bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-05-05: Circulating HER2 extracellular domain (ECD) predicts a poor prognosis for metastatic breast cancer patients
Authors: Wang X-j , Shao X-Y , Xu X-H , Chen Z-H , Wang S , Cai J-F , Huang J , Huang P , Lou C-J , Ling Z-Q , Han MX 
Published: August 2014

Abstract
Background: Amplification or overexpression of HER2 has been shown to play an important role in approximately 30% of breast cancers and is strongly associated with increased recurrence and a worse prognosis. The HER2 extracellular domain (ECD) may be cleaved and shed from the surface of breast cancer cells and serum HER2 ECD levels can be detected by enzyme-linked immunosorbent assay (ELISA). In this study, we explored the relationship between circulating HER2 ECD and tissue HER2 status, then we also examined its predictive value in a cohort of metastatic breast cancer patients.
Methods: Two hundred and seven metastatic breast cancer patients from March 2009 to July 2011 were involved in this prospective study at Zhejiang Cancer Hospital. The patients were identified histopathologically as having breast cancer by pathologists and staged mainly based on the pathology, the clinical manifestation, and the imaging findings of CT and MRI according to the classification system of the International Union Against Cancer. Serum HER2 ECD levels were measured by ELISA. Tissue HER2 was determined by IHC and FISH in tumor samples, respectively.
Results: The level of serum HER2 ECD was at least more than 15 ng/ml in 31.4% (65/207) metastatic breast cancer patients, 39.1%(43/110) in HER2-positive patients and 23.4%(22/94) in HER2-negative cases, respectively, P = 0.017. We also found that high serum HER2 ECD levels (≥15 ng/ml) were significantly associated with elevated serum CEA (52.1% v 21.5%, OR 3.978, 95%CI 2.138–7.401, P = 0.000), CA125 (48.5% v 23.5%, OR 3.064, 95%CI 1.650–5.691, P = 0.000), CA153 (53.2% v 17.1%, OR 5.48, 95%CI 2.897–10.366, P = 0.000), LDH (53.3% v 23.1%, OR 3.798, 95%CI 2.011–7.173, P = 0.000) and AKP (51.2% v 26.5%, OR 2.911, 95%CI 1.442–5.879, P = 0.002), respectively. For the effect of HER2 ECD on the site of relapse, still there were statistically significant correlation between increased serum HER2 ECD levels and liver involvement (42.7% v 24.0%, OR 2.358, 95%CI 1.294–4.297, P = 0.005), brain metastasis (50.0% v 26.7%, OR 2.744, 95%CI 1.397–5.391, P = 0.003) and visceral involved (37.9% v 14.8%, OR 3.511, 95%CI 1.548–7.961, P = 0.002), respectively. While serum HER2 ECD levels were not related to age, BMI, tumor size, lymph node involvement and hormone receptors status, respectively (P&gt;0.05).
Conclusions: Monitoring the circulating levels of the HER2 ECD in patients with metastatic breast cancer provides a real-time assessment of tumor burden and indicates poor prognosis, and may provide important information for reassessment of HER2 in HER2-negative metastatic breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-05.
Abstract P2-05-10: 64Cu-DOTA-trastuzumab positron emission tomography imaging of HER2 in women with advanced breast cancer
Authors: Mortimer JE , Conti P , Shan T , Carroll M , Kofi P , Colcher D , Raubitschek AA , Bading JR , Miles J 
Published: August 2014

