bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES3-2: Challenges to Clinical Application of New Discoveries in the Genetics of Breast Cancer Predisposition
Authors: Robson ME 
Published: April 2011

Abstract
In the United States, testing for mutations in BRCA1 and BRCA2 has become a routine part of the management of individuals at risk for hereditary breast and ovarian cancer. Most providers accept the clinical utility of such testing. This acceptance rests upon a consensus that clinical management of mutation carriers should differ from that of non-carriers. The factors that justify differential management are: 1) the strength of the predisposition, 2) the strong association between mutation and risk in an individual, which allows presymptomatic testing, 3) the risks for component tumors that may not be evident from the family history, and 4) the availability of interventions that are perceived to be effective, even if the evidence base demonstrating such effectiveness is less than robust. Evolving evidence that affected mutation carriers may benefit from specific local or systemic treatment approaches further increases acceptance. Only a small number of breast cancer patients carry BRCA1 and BRCA2 mutations. A few more women carry other high penetrance alleles, but the clinical utility of testing for some of these (e.g. TP53) is less clear than for BRCA1/2, which illustrates that the strength of a predisposition is not the only determinant of clinical utility. High penetrance alleles only account for a small fraction of the hereditable risk of breast cancer. Several groups have described a number of rare variants of lesser risk (RR approximately 2), such as ATM, CHEK2, BRIP1, and PALB2). Large genome-wide association studies have identified additional common variants with even lower relative risks. The identification of these rare and common risk variants may provide important insights into breast cancer biology, but the clinical utility of testing is limited at the present time. We will discuss possible approaches to incorporating information about these risk variants into clinical practice.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES3-2.
Abstract ES6-2: Cell to Cell Variability in the Responses of Tumor Cells to Death Ligands and Other Anti-Cancer Drugs
Authors: Sorger PK , Spencer S , Gaudet S , Aldridge B , D Flusberg 
Published: April 2011

Abstract
Cell to cell variability in phenotype and fate is important for tissue homeostasis, the emergence of drug resistance and the evolution of tumors. I will discuss cell to cell variability in the responses of clonal populations of human cells to TRAIL, a prototypical inducer of receptor-mediated (extrinsic) apoptosis and an investigational therapeutic, as well as to other pro-apoptotic drugs. Some TRAIL-treated human cells die within ∼40 min, others only after 12 hr and some live indefinitely. During this variable delay initiator caspases (ICs) are active in processing substrates such as Bid and downstream effector caspases (ECs) but mitochondrial membrane permeablization (MOMP) does not occur and (ECs are catalytically inactive. We have explored three explanations for cell to cell differences among members of a clonal and notionally uniform population: (i) genetic or epigenetic variation (ii) the involvement of one or more biochemical processes subject to stochastic fluctuation (iii) difference in cell state such as position in the cell cycle or protein concentrations. To distinguish these three possibilities we compared the fates of sister cells exposed to TRAIL and other drugs using live-cell microscopy. Genetic and epigenetic factors are transmitted with near-perfect fidelity; reaction rates dominated by stochastic fluctuations are no more similar in sisters than in any two cells chosen at random and variability arising from differences in mRNA or protein levels should be transiently heritable (because division is a binomial process in which sister cells inherit roughly equal numbers of abundant cytosolic and nuclear factors but drift towards the population average over time). The later explanation is correct — natural fluctuations in protein levels dominate phenotypic heterogeneity in extrinsic apoptosis and cause transient phenotypic heritablility. Variability can be manipulated by protein over-expression and drugs and I will describe analytic methods for modeling these perturbations mathematically. A key conclusion from this work is that variability in the responses of cells to drugs is inherent to the stochastic operation of the biochemical pathways that anti-cancer drugs target. Fractional killing is one inevitable consequence.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES6-2.
Abstract ES9-1: Long-Term Management of Pain Due to, and after, Primary Treatment of Breast Cancer
Authors: Rabow MW 
Published: April 2011

