bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES4-3: Risk of Developing Second Primary Breast Cancer among Survivors of Breast Cancer
Authors: Bernstein JL 
Published: August 2014

Abstract
Of the nearly 226,870 US women expected to develop breast cancer in 2012 and the over 3 million breast cancer survivors currently residing in the US, five to ten percent will develop a subsequent primary in the contralateral breast (CBC) (www.cancer.org). This risk of developing CBC is higher than the overall risk of breast cancer in the general population. The rising incidence of breast cancer, coupled with an improved survival potential after cancer diagnosis has placed an increased number of women at risk for CBC, yet the epidemiology is poorly understood. Despite common genetics and exposures shared by both breasts, only a fraction of women who survive their first primary will develop a second primary in the contralateral breast. Epidemiologic studies have identified factors associated with an increased risk of developing CBC, including family history of breast cancer, early age at diagnosis, hormonal factors, reproductive history, body-mass index, and tumor characteristics of the first primary e.g., lobular histology, stage and estrogen receptor (ER) status. The risk of developing CBC has also been associated with mutations of specific genes including BRCA1, BRCA2, and CHEK2. Importantly, the treatment a woman receives for her first primary breast cancer can also influence her risk of developing CBC; chemotherapy, hormonal therapies and tamoxifen significantly reduces the risk of developing CBC while the radiation received to the contralateral breast during radiotherapy increases the risk of CBC. Despite the number of established risk factors for increased CBC risk, their combined effect accounts for only a small portion of the CBCs that develop each year. It is unclear whether, and to what extent, genetic factors and radiation, individually or via interaction, contribute to the development of CBC. This talk will review the state of the field.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES4-3.
Abstract ES5-3: Investigating Breast Cancer with Single-Cell Sequencing
Authors: Navin NE 
Published: August 2014

Abstract
Tumors evolve from single cells. As they evolve, they acquire complex somatic mutations and diversify, forming distinct subpopulations of cells. This intratumor heterogeneity confounds basic research and clinical practice because tools do not exist to resolve it. Standard genomic methods are limited to reporting an average signal from a complex population of cells, because they require a large amount of input material. These bulk methods may mask population diversity and rare cells in the tumor - that may be the most malignant. To address this limitation my laboratory has developed single-cell sequencing tools to delineate intratumor heterogeneity and investigate mutational evolution in human cancers. We developed a method to profile genomic copy number in single cells and used this method to study genome evolution in triple-negative (ER−/PR−/Her2-) breast tumors (Navin et al., 2011 Nature) which revealed a punctuated model for copy number evolution. Recently, we have extended this method to obtain whole-genome, high-coverage sequencing data from single human tumor cells. From this data we can detect the full spectrum of genomic mutations, including point mutations, indels and microdeletions in single human cells. We applied this method to study clonal diversity in an estrogen-receptor-positive breast carcinoma and sequenced four single cells in addition to a population sample. In the population we detected only 36 coding mutations. However, our whole-genome single-cell sequencing data revealed hundreds of additional coding mutations, suggesting extensive clonal diversity in the tumor. Our data from this tumor support a mutator phenotype model for tumor progression, in which cancer is driven by elevating the rate of random mutations. Our studies show that a wealth of information can be obtained from studying single cancer cells, data that could not be obtained by analyzing the tumor en masse. We expect single-cell sequencing to have major clinical applications in early detection, analyzing scarce tissue samples and monitoring residual disease in patients with cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES5-3.
Abstract ES6-2: Evolving Trends in Implant Breast Reconstruction
Authors: Pusic A 
Published: August 2014

Abstract
For women undergoing mastectomy, implant breast reconstruction is increasingly common. Over the past 5 years, new trends in implant reconstruction have been evolving. The use of ‘next-generation’ silicone implants, acellular dermal matrices and fat grafting have expanded the range of options available to patients. In addition, for women undergoing both skin-sparing and nipple-sparing mastectomies, there is growing experience with single-stage implant reconstruction (i.e. implant placement directly at the time of mastectomy without use of a tissue expander). Finally, indications for post-mastectomy radiation continue to increase and this has important implications for long-term patient satisfaction with implant reconstruction.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES6-2.
Abstract ES8-2: Breast Cancer Stroma: A Predictor of Clinical Outcome and Tumour Heterogeneity
Authors: Bertos N , Finak G , Lesurf R , Saleh SM , Zhao H , Souleimanova M , Meterrisian S , Omeroglu A , Hallett M , Park M 
Published: August 2014

