bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2-13-01: Gene Profiling of Whole Blood May Identify Patients with BRCA Mutations.
Authors: Mina LA , Gokmen-Polar Y , Goswami C , Storniolo AM , Li L , Badve S , Sledge GW 
Published: June 2012

Abstract
Background:The BRCA1 and the BRCA2 proteins play a role in DNA repair and confer genomic stability to the cell. Identifying BRCA mutation carriers has become an important tool for prevention as well as guiding therapy in cancer patients. We proposed to test the hypothesis that gene expression analysis of peripheral whole blood can reliably detect these mutations.
Materials and methods: Following IRB approval, 10cc of blood was collected from 36 women (BRCA1 (n=8), BRCA2 (n=9), Hereditary breast cancer without BRCA (FAM) (n=7), sporadic breast cancer (SPO) (n=11)). 3 of BRCA1 and 5 of BRCA2 samples were from women without cancer. Following RNA extraction (using the method described by Beekman et al) and quality assessment, Illumina® Whole-Genome DASL™ microarray (Human Ref-8 BeadChips) analysis was performed. The raw data was normalized and analyzed using Partek® Genomic Suite. Differentially expressed genes were identified using ANOVA analysis. Geneset specific supervised analysis was performed to visualize the inherent similarities and differences in the gene expression amongst different groups for 1) DNA repair and 2) Immune-system-related genes. Ingenuity Pathway Analysis (IPA) was performed to interpret the data in the context of biological processes, pathways and networks.
Results: Twenty-nine of the 87 immune-related genes were up-regulated in BRCA1 and BRCA2 groups compared to SPO or FAM groups; these included IL7R, CD53, CD2, CD48 and HLA-DRA. Twenty-five of the 79 DNA repair genes were up-regulated in BRCA1 and BRCA2; these included FANCC, RAD51L3, MSH2, MSH6 and PCNA. In IPA analysis, the comparison of BRCA1 vs. REST (BRCA2 + FAM + SPO) showed a strong immunologic signal, with the top altered biological processes including “Immunologic disease”, “Infection mechanism”, “Immune cell trafficking” and “cell-mediated immune response “. The top 5 canonical pathways also reflected a similar pattern and included “iCOS-iCOSL Signaling in T Helper Cells”, “OX40 Signaling Pathway”, “Calcium-induced T Lymphocyte”, “Apoptosis Regulation of IL-2 Expression in Activated and Anergic T Lymphocytes” and “Protein Ubiquitination Pathway”. When BRCA2 was compared with the REST (BRCA1 + FAM + SPO), a much weaker signal was noted with none of the canonical pathways being significantly altered. PAM analysis showed that a set of 16 genes could differentiate the BRCA patients from the rest with an error rate of 5%. Further validation of this geneset is being performed.
Conclusion: Gene profiling in whole blood may offer an easy, reliable and inexpensive way to identify patients with BRCA mutation. Further studies are currently underway to validate our results in a larger patient population.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-01.
P2-13-07: Prevalence of Germline BRCA1 and BRCA2 Deleterious Mutations in Brazilian Patients with High-Risk of Breast and Ovarian Cancer.
Authors: Diz MDPE , Escobar KA , Guindalini RSC , Pasini FS , Snitkoviski ML , Maistro S , Hoff PMG , Federico MHH 
Published: June 2012