Abstract
As more women are living longer after treatment for breast cancer, survivorship issues take on even greater importance. As a result of effective breast cancer treatment, approximately one-half of survivors experience chronic pain due to the lasting sequelae of surgery, radiation, chemotherapy, and/or endocrine treatment. Research also suggests that these pain symptoms are under-reported and under-treated. The sources of chronic pain after breast cancer surgical treatment include nerve injury, scarring, lymphedema, and post-breast cancer treatment syndrome. After radiation, scarring, neuropathy, and lymphedema are possible. Multiple cytotoxic chemotherapy agents, including Paclitaxel, can cause a chronic painful peripheral neuropathy. Endocrine treatments, including Aromatase Inhibitors and bisphosphonates, are associated with bone, muscle and joint pain.
Treatment for these pain syndromes should be guided by basic principles of analgesia and directed by an understanding of the type of pain involved (nociceptive or neuropathic). Evidence-based treatment modalities include pharmacologic agents, including NSAIDS, acetaminophen, opioids and co-analgesics including neuropathic agents and antispasm medications. Non-pharmacologic treatments include exercise, physical therapy, heat, and cold. Integrative practices may be effective as well, including acupuncture, guided imagery, and massage. Diet and weight loss also have a role. Finally, emotional support for patients facing chronic pain, as will as the attendant concerns about the meaning of that pain, is key in helping ameliorate the distressing experience and disability of chronic pain. Support groups, cognitive behavioral therapy, and psychodynamic therapy all may be helpful to the survivor facing chronic pain after breast cancer treatment.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES9-1.
Abstract MS1-1: Noncoding RNA — The New Frontier in Breast Cancer Patients Management
Authors: Calin GA 
Published: April 2011

Abstract
MicroRNA and other short or long non-codingRNAs alterations are involved in the initiation, progression and metastases of human breast cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. The causes of the widespread differential expression of non-codingRNAs in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the processing machinery. MicroRNA and other short or long non-codingRNAs expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify non-codingRNAs that may represent downstream targets of activated oncogenic pathways or that are targeting protein coding genes involved in breast cancer. Recent studies proved that miRNAs and non-coding ultraconserved genes are main candidates for the elusive class of cancer predisposing genes and that other types of non-codingRNAs participate in the genetic puzzle giving rise to the breast malignant phenotype. These discoveries could be exploited for the development of useful markers for diagnosis and prognosis, as well as for the development of new RNA-based cancer therapies.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS1-1.
Abstract MS2-1: Trends in the Local Treatment of Breast Cancer
Authors: Tuttle TM 
Published: April 2011

Abstract
The objective of this presentation is to evaluate recent patterns in the local treatment of breast cancer in the United States. We will concentrate on 3 specific trends: 1) mastectomy/breast-conserving surgery (BCS) rates; 2) contralateral prophylactic mastectomy (CPM) rates; and 3) use of radiation therapy (RT) after BCS. Although some single-institutional studies have reported that mastectomy rates have recently increased, a recent population-based study reported that the rates of BCS have remained stable or slightly increased over the past decade in the United States. Both single-institutional and population-based studies have reported that CPM rates have markedly increased in recent years. On the other hand, unilateral mastectomy rates have decreased. Despite the potential benefit of RT after BCS, population-based studies indicate that an increasing number of women are not receiving RT after BCS, particularly high-risk women. These trends have important potential untoward consequences, including overtreatment for some patients and undertreatment for others. Several strategies are being developed to ensure adequate local therapy for breast cancer patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS2-1.
Abstract MS2-2: Nipple-Sparing Mastectomy with Nipple Areola Intra-Operative Radiotherapy: One Thousand and One Cases of a Five Years Experience at the European Institute of Oncology of Milan (EIO)
Authors: Petit J-Y 
Published: April 2011

Abstract
Background: in order to reduce mutilation, nipple-areola complex (NAC) conservation can be proposed for a treatment of breast cancer when mastectomy is indicated. To reduce the risk of retro areolar recurrence, a novel radiosurgical treatment combining subcutaneous mastectomy with intraoperative radiotherapy (ELIOT) is proposed. Methods: In a series of more than 1900 Nipple Sparing Mastectomies (NSM) performed at the European Institute of Oncology (IEO-Milan), 1007 (in which 37 bilateral), were registered from March 2002 to November 2007, for invasive carcinoma in 82% of the patients and in situ carcinoma in 18%. Clinical complications, aesthetic results, oncological and psychological results were recorded. A comparison was performed between the 843 patients who received ELIOT and the 208 who underwent delayed one-shot radiotherapy on the days following the operation.
Results: The median follow up time was 52 months (range 1.16-100.73) for a minimum follow up of a 6 months for 100% of the patients. The NAC necrosed totally in 40 cases (3,9%) and partially in 66 (6.5%) and was removed in 60 (5.5%). Twenty four infections (2.56%) were observed and 51 (4.85%) prostheses removed. The median rate of the patients for global cosmetic result on a scale ranging from 0 (worst) to 10 (excellent) was 8.
Evaluation by the surgeon in charge of the follow-up gave a similar result. Only 11% of the patients reported a partial sensitivity of the NAC. Of the 31 local recurrences (3%) 21 occurred close to the tumour site or in other quadrant, 7 close to the NAC corresponding to the radiation field and 3 Paget. Overall, 82 cases of metastases (8.1%) and 28 deaths (2.7%) were observed. No significant outcome difference was observed between the 843 patients receiving intraoperative radiotherapy (ELIOT) and 208 patients receiving delayed irradiation. LR rate of a series of 597 NSM with invasive carcinomas was 25 (4.18%) after a follow up of 59 months Our psychological analysis concluded that sixty eight per cent of patients were satisfied with their reconstructed breast and 97% were satisfied with the preservation of the NAC.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS2-2.
Abstract MS3-1: The Role of Providers in Breast Cancer Disparities
Authors: Keating NL 
Published: April 2011