Abstract
Background: We propose to utilize64Cu-DOTA-trastuzumab with PET imaging to assess the in vivo expression of HER2 in women with advanced breast cancer. We hypothesized that the uptake of HER2 in normal tissues compromises the quality of radiographic images and that the pre-administration of trastuzumab prior to injection of64Cu-DOTA-trastuzumab would improve image quality. Two different doses of cold trastuzumab (5 mg and 50 mg) were tested. Once the dose of cold trastuzumab was established in women with documented HER2 positive metastatic disease, we initiated a second study of64Cu-DOTA-trastuzumab PET imaging in women whose cancers were HER2 1+ and 2+ by immunohistochemical staining.
Methods: Patients with biopsy confirmation of recurrent disease located outside the breast and axilla considered for study. Complete staging workup included CT of the chest, abdomen, and pelvis, bone scintigraphy and18F FDG PET. At lease 1 non-hepatic site of metastasis that was &gt; 2 cm separate from the biopsy site was also required. HER2 status was assessed by both IHC and FISH. In the first study all patients were required to have HER2 positive disease and could not have received anti-HER therapy for &gt; 2 months. Immediately prior to injection of64Cu-DOTA-trastuzumab, a cold dose of either 5 mg or 50 mg of trastuzumab was administered.64Cu-DOTA-trastuzumab PET imaging was performed at 24 and 48 hours.
Results: Eight women with HER2 positive metastatic breast cancer have undergone64Cu-DOTA-trastuzumab PET imaging: 2 received a pre-64Cu-DOTA-trastuzumab PET dose of 5 mg trastuzumab and 6 received 50 mg.64Cu-DOTA-trastuzumab PET effectively visualized and provided uptake measurements for presumably HER2+ metastatic lesions in bone, liver, lung and, to a lesser degree, lymph nodes. The 50 mg dose resulted in approximately 75% decrease in liver uptake of64Cu and improved the visualization of hepatic metastasis. We have initiated the second phase of the study utilizing the pre-administration of 50 mg trastuzumab in women with HER2 1+ and 2 + disease. To date we have imaged one patient.
Conclusion:64Cu-DOTA-trastuzumab PET imaging is feasible and image quality is improved with the pre-administration of 50 mg trastuzumab. Enrollment of women with IHC 1+ and 2+ disease continues. This work was supported by the Department of Defense grant # 1024511.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-10.
Abstract P2-06-04: Impact of genomic testing on chemotherapy utilization
Authors: Riley L , Nakijima H , Balinger K , Anderson D 
Published: August 2014

Abstract
Genomic testing for breast cancer has become a common practice. The two main tests at our institution are Oncotype DX® and MammaPrint®. Each test has unique features and criteria. We sought to compare the practice pattern between these tests and compare them to patients who did not undergo any genomic testing.
Methods: This is a retrospective review of all breast cancer patients between May 2008 and August 2011. Data was primarily thorough our tumor registry database. In some cases individual charts were also reviewed. Results: We analyzed 1093 breast cancers in 1064 patients. The average age was 62. The stage at diagnosis was 19% DCIS, 41% stage I, 24% stage II, 11% stage III and 5% stage IV. Of the 1093 cancers, 70 (6%) had an Oncotype test performed, 180 (16%) had a MammaPrint test done, 4 (0.4%) had both test, and 839 (77%) had no genomic test performed. Patients with an Oncotype test were more likely to be stage I than those with a MammaPrint (66% vs 48%). Additionally, patients who had a MammaPrint test more often received chemotherapy when compared to either the Oncotype test or no genomic testing.

With a mean follow-up of 1.5 years, there have been 28 recurrences (0 in the Oncotype group, 5 in the MammaPrint group, and 23 in the no genomic testing group). All five of the MammaPrint recurrences were high risk and received adjuvant chemotherapy. Of the 23 recurrences in the no genomic testing group, eight patients were node negative and could have been considered appropriate for genomic testing, 6 of these eight did not have adjuvant chemotherapy.
Conclusions: There are distinct practice pattern differences between Oncotype DX® and MammaPrint® utilization. MammaPrint testing was ordered more often in higher staged patients and was associated with an increased use of chemotherapy. This may relate to MammaPrint's previous requirement for fresh tissue that typically occurs before the final nodal status is known. This difference should diminish with the recent availability of MammaPrint on FFPE tissue. All patients who underwent genomic testing and developed a recurrence had been treated with adjuvant chemotherapy. In contrast, patients who did not have a genomic test and experienced a recurrence may have benefited from genomic testing.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-06-04.
Abstract P2-10-23: Lymphovascular Invasion (LVI) and Overall Survival in Node-negative and Node-positive Breast Cancer Patients: A Meta-analysis.
Authors: Sahebjam S , Diaz-Padilla I , Ocana A , Seruga B , Amir E 
Published: August 2014

