bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-11-11: A Comparison of Breast Cancer Treatment Rates in British Columbia, Scotland, and Western Australia, and a Comparison with Models of “Optimal” Therapy
Authors: Fong A , Shafiq J , Saunders C , Thompson A , Tyldesley S , Barton MB , Dewar JA , Ng W , Jacob S , Speers C , Olivotto I , Delaney GP. 
Published: April 2011

Abstract
Background: Evidence-based optimal utilization models provide estimates of optimal radiotherapy, chemotherapy and hormonal therapy utilization by stage and other clinically relevant patient sub-groups. We therefore compared predicted utilization with actual utilization of radiotherapy, hormone therapy and chemotherapy in 3 jurisdictions with population-based stage and treatment data: British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia.
Methods: Previously published optimal radiotherapy, chemotherapy, and endocrine therapy treatment utilization trees for an Australian population were modified to incorporate epidemiological data from British Columbia, Dundee, and Perth, such that the optimal trees for each region reflected the casemix for each region. Frequency data on patient, tumour, and surgical factors were used to calculate optimal treatment rates for each region. Optimal rates were then compared with actual rates of surgery, radiotherapy, chemotherapy, and endocrine therapy use obtained from 2 population-based and 1 institution-based cancer registries for patients diagnosed with breast cancer between 2000 to 2004. Information on region-specific treatment guidelines was also collected.
Results: Region-specific optimal treatment utilization rates at diagnosis varied between 80% and 81% for radiotherapy (62 to 64% when patient preference is taken into account), 53% to 56% for chemotherapy, and 49% to 54% for endocrine therapy. The predicted ranges were due to local variations in demographics, and tumour stage. Actual radiotherapy utilization was 57%, 49%, and 52%; chemotherapy utilization was 32%, 24%, and 29%; and endocrine therapy utilization was 56%, 64%, and 52% for British Columbia, Dundee, and Perth, respectively. Conclusion: There are significant differences in actual treatment utilisation rates between the study populations. It is unlikely that all of this variation is due to differences in tumour characteristics alone. Actual utilization rates were lower than the calculated optimal rates for radiotherapy and chemotherapy, and higher for endocrine therapy. Differences between actual regional rates of treatment utilization were seen, and were associated with differences in mastectomy rates, and guideline recommendations for treatment use in that region. This methodology allows comparison of the treatment that occurs in a jurisdiction against what would be considered optimal based on evidence.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-11.
Abstract P3-11-13: Impact of Young Age on the Presentation, Management and Outcome of Breast Cancer in a Multi-Ethnic Asian Setting: Results from the Singapore-Malaysia Hospital-Based Breast Cancer Registry
Authors: Bhoo Pathy N , Yip C-H , Taib NA , Saxena N , Iau P , Bulgiba AM , Lee S-C , Hartman M , Verkooijen HM. 
Published: April 2011

Abstract
Background: The proportion of very young women with breast cancer is high in Asia, ranging between 10% and 25%. Material and methods: Within the multi-institutional Singapore-Malaysia hospital-based breast cancer registry, we compared tumor characteristics, treatment and survival of very young (&lt;35 years; n=210) and older (35-55 years; n=2,152) breast cancer patients diagnosed between 1990 and 2007. Overall survival (OS)was estimated by Kaplan-Meier analysis. Cox regression analysis was used to compute hazard ratios (HR) after splitting follow-up time along the age-axis and calendar-time axis.
Results: Compared to older breast cancer patients, young patients presented with larger tumor (median diameter 25mm vs 30mm respectively: P&lt;0.001), and less estrogen receptor positive (54% vs 46% respectively: P&lt;0.01), and progesterone receptor positive tumors (57% vs 47%: P&lt;0.01). Young women were more likely to receive chemotherapy (70% vs 61%: P&lt;0.01), and less likely to be given hormone therapy (36% vs 57%: P&lt;0.001).
Among those with stage 0 to stage II disease, 5-year OS was 71.3% (95%CI: 61.7%-80.9%) in young patients and 85.6% (95%CI: 83.2%- 88.0%) in older women. After adjustment for stage, tumor profile and treatment, young patients had approximately 50% higher risk of death than their older counterparts (HR:1.46; 95% CI: 1.23-1.73). Ethnicity, tumor size, pathological lymph node staging, loco-regional therapy, and chemotherapy, were significant independent predictors of overall survival among young patients with breast cancer.
Conclusion: Asian women diagnosed at a very young age, present with less favorable tumor characteristics and stage distribution. They have a 50% higher risk of death following their disease, which is independent of their stage at diagnosis, tumor characteristics and treatment.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-13.
Abstract P3-11-14: Comparison of Breast Cancer Management at the Extremes of Age — A Single Centre Study
Authors: Dordea M , Jones R , Pujol Nicolas A , Sar S , Batson S , Fetherston A , Truran P , Solomon J , Iwuchukwu O. 
Published: April 2011

