bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-13-09: Evaluation on the risk factors and prognosis for patients with synchronous bilateral breast cancer in a Chinese cohort
Authors: Chen J-J , Wang Y , Xue J-Y , Yang B-L , Huang S , Chen Y , Chen J-Y , Yang W-T , Shao Z-M , Wu J 
Published: August 2014

Abstract
Background: There has been an increasing rate of synchronous bilateral breast cancers, mainly because of the increased morbidity, improved detection abilities, better prognosis and higher life expectancy of breast cancer patients. However, evidences in the literature regarding the risk factors of bilateral breast cancers are scare, and the survival of synchronous bilateral breast cancers still remain controversies. The purpose of the present study is to investigate the risk factors and prognosis of bilateral breast cancers in a Chinese cohort.
Methods: The present study included 181 patients with synchronous bilateral breast cancer and 10,831 patients with unilateral breast cancer treated in Fudan University Shanghai Cancer Center between Jan 2007 and Dec 2012. Patients with metastases or inflammatory diseases, or metachronous bilateral breast cancer (after 6 months of first cancer) were excluded. Age of the cases, family history, menopausal status, histology types, pathological stages, types of accompanied benign lesions, and patterns of surgeries and adjuvant therapies were examined to investigate the risk factors of bilateral breast cancers.
Results: Patients with synchronous bilateral breast cancer were significantly elder than those with unilateral breast cancer (mean age 53 yrs vs. 51yrs, p&lt;0.001). Presence of sclerosing adenoma and lobular carcinoma component were the two independent risk factors of early-stage synchronous bilateral breast cancer, with the relative risk rate at 5.52 (95% CI: 3.04-10.01) and 5.00 (95% CI: 2.64-9,47), respectively. The rate of in situ carcinoma with or without microinvasion was significantly higher in patients with sclerosing adenoma associated synchronous bilateral breast cancers at 64.3%. With a median follow-up of 35 months, the disease free survival for synchronous bilateral breast cancer was 95.0%, similar to that of unilateral breast cancer. However, for synchronous bilateral breast cancer patients with N3 disease or previously received neoadjuvant therapy (20 cases), the 1.5 year-disease free survival was merely 50%, significantly worse than that of unilateral breast cancer with N3 disease or previous neoadjuvant therapy.
Conclusion: The rate of synchronous bilateral breast cancer was higher in patients with sclerosing adenosis or lobular carcinoma component. The prognosis for early-stage synchronous bilateral breast cancer was similar to those with early-stage unilateral breast cancer. However, among patients with N3 disease or previously received neoadjuvant therapy, synchronous bilateral cohort was associated to worse survival compared with unilateral cohort.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-09.
Abstract P5-14-18: Indication of post-mastectomy radiation associated with risk of local recurrence in breast cancer patients with 1-3 lymph node metastasis
Authors: Saruwatari A , Ishida M , Koi Y , Akiyoshi S , Igawa A , Oikawa M , Koga C , Nishimura S , Nakamura Y , Ohno S 
Published: August 2014