Abstract
Background: Germline mutations in the BRCA1/2 genes account for the majority of hereditary breast ovarian cancer (HBOC). Distribution and prevalence of clinically relevant mutations in BRCA1/2 differ among different populations. All of the Brazilian studies published to date have not performed complete sequencing of both genes, restricting their analyses to selected exons. In addition, a highly heterogeneous mutation spectrum was observed. The lack of data concerning the prevalence and profile of BRCA1/2 deleterious mutation and the appropriated screening criteria for DNA sequencing in the Brazilian population complicates the design of screening strategies.
Objective: To accurately determine the contribution of BRCA1/2 germline mutations in a well characterized sample of Brazilian breast and ovarian high-risk pts.
Methodology: A total of 73 unrelated pts attending a Brazilian public hospital from September 2005 to July 2006, with HBOC risk ≥10% according to Frank, Evans or BRCAPRO algorithms, underwent complete sequencing and MLPA analysis of BRCA1/2 genes. Demographic data and tumor pathological features were extracted from prospectively registered medical records.
Results: Mean age, median of cancer cases in families and median score by Frank, Evans and BRCAPRO algorithms were respectively 48y (24-78), 4 (0-13), 11.2 (0-56,3), 13.4 (0,1-100) and 16 (2-75). A total of 79 unknown clinical significance mutations were identified: 44 in BRCA1 and 35 in BRCA2. Known deleterious mutations were identified in 8 pts. Four in BRCA1: R71G at exon 5, 5382insC at exon 20 (2 patients) and R1751X at exon 20; and four in BRCA2: R2318X at exon 13, R3128X at exon 25, 5844del5 and 6633del5 at exon 11. Several polymorphisms were found in all pts. No mutation was detected by MLPA technique. One novel frameshift deleterious mutation in BRCA2: 6610insTT at exon 11 which results in a stop codon was detected in a breast cancer patient and in four of her relatives from a family with high-risk of HBOC. Taking into account the novel mutation, the prevalence of BRCA1/2 mutation in high-risk pts in our cohort is 12,3%. Pts characteristics presented in [table 1]. Conclusion: To the best of our knowledge, the study represents the first report of the complete sequencing and MLPA analysis of BRCA1/2 genes in large Brazilian series of HBOC high-risk pts. The prevalence of germline mutations found in the present study was similar to the reported by other studies examining high-risk populations.

B1=BRCA1; B2=BRCA2; BC=breast cancer; IDC=invasive ductal carcinoma; MC=medullary carcinoma; ILC=invasive lobular carcinoma; HR=hormone receptor; (b)=bilateral, N/A=not available; N/C=never had cancer; pos=positive; neg=negative, ind=indeterminate
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-07.
P2-13-09: First Statewide Experience with Telephone Delivery of Cancer Genetic Counseling.
Authors: Pruski-Clark J , Trivedi A , Kelle S , Rebecca S 
Published: June 2012

Abstract
Background: National guidelines and multiple professional medical societies recommend genetic counseling as the standard of care for women with a personal and/or family history suggestive of a hereditary cancer syndrome. In addition, the ability to provide risk assessment and genetic counseling is a requirement for accreditation of breast centers by organizations such as the National Accreditation Program for Breast Centers (NAPBC) and the Commission on
Cancer. However, there is clear evidence that this standard is not being achieved. Many individuals are undergoing genetic testing for these syndromes without adequate pre- and post-test counseling and, on the other hand, many individuals who are appropriate for genetic testing are not being identified and referred for genetic counseling and therefore not receiving potentially life-saving genetic information and services. A number of factors have been identified as contributors to these poor public health outcomes, including a lack of available genetic counseling services due to a limited number of trained genetics professionals and their limited geographic distribution. Research has demonstrated the effectiveness of cancer genetic counseling delivered by telephone, but to date, almost no real-world experience has been reported. We provided statewide access to board-certified genetic counselors via telephone in Michigan beginning in February 2010 and report our experience with the first 200 patients at risk for hereditary breast and ovarian cancer.
Materials and Methods: Baseline data were analyzed for all Michigan patients undergoing telephone genetic counseling through Informed Medical Decisions since service delivery began in February 2010. Variables include demographics, geographic location, personal cancer history, family cancer history, Gail risk and test appropriateness criteria.
Results: Analysis has been completed on the first 200 patients referred for consideration of hereditary breast and ovarian cancer. Outcomes include testing, results and, where applicable, reasons testing was not pursued, patient and provider satisfaction, as well as trends over time in patient volumes, providers using the service and uptake by geographic location.
Conclusion: Based on statewide experience in Michigan, telephone cancer genetic counseling is a viable method for service delivery in the real world. The Michigan experience can serve as a cost-effective model for improving genetic services in other locations with limited access to genetic experts.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-09.
P2-13-10: Detection, Visualization and High Resolution Physical Mapping of Large Rearrangements by Molecular Combing in the Hereditary Breast Cancer Genes BRCA1 and BRCA2.
Authors: Ceppi M , Roleau E , Cheeseman K , Thomas A , Briaux A , Lefol C , Walrafen P , Bensimon A , Lidereau R , Conseiller E 
Published: June 2012