Abstract
Background: Literature describes age-dependent variations in breast cancer treatment, showing that older women are less likely to receive standard treatment than younger women. Statistically the elderly population is at highest risk of suffering from breast cancer. There is a renewed interest in discussing the issues around the management of breast cancer in the elderly age group, including a feeling of leniency or lack of aggressiveness in the overall management of such patients.
Methods: We undertook a retrospective analysis of 386 consecutive presentations of symptomatic breast cancer from 1998 to 2005. Patient demographics, tumour, treatment and outcome data were recorded. A cut off of &lt;40 and &gt;75 years of age was set to define our groups. Results: 69 cases of breast cancer in the ‘young’ age group and 255 cases of breast cancer in the ‘old’ age group were recorded. The younger patients had significantly more high-grade (BM Grade 3) tumours than their older counterparts (50.7 vs 26.6%, P&lt;0.001) and a higher proportion of invasive ductal carcinomas (86.8 vs 73.1%, p=0.006). There were no significant differences in tumour size and node positivity between the two groups.
Discussion: Our results show that for similar tumour sizes and nodal status the elderly age group receives less surgical and adjuvant therapy. Despite under management of the ‘old group’ our ‘young’ group suffers from higher and earlier recurrence. The overall disease related mortality is similar in both groups, however significantly worse if the ‘young’ group is compared with the ‘old’ group receiving surgical intervention. We suggest that young breast cancer patients have a worse overall prognosis when compared to surgically fit elderly counterparts and that perceived gaps in management could be explained by lack of physiological reserve in the elderly (sister paper). Use of geriatric assessment tools in a multidisciplinary setting may help in targeting the surgically fit population and avoid under treatment.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-14.
Abstract P3-12-04: RAD51 135G&gt;C Does Not Modify Breast Cancer Risk in Non-BRCA1/2 Mutation Carriers: Evidence from a Meta-Analysis of 12 Studies
Authors: Yu K-D , Shao Z-M. 
Published: April 2011

Abstract
A single-nucleotide polymorphisms (SNP) in the 5'-untranslated region (UTR) of RAD51, 135G&gt;C (rs1801320), was reported to be associated with an increased risk of breast cancer among BRCA2 as well as BRCA1 carriers. A few studies have also investigated the genetic contribution of RAD51 135G&gt;C to the risk of sporadic breast cancers or breast cancer in non-BRCA1/2 carriers, though the results are yet controversial andinconclusive. We in this study performed a more precise estimation of the relationship between 135G&gt;C and breast cancer among non-BRCA1/2 mutation carriers by meta-analyzing the currently available evidence from literature. A total of 12 studies involving 7,065 cases and 6,981 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, there was no evidence for a significant association between 135G&gt;C and breast cancer risk in non-BRCA1/2 mutation carriers (for CC vs. GG: OR = 0.995, 95% CI: 0.741-1.336; for GC vs. GG: OR = 0.959, 95% CI: 0.869-1.057; for dominant model: OR = 0.988, 95% CI: 0.902-1.082; and for recessive model: OR = 1.037, 95% CI: 0.782-1.376).
We also performed subgroup analysis by ethnicity (Caucasian) as well as did analysis using the studies fulfilling Hardy-Weinberg equilibrium, and the results did not change. In summary, the present meta-analysis suggests that the RAD51 135G&gt;C does not modify breast cancer risk in non-BRCA1/2 mutation carriers.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-04.
Abstract P3-12-07: Polymorphisms in the UDP-Glucuronosyltransferase 2B Gene Family and Risk of Breast Cancer in Women of African Descent
Authors: Sun C , Huo D , Nemesure B , Hennis A , Witonsky D , Niu Q , Di Rienzo A , Olopade OI. 
Published: April 2011