Abstract
Objective: Post-mastectomy radiotherapy (PMRT) is strongly recommended for breast cancer patients with 1 to 3 axillary lymph node metastasis (N1-3) in NCCN guidelines Version 3.2013 (category 1), whereas the indication of that treatment should be considered individually according to the risk of local recurrence (St Gallen Consensus Meeting 2013). In order to support decision making of PMRT, we evaluated the risk factors of local recurrence after mastectomy.
Patients and methods: We reviewed retrospectively 2422 cases with Stage I – III primary breast cancer receiving surgery at National Kyushu Cancer Center between 2000 and 2009. Seven hundred seventy six of them underwent mastectomy, and 547 of them received no PMRT. We analyzed the risk of local recurrence in relation to clinicopathologial factors, the status of hormone receptor and HER2, especially in cases with N1-3.
Results: Among 547 cases with no PMRT, there were 364 cases with no LN metastasis (N0), 146 N1-3, and 37 N≥4, and 5-year local disease free survival (DFS) rates were 97.0%, 91.2%, and 73.4%, respectively. In N1-3 (146) cases who underwent no post-operative regional radiotherapies, the 5-year DFS in extent of lymph vessel infiltration (ly) were: ly0 was 97.9% (50) and ly1-3 was 87.9% (92) (ly unknown were 4). In the ly0 cases, the 5-year local DFSs were 100% in grade 2 and 85.7% in grade 3; 100% in ER positive and 90.0% in ER negative; 90.9% in HER2 positive and 100% in HER2 negative. Those in the cases of ly1-3 were 94.5% and 73.4%, 88.7% and 76.6%, and 91.0% and 64.3%, respectively.
Conclusion: In patients with N1-3 breast cancer, the risk of local recurrence after mastectomy was significantly related to grade, extent of lymph vessel infiltration, ER and HER2. PMRT could be omitted in case with ly0,additionaly with grade 1-2, ER positive and HER2 negative. The remaining cases have the risk of local recurrence over 10%, if they don't receive PMRT, in which the indication of PMRT should be considered.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-18.
Abstract P5-15-03: Prediction of positive resection margins in patients with non-palpable breast cancer
Authors: Barentsz MW , Postma EL , van Dalen T , van den Bosch MA , Hui M , Gobardhan PD , Witkamp AJ , van Diest PJ , van Gorp J , van Hillegersberg R , Verkooijen HM 
Published: August 2014

Abstract
Background
Obtaining tumor free resection margins is essential in patients undergoing breast conserving surgery. Several risk factors associated with positive margins are described in literature. We developed a prediction model to predict positive resection margins in patients undergoing breast conserving surgery of non-palpable lesions.
Methods
A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery at five different hospitals in the Netherlands. A prediction model for positive resection margins was built using multivariate regression analysis and internally validated by bootstrapping.
Results
Positive resection margins were present in 69/576 (12%) patients. Factors associated with positive margins included microcalcifications on mammography (OR 1.8, 1.0-3.2), tumor not visible on ultrasound (OR 2.6, 1.2-5.6), presence of DCIS (OR 2.3, 1.3-4.0), multifocality (OR 3.5, 1.0-12.1), caudal location in the breast (OR 1.9, 1.1-3.5), and invasive tumor size (OR 1.83, 1.6-2.7). Together, these factors were able to moderately discriminate between patients with positive versus negative margins (area under the ROC 0.71, 95% CI 0.648 – 0.780). After internal validation the discrimination was slightly lower with an AUC of 0.694. Prevalence of positive margins was 5.2% in the highest risk quintile versus 26.3% in the lowest quintile.
Conclusion
A model predicting positive resection margins after breast conserving surgery in non-palpable breast cancer was built. This model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning (eg. preoperative MRI) and informing of patients.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-03.
Abstract P5-15-04: Clinical benefits of using nomogram for predicting positive resection margins in breast conserving surgery
Authors: Lee E , Han W , Moon H-G , Kim J , Lee JW , Kim MK , Yoo T-K , Kim J , Noh D-Y 
Published: August 2014

Abstract
Achieving a clear resection margin in breast conserving surgery (BCS) is an important factor in tumor recurrence in breast cancer. To obtain clear resection margins and reduce re-excision rates, some surgeons obtain intraoperative assessments of the margins of excised specimens, using intraoperative frozen biopsy. But intraoperative frozen biopsy has several problems such as low sensitivity or longer operation time. We have previously reported a nomogram for prediction of positive resection margin by integrating preoperatively available clinical and pathologic information. The factors were the presence of microcalcification, mammographic density, tumor size discrepancy between magnetic resonance imaging and ultrasonography, and the presence of ductal carcinoma in situ or lobular carcinoma in needle biopsy specimens.
We conducted a prospective trial to examine the accuracy and clinical benefits of the nomogram in 442 breast cancer patients (nomogram group) who underwent BCS between Dec 2011 and March 2013, and compared the clinical outcome with that of the 253 patients (control group) who underwent BCS between Jan 2011 and Oct 2011. For nomogram group, the intraoperative frozen section biopsy was omitted in patients with low nomogram scores.
Applying our nomogram did not increase the rate of reoperation due to resection margin positivity when compared to the control group (6.56% vs. 4.25%, respectively, p = 0.22). In the nomogram group, the reoperation rate in patients with low nomogram score who did not undergo intraoperative frozen biopsy was 3.2%, and this is lower than the reoperation rate in the control group. Additionally, we experienced a significant reduction in operation time by 15 minutes when compared to the control group (p&lt;0.001).
In conclusion, our results show that out nomogram for predicting positive resection margin for patients who receive BCS can significantly reduce the operation time without increasing reoperation rate.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-04.
Abstract P5-15-05: The impact of a change in margin width policy on rates of re-operation for breast conserving surgery
Authors: Richardson CE , Arima Y , Wishart GC , Ambler GK , Benson JR 
Published: August 2014

