Discussion: Further analysis by high through-put profiling of the remnant tumor burden in breast cancer patients after surgery comprising the cells circulating in peripheral blood may contribute to better characterize the targets of systemic therapy in order to individualize cancer therapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-37.
Abstract P3-10-38: Histopathological Subclassification of Triple Negative Breast Carcinoma Using Prognostic Scoring System
Authors: Miyashita M , Ishida T , Tamaki K , Amari M , Ohuchi N , Sasano H. 
Published: April 2011

Abstract
Purpose: Triple negative breast carcinoma (TNBC) is currently being required to be classified pluralistically in order to provide the most appropriate therapy to the patients. We attempted to subclassify TNBC cases into subgroups based on clinical outcome or prognosis of the patients with TNBC using archival specimens. Materials and Methods: We analyzed 102 Japanese cases of invasive TNBC who underwent surgery between January 1998 and December 2007. The clinicopathological factors and clinical information of these patients were retrospectively retrieved from charts of the patients. Immunohistochemical staining was performed for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor 1 (EGFR1), CK5/6, Ki-67 and CD31 for microvessel density (MVD). Results: Median follow-up time of the patients was 68.5 months. Multivariable analysis demonstrated that the pathologic node status was the most significantly associated with relapse-free survival (RFS) and breast cancer-specific survival (BCSS) of the patients. Pathological tumor size, basal-like type, Ki-67 labeling index (LI) and MVD were also independently associated with RFS and BCSS. Based on these results, we devised the Risk Score system reflecting Hazard ratios (HRs) of these prognostic factors above.
Multivariate analysis and the Risk Score for TNBC patients.
With this system, TNBC patients in this study were classified into three subgroups; patients with score 0-3 are in low risk group, score 4-7 in intermediate risk group and score 8- in high risk group. These three groups had statistically significant differences for risk of relapse and breast cancer-specific death, respectively.
Conclusions: We propose the Risk Score system, which incorporated pathologic nodal status, size of the primary tumor, the presence or absence of basal-like features, Ki67 LI and MVD of the patients in order to predict postoperative clinical course of the Japanese patients with TNBC. Such a classification which can be performed in diagnostic pathology laboratory can be useful as a decision-making tool for triple negative patients.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-38.
Abstract P3-11-02: Aspirin Use in the Community and the Risk of Breast Cancer
Authors: McCowan C , Carroll S , Makubate B , Dewar JA , Schweiger S , Thompson AM. 
Published: April 2011

Abstract
Introduction: Breast cancer is the most common cancer in women with incidence rates increasing annually. Laboratory work at Dundee had suggested aspirin may be a chemo-preventive agent for breast cancer, although a recent US study has shown no effect of aspirin use in reducing breast cancer in premenopausal women.1 Using routine population datasets in Tayside, this study examined the use of aspirin and the development of breast cancer.
Methods: From the cancer registry all women in Tayside with an incident breast cancer from 1998 onwards were identified. Prescribing records for all women aged 30 and over were extracted for the period 1993 to 2003. Women with a breast cancer diagnosis prior to 1998 were excluded. Use of aspirin was examined with dosing and duration of use calculated. Cox proportional hazards models were used to determine if drug use reduced the risk of breast cancer
Results: There were 117,948 women aged 30 or over on the 1st January 1998 who were resident throughout the study period or until their death. 1,761 had a diagnosis of breast cancer prior to 1st January 1998 and so were excluded from further analysis. There were 23,970 (20%) women who encashed a prescription for aspirin between 1st January 1993 and 31st December 2003.
The median duration of aspirin use was 3.1 years (IQR 0.6-6.2) and patients took aspirin for a median 6 days (IQR 5-7) per week over that period. There were a total of 1,420 (1.2%) cancers recorded during the study period.
Ever use of aspirin was associated with a reduced risk of breast cancer (HR=0.635, 95% CI 0.550-0.733, P&lt;0.001) after allowing for age and social. Increasing duration of aspirin was associated with reducing risk of cancer compared to never users and higher aspirin usage was also associated with a decreasing risk.
Conclusions: Aspirin would seem to be an effective chemo-preventive agent from this population based study. However further research is required to determine its effectiveness and to identify the groups of patients who may benefit the most from its use.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-02.
Abstract P3-11-08: Incidence and Outcome of Male and Female Breast Cancer: A Multinational Population Based Study
Authors: Miao H , Verkooijen HM , Chia KS , Pukkala E , Larønningen S , Mellemkjær L , Czene K , Hartman M. 
Published: April 2011