Abstract
Breast cancer heterogeneity is one of the principal obstacles both to predicting outcome and to determining an effective course of treatment for this disease. Individual cases demonstrate heterogeneity at multiple levels, including those parameters assessed by studies of gene expression, chromosomal aberrations, and classical and immuno-pathology. Although genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer outcome by identifying gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer–related pathways and processes, relatively little is known about the effects of heterogeneity in the tumor microenvironment. We have addressed changes in stroma by analyzing changes in gene expression in stromal tissue associated with breast tumors when compared to normal breast tissue. We have integrated gene expression data from laser capture microdissected breast tumor stroma with matched normal stroma. Using this approach we have identified that the microenvironment of a breast tumor can be classified into one of six distinct molecular phenotypes exhibiting distinct biological functions and carrying prognostic information independent of existing therapeutic biomarkers and tumor subtypes. A trained predictor of 23 genes was developed and contains new information to stratify breast cancer subtypes. This is independent of clinical parameters and published predictors of outcome and identifies patients with poor outcome in multiple breast cancer expression data generated using using whole tissue. The stromal predictor selects poor outcome patients from multiple clinical subtypes of breast cancer and contains genes representing distinct biological features, including differential immune response, angiogenic response, as well as a hypoxic response. Elements of this signature are present in murine models of breast cancer. These results highlight the complex relationship between the tumor and its microenvironment, and underline the role that the stroma plays in tumor progression.
These results demonstrate an important role for the tumor microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome. Novel therapies could be targeted at the processes that define the stroma classes, suggesting new avenues for the development of individualized treatment regimens.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES8-2.
Abstract OT1-2-01: NSABP B-43: A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx)
Authors: Cobleigh MA , Anderson SJ , Julian TB , Siziopikou KP , Arthur DW , Rabinovitch R , Zheng P , Mamounas EP , Wolmark N 
Published: August 2014

Abstract
Background: A significant amount of DCIS is ER negative and/or overexpresses HER2. This provides an opportunity to test molecular therapy in DCIS.
In xenograft models and cell lines, T boosts RT effectiveness. In T-treated HER2+ patients, apoptosis occurs within 1 wk of single agent T use, with T found in ductal aspirates. Ample safety evidence for T exists. T given during whole breast irradiation (WBI) may improve results for lumpectomy (Lx) resected HER2+ DCIS. A trial to examine this question will enhance the understanding of breast tumor biology and the prevention of such tumors and could possibly extend breast-conserving surgery benefits for women with DCIS.
Method: After Lx for pure DCIS, each patient's DCIS lesion is centrally tested for HER2 by IHC analysis. HER2 2+ tumors undergo FISH analysis. HER2 3+ or FISH+ patients can be randomly assigned to 2 doses of T, 3 weeks apart during WBI or to WBI alone.
Women ≥18 yrs. with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are clinically or pathologically node negative are eligible. Centrally tested DCIS must be HER2 +. ER and/or PR status must be known before randomization.
Primary aims are to determine if T decreases ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. B-43 will determine if DFS, recurrence-free interval, and OS can be improved with the use of T. 2000 patients will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at163 ipsilateral breast cancer events (7.5–8 yrs. after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 ipsilateral breast cancer events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 5–31-12, 939 patients have been randomized.
NCT00769379Grant support: PHS NCI-U10-CA-69651, -12027, and NCI P30-CA-14599 from the US NCI and Genentech, Inc.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-2-01.
Abstract OT2-3-04: A PILOT PHASE II STUDY TO EVALUATE THE IMPACT OF DENOSUMAB ON DISSEMINATED TUMOR CELLS (DTC) IN PATIENTS WITH EARLY STAGE BREAST CANCER (ESBC)
Authors: Li J , Rugo HS 
Published: August 2014