Abstract
Background: The definition of a negative surgical margin in prospective randomized trials of breast conserving surgery (BCS) is ‘no tumour at ink’ with no conclusive evidence that wider margins of 1mm, 2mm or 5mm are essential for optimal outcomes in the era of modern radiotherapy techniques and systemic therapy. Our group have previously shown that residual tumour is present in only 6% of specimens when re-excision is prompted by a margin of 2 – 5mm compared with 40% for when primary tumour margins are ≤2mm. An audit was undertaken to determine the effect of a change in margin mandate from 5mm to 2mm on rates of re-excision and residual disease in re-excision specimens.
Methods: Data were collected retrospectively from 410 women undergoing BCS for symptomatic and screen-detected invasive and non-invasive disease between November 1st 2009 and October 31st 2011. Rates of re-excision and residual disease in re-excision specimens were compared for 215 patients in the 12 months immediately before (Group 1) and 195 patients in a similar time period after (Group 2) a change in margin policy. All impalpable lesions had conventional intra-operative specimen imaging. Statistical analysis was performed using Fisher's exact test.
Results: Amongst these 410 BCS patients, there were similar proportions of symptomatic and screen-detected cases in each group, but slightly more wire-localized procedures in group 2 (59.5% versus 48.4%; p = 0.029). Rates of patient re-excision were 21.9% (47/215) for group 1 and 25.6% (50/195) for group 2 with no significant difference between margin mandates of 5mm and 2mm respectively (p = 0.42). Eleven patients in each group had a completion mastectomy with 6 and 4 patients in Groups 1 and 2 respectively undergoing &gt;1 re-excision. There was a trend for an increased proportion of residual disease following a change in margin policy (30.2% group 1, 40.7% Group2; p = 0.32) and the majority of re-excision cases had ductal carcinoma in situ alone or combined with invasive cancer in the primary specimen (&gt;80%). There was no significant difference in the proportion of wire-localizations for all re-excisions (≥1) between Group 1 (31/42 = 74%) and Group 2 (25/43 = 58%) (p = 0.17).
Conclusion: A reduction in target surgical margin width from 5mm to 2mm has not decreased rates of re-excision but yields a trend towards an increase in proportion of specimens with residual disease. Longer follow up is required to assess rates of local control and further analyses will ascertain whether a less stringent margin policy is more appropriate for contemporary BCS where adjuvant treatments contribute to local control.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-05.
Abstract P5-16-03: Influence of radiotherapy boost in patients with ductal carcinoma in situ of breast cancer: A multicenter, retrospective study in Korea (KROG 11-04)
Authors: Kim JH , Choi DH , Park W , Ha SW , Kim K , Ye JW , Suh C-O , Shin KH , Kim DW , Lee JH 
Published: August 2014