Abstract
Introduction: LVI is an important prognostic factor in patients with lymph node-negative invasive breast cancer. The prognostic value of LVI in lymph node-positive disease or in other subgroups remains unclear. Here we present a meta-analysis of studies assessing the impact of LVI on overall survival (OS) in different subgroups of breast cancer patients.
Methods: A published data meta-analysis was conducted. Studies reporting hazard ratios (HR) for the association of LVI with OS in a multivariable model were included. Those not reporting HR or utilizing only univariable analyses were excluded. HR and 95% confidence intervals (CI) were extracted or computed and pooled using the DerSimonian and Laird random effects model. Subgroup analyses were conducted for the differential effect of lymph node involvement, estrogen receptor (ER) status, extent of LVI and decade in which the study was conducted (pre 1990, 1990–1999 and 2000 onwards).
Results: Twenty studies comprising 40,417 patients were included in the analysis. There was marked heterogeneity in the effect size between studies (Cochran Q p &lt; 0.001, I2=62%). When all studies were pooled, LVI was significantly associated with worse OS (HR:1.70 95% CI 1.49–1.95, p &lt; 0.001). Among studies selecting patients by lymph node status, the association between LVI and OS was similar for lymph node positive and negative patients (HR:2.03 and 2.41 respectively, subgroup difference p = 0.56). There were no significant differences based on ER-status (subgroup difference p = 0.75) or decade of study (subgroup difference p = 0.21). Pooled assessment of the effect of extent of LVI was not possible as this parameter was not consistently reported.
Conclusion: LVI is associated with similarly detrimental OS regardless of lymph-node or ER status. Improvements in adjuvant therapies over the past 20 years do not appear to have diluted the impact of LVI on OS. The marked heterogeneity in the effect size may result from differences in the extent of LVI.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-23.
Abstract P2-11-12: Proactive approach to risk reduction and early detection of breast cancer related lymphedema
Authors: Fu MR , Guth A , Kleinman R , Cartwright F , Haber J , Axelrod D 
Published: August 2014

Abstract
Advances in surgery and post-operative treatment continue to reduce the incidence of late effects of cancer treatment such as lymphedema. Yet, many breast cancer survivors still face considerable post-operative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate a nursing educational and behavioral program “The Optimal YOU” to enhance lymphedema risk reduction, focusing on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal Body Mass Index (BMI) as well as preoperative and subsequent follow-up assessment of limb volume changes and symptoms.
A quasi-experimental design with repeated-measures was used. The Study outcomes included lymph volume changes by infra-red perometer, lymphedema-related symptoms, and BMI by Bioimpedance at pre-operative baseline, post-operative, 6-month, and 12-month follow-up. A total of 147 patients were recruited and received the program, 141 patients completed the study (4% attrition rate).
Majority (over 90%) of patients maintained preoperative limb volume and improved their symptom experience at 12-month follow-up. During the study period, only 7 patients (5%) had measurable lymphedema. At 12-month follow-up, among the 7 patients who developed measurable lymphedema, 2 patients' limb volume returned to pre-operative level without compression therapy only by maintaining exercises of The Optimal YOU to promote daily lymph flow. About 80% of patients maintained or improved their preoperative BMI.
Implementation of this nursing educational and behavioral intervention is effective to enhance lymphedema risk reduction and early detection. Findings of the study provided evidence to support the emerging policy change in lymphedema care, shifting treatment-focus care to proactive risk reduction.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-12.
Abstract P2-13-08: Comparison of Compliance to Anti Estrogen Therapy in Patients with Early Breast Cancer followed at Tertiary Centers versus Through Family Physicians and Primary Surgeons: A Practice Review
Authors: Alkhayyat SS , Younus J , Mirza FN , Stitt L 
Published: August 2014

