bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3-06-03: Hypodiploidy, 1pter Loss and Inactive X Chromosome Retention Are Associated with BRCA1 Somatic or Germline Inactivation in Basal-Like Breast Carcinomas: Proposal for a New BRCAness Genomic Signature.
Authors: Manié E , Popova T , Vincent-Salomon A , Dubois T , Delattre O , Sastre-Garau X , Stoppa-Lyonnet D , Stern M-H 
Published: June 2012

Abstract
Basal-Like Carcinomas (BLCs) are high grade ductal carcinomas identified by large scale transcriptomic analyses among carcinomas with triple-negative phenotype (ER- PR- HER2−). A particular relationship between this phenotype and the BRCA1 breast cancer susceptibility gene has been described based on several observations including high genomic similarities of sporadic and BRCA1 BLCs. BRCA1 mutated patients have been shown to strongly benefit from treatments using PARP inhibitors. However, significant benefit of this treatment was not demonstrated in sporadic triple-negative breast cancers in association to standard chemotherapy in phase III clinical trials, which emphasizes the necessity for a better selection of DNA repair deficient tumors. The goal of this study was to determine whether BRCA1 inactivation leads to particular genomic alterations that could be used to identify BRCA1 deficient sporadic BLCs.
Genomic profiling was performed using SNP-arrays (Affymetrix and Illumina) and high quality profiles were obtained for 60 BLCs with more than 35% of tumor cells. The series contained 28 BRCA1 BLCs and 32 sporadic BLCs consisting in 10 sporadic BLCs with BRCA1 somatic inactivation by promoter methylation (BRCA1-like BLCs) and 22 sporadic tumors without BRCA1 methylation (nonBRCA1 BLCs). Genomic data was mined with GAP methodology (Popova et al, Genome Biol 2009), which allows absolute copy-number evaluation with DNA content calculation and clarification of Loss Of Heterozygosity (LOH) status.
Genomic patterns of BLCs were characterized by frequent and highly recurrent allelic losses. Comparison between BRCA1, BRCA1-like and nonBRCA1 BLCs confirmed their overall similarity, and identified few significant differences enhanced when BRCA1 and BRCA1-like BLCs were considered as one group. Firstly, hypodiploidy characterized BLCs with BRCA1 germline and/or somatic inactivation. Secondly, the lpter region was found more often lost in BRCA1 and BRCA1-like BLCs than in nonBRCA1 BLCs. Thirdly, retention of inactive X chromosome was a characteristic of BLCs with BRCA1 germline and/or somatic inactivation. Finally, a BRCA1ness score based on the above described difference is proposed.
In conclusion, despite a strong similarity of genomic patterns in BLCs, BRCA1 inactivation leads to few key genomic aberrations which constitute a new BRCA1 molecular signature namely hypodiploidy, 1pter loss and inactive X chromosome retention. This signature needs to be further evaluated in terms of response to PARP inhibitors in order to evaluate its capacity to identify patients that will benefit from this treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-06-03.
P3-07-07: Effect of Sentinel Lymph Node Biopsy without Axillary Lymph Node Dissection on Overall Survival in Patients with T1 or T2 Node-Positive Breast Cancer: A Report from the Korean Breast Cancer Society.
Authors: Park HS , Chae BJ , Song BJ , Jung SS 
Published: June 2012