Abstract
Background: Male breast cancer is a rare disease as its incidence rate is about 0.5% to 1% of that of female breast cancer. Given its scarcity, few studies have assessed the risk and prognosis.
Methods: We performed a multi-national population based study of 569,771 female breast cancer patients and 3,615 male breast cancer patients diagnosed in Denmark, Finland, Switzerland, Norway, Singapore and Sweden from 1943 to 2007. We calculated incidence and mortality as well as overall survival for both sexes. Life table analysis and Cox proportional hazard model were used to analyze the survival.
Results: The overall incidence rates, adjusted to the World Standard Population, of breast cancer were 60.2 per 100,000 in women and 0.4 per 100,000 in men. Women were diagnosed with breast cancer at a younger median age (61.4 years) than men (68.9 years). Among the 203,093 patients (35%) with information on TNM stage, 50% of the women and 47% of men were classified as stage I whilst stage III and stage IV cases accounted for 11% and 20% for women and men respectively. The 5-year cumulative survival was 66.2% for women and 53.0% for men. The adjusted relative risk of death was 24% higher in men [HR 1.24 (95% CI, 1.19-1.28)] as compared to women after controlling for age and time at diagnosis. Men had an 18% higher relative risk of death [HR 1.18 (95% CI, 1.09-1.27)] compared to women after further adjustment for TNM stage. Conclusion: Male breast cancer patients have later onset and worse prognosis than female patients. This may be due to the difference in tumour characteristics and treatment.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-08.
Abstract P3-11-12: Influence of Hormone Therapy Prior to Breast Cancer Diagnosis on Prognosis of Postmenopausal and Perimenopausal Breast Cancer Patients
Authors: Baumgaertner AK , Haeusler A , Seifert-Klauss VR , Schuster T , Schwarz-Boeger U , Kiechle M. Klinikum 
Published: April 2011

Abstract
Introduction: Use of hormone therapy (HT) has been associated with higher incidence of hormone receptor positive breast cancer in postmenopausal women. However, it is unclear if breast cancers developing after HT use are different in course of disease and prognosis from tumors growing without prior exogenous hormone use.
Methods:
Women with hormone receptor positive breast cancer diagnosed between 1984 and 2006 at our university breast cancer center (n=1247) were analyzed in a single-center retrospective trial. Outcome data comparing overall survival, local and distant recurrence were extracted from the hospital cancer data base and the local breast cancer registry, as well as from primary care-giving gynecologists and by review of patient charts. Cases were stratified according to hormone therapy use before breast cancer diagnosis. This is the first analysis differentiating between perimenopausal and postmenopausal patients.
Results:
1053 patients with hormone receptor positive non-metastasized invasive breast cancer were included in the final analysis. 198 (18.8%) women were premenopausal, 126 (12.0%) were perimenopausal and 729 (69.2%) were postmenopausal. Information on former HT use was available for 933 (88.6%) patients. 542 (51.4%) patients had never used HT, including 194 premenopausal patients. 324 (44.4%) postmenopausal and 67 (53.2%) perimenopausal women had used HT before breast cancer diagnosis. At time of first diagnosis there was a significantly higher rate of early stage and nodal negative disease in postmenopausal HT users versus non users (P&lt;0.01 and p=0.02 respectively).
In multivariate analysis, HT use prior to diagnosis in postmenopausal patients resulted in longer time to progression and longer overall survival (RR 0.84 and RR 0.70 with p=0.34 and p=0.07 respectively). In perimenopausal patients however, HT use prior to breast cancer diagnosis was associated with shorter time to progression and overall survival (RR 2.41 and RR 3.32 with p=0.99 and p=0.05 respectively). Higher BMI in perimenopausal women had a significant influence on prognosis with RR=1.14 for TTP and RR=1.23 for OS, whereas it had no effect in the postmenopausal group.
Conclusion: According to this retrospective analysis, hormone therapy prior to breast cancer diagnosis has different effects on outcome parameters depending on patients’ menopausal state. Whereas in postmenopausal patients HT was associated with better prognosis, in perimenopausal women it might have detrimental effect.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-12.
Abstract P3-12-02: Polymorphisms, Endogenous Hormone Levels and Breast Cancer Risk in Premenopausal Women
Authors: Walker K , Johnson N , Palles C , Folkerd E , Hillier SG , Moss S , Gibson L , Dowsett M , Peto J , dos Santos Silva I , Fletcher O. 
Published: April 2011