Abstract
Background: Bone is the most common site of metastases in breast cancer (BC). The detection of keratin + cells (DTC) in bone marrow (BM) has been shown to correlate with an increased risk of disease recurrence. Receptor activator of nuclear factor kappa b (RANK) is critical to bone turnover. Pre-clinical studies have shown that the ligand to RANK (RANKL) can induce metastases of RANK-expressed tumor cells, and that treatment with a RANKL inhibitor can reduce BC metastases. Our previous study suggests that higher RANK expression in tumor at the time of diagnosis correlates with worse recurrent free survival (RFS). Denosumab, a humanized RANKL inhibitor, has been approved in patients (pts) with osteoporosis and metastatic BC to bone.
Trial design: We designed a nonrandomized, open label phase II pilot study evaluating the impact of denosumab on DTCs in pts with ESBC and DTCs following (neo) adjuvant chemotherapy. A total of 45 pts will be enrolled; treatment (Rx) consists of denosumab by subcutaneous injection monthly for 6 months, then every 12 weeks for 6 months for a total of one year. BMA will be repeated at 6 and 12 mo; samples will be evaluated for DTC and for specific gene expression.
Eligibility criteria: Eligible pts have completed adjuvant chemotherapy and at least 3 months (mo) of hormonal Rx as indicated, and have &gt;10 DTC on screening bone marrow aspiration by immunomagnetic enrichment + flow cytometry (IE/FC).
Specific aims: The primary efficacy endpoint is the reduction of DTC/ml from &gt;10DTC/ml to ≤ 10DTC/ml at 6 mo and one year, and the feasibility of denosumab use in this setting. Secondary and exploratory endpoints are to evaluate the correlation of DTC at each time point with BC recurrence, and to analyze gene expression of markers related to bone destruction and inflammation in sorted DTC.
Statistical methods: A total of 45 pts will be enrolled. Based on results from a previous trial testing zoledronic acid in a group of pts with similar eligibility, we expect to have evaluable BMA on 37 (82%) at 1 year. With standard Rx we expect 5% or fewer will have counts ≤10 DTC/ml at 1 year. Using STATA routine sample size (SAMPSI: sample size and power for means and proportions), as long as 20% of pts in treated group become DTC-negative, we will have 89% power to detect this degree of efficacy. These calculations are based on an “exact” test of the proportion of successes; those with reductions to ≤10DTC/ml in sample sizes of 37 based on one-sided testing at a 5% level of significance. We will compare the DTC/ml at 6 and 12 mo to baseline to evaluate reduction in counts.
Present accrual and target accrual: trial will be open in July, 2012 with target accrual of 45 pts.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-04.
Abstract OT3-3-07: Neoadjuvant bevacizumab with weekly nanoparticle albumin bound (nab)-paclitaxel plus carboplatin followed by doxorubicin plus cyclophosphamide (AC) for triple negative breast cancer.
Authors: Snider JN , Allen JW , Young R , Schwartzberg L , Javed Y , Jahanzeb M , Sachdev JC 
Published: August 2014

Abstract
Background: Triple negative breast cancer (TNBC) predominantly clusters with “basal like” subtype on genomic profiling. Over-expression of Secreted Protein Acidic and Rich in Cysteine (SPARC) has been observed in basal like breast cancer (Charaffe-Jaufrett et al. Oncogene 2006; 2273–84). Endothelial transcytosis of nab- paclitaxel occurs via albumin- gp60 receptor-caveolin 1 interaction. SPARC entraps the albumin resulting in higher intratumoral accumulation, which may explain the increased efficacy of nab-paclitaxel (Desai et al. Translational Oncology 2009; 59–63). Exploiting this mechanism & the dysfunctional BRCA mediated DNA repair in basal tumors, we hypothesize that nab-paclitaxel + the DNA damaging drug carboplatin would produce high response rates in TNBC. Adding bevacizumab may enhance efficacy by blocking angiogenesis. In TNBC, pathologic complete remission (pCR) to neo-adjuvant therapy correlates with better disease-free survival (DFS). We hypothesize that high pCR rates can be achieved for patients with TNBC with this combination translating to an improved DFS than seen historically.
Methods: Patients with palpable & operable TNBC ≥ 2 cm are eligible for this single stage phase II trial. pCR (defined as the absence of invasive tumor cells) in the breast is the primary end point, while pCR in the breast + axillary nodes & pCR + near pCR (residual tumor &lt; 5mm) in the breast are secondary end points. 57 evaluable patients are needed, assuming a pCR rate of 25% vs. 40% for the null & alternate hypotheses respectively. 35 patients have been accrued to date. Patients receive carboplatin AUC 6 day 1 & nab-paclitaxel 100mg/m2 days 1, 8 & 15 of a 28 day cycle for 4 cycles and then dose dense AC for 4 cycles. Bevacizumab is given at 10mg/kg Q 2 weeks with chemotherapy for the first 6 cycles. Surgery & radiation are per institutional standards. Bevacizumab is continued postoperatively to complete 1 year of treatment. A core biopsy for collection of fresh tumor tissue is required prior to the start of study treatment. Blood is collected at baseline, and after 4 & 8 cycles for biomarker analysis. Genomic and expression profiling will be undertaken for correlation with response.
This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support from Celgene Corporation.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-07.
Abstract OT3-4-03: Prospective neo-adjuvant registry trial linking MammaPrint, subtyping and treatment response: Neo-adjuvant Breast Registry – Symphony Trial (NBRST)
Authors: Whitworth P , Gittleman M , Akbari S , Nguyen B , Baron P , Rotkiss M , Beatty J , Gibson J , Stork-Sloots L , de Snoo F , Beitsch P 
Published: August 2014