Abstract
The BRCA1 and BRCA2 genes are involved, with high penetrance, in breast and ovarian cancer susceptibility. About 2% to 4% of breast cancer patients with a positive family history who are negative for BRCA1 and BRCA2 point mutations can be expected to carry large genomic alterations (deletion or duplication) in one of the two genes, and especially BRCA1. However, large rearrangements are missed by direct sequencing.
Molecular Combing is a powerful FISH-based technique for direct visualization of single DNA molecules, allowing the entire genome to be examined at high resolution in a single analysis. We have developed a novel genetic test based on Molecular Combing. For that purpose, we designed specific BRCA1 and BRCA2 “Genomic Morse Codes” (GMC), also covering the non-coding regions and including large genomic portions flanking both genes. We developed a measurement strategy for the GMC signals, and validated our approach by blindly testing 10 breast cancer patients with a positive family history and 10 control patients. Large rearrangements, corresponding to deletions and duplications of one or several exons and with sizes ranging from 3 kb to 40 kb, were detected on both genes, including the characterization of 4 new mutations (for BRCA1: Del ex 3, Del ex 24 and Dup ex 3; for BRCA2: Dup ex 17–20). The identified mutations confirmed the results obtained with high-resolution zoom-in aCGH (11 k) in the same patients, with a resolution in the 1–2 kb range. Importantly, the developed GMC allowed to unambiguously localize several tandem repeat duplications on both genes, and to precisely map large rearrangements in the problematic Alu-rich 5'-region of BRCA1.
We propose the developed Molecular Combing genetic test as a valuable tool for the screening of tandem repeat duplications, CNVs, and other complex rearrangements in BRCA1 and BRCA2, such as translocations and inversions, to be combined in clinical settings with an essay that allows the detection of point mutations. We see the main application of the developed molecular diagnostic tool as a predictive genetic test. However, we envisage to extended the application of the developed tool as a companion diagnostic test, for instance in the screening of BRCA-mutated cells in the context of the development of PARP inhibitors. Thus, the genetic test may be applied not only to clinical blood samples, but also to circulating cells and heterogeneous cell populations, such as tumor tissues.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-10.
P2-14-10: Are There Variations in Invasive Tumour Characteristics between Different Ethnic Groups?
Authors: Hariri B , Lo M , Gandamihardja T , Lewis J , Hogben K 
Published: June 2012

Abstract
Introduction: Studies have shown that ethnic minorities with breast cancer are more likely to present at a younger age and with more aggressive tumours. The aim of this study was to examine the variation in tumour characteristics and surgical outcomes in different ethnic groups in our breast unit over a 12-month period.
Methods: A retrospective study was performed on all patients with a new diagnosis of breast cancer, either screen-detected or symptomatic, between January to December 2009. Using our Trust databases, data on patient demographics, tumour characteristics, and ethnicity were collected. Where ethnicity was not documented, patients were contacted by telephone to complete the database. Those unable to be contacted were excluded from the study. Other exclusion criteria include those with recurrent ipsilateral breast cancer.
Results: A total of 270 patients (265 females) were included in our study, of which 235 (87%) had invasive cancers (ductal carcinoma, lobular carcinoma, tubular carcinoma, mucinous carcinoma, cribriform carcinoma, papillary carcinoma, sarcoma) and the remaining 35 patients (13%) had non-invasive cancers (ductal carcinoma in-situ, lobular carcinoma in-situ, papilloma, columnar cell hyperplasia).
We were unable to contact 23 (8.5%) patients to ascertain their ethnicity, and therefore these have been excluded from our results.