Abstract
Introduction: Sentinel lymph node biopsy (SLNB) is accepted as an alternative method to axillary lymph node dissection for staging axillary lymph node status in clinically node-negative breast cancer. Current practical guidelines recommend that axillary lymph node dissection (ALND) should be performed in cases with sentinel node metastasis, and most of node-positive patients should receive adjuvant systemic therapy to reduce locoregional/distant recurrence and to improve overall survival irrespective of the number of lymph node metastasis. However, patients with ALND are more likely to develop lymphedema than those with SLNB alone, and appropriate systemic chemotherapy or hormone therapy significantly reduce locoregional and distant recurrence in early breast cancer patients. For this reason, the previous prospective study, American College of Surgeon Oncology Group Z0011 trial, was conducted and it suggested that there is no difference in overall survival between node-positive patients who received breast conserving treatment with SLNB alone and those with ALND after SLNB. This study is aimed to evaluate the difference of survival between node-positive patients who underwent SLNB alone and those who received ALND after SLNB using the Korean Breast Cancer Society registry.
Methods: In 87671 patients with breast cancer in the registry, we enrolled 2581 patients who meet the eligible criteria in the study. All enrolled patients had T1 or T2 breast cancer, and received mastectomy or breast conserving treatment followed by documented adjuvant systemic therapy between Jan. 2001 and Apr. 2011. Log-rank test and Cox-proportional hazard model were used to access the difference of overall survival according to the axillary procedure.
Results: There were 197 patients with SLNB alone and 2384 patients with ALND after SLNB, respectively. Smaller tumor size, lower number of nodal metastasis, and higher proportion of breast conserving surgery were shown in patients with SLNB alone than in those with ALND after SLNB. There was no significant difference in overall survival between 2 groups in the log-rank test. ALND after SLNB showed no significant improvement on overall survival in Cox-propotional hazard model adjusted by tumor size, number of nodal metastasis, and operation type (P=0.78, HR=0.73, 95% CI=0.08−6.62).
Conclusion: The current study suggests that ALND after SLNB in cases with sentinel lymph node metastasis may not influence on the improvement of overall survival and supports the results of Z0011 trial. Further validation studies are necessary to expand the understanding of the role of performing SLNB alone in patients with node-positive breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-07.
P3-07-19: Long-Term Outcome of Internal Mammary Lymph Node Detected by Lymphoscintigraphy in Early Breast Cancer.
Authors: Koo MY , Lee JE , Nam SJ , Yang J-H , Lee SK , Kim S , Choi M-Y , Cho DH , Kim J , Lee J , Jung SP 
Published: June 2012

Abstract
Purpose: The purpose of this study is to determine the long-term significance of internal mammary lymph node (IMLN) detected by lymphoscintigraphy.
Background
IMLN metastasis is an important prognostic indicator in breast cancer. However, the necessity of internal mammary sentinel lymph node (IMSLN) biopsy for accurate staging, for choosing adjuvant treatment, and as a prognostic indicator, has remained controversial.
Methods: From January 2001 until December 2006, 525 female breast cancer patients underwent radical surgery after preoperative lymphatic scintigraphy. We retrospectively analyzed the follow-up results, recurrences and deaths of all patients.
Results: There was no significant difference in clinicopathologic characteristics between the axilla and the IMLN group. The median follow-up period was 118.8 (range, 7–122) months in the axilla group and 107.7 (range, 14–108) months in the IMLN group. During the median follow-up period, the breast cancer-related death rate in the axilla group was 3.6%, which was not significantly different from that of the IMLN group (1.3%) (P = 0.484). The five-year survival rates (5YRS) did not differ between the two groups (P = 0.306). The overall recurrence rate and the locoregional (LR) recurrence rate also did not differ between the two groups (P = 0.835 and P = 0.582, respectively. The recurrence rate of IMLN (both ipsilateral and contralateral) metastasis was very low, accounting for 0.5% in the axilla group and 1.3% in the IMLN group (P = 0.416).
Conclusion: The long-term follow up results showed that there was no significant difference in both overall outcome and regional recurrence between the two groups. Therefore, the necessity of identification of nodal basins outside the axilla or the necessity of IMLN sentinel biopsy should be reconsidered.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-19.
P3-07-29: Validating the Lymph Node Ratio as a Prognostic Indicator among South East Asian Breast Cancer Patients.
Authors: Saxena N , Hartman M , Bhoo Pathy N , Aziz R , Siew EL , Lee SC , Yip CH , Verkooijen HM 
Published: June 2012