Abstract
Recent research suggests that racial disparities in health care may be driven in part by differences in where minority patients seek care. Minority patients are more likely to receive care in lower performing hospitals and to be treated by physicians that are less well trained and have less access to important clinical resources than those treating white patients. We analyzed Surveillance, Epidemiology, and End Results (SEER)-Medicare to understand more about the influence of providers on care for older women with early-stage breast cancer.
In a first analysis, we assessed the hospitals where white and black women with early-stage breast cancer received care. We observed that a small number of hospitals treated the majority of black patients (e.g., 81% of black patients had surgery at 82 of the 481 (17%) hospitals). We found that black women were more likely than white women to undergo breast cancer surgery at hospitals with lower rates of radiation following breast-conserving surgery. This difference in site of surgery explains some of the racial disparities in receipt of definitive primary therapy for early-stage breast cancer.
In a second set of analyses, we assessed the role of distance, hospital racial composition, hospital safety net status, and other hospital characteristics on patient's choice of hospital. Preliminary analyses suggest that proximity to certain hospitals explains only a portion of the greater distribution of black breast cancer patients in lower-quality hospitals. Black women with breast cancer appear to seek care in hospitals that also care for greater numbers of black patients with other medical conditions. Additional analyses are exploring the influence of other hospital characteristics on choice of hospital.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS3-1.
Abstract MS3-2: Advances in Breast Cancer Risk Assessment, Screening and Prevention: Adapting the Lessons to an Underserved Latina Population
Authors: Weitzel JN 
Published: April 2011

Abstract
Breast cancer (BC) is the most common cancer and the leading cause of cancer death in Latina women. Mutations in BRCA genes are associated with 5% of all BC and a larger proportion of young women with BC. Genetic cancer risk assessment (GCRA) has the potential to identify persons at increased risk for cancer prior to the onset of disease, when early detection or prevention strategies would be most effective. Despite clinical studies documenting the efficacy of cancer risk reduction measures in high-risk individuals, low-income, underinsured or ethnic minority individuals have a disproportionate burden of cancer and limited access to GCRA. City of Hope Cancer Screening & Prevention Program Network outreach clinics were established in two regional indigent healthcare delivery systems. Consultations are facilitated by an experienced bilingual cancer risk counselor/physician team and risk management recommendations are given based on BRCA test results or empiric risk estimates. We observed a high prevalence of deleterious BRCA mutations (25–34%) among Latinas seen in a large network of high-risk clinics from Texas to Northern California, and also identified a unique recurrent large BRCA1 rearrangement of presumed Mestizo origin. We also established that the BRCA1 185delAG detected in several independent Latina families shared a common ancestral origin with Jewish carrier families. The presence of additional recurrent mutations led us to pursue ancestry informed strategies for more cost-effective BRCA analyses in underserved Latina populations. Our clinical studies indicate that underserved patients embrace the opportunity for GCRA services, attend their scheduled consultations, have a high level of participation in follow-up surveys and show a positive impact on cancer screening and prevention behaviors.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS3-2.
Abstract P1-01-06: How Often Does a Positive Sentinel Lymph Node Biopsy Prompt an Isolated Delayed Axillary Lymph Node Dissection?
Authors: Benson JR , Wishart GC , Forouhi P , Provenzano EN. 
Published: April 2011