Abstract
Background: The UDP-glucuronosyltransferase 2B (UGT2B) enzymes catalyze glucuronidation, which is an important clearance pathway of steroid hormones, and medications, and potential carcinogens. As steroid hormones play a central role in breast cancer development, genetic polymorphisms in the UGT2B gene family may affect breast cancer susceptibility.
Methods: We evaluate two missense mutations in UGT2B15 (rs1902023, D85Y and rs4148269, K523T), one missense mutation in UGT2B7 (rs7439366, H268Y), and one single nucleotide polymorphism (SNP) 497 bp upstream to UGT2B4 (rs13129471) using pooled case-control studies of breast cancer, which included 1,287 cases and 851 controls. Cases and controls were enrolled in Nigeria, Barbados, and the US, and all are women of African ancestry.
Results: All four SNPs followed Hardy-Weinberg equilibrium in each ethnicity group. We found the rs13129471 SNP was significantly associated with breast cancer risk after adjusting for ethnicity (P=0.003). Compared with homozygous genotype for the A-rs13129471 allele, the odds ratio for heterozygous genotype and homozygous genotype for the G-rs13129471 allele was 1.02 (95% CI: 0.81-1.28) and 1.50 (1.15-1.95), respectively. The association was stronger in Nigerian women (P=4x10- 5) and the corresponding odds ratio was 1.13 (95% CI: 0.85-1.49) and 2.39 (1.61-3.55). No significant association was found for the other three non-synonymous SNPs.
Conclusion: Our results suggest that polymorphism in the UGT2B4 gene may be associated with breast cancer risk in women of African ancestry and the association may follow a recessive model. The finding needs to be confirmed in other populations.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-07.
Abstract P3-12-11: Combining Genotype at Low Penetrance Breast Cancer Loci with Family History Risk Leads to Significant Risk Reclassification
Authors: Martin AJ , White S , Onen A , Gale J , Dunlop J , Baker L , Thompson AM , Pharoah PDP , Berg JN. 
Published: April 2011

Abstract
Background: A significant proportion of women are at increased genetic risk of breast cancer. Mutations in high penetrance genes such as BRCA1 and BRCA2 are only responsible in the minority of cases, with low penetrance polymorphisms in other genes expected to account for the majority of the remaining genetic risk. An increasing number of such low penetrance polymorphisms are being identified, but each polymorphism only contributes a small amount to overall risk. Currently, in clinical practice, women who are at increased risk of breast cancer are identified by their family history, and the role of genetic testing for multifactorial risk remains uncertain. We have taken the population frequency and genotype relative risk information for the 18 most established low penetrance breast cancer risk loci and explored the effect of combining information from these loci, with risk derived from family history. Results: Genotyping at these 18 loci could provide significant risk information for an individual. The top 1% of women in the genotype risk distribution would have a risk of breast cancer of 2.11 times the general population. At this level of risk, they would qualify for breast cancer screening from age 40 according to evidence based guidelines issued by the UK National Institute of Clinical Excellence (NICE). In addition, the top 5% of the population are at 1.67 times risk of breast cancer and would have the same risk at age 40 as a 50 year old at population risk who would qualify for breast screening according to UK and US National Screening Guidelines. To investigate whether low penetrance genotype has greater potential if combined with other risk factors, we used a simple multiplicative model to combine family history risk of cancer derived using BOADICEA with genotype information. Our data suggest that genotype would result in a significant reclassification of individual risk. For example, 10% of women who only had a sister affected with breast cancer at 55 would qualify for additional screening under NICE criteria if genotype were taken into account. Extending this approach with 160 complex family histories from the Tayside family history breast clinic, we have shown that genotyping could result in reclassification and change of management for 19.1% of women being assessed in this clinic, with 12.4% of women moving into a higher risk category, and 6.7% of women moving into a lower category. Discussion: These data suggest that genotyping for low penetrance breast cancer risk loci is clinically relevant, and that it will be more powerful if it can be combined with other established risk factors.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-11.
Abstract P3-12-12: HER2 Evaluation in Relation to Breast Cancer Treatment Decisions in a Managed Care Plan
Authors: Weinmann S , Goddard KAB , Richert-Boe KE , Chen C , Bulkley JE , Wax C. 
Published: April 2011

Abstract
Background: In 18-20% of breast cancer tumors, the human epidermal growth factor receptor 2 (HER2) gene is abnormally amplified with increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation, shorter disease-free survival, and poorer overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about HER2 testing practices and associated treatment in real-world settings. This study examined uptake, use, and appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions in a large integrated health system.
Methods: We identified 3,634 patients with primary breast cancer diagnosed from 1998-2007 who were members of the Kaiser Permanente Northwest health plan. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment from tumor registry and pharmacy datasets. We defined women as evaluated for HER2 if they received HER2 testing by immunohistochemistry (IHC) and/or fluorescent in-situ hybridization (FISH). We manually abstracted medical charts for a subset of patients to verify findings and investigate anomalies. We compared testing and treatment results to professional guidelines. Results: From 1998-2000, the percentage of patients with invasive breast cancer who underwent HER2 evaluation increased from 12% to 94%; from 2000-2007, 94% (2304/2461) received HER2 testing over all years combined. In most cases, an equivocal or positive IHC test was followed by FISH. Only 2.4% of women with ductal carcinoma in situ (13/538), for whom HER2 testing is not recommended, were tested, and the proportion remained consistently low over the entire study period. Trastuzumab use increased five-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result, while the remainder had equivocal HER2 results or received treatment outside thedelivery system. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. We estimate that, after correcting for errors in the datasets, professional guidelines were followed for over 97% of patients diagnosed since 2000.
Conclusions: Kaiser Permanente Northwest is systematically performing HER2 evaluation on patients with invasive breast cancer, and the information is used to make appropriate treatment decisions. This information should be gathered in other health care settings for comparison.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-12.
Abstract P3-13-04: The Role of PSPHL in Breast Cancer in African American Women
Authors: Field LA , Rummel S , Shriver CD , Ellsworth RE. 
Published: April 2011