Abstract
Background: Several studies in Caucasian settings have suggested that the lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is a superior prognostic indicator for breast cancer as compared to the absolute number of nodes involved (pN stage). This study validates the prognostic performance of LNR in the South East Asian setting.
Methods: All patients diagnosed with non-metastatic invasive breast cancer at the National University Hospital (Singapore) or University of Malaya Medical Center (Kuala Lumpur) between 1990 and 2007 and with information on axillary nodes removed and involved were included for analysis (n = 1589). Multivariate Cox regression analysis was performed to evaluate the prognostic value of the LNR [low (&gt; 0 and &lt;0.2), intermediate (0.2 to 0.65) and high risk (&gt;0.65 to 1)] and pN staging [pN1, pN2 and pN3] for all cause mortality. Patients staged pN0/LNR 0 were excluded from analysis.
Results: According to the LNR classification, 758 patients were categorized as low risk, 574 as intermediate risk and 257 as high risk LNR. For classic pN staging, 879 were pN1, 447 pN2 and 263 pN3. Women in the intermediate risk category (0.2 to 0.65) had a 1.5 fold increased risk of death [Adjusted hazard ratio [HRadj] of 1.5 (95%CI, 1.2 to 1.9]), and women with high risk (&gt;0.65 to 1) LNR had a 3.2 fold increased risk of death [HRadj of 3.2 (95%CI, 2.6 to 4.1)] as compared to the low risk women (&gt;0 and &lt;0.2). Similarly, women with pN2 disease had a 1.9 fold increased risk of death [HRadj of 1.9 (95%CI, 1.5 to 2.4)], and women with pN3 disease had 3.1 fold increased risk of death [HRadj 3.1 (95%CI, 2.5 to 3.9)] compared to pN1 patients.
Conclusion: Among South East Asian breast cancer patients, both the Lymph Node Ratio and the pN Staging system seem to be equally good at predicting all cause mortality.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-29.
P3-07-46: Accuracy of SPIO-Enhanced MR Imaging Alone for the Diagnosis of Sentinel Node Metastases in Patients with Breast Cancer.
Authors: Motomura K , Nakahara S , Ishitobi M , Komoike Y , Koyama H , Inaji H , Horinouchi T , Nakanishi K 
Published: June 2012

Abstract
Background
Superparamagnetic iron oxide (SPIO)-enhanced MR imaging has been reported to be promising for the detection of metastases in sentinel nodes localized by CT lymphography in patients with breast cancer (Motomura, Ann Surg Oncol 2011). The current SPIO technique involves imaging before and after contrast administration. This study evaluated the accuracy of SPIO-enhanced MR imaging alone without unenhanced imaging.
Methods: This study included 120 patients with breast cancer demonstrating clinically negative nodes. Sentinel nodes were identified by CT lymphography, and MR imaging of the axilla before and 18–24 hr after interstitial administration of SPIO was performed. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if there was an absence of low signal intensity either in the entire node or in a focal area on SPIO-enhanced MR imaging. The diagnostic accuracy of the SPIO-enhanced imaging alone was compared with that of combined unenhanced and SPIO-enhanced imaging.
Results: The mean number of sentinel nodes identified by CT lymphography was 1.2 (range 1–3). Pathologic evaluation demonstrated that 28 (23.3%) of 120 patients showed metastasis to at least one node. One false negative result was added when the evaluation was based solely on SPIO-enhanced MR imaging. Consequently, the sensitivity decreased from 84.0% to 80.0% and the accuracy decreased from 89.2% to 88.3%, respectively, in the SPIO-enhanced MR imaging alone. However, the differences in sensitivity and accuracy between SPIO-enhanced MR imaging alone and the combined unenhanced and SPIO-enhanced imaging were not significant (McNemar's test; p=1.0). The specificity of enhanced imaging alone and that of combined unenhanced and SPIO-enhanced imaging were both 90.5%.
Conclusions: A single MR imaging examination performed after SPIO administration can be used for accurate diagnosis of sentinel node metastases, and thus reduce the time and cost of imaging.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-46.
P3-07-47: Validated Nomogram To Predict Sentinel Lymph Node Positivity in Breast Cancer Patients.
Authors: Kaplan R , Qiu Q , Monni S , D'Alfonso T , Shin SJ 
Published: June 2012