Abstract
Background: Endogenous sex hormone levels are widely believed to be implicated in the etiology of breast cancer through indirect evidence such as early menarche and late menopause, and from direct evidence of an association between circulating levels and breast cancer risk in postmenopausal women. Epidemiological studies suggest that levels may be partly genetically determined, particularly in premenopausal women. Few studies have attempted to identify polymorphisms associated with endogenous hormone levels in premenopausal women, and their findings have been limited.
Quantification of hormone levels in premenopausal women is difficult because of their cyclical nature. In particular, estrogen has a marked peak in the follicular phase and a further wider peak in the luteal phase. Methods: 789 healthy premenopausal women from the Mammography Oestrogens and Growth Factors (MOG) study and the British Breast Cancer (BBC-NCRN) study each provided a single blood sample and up to 7 urine samples. We developed a protocol designed to capture peak follicular phase urinary estrone glucuronide (E1G), and luteal phase E1G. Repeated measurements of creatinine-adjusted E1G levels were used to describe features of the E1G curve such as mean and peak follicular E1G, and luteal E1G. Endogenous sex hormone binding globulin (SHBG) and the androgens testosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were measured on single plasma samples. 691 tagging SNPs capturing common variation in genes within the estrogen synthesis and metabolism pathways were successfully genotyped. Linear regression was used to evaluate the effect of each polymorphism on (log-transformed) measures of urinary E1G levels, SHBG levels and plasma androgen levels.
Results: We identified a SNP with minor allele frequency of 7%, in which the minor allele was associated with a 20% reduction in circulating levels of E1G (P&lt;10-8) in healthy premenopausal women. We are currently genotyping this SNP in 12,000 breast cancer cases and 12,000 controls to test whether the reduction in circulating estrogen levels affects breast cancer risk.
Conclusions: Circulating hormone levels in premenopausal women may provide a useful intermediate phenotype in the search for low-penetrance breast cancer risk alleles.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-02.
Abstract P3-12-09: Numb Expression Varies by Hormone Receptor Status among Danish Breast Cancer Patients
Authors: Zhou W , Rasmussen B , Busch-Sørensen M , Demuth T , Reilly J , Bergstrom D , Pearson J , Møller S , Ejlertsen B. 
Published: April 2011

Abstract
Background: Numb-mediated regulation of Notch signaling pathway might play a causative role in early breast cancer. Little information is available on whether Numb expression differs according to tumor characteristics including hormone receptor status. We investigated Numb expression status in archival tissue from primary tumor of 197 breast cancer patients identified within the 2004 cohort of the Registry of the Danish Breast Cancer Cooperative Group's (DBCG), where patients were treated according to the guidelines of the DBCG.
Materials and Methods: Numb expression was measured by immunohistochemistry method, and Numb(-) was defined as Numb immunoreactivity present in less than 10% of the invasive tumor cells. Chi-square test was used to assess the correlation between Numb(-) and hormone receptor status.
Results: The median age was 57 years (range, 26-98), 32% were premenopausal. 82% were ductal, 9% lobular, 9% others. 10% were grade I, 41% grade II, 47% grade III, 2% non-graded. 70% were node positive. 60% were ER+, 41% PR+, and 24% were HER2+ by IHC and FISH. 58% were operated by mastectomy, 42% by lumpectomy. The adjuvant treatment comprised Tamoxifen (36%), cyclophosphamide/methotrexate/fluorouracil (CEF, 19%), CEF+Tamoxifen (11%), and 22% were missing treatment information. 49% relapsed and 3% metastasized during 10 year of follow up. Overall, 10% (19 out of 197) of patients were Numb(-). Numb expression was significantly associated with hormone status, with a Numb(-) frequency of 24% (9/37) among ER+/PR-/HER2-, 9% (6/65) among ER+/PR+/HER2-, 6% (3/47) among HER+ (1/16 among ER+/PR+/HER2+ and 2/31 among ER-/PR-/HER2+), and 2% (1/47) among ER-/PR-/HER2- patients (P&lt;0.01). Similar differences were observed using the H-score matrix where the IHC intensity was summarized with a range of 0-300.
Discussion: Our results suggested Numb(-) is correlated with hormone status, with the higher frequency of Numb(-) among ER+/PR-/HER2- patients, and lower frequency among other groups, particularly the triple negative group.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-09.
Abstract P3-13-01: Delayed Chemotherapy-Induced Nausea and Vomiting in Asian Women with Breast Cancer
Authors: Bourdeanu L , Mortimer J , Somlo G , Hurria A , Chung C , Frankel P , Luu TH. 
Published: April 2011