Table 1. Tumour characteristics and surgical intervention in patients with invasive breast cancer in 2009
Conclusion: We found that the age of breast cancer presentation was lowest in Black and Asian patients (mean age 52 years and 54 years, respectively), compared to White (mean age 59 years). Furthermore, compared to white patients, tumours in Asian patients were larger (62.5% vs 47.2%), of higher grade (83.3% vs 75.2%), more likely to be ER negative (16.7% vs 12.4%), and tended to be lymph node positive (41.7% vs 34.2%). These may explain the higher mastectomy rate in Asian patients (n=12, 50%).
The reason for the younger presentation age in the ethnic Asian group is unclear. However, it is possible that their cancer may have different tumour biology. Other studies have suggested reasons such as birth cohort effect and obesity.
Reflecting the United Kingdom's population the majority of patients that present to our breast unit are White and the number of Asian patients remains small. An increase in the sample size may strengthen our results.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-10.
P2-15-03: Nipple-Sparing Mastectomy for Breast Cancer in Japanese Experience: An Assessment from Long Follow-Up Data of Complication and Cancer Control in 806 Patients.
Authors: Sakurai T , Sakurai T , Umemura T , Jinta E , Suzuma T , Yoshimura G 
Published: June 2012

Abstract
[Introduction] Mastectomy has been conducted in general for cases in which breast conservation is inapplicable. Since Nipple-sparing Mastectomy (NSM) conserves nipple-areola, it is not only more advantageous in an aspect that nipple-areola reconstruction isn't required in case of breast reconstruction compared with mastectomy but also significantly meaningful because the sensation of nipple-areola is preserved in about 70% cases by skin flap preparation based on thick flap method we have adopted. On the other hand, NSM is controversial relating to complication of surgery and recurrence as well.
[Objective] We've made (1) review of safety in NSM surgical technique, (2) discussion over recurrence and prognosis comparing with those in mastectomy, and (3) consideration of performance in immediate reconstructions.
[Result] (1) Of all cases of NSM, the number of cases in stage 0, 1, 2A, 2B, 3 and 4 was 21, 305, 239, 123, 112 and 6 respectively. During 104 months of follow-up period in average, total of seven complication cases (0.9%) were observed, including two flap necrosis cases and five postoperative bleeding cases, but no nipple necrosis case was recorded. Although nipple-areola recurrence rate (%) in stage 0, 1, 2A, 2B and 3A was 0, 2.9, 4.6, 2.4 and 5.3 respectively, prognosis of nipple-areola recurrence cases was good showing no difference between stages (OS: 60M; 93%, 100M; 84%). Skin flap recurrence rate (%) in stage 0, 1, 2A, 2B and 3 was 0, 3.2, 3.3, 4.0 and 14.2 respectively, and prognosis of skin flap recurrence cases was significantly worse in stage 2B and 3 compared with that in stage 1 and 2A (p &lt; 0.001).
(2) We analyzed local recurrence rate, recurrent free survival and overall survival between 806 of NSM cases and 200 of mastectomy cases which had been performed during the same period, and the result showed no significant difference in those rates between NSM and mastectomy cases.
(3) Infectious complication was observed in one out of 18 immediate reconstruction cases using free dermal fat graft. Among 124 immediate reconstruction cases using implant, complications were observed in five postoperative bleeding.
[Conclusion] NSM was excellent in cosmetic aspect showing equivalent results in local recurrence rate and prognosis compared with those in mastectomy cases. Besides, patient's satisfaction was also higher in those who had had NSM alone without reconstruction. Our long term follow-up data shows that NSM may be considered as an alternative option for mastectomy in cases in which breast-conserving surgery is inapplicable in breast cancer patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-03.
P2-15-05: Excision of the Primary Tumour in Patients with Metastatic Breast Cancer – Will E2108 Provide the Definitive Answer?
Authors: Samiee S , Berardi P , Bouganim N , Vandermeer L , Arnaout A , Mirsky D , Dent S , Caudrelier J-M , Chasen M , Clemons M 
Published: June 2012