Abstract
Background: Sentinel lymph node(SLN) biopsy is commonly used to assess axillary lymph node status in breast cancer patients. Intraoperative (frozen section) evaluation of SLN may lead to immediate axillary dissection if the lymph node is found to be positive. In light of the recent outcomes of the Z00011 trial, the use of intraoperative evaluation for SLN should diminish since only select patients appear to benefit from axillary dissection. We have previously reported that tumor size and lymphovascular invasion (LVI) strongly predict SLN positivity in a cohort of 350 breast cancer patients [Modern Pathology (2011) 24, 30A]. From this test cohort, we developed a nomogram which could help identify patients more likely to have sentinel lymph node positivity. The aim of this study was to validate the efficacy of this nomogram by applying a new, non-overlapping cohort of breast cancer patients who had undergone sentinel lymph node sampling. Materials and Methods: 93 breast cancer patients aged 29–82 (mean:59) who underwent excision (54, 58%) or mastectomy (39, 42%) with a SLN biopsy were studied. Patients who had undergone neoadjuvant chemotherapy were excluded. Clinicopathologic parameters such as number of sentinel lymph nodes removed and/or positive, number of non-sentinel lymph nodes removed and/or positive, tumor size, histologic type/grade, presence of lymphovascular invasion, biomarker expression (ER,PR, HER-2/neu) and multifocality were recorded. Statistical analysis was performed to identify which variables correlated with SLN positivity in this validation cohort. In addition, the probability of SLN positivity for each case was determined by using the nomogram and this value was then compared to the patient's true SLN status. Results: When analyzed separately, tumor size (p=0.03) and LVI (p=0.01) were variables that were significantly associated with SLN positivity in both the test and validation cohorts. Employment of the nomogram demonstrated that 60% of patients who were predicted to have a positive SLN with at least 0.8 probability were truly positive by histologic and immunohistochemical examination. Moreover, 89% of patients who were predicted to have a negative SLN with at least 0.8 probability were truly negative by histologic and immunohistochemical examination. Conclusions: We conclude that the utility of this nomogram prior to surgery can help predict SLN positivity. This can serve as a complimentary adjunctive tool to better select patients who will likely need intraoperative evaluation of their sentinel lymph node due to their higher risk of sentinel node positivity and thus, benefit from the option of immediate axillary dissection at that time.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-47.
P3-09-06: Changes of Serum Vitamin D According to the Breast Cancer Treatment.
Authors: Kim HJ , Yi OV , Koh BS , Yu JH , Lee JW , Son BH , Ahn SH 
Published: June 2012

Abstract
Background: Vitamin D deficiency is associated with increased breast cancer risk and decreased breast cancer survival. The purpose of this study was to determine the effect of breast cancer adjuvant treatment to the vitamin D status, as measured by the serum hydroxyvitamin D (25OHD) in breast cancer patients.
Patients and Methods: For 589 patients who was diagnosed as a non metastatic breast cancer in 2009 at the asan medical center, blood was prospectively analyzed in batches for serum 25 OHD level at basal and at 6 and 12month. We excluded the patients who took a vitamin D supplementation and got a neoadjuvant chemotherapy. Vitamin D sufficiency was defined as serum as 30ng/ml or greater, insufficiency as 20 to 29 ng/ml and insufficiency as less than 20ng/ml.
Results: At baseline, mean serum 25OHD was greater in summer (April to Oct) than Winter(Nov to May) (28.2ng/ml vs 32.9ng/ml respectively, p=0.000). The patients who did not get a chemotherapy and antihormonal therapy as baseline, the patient with chemotherapy showed decreased serum 25OHD level than who without chemotherapy in 6 month but not in 12 month (p=0.003, vs p=0.156 respectively). The patients who had taken anti-hormonal therapy showed significant increasing serum 25OHD in 6 month and 12 months (p=0.000 both). For the patients who got both chemotherapy and anti-hormonal therapy, the changes of serum 25OHD level is smaller than the patients who got a chemotherapy only.
For the patients who got a chemotherapy, 57% of patients were vitamin D sufficient at baseline, but 27% of patients in 6 month and 49% in 12 month (p=0.001).
Conclusion: Vitamin D status was worsen during chemotherapy but recovered after chemotherapy. Anti hormonal therapy make the serum vitamin D level increased. The translational research about the effect of chemotherapy and anti-hormonal therapy to the vitamin D status should be warranted.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-09-06.
P3-10-04: Halting Early Breast Cancer Progression with Omega-3 Ethyl Esters: Altering Tumor Microenvironment in 21T Series Cell Lines.
Authors: Chen CH , Rhodes ME , Fabian C , Hursting SD , deGraffenried LA 
Published: June 2012