Abstract
Background: Chemotherapy-induced nausea and vomiting (CINV) remain among the most frequently reported distressing side effects associated with a doxorubicin-based chemotherapy regimen, and it can significantly affect patients’ quality of life and compliance with therapy. Despite the significant advances in antiemetic management in preventing and controlling CINV, as many as 50% of patients still experience some degree of nausea and vomiting. The main risk factor for the degree of CINV is the emetogenic potential of the chemotherapeutic agents. However, several patient-related risk factors have been identified, including individuals’ genetic makeup. Although several studies have noted that ethnicity influences nausea and vomiting related to motion sickness, fluorescein dye, and pregnancy, no studies have evaluated the relationship between ethnicity and CINV; specifically, if there is a higher incidence of severe CINV in patients of Asian descent.
Methods: A retrospective, comparative, correlational chart review was performed to abstract all relevant variables. The association between CINV and ethnicity was examined through chi square analysis.
Results: Data from a convenience sample of 300 women with breast cancer who received chemotherapy that includes doxorubicin between 2004 and 2008 at City of Hope in Duarte, CA, were evaluated. The sample consisted of Caucasians (46.3%), African Americans (3.7%), Asians (24.0%), and Hispanics (26.0%). The results of this study indicate that Asian women with breast cancer undergoing treatment with chemotherapy that includes doxorubicin experienced statistically significantly more severe CINV (grade ≥ 2) than their non-Asian counterparts (X2 = 10.601, p = .001). Conclusion: This study provides strong but preliminary evidence that Asian ethnicity plays a role in the development of severe CINV. When managing chemotherapy toxicities in women with breast cancer, healthcare providers are advised to optimize their patients’ outcomes by ensuring that therapy is tailored according to each patient's individual risk profile. Consideration of the antiemetic therapy should accommodate patient characteristics, specifically being of Asian descent. In this way, effective prevention of CINV can be maximized during a patient's initial treatment.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-01.
Abstract P3-13-03: Association between Ethnicity and Survival after Breast Cancer in a Multi-Ethnic Asian Setting: Results from the Singapore-Malaysia Hospital-Based Breast Cancer Registry
Authors: Bhoo Pathy N , Verkooijen HM , Taib NA , Saxena N , Iau P , Bulgiba AM , Lee S-C , Yip C-H , Hartman M. 
Published: April 2011

Abstract
Background: Little is known on the impact of ethnicity on survival after breast cancer in the multi-ethnic Asian setting. Material and Methods: Using the multi-institutional Singapore-Malaysia hospital-based breast cancer registry, we investigated the association between ethnicity and risk of mortality after breast cancer in 3,366 patients diagnosed between 1990 and 2007 (Chinese: 77%, Malay: 15%, Indian: 8%). Kaplan-Meier analysis was used to estimate overall cumulative survival (OS). Multivariable hazard ratios (HR) adjusted for tumor and treatment characteristics were computed using Cox regression analysis after splitting follow-up time along the age-axis and calendar-time axis. Results: Malay patients presented at younger age compared to Chinese and Indians (47years vs 52years vs 53years, respectively, P&lt;0.001) with larger tumors (35mm vs 24mm vs 30mm, respectively, P&lt;0.001), and at later stages (TNM stage III or IV) (37% vs 23% vs 25%, respectively, P&lt;0.001). Malay women were least likely to have undergone surgery, and most likely to receive chemotherapy. Five-year OS was 71.9% (95% CI: 69.7%-74.1%) in Chinese, 47.2% (95%CI: 41.9%-52.5%) in Malays and 62.7% (56.0%- 69.4%) in Indians.
After adjustment for tumor and treatment characteristics, Malay patients had approximately 60% higher risk of death than the Chinese (HR:1.57; 95%CI:1.40-1.77). Indian ethnicity was not significantly associated with risk of mortality after breast cancer compared to Chinese (HR:1.12; 95%CI: 0.98-1.30).
Conclusion: In the Asian setting, Malay ethnicity seems to be associated with significantly poorer survival after breast cancer, independent of tumor and treatment profile. The underlying reasons for this association are unclear but may be explained by variations in susceptibility to treatment, co-morbidity and lifestyle after diagnosis of breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-03.