Abstract
Background: Younger age at diagnosis and poorer prognosis in African American women (AAW) with breast cancer have led to a number of studies evaluating gene expression differences in tumors from AAW compared to those from Caucasian women (CW). Studies have found that PSPHL expression is significantly higher not only in breast but also in prostate and endometrial tumors from African Americans compared to Caucasians. SNP rs6700 in the 3’ UTR of PSPHL has been found to correlate with expression. Here, we investigated how rs6700 affects PSPHL expression levels in AAW and CW with and without breast cancer.
Methods: Genomic DNA was isolated from 74 women with (35 AAW and 39 CW) and 37 women without breast cancer (23 AAW and 14 CW). rs6700
was genotyped using TaqMan SNP Genotyping assay C__314922_10.
PSPHL expression levels in breast tissue were measured in these same women using TaqMan Gene Expression assay Hs00863464_m1 using RNA isolated from laser microdissected breast tumor cells or normal breast tissue from women with or without breast cancer, respectively.
Results: PSPHL expression in breast tumors from AAW was significantly higher than in CW (P = 6 x 10-6). The median fold change in expression in AAW was 42.2; while only 2 (6%) AAW had no detectable expression of PSPHL, 21/39 (54%) CW did not express PSPHL. The minor allele frequency (T) in AAW with breast cancer was 0.41 compared to 0.06 in CW with breast cancer. In both AAW and CW, median levels of PSPHL expression were lowest (15.45 in AAW, 0 in CW) in women with the C/Cgenotype. In addition, all patients whose tumors had no detectable PSPHL expression had the C/C genotype. In women without breast cancer, the C/C genotype was also correlated with lower PSPHL expression and was more frequent among CW compared to AAW (79% and 39%, respectively).
Conclusions: PSPHL is more highly expressed in both diseased and normal breast tissue from AAW compared to CW and expression of PSPHL correlated with rs6700 genotypes. Although the function of PSPHL is unknown, it may function in cellular proliferation. Higher expression in AAW may, therefore, promote the development of tumors in AAW. It must be noted, however, that the frequency of the C allele is significantly lower in the African American population as a whole (53% vs. 92%); therefore, differences described here may reflect population differences rather than any specific contribution to breast cancer etiology. However, due to the higher expression of PSPHL in African Americans with other hormone-dependent cancers, its role in tumorigenesis requires further study.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-04.
Abstract P3-13-05: Estrogen Receptor-Positive Breast Cancer in Japanese Women: Trends in Incidence, Characteristics and Prognosis
Authors: Yamashita H , Iwase H , Toyama T , Takahashi S , Sugiura H , Yoshimoto N , Endo Y , Kobayashi S. 
Published: April 2011

Abstract
Background: The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. Patients and Methods: We examined the characteristics of patients and tumors treated in three time periods between 1982 and 2010. Estrogen receptor (ER), progesterone receptor (PgR), and HER2 status were assessed by immunohistochemistry. Correlation of hormone receptor levels with clinicopathological factors and prognosis was analyzed in ER-positive, HER2-negative breast cancer in two age groups (≥50 years vs. &gt;50 years).
Results: A total of 1903 women with breast cancer, who were treated at Nagoya City University Hospital, were included in this study. The frequency of ER-positive breast cancer in women aged 50 years or younger increased greatly over the interval studied (1982-1991: 52.5%, 1992-2001: 72.6%, 2002-2010: 87.1%, P &lt; 0.0001). The frequency of ER-positive tumors was also significantly increased in women over 50 years of age (1982-1991: 69.4%, 1992-2001: 73.3%, 2002-2010: 78.6%, P = 0.029). In ER-positive, HER2-negative breast cancer, tumor grade was negatively correlated with expression levels of ER (P = 0.0029) and PgR (P &lt; 0.0001). Interestingly, PgR levels were significantly higher in women aged 50 years or younger than in women over 50 years old (P &lt; 0.0001). In both age groups, the prognosis for patients with ER-positive, HER2- negative breast cancer significantly improved over time, due to advances in adjuvant therapies. ER and PgR expression levels were not associated with disease-free survival. Lymph node status and tumor size were strong prognostic factors regardless of the biological characteristics of the tumors in ER-positive, HER2-negative breast cancer in both age groups. Conclusions: It is necessary to establish risk factors, both genetic and environmental, capable of predicting the risk of ER-positive breast cancer and thus enable the efficient selection of candidates for hormone receptor-targeted chemoprevention. Furthermore, new approach should be considered to improve survival for node-positive, ER-positive breast cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-05.