Abstract
Purpose
We aimed to estimate the effect of boost radiotherapy on local relapse-free survival (LRFS) in patients with ductal carcinoma in situ (DCIS) of breast cancer.
Material and Methods
We included patients from 8 institutions who met the following inclusion criteria: having tumor status Tis, age 18 years or older at diagnosis, having had breast conserving surgery (BCS) and radiotherapy within 12 weeks after surgery. From January 1995 through December 2006, 594 patients with DCIS breast cancer treated with BCS and radiotherapy were analyzed retrospectively in a study by Korean Radiation Oncology Group (KROG). All patients received whole breast radiotherapy (median 5040 cGy) after BCS. Among them, 154 patients (25.9%) received boost radiotherapy (median 1000 cGy) after whole breast radiotherapy. Patients who received boost radiotherapy had higher tumor grade, more comedo pattern and less papillary pattern. Other patients’ or tumor characteristics were not statistically different between boost group and no boost group.
Results
After median follow-up of 89 months (range 26-200), 5 year and 10 year LRFS was 98.3% and 95.6%. There was no statistically significant difference of LRFS between boost group and no boost group.
Local relapse free survival according to boost radiotherpay 5-year LRFS* (%)10-year LRFS (%)p-value**Boost group98.196.20.626No boost group98.495.4 *Local relapse free survival, **Log-rank test
Nineteen (3.2%) patients had ipsilateral breast recurrences, of whom, 12 patients had invasive breast cancer and 7 had DCIS. Positive HER2 receptor was associated with higher invasive recurrences.
Ipsilateral breast recurrences according to HER2 receptor TotalHER2 receptor (+)HER2 receptor (-)p-value*Ipsilateral breast121110.017Invasive8800.023DCIS**4310.642*Fisher's exact test, **Ductal carcinoma in situ
Nine (1.5%) patients developed contralateral breast cancer, of whom, 6 were invasive breast cancer and 3 were DCIS. On multivariate analysis, only margin status was a significant prognostic factor for LRFS.
Conclusion
In the absence of randomized trials, boost radiotherapy could not decrease local recurrence in DCIS of breast cancer after BCS and radiotherapy. In addition, patients with positive HER2 receptor would need further treatment like target agent, trastuzumab. NSABP B-43 study result would answer the question.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-16-03.
Abstract P5-16-07: Intracystic papillary carcinoma of the breast: Implications for therapy from the surveillance epidimiology and end results database
Authors: Howard-McNatt M , Brown D , Levine E , Isom S 
Published: August 2014

Abstract
Intracystic papillary carcinoma is a rare breast neoplasm that has been classified as a variant of ductal carcinoma in situ. However, patients can develop metastatic disease. The indication for radiation and lumpectomy versus mastectomy as far as survival is unknown.
Methods: We identified 2,649 female patients with intracystic papillary carcinoma from the Surveillance, Epidemiology, and End Results (SEER) registry. Differences in demographics, clinical features and survival of patients were assessed using the Kaplan-Meier method and Cox regression.
Results: The median patient age was 66 years. The majority of patients were white and those who presented with Stage 0 disease. Most patients did not have their lymph nodes examined and only 34% received radiation therapy treatments. Using a log-rank test, survival was significantly different by race, with whites having a better survival than black patients (p&lt;0.001). Furthermore, early stage disease (p&lt;0.001) and those who received radiation (p&lt;0.0001) had improved survival. In a Cox regression survival model adjusting for age, stage, and grade, patients who were black (hazard ratio [HR], 1.85) had a significantly higher risk of death than whites. Patients who received radiation therapy (HR, 0.49) had an improved survival over those who did not undergo radiation therapy treatments. There was no difference in survival in patients who received either a lumpectomy or mastectomy.
Conclusion: Intracystic carcinoma of the breast has a good overall survival. Survival is improved in white patients and in patients who receive radiation therapy. This suggests that radiation therapy should be offered to women with intracystic papillary cancer who undergo breast conserving surgery.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-16-07.
Abstract P5-17-03: A new strategy for testing therapies to be effective against seemingly untreatable cancers
Authors: Singh B , Raythatha MR , Shamsnia A , Lucci A 
Published: August 2014