Abstract
Background: Intra-operative nodal assessment can avoid delayed axillary lymph node dissection (ALND) in a proportion of sentinel lymph node biopsy (SLNB) patients. Several different methods are currently being practiced with no single one perceived as optimal in terms of performance, patient care, logistics and cost. Both frozen section and imprint cytology are inconsistent and of variable sensitivity compared to paraffin embedded H&E sections and have not yet been surpassed by molecular assays based on reverse-transcription technologies. Modern approaches to axillary management can contribute to reduction in absolute numbers of isolated completion ALND cases without intra-operative nodal assessment. Methods: A retrospective analysis was undertaken of 549 consecutive patients involving a total of 550 non-invasive (extensive or localised ductal carcinoma in situ with mass lesion) and invasive tumours measuring &lt;5cm in maximum radiological size with clinically negative nodes (1 bilateral case). This group of patients were all eligible for SLNB according to unit guidelines. Those patients having SLNB before neoadjuvant therapy (32) or immediate breast reconstruction (IBR) (56) were excluded from further analysis together with 23 patients undergoing single stage axillary surgery (level I/II ALND) due to advanced age or co-morbidity. The remaining 438 patients were potentially liable for an isolated delayed completion ALND consequent to a positive SLNB. Most of these (84%) had an axillary ultrasound examination (368/438) with 58 proceeding directly to ALND based on positive nodal core biopsy (49), suspicious nodes with (6) or without (3) a negative biopsy.
Results: Amongst 381 cases of SLNB, 87 were node positive (22.8%) and proceded to completion ALND. Just over half of these had an isolated delayed ALND (50), whilst 37 patients had ALND combined with an additional surgical procedure (cavity re-excision; mastectomy with or without IBR). The recall rate for isolated ALND was 9.1% (50/549) when calculated as a percentage of all patients initially eligible for SLNB and 11.4% when the denominator was the number of tumours suitable for primary surgical treatment with SLNB or ALND based on axillary ultrasound (50/439). Within the authors’ practice, this represents a caseload for each surgeon of about 7 per annum.
Conclusion: Intra-operative node assessment may be more difficult to justify for all SLNB patients in the context of contemporary practices. A significant proportion of patients are either deselected for SLNB by axillary ultrasound (approximately one-third of node positive patients overall) or can have completion ALND performed alongside definitive or additional breast surgery. Intra-operative analysis may further reduce these low recall rates for isolated ALND but may not be cost-effective nor logistically feasible within many healthcare systems.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-06.
Abstract P1-01-07: Touch Imprint Cytology for Intraoperative Evaluation of Sentinel Lymph Node in Patients with Early-Stage Breast Cancer: A Five-Year Experience
Authors: Chen J-j , Yang B , Chen J-y , Liu Z-b , Huang X-y , Yang W-t , Xu W-p , Shao Z-M , Shen Z-z , Wu J. 
Published: April 2011

Abstract
Background: Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients for axillary lymph node dissection during the same operation and reduces the need for re-operation. Touch imprint cytology (TIC) serves as a main intraoperative assessment of SLNs in our institute for over five years. The purpose of the present study is to evaluate the clinical value of TIC as an intraoperative assessment for the diagnosis of SLN.
Methods: Patients treated for early-stage breast cancer between Feb-2005 and May-2010 enrolled in the study. TIC was routinely performed intraoperatively, the result of which was correlated with definitive histological assessments of serial section with Hematoxylin-Eosin staining. Subsequent immunohistochemistry staining with CK-19 and MUC-1 were performed for research purposes. The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram was applied in this retrospective study to estimate probability of SLN involvement of each case. Results: A total of 1,077 patients with early-stage breast cancer enrolled in the study, and 3,048 SLNs were successfully harvested during the surgeries. Among those, 265 (24.6%) patients proved to have at least one SLN that was positive for carcinoma. Altogether, 397 (13.0%) involved nodes were removed from patients in the aforementioned patient pool. Based on the final pathology report, the sensitivity, specificity and overall accuracy of TIC was 83.4%, 99.0% and 95.2%, respectively on a per patient basis, and 78.3%, 99.4% and 96.7%, respectively on a per node basis. The sensitivity for macrometastasis and micrometastasis are 88.6% and 39.3%, respectively on a per patient basis, while 87.4% and 31. 3%, respectively on a per node basis. Of the patients included in this study, 98.7% had a positive SLN within their first three harvested SLNs. All the patients who were at a &lt;10% chance of SLNs metastases according to the MSKCC nomogram were proved to be node negative by the final pathology. Conclusion: TIC is feasible and is able to detect macrometastasis in SLNs with an acceptable accuracy for clinical use in early-stage breast cancer patients while its ability to detect micrometastasis is limited. Limiting intraoperative TIC to the first three harvested SLNs in the diagnosis of SLN metastasis may make this diagnostic procedure significantly cheaper and easier for pathologists to perform. The MSKCC nomogram could be applied as a screening tool. Intraoperative assessment for SLNs, such as TIC, could be spared for patients with extremely low MSKCC scores (&lt;10%).
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-07.