Abstract
Background: The FDA-approved MammaPrint 70 gene profile is performed on a diagnostic multi-gene array. This platform enables additional gene expression profiles to be analyzed simultaneously on one tumor specimen. One such gene expression profile is BluePrint, an 80 gene molecular subtyping profile that discriminates between three distinctive subtypes; Basal-type, Luminal-type, and HER2-type. By combining MammaPrint and BluePrint, patients can be stratified into the following subgroups: Luminal-type/MammaPrint Low Risk; Luminal-type/MammaPrint High Risk; HER2-type and Basal-type. Marked differences are observed in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint [Glück et al. ASCO 2012].
Trial design: NBRST is a prospective observational, case-only study linking MammaPrint and BluePrint to neo-adjuvant treatment response and Distant Metastases-Free Survival (DMFS) and Relapse-Free Survival (RFS). MammaPrint and BluePrint are assessed on fresh or formalin-fixed, paraffin-embedded core needle biopsy samples. Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative.
Eligibility: The study will include women aged 18–90 with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy or neo-adjuvant hormonal therapy, after successful MammaPrint and BluePrint assessment, and who provide written informed consent. Additional inclusion criteria are that women must have had no excisional biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for the treatment of breast cancer.
Objectives: The main objectives of this registry study are to: 1. Measure chemosensitivity (as defined by pathological complete response [pCR]) or endocrine sensitivity (as defined by decrease in longest tumor diameter or RCB1) in the molecular subgroups as determined by combining MammaPrint and BluePrint results.2. Compare local IHC and FISH results with TargetPrint results and BluePrint results.3. Document impact of MammaPrint, TargetPrint and BluePrint results on treatment decisions.4. Assess the 2–3 and 5-year DMFS and RFS for the different molecular subgroups.
Statistical methods: Comparison of response rates between different molecular subgroups will be conducted using the Pearson Chi-square test.
Accrual: The trial started in August 2011 and there are currently 36 participating sites in the US. To date (June 06, 2012), 158 of the planned 400 patients have been enrolled.Clinical trial registry number: NCT01479101.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-4-03.
Abstract P1-01-13: Patterns of definitive axillary management in the era prior to reporting ACOSOG Z0011: comparison between NCCN Centers and hospitals in Michigan
Authors: Breslin T , Hwang S , Mamet R , Hughes M , Otteson R , Edge S , Moy B , Rugo H , Wong Y-N , Wilson J , Laronga C , Weeks J , Silver S , Marcom P 
Published: August 2014

Abstract
Background: The results of the ACOSOG- Z0011 trial have had potential practice changing implications for the management of patients with positive sentinel lymph node (SLN) undergoing lumpectomy and radiation for breast cancer. However, some evidence suggests a shift in axillary management even prior to the initial report of data supporting sentinel lymph node biopsy (SLNB) alone in mid-2010. We analyzed data in the National Comprehensive Cancer Network (NCCN) outcomes database from NCCN centers and the Michigan Breast Oncology Quality Initiative (MiBOQI) hospitals to examine institutional practice patterns with respect to use of completion axillary dissection (CALND) for SLN positive breast cancer in the years leading up to publication of these trial results. We hypothesized that CALND would be omitted more frequently in women treated at NCCN centers compared to those treated at MiBOQI programs.
Methods: We identified 2,172 women with clinical T1/T2 N0 breast cancer who underwent breast surgery and SLNB and had a positive SLN from 2007 through 2010 at one of 12 participating NCCN centers or 12 MiBOQI sites. Patient and tumor characteristics, definitive breast procedure, year of diagnosis, and institutional affiliation were analyzed as predictors of use of SLNB alone in univariate Chi-Square and multivariable logistic regression models.
Results: CALND was omitted in 314 (14.5%) of the 2,172 patients. Over time, there was a dramatic increase in the use of SLNB alone (12% in 2007 to 23% in 2010). In the univariate analyses, increased patient age, later year of diagnosis, lower T stage, and lower pathologic N stage were significant predictors of use of SLNB alone (all p &lt; .0001). There was no association between definitive breast surgery type, hormone receptor status, Her-2 Neu status, or institutional affiliation and use of SLNB alone. In the multivariable model, older age at diagnosis, later year of diagnosis, and lower pathologic N stage remained significant independent predictors of SLNB alone. There were no significant differences in rates of omission of CALND between NCCN and MIBOQI sites.

Conclusions: Omission of CALND occurred frequently in women with SLN positive breast cancer cared for in both NCCN and MiBOQI institutions in advance of reporting results of ACOSOG-Z0011. This shift was seen in management of patients undergoing lumpectomy as well as mastectomy. Further study is warranted to determine the extent of durable practice changes as well as any impact on survival and local-regional control.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-13.