Abstract
Observable infiltration of immune cells in stages of early breast cancer progression mirrors two recently conceptualized factors of carcinogenesis: tumor microenvironment and tumor-promoting inflammation.
Clinical studies using immunohistochemical staining for CD45 in patient-derived breast tissue demonstrate the involvement of leukocytes in breast cancer development, but the lack of an appropriate in vitro model has hindered molecular studies thus far. However, the 21T series cell lines effectively mimic breast cancer progression. This cell line series was obtained from the same breast cancer patient and consists of three cell lines representing atypical hyperplasia (21PT), ductal carcinoma in situ (21NT) and invasive carcinoma (21MT-1). This unique cell line series is used in our molecular study of omega-3 ethyl esters as breast cancer preventive agents. Preliminary invasion assays have described varying degrees of monocyte recruitment according to stages of progression. 21PT cells when plated on the bottom chamber failed to mobilize monocytes as effectively as 21NT or 21MT-1 and the addition of omega-3 ethyl esters suppressed the baseline invasion capacity of monocytes by 30%. Epidemiologic studies suggest that omega-3 fatty acids can act as potent cancer preventive agents and are possibly more potent when used in an ethyl ester form. Based on this, we hypothesize that omega-3 ethyl esters may prohibit early breast cancer progression through inhibiting immune cell infiltration and disrupting the formation of a tumor-promoting inflammatory and oxidative microenvironment. Phenotypic studies aim to interrogate the effect of omega-3 ethyl esters on tumor microenvironment including chemokine secretion and MMP production whereas molecular experiments probe into the importance of the Wnt pathway as a key player in the transition from ADH to DCIS. This study will demonstrate how omega-3 ethyl esters may function as breast cancer preventive agents as well as provides a model of study to test the efficacy of cancer preventive agents in vitro.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-10-04.
P3-12-05: Breast Cancer Recurrence: 2nd Conservative Treatment Versus Mastectomy.
Authors: Michel V , Houvenaeghel G , Bannier M , Tallet A , Minsat M , Lambaudie E , Salem N , Butarelli M , Resbeut M 
Published: June 2012

Abstract
Objectives: Mastectomy (Mt) is considered standard treatment for isolated local recurrence (LR) of breast carcinoma. The aim of our study was to evaluate a second conservative treatment (defined as lumpectomy followed by interstitial brachytherapy (LpIB)) and to determine if it compares favorably with the current standard treatment. Materials and methods: Between January 1981 and December 2009, 348 patients were treated to the Paoli Calmettes Institute (IPC) for an isolated LR: 232 (66,7 %) underwent Mt, 62 (17,8 %) received a second radio-surgical conservative treatment (LpIB) and 54 (15,5 %) a 2nd single surgical treatment (Lp).
We classified each population according to the well known prognosis factors.
Then, populations Mt and LpIB were matched taking into account these criteria to compare the overall survival (OS), metastasis free survival (MFS) and 2nd local recurrence free survival according to the treatment delivered.
Results: On 348 reviewed patients, with a median follow-up of 73,3 months, 65 patients died (42/232 Mt, 8/62 TecCur, 15/54 Tec) and 100 presented metastasis (64/232 Mt, 15/62 TecCur, 21/54 Tec). There was no difference in MFS for the 2 groups, LpIB and Mt (80 % at 5 years) and the OS was non significantly better in the group LpIB compared to the group Mt (90 % and 82 % at 5 years respectively, p=0,28), whereas in the LpIB group 17% and 30% presented a relapse at 5 years and 10 years respectively.
They subsequently underwent a salvage mastectomy.
Worse results were obtained with lumpectomy alone (OS = 72 % and MFS = 68 % at 5 years) compared with 2 other option treatments.
Conclusion: A second conservative treatment for breast cancer recurrence, i.e. lumpectomy and interstitial brachytherapy, is possible for selected patients, without any negative impact on overall survival, nor metastasis free survival.
Keywords: Local recurrence, interstitial brachytherapy, lumpectomy, conservative treatment, mastectomy, overall survival, metastasis free survival, breast carcinoma.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-05.