Abstract
Background: Approximately 10% of new breast cancer patients will present with overt synchronous metastatic disease. Controversy exists about the optimal local management of these patients. While several series suggest that removal of primary tumour is associated with a survival benefit, the retrospective nature of these studies raises considerable methodological challenges. We decided to evaluate the experience at our centre around the impact of surgery in patients with synchronous metastasis.
Method: Case records of all patients seen with primary breast cancer and concurrent distant metastases between 2005 to 2007 were reviewed. Demographic and treatment data was collected. The study endpoints compared both overall survival and symptomatic local progression rates between patients who had breast surgery and those who did not.
RESULTS: 111 patients were identified. Median follow-up 40 months (0.6-71 months). Patients were divided into two groups: those patients who underwent breast surgery (n=48; 29/48 had surgery immediate prior to metastatic diagnosis) and those that did not have surgery(n = 63). The surgical group were less likely to present with T4 tumours (20% vs 36%), N3 nodal disease (8% vs 19%) and visceral metastasis (67% vs 73%)when compared with non-surgical group. Improved overall survival (49 months vs 33 months; p=0.01) and less symptomatic local progression rates ( 15% vs 43%, p &lt; 0.001 ) were seen in the surgical group compared to the non-surgical group.
CONCLUSIONS: The optimal local management of patients with metastatic breast cancer is unknown. Despite the surgery group demonstrating an improved overall survival and symptomatic local control, this group had less aggressive disease at presentation. These results confirm the need for prospective randomized studies. E2108, an ongoing Phase III Trial, was designed to assess the effect of breast surgery in metastatic patients responding to first line systemic therapy. If excision of the primary tumour is associated with a survival benefit, then the pre-selected subgroup of patients that have responded to initial systemic therapy is the desired population to put this hypothesis to test.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-05.
P2-15-07: The Need for Additional Surgeries to Adequately Excise Early Breast Cancers May Have a Negative Impact on Local Recurrence.
Authors: Warburton R , Alriyees L , Wang DY , Wong SL , Leong W 
Published: June 2012

Abstract
Background: Breast conservation surgery (BCS) is considered the standard of care for the treatment of early stage breast cancer (ESBC, AJCC stage 1 and 2). 20 to 50% of patients will require further surgery for positive or close margins. There is recent data suggesting that re-operation can have a negative impact on local and distant recurrences. Our aim is to examine the effects of multiple surgeries to obtain adequate margins on breast cancer recurrence, metastatic disease and survival.
Methods: We reviewed a prospectively maintained breast cancer database at the University Health Network and included all women who had BCS for their first diagnosis of ESBC between January 2004 and December 2007. Patients with neoadjuvant chemotherapy were excluded. We collected patient demographics, surgical pathology, adjuvant therapy and follow up outcome data, which included local recurrence, distant recurrence, cancer-specific survival and overall survival. Clinical and pathologic features were compared using chi-square analyses. Patients who had one lumpectomy were compared to those who had multiple surgeries by using Kaplan-Meier survival curves and log rank test.
Results: Of a total of 744 patients (8 patients had bilateral cancer) 577 (77.6%) had one lumpectomy only (Group 1). 167 (22.4%) patients required further surgery (group 2 = LR+LM+LRM): 83 (11.1%) had a re-excision (LR), 69 (9.3%) had mastectomy (LM) and 15 (2%) had a re-excision followed by a mastectomy (LRM). Thus, a total of 85 (11.4%) patients had mastectomy to achieve adequate margins. All clinicopathologic factors and adjuvant systemic treatments were similar between the two groups except for age and use of adjuvant radiotherapy, which was related to that fact that many of those in group 2 had mastectomy. We observed a difference in disease-free survival favoring patients with lumpectomy only (group 1–3.4% vs. group 2–8.1%, p= 0.01) but there was no difference in distant metastasis (4.5% vs. 5.6%, p=0.56), cancer-specific survival (97.6% vs. 95.6%, p=0.20) and overall survival (6.9% vs 6.3%, p= 0.76) at a median follow up of 4.54 years.
Conclusion: Despite having similar stage, grade, receptor status and adjuvant systemic therapies, having multiple surgeries for primary breast cancer appeared to be associated with decreased disease-free survival but had no difference in rates of distant metastatic disease, cancer-specific survival and overall survival.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-07.