Abstract
Background: Poor adherence or non-compliance to pharmacologic therapies in chronic diseases is a major clinical problem. Adherence to adjuvant anti-estrogen therapies among patients with early breast cancer (EBC) is variable as reported in different clinical trials. Cancer centres, at present, frequently refer patients with EBC on adjuvant anti-estrogen therapy back to their surgeons and family doctors for follow up. In order to find any difference in compliance for such patients, we reviewed patients followed by their primary surgeons and family doctors (peripheral cohort) for adherence and compared them to patients regularly followed in the cancer center (central cohort).
Patients and Methods: Women with EBC receiving anti-estrogen therapy were identified from breast cancer database at London Regional Cancer Program LRCP). A standardized telephone interview was conducted with patients. We assumed that adherence in the central cohort will be 20% higher than the peripheral cohort. Patient are considered adherent if they took more than 80%, Non-adherent if they took less than 50% and semi-adherent if they took 50–80% of the prescribed medication.
Results: We recruited a total of 160 patients (80 patients in each cohort). Seventy seven (96.3%) patients in central cohort were compliant and 76 (95%) patients were compliant in the peripheral cohort. The HR was 0.7 (p &gt;.999)
Conclusion: From our retrospective review, we did not observe any significant difference in the adherence to adjuvant anti-estrogen therapy in patients with EBC. The present process of discharging such patients to surgeons and family physicians for follow up does not seem to affect their compliance.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-08.
Abstract P2-14-02: Preclinical Evaluation of Enzalutamide in Breast Cancer Models
Authors: Cochrane DR , Bernales S , Jacobsen BM , D'Amato NC , Guerrero J , Gómez F , Protter AA , Elias AD , Richer JK 
Published: August 2014

Abstract
Background: The vast majority of breast cancers express the androgen receptor (AR) with ∼80% of ER+ and 30% to50% of ER− tumors being positive for AR by immunohistochemistry (IHC). Approximately 30% of breast cancer patients with estrogen receptor positive (ER+) tumors do not respond to tamoxifen or aromatase inhibitors and AR signaling has been implicated as a possible mechanism of this insensitivity. AR overexpression has also been associated with resistance to either tamoxifen or aromatase inhibitors in cell line models.
Hypothesis: ER+ breast cancers can switch from estrogen to androgen-dependent growth as they become resistant to traditional endocrine therapies and AR can serve as a therapeutic target in AR+ breast cancers, irrespective of ER status.
Methods: The proliferative effect of dihydrotestosterone (DHT) and estradiol (E2) in the presence enzalutamide (formerly MDV3100) was examined in vitro and in xenograft studies using models of both ER+ and ER− breast cancer that express AR. Furthermore, AR and ER were examined by IHC in clinical specimens from breast cancer patients treated with neoadjuvant exemestane and adjuvant tamoxifen. Tumor tissue was compared to adjacent normal breast epithelium.
Results: In ER+ models, bicalutamide and enzalutamide both inhibited DHT-mediated proliferation, while enzalutamide uniquely inhibited E2-mediated proliferation. In vivo, enzalutamide significantly reduced estrogen- and androgen-mediated growth of MCF7 (ER+/AR+) xenograft tumors. Remarkably, enzalutamide demonstrated an anti-proliferative effect comparable to tamoxifen. in vitro, enzalutamide inhibits E2-stimulated tumor cell proliferation and E2 bound ER activation of genes such as PR and SDF-1, despite no observed binding of enzalutamide to ER alpha or beta. In ER−/AR+ MDA-MB-453 xenografts, enzalutamide treatment resulted in decreased nuclear AR localization, increased apoptosis and tumor growth inhibition.
Conclusions: Enzalutamide demonstrated significant anti-tumor activity in preclinical models of breast cancers that express AR, regardless of ER status. When enzalutamide opposes DHT, it functions by excluding AR from the nucleus, thereby reversing the anti-apoptotic effect of AR. In contrast, when opposing E2, it causes a decrease in tumor cell proliferation. Profiling of ER+ xenografts is underway to further elucidate the mechanism by which this occurs.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-02.
Abstract P2-14-06: A phase II trial of low dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to an aromatase inhibitor.
Authors: Howell SJ , Seif MW , Armstrong AC , Cope J , Wilson G , Welch RS , Misra V , Ryder D , Blowers E , Palmieri C , Wardley AM 
Published: August 2014