Abstract
Background: Despite a tremendous progress in understanding the genome and biology of cancer, there has been only a slow and limited progress in treating advanced disease and metastases. One main reason for this lack of progress is that preclinical testing is performed with little attention to the true nature of the disease. Most therapy-resistant cancers are highly heterogeneous and they constantly evolve. Methods: Here we describe a strategy for getting to the roots of an aggressive cancer and then evaluating therapies (single agent and combination therapies) for their ability to eradicate such roots. To model the roots of often untreatable disease, i.e., triple-negative inflammatory breast cancer, we started with a well-characterized SUM149 cell line (harbors BRCA1 mutation, oncogenic p53 mutation, has defective RB pathway due to p16 deletion, and lacks of PTEN protein expression). The roots can be selected by applying metabolic challenges (e.g., lack of glucose or glutamine in culture medium). The cell-based model based on most adaptable subpopulation of cancer cells is ideally suited for evaluating combination therapies that are required for combating a heterogeneous and evolving disease. Results: The rare metabolically adaptable (MA) variants (0.01% cells in SUM149 cell line), which can survive and grow without glutamine indefinitely, are structurally adaptable as well (highly enriched in mesenchymal phenotype), resistant to chemotherapeutic drugs, and highly metastatic to multiple organs- lungs, liver, brain, and skin from fat pad xenografts in nude mice (Singh et al., PLoS ONE, 2012). Our function-based selection is more powerful than the biomarker-based selections for isolating the type of rare cells that drive the disease. Our recent CGH array and gene expression microarray data provided evidence of widespread chromosomal imbalances associated with the selection and evolution of MA variants. Interestingly, these analyses revealed that the molecular networks that drive obesity (thus important in cancer) are also important in the survival of MA variants. We are now investigating a variety of experimental therapies (safe sensitizers, inhibitors of drivers, and chemotherapies) to identify those which may eradicate most adaptable breast cancer cells in patients with triple-negative breast cancer. It is noteworthy that our assessment of response versus resistance to therapies is based on long-term assays (1-2 months). Short-term assays, which are often used to assess proliferation and apoptosis, are not good at predicting response in the clinic. Conclusions: Our studies suggest that the MA cells are resistant to most drugs tested thus far as single agent, supporting the validity of our cell-based model. The strategy described here to realistically model therapy resistance and to overcome it has a potential of big clinical impact if it can be aligned with clinical trials.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-17-03.
Abstract P6-02-02: mRNA expression of death associated protein 3 (DAP3) and human breast cancer: Clinical correlations and in vitro evidence
Authors: Wazir U , Ye L , Sanders AJ , Kasem A , Jiang WG , Sharma AK , Mokbel K 
Published: August 2014

Abstract
BACKGROUND: To our knowledge, this study is the first to focus on the potential role for death-associated protein 3 (DAP3) in human breast cancer.
MATERIAL AND METHODS: mRNA expression of DAP3 in breast cancer tissues (n = 127) and normal background tissues (n = 33) were determined using quantitative polymerase chain reaction (qPCR) and were correlated with clinico-pathological data accumulated over a 10-year follow-up period.
Furthermore the effects of DAP3 knock down in breast cancer cell lines (MCF-7 and MDA-MB-231) were investigated. The cells were subjected to conventional growth, adhesion and invasion assays.
In addition to the above, electric cell-substrate impedance sensing (ECIS) assay and annexin V/propidium iodide binding apoptosis assay were performed. For the apoptosis assay, the cells were subjected to 48 to 72 hours of serum hunger (depending on cell line) before being analyzed using a flow cytometer.
RESULTS: The expression of DAP3 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. NPI3, p = 0.036), TNM stage (TNM1 vs. 3, p = 0.07), and tumour grade (grade 1 vs. 3, p = 0.08). Lower DAP3 expression levels were significantly associated with local recurrence (p = 0.013), distant metastasis (p = 0.0057) and mortality (p = 0.019).
Kaplan-Meier plot analysis suggests that patient with higher levels of DAP3 expression had better overall survival compared to patients with lower levels of DAP3 expression (p = 0.075).
DAP3 knock down strains in both cell lines demonstrated increased growth and migration compared to controls during ECIS.
In addition, DAP3 knock down strains of MCF-7 appeared more resistant to serum hunger when compared to controls during the apoptosis assay.
CONCLUSIONS: This study demonstrates an inverse association between DAP3 mRNA levels and tumour stage and clinical stage in breast cancer. This is in keeping with the role of DAP3 as a pro-apoptotic protein. The in vitro evidence lends further credence to this hypothesis. The role of DAP3 may require further investigation to better understand the role of apoptosis in breast carcinogenesis, and may potentially serve as a prognostic marker for human breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-02-02.