bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-11-19: Healthcare Resource Utilization among Breast Cancer Patients with Bone Metastases and Skeletal-Related Events: A Population-Based Cohort Study in Denmark (1997 - 2009).
Authors: Yong M , Christiansen CF , Gammelager H , Sværke C , Chia V , Atchison C , Fryzek J 
Published: June 2012

Abstract
Background
The healthcare resource utilization (HRU) of breast cancer patients who develop bone metastases and skeletal-related events (SREs) has not been well-characterized. Our objective was to describe the HRU associated with SREs in a large population-based cohort of Danish breast cancer patients with bone metastases and one or more SRE.
Methods: We identified women diagnosed with incident breast cancer from January 1, 1997 through December 31, 2006 using the Danish Cancer Registry. We followed this cohort of patients for development of subsequent bone metastases and SREs identified through the Danish National Registry of Patients through December 31, 2009. SREs were defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Among patients with only one SRE, the HRU period, composed of all HRU occurring within a 90-day period after the SRE and within a two-week diagnostic period prior to the SRE, was assessed. For patients with multiple SREs (each one separated by less than 90 days), the HRU period, composed of all HRU occurring within a two-week diagnostic period prior to the first SRE up until 90 days after the last SRE, was described. Patients may have had multiple HRU periods if SREs were separated by more than 90 days. The HRU summarized included number of inpatient hospitalizations, length of hospitalization stay, outpatient physician visits, emergency room visits, and procedures.
Results: We identified 1,148 patients with bone metastases and SREs among 38,485 breast cancer patients. The mean age at breast cancer diagnosis for those who developed bone metastases and SREs was 59 years (SD, 13 years) and the majority (72%) of patients had multiple SREs during the first HRU period. Approximately 20% to 30% of patients with single and multiple SREs, respectively, died within the first HRU period. Overall, length of hospitalization was longest for patients with spinal cord compression followed by patients with pathologic fracture. In general, patients with multiple SREs had higher HRU compared to those with a single SRE in the first HRU period, particularly in length of hospitalization stay.
Conclusion: SREs secondary to bone metastases are serious events. In Denmark, high HRU was observed in all patients with SREs, but especially in those with multiple SREs, where increased lengths of hospitalization were observed.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-19.
P4-12-11: Myelodysplastic Syndrome Post Primary Breast Cancer Treatment: Cases from a Community Cancer Center: 1990–2010.
Authors: Kaplan HG , Malmgren JA , Atwood MK 
Published: June 2012

Abstract
Background: Myelodysplastic syndrome (MDS) has not been well documented or described post breast cancer (BC) treatment. Methods: A cohort of all breast cancer patients from 1989 to 2010 at our institution were followed for incidence of blood disorders of any type by our registry system and by linkage to the Surveillance, Epidemiology and End Results (SEER) registry for our area. All cases of post breast cancer leukemia were reviewed for incidence of MDS from a cohort of 9846 cases diagnosed between 1990 and 2010. Coding of cases was assigned by the SEER registry using ICD-0 codes for type of leukemia from pathology reports. 20 cases of MDS were identified and confirmed using SEER coding for MDS and death certificate review if applicable. Variables of interest included age, race, treatment received, recurrence and treatment for recurrence, time interval from breast cancer diagnosis to leukemia diagnosis and time from leukemia diagnosis to follow up or death. Cytogenetic studies were available on 5 of the 20 patients.
Results: Mean age of the patients was 56 years, range 33–79, with 65% &lt; age 65. 90% of the patients were white and 10% Asian. TNM BC stage distribution was stage 0=2, stage I=8, stage II=8, and stage III=2. MDS was diagnosed at a median time post BC diagnosis of 65 months, range 8–205 months including 5 patients treated for recurrence and median 47 months, range 8–205 months excluding patients with recurrence. Nine patients had initial chemotherapy treatment, two without initial adjuvant therapy received chemotherapy for recurrence, and 9 received radiation only. Eight of eleven patients who received chemotherapy were treated with doxorubicin. All eleven received cyclophosphamide. Five of the 20 cases had MDS, not otherwise specified (NOS) (9989), 4 cases had MDSaAML, 3 MDS treatment related (9987), 3 refractory anemia (RA) (9980), 3 refractory anemia with excess blasts (RAEB) (9983), 1 RA with sideroblasts (9982), and 1 MDS with 5q deletion. Three of the five patients with cytogenetics available had chromosome 7 abnormalities and one had 11q21,23. Eleven of the 20 patients (55%) died of MDS or MDSaAML with a mean survival of 17 months, range 0.5-72 months. Six patients were alive at follow up with mean survival 56 months, range 43–89. Two of the surviving patients had stem cell transplants. The remaining three patients died of other causes with mean survival 66 months, range 7–109 months. Mean survival of all patients was 36.26 months, range .53-109 months with a significant difference in survival time between the patients that died of MDS, those alive at follow up and those that died of other causes (F statistic 6.56, p=.008).
Discussion: MDS is a significant complication of breast cancer treatment with radiation and/or chemotherapy with a high rate of associated mortality.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-11.
P4-12-14: Pilot Study Utilizing Fluorine-18 Fluorodeoxyglucose (F-18 FDG) Positron Emission Tomography–Computed Tomography Scan (PET-CT Scan) To Investigate Brain Metabolic Changes during Treatment in Women with Breast Cancer.
Authors: Virani S , Lagos R , Hobbs G , Marano G , Nagaiah G , Abraham J 
Published: June 2012