Abstract
Background High dose estrogen (HDE) is an effective but toxic treatment for postmenopausal women with advanced breast cancer (ABC). In vitro, prolonged periods of estrogen deprivation (ED) sensitises cancers to the inhibitory effects of estrogen. We hypothesised that the profound ED seen with third generation aromatase inhibitor (AI) would sensitise cancers to LDE which would be better tolerated.
Methods Single arm phase II study in postmenopausal women with measurable ER+ ABC and demonstrated clinical benefit (CB) with a third generation AI. Treatment: estradiol valerate 2mg daily. Primary endpoint: CB rate (CBR) was correlated with baseline and dynamic LH/FSH levels and on-treatment estradiol levels. Secondary endpoints included TTF, PFS, toxicity and QoL. If LDE was effective, retreatment with the AI on which the cancer had progressed prior to study entry was offered on progression. If LDE was ineffective HDE was offered.
Results 21/50 patients were recruited before early closure due to slow accrual. 19 were assessable for efficacy and toxicity (1 ineligible; 1 no LDE). CBR was 5/19 (26%; 95%CI 9.1%,51.2%). Median TTF 2.8months (range 0.5–29.8). CBR durations were 11.1, 16.8, 17.3*, 19.8, 29.8 months (*censored). 4 stopped treatment early due to toxicity (G4 hypercalcaemia/ G2 vaginal bleeding (VB) plus G4 hyponatraemia/ G2 mucositis/ G2 headaches) 1 with SD at 3 months and 3 before response assessment. Other common toxicities were all G1/2 and mainly limitted to nausea (8/19), breast pain (7/19) and tumour flare (7/19). VB occurred in 8/11 without prior hysterectomy. Baseline LH correlated with CBR by logistic regression (p = 0.01). Of 3 retreated with the same AI post LDE; 1 had PR, 1 SD ≥6months and 1 PD. One woman received HDE after failure of LDE and achieved a PR.
Conclusion LDE is an effective and largely well tolerated treatment in women with acquired resistance to AI. VB is common without prior hysterectomy. Rechallenge with the same AI post LDE seems effective and may offer an extra line of endocrine therapy. This should be tested in future trials.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-06.
Abstract P3-02-08: Is repetition of the contralateral mammogram of patients referred from breast cancer screening for unilateral findings necessary?
Authors: Castro C , Schipper R-J , van Roozendaal L , van Goethem M , Lobbes M , Smidt M 
Published: August 2014

Abstract
Introduction - The Netherlands started a nationwide breast cancer screening program in 1989, including women from the age of 50 until 75. Screening mammograms are performed two yearly in a mobile unit and consist of a bilateral two-view mammogram of the breast (mediolateral oblique and craniocaudal views).
If indicated, patients are referred to a breast clinic for diagnostic analysis. This work-up consist of among others repeating the bilateral two-view mammogram. Since the screening is digitalized, repeating of at least the mammogram of the non suspicious side might be unnecessary.
The aim of this study is to determine the additional value of repeating the contralateral mammogram in patients referred for a suspicious unilateral lesion.
Material and methods – 395 patients were referred from breast screening program to our institution for unilateral findings between October 2009 and August 2011. In all patients a bilateral mammogram was repeated and analyzed by an experienced breast radiologist. In the case of breast cancer a breast magnetic resonance imaging (MRI) was performed for preoperative staging. Anonymised data concerning the date of registration of the screening mammogram, the referred side (left/right or bilateral), age, screening's BI-RADS classification, breast density, biopsy results and breast MRI results were collected.
Results - Of the 395 patients referred for a suspicious unilateral finding, a malignancy on the referred side was observed in 144 patients (36.5%). In five patients bilateral breast cancer was detected. In one patient no malignancy was detected on the referred side, though on the contralateral side. Three of these six contralateral malignancies were directly mammographically detected. All six malignancies were detected with preoperative breast MRI.
Conclusion - Repetition of the two-view mammogram of the contralateral side in patients referred with a unilateral suspicious finding seems unnecessary, since all contralateral malignancies were depicted on the preoperative staging breast MRI recommended according to the EUSOBI-guidelines. Omission of the contralateral mammogram could lead to reduction of associated health care costs, radiation exposure, and patient discomfort caused by the exam.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-08.