Abstract
BACKGROUND: Approximately 25% of the patients undergoing chemotherapy develop cognitive changes. Similarly, significant neurocognitive changes in verbal memory and executive functioning have been reported in patients undergoing endocrine therapy. Though extensively studied, specific changes in the brain associated with cognitive dysfunction are still not clear. We performed an IRB-approved retrospective pilot study utilizing brain images from standard PET-CT scans in patients being treated for breast cancer. Comparison was made between patients initial and follow-up scans to look for metabolic changes.
MATERIALS AND METHODS: Thirty nine patients with a diagnosis of breast cancer were identified from radiology database of West Virginia University Hospitals, who underwent at least two PET-CT scans during their treatment for breast cancer from 2004–2009. Patients with brain metastasis were excluded. NeuroMIM® software analysis program was used to compare a comprehensive database of physiologic brain anatomy and metabolism with F-18 FDG perfusion brain images from the patients. Comparison was made in sixty-three defined brain regions. For each patient, two scans at approximately twelve month intervals were analyzed. The data sets from initial scans were compared with the follow up.
RESULTS: A total of 37 patients received cytotoxic chemotherapy, 2 patients received only endocrine therapy. Data analysis using the signed-rank test shows that the collective Z-score values change between the initial and follow up scans. When data analysis is applied to the individual brain regions, the Lingual Gyrus (p=0.012) and the Angular Gyrus (p=0.056)show statistically significant and near significant decreases in brain metabolism respectively. These regions are attributed with language, mathematics and cognition. Several additional regions such as the fusiform gyrus and the primary visual cortex show p-values between 0.05 and 0.10, which indicate “trending”. These regions may demonstrate statistically significant decrease in metabolism if the sample size is increased.
DISCUSSION: The Lingual and the Angular Gyrus show a statistically significant and near significant decrease in glucose metabolism respectively, in patients receiving treatment for breast cancer. Limitations of this study include lack of baseline brain imaging and its clinical correlation with cognitive function. Based upon these preliminary findings prospective studies are being planned.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-14.
P4-14-01: Weight-Adjusted Change of Unilateral Arm Volumes for Quantification of Lymphedema after Bilateral Breast Surgery.
Authors: Miller CL , Specht MC , Ancukiewicz M , Skolny MN , O ‘Toole J , Taghian AG 
Published: June 2012

Abstract
Background: Accurate quantification of breast cancer-related lymphedema (BCRL) is important for early detection and successful management. Arm volume changes after unilateral breast surgery can be calculated through relative volume change (RVC) of the affected arm using the contralateral arm as a control (Ancukiewicz et al Int J Radiat Oncol Biol Phys 79(5):1436–43 2011). However there currently exists no accurate method for quantifying arm volume changes in patients after bilateral breast surgery. As the number of women undergoing bilateral mastectomies continues to increase, it is critical to develop a method to quantify arm volume changes in this population for detection of lymphedema. Our aim was to develop a weight-adjusted formula for unilateral arm volume changes independent of the contralateral arm for application in the setting of bilateral breast surgery.
Materials and Methods: We analyzed longitudinal measurements of arm volumes in 141 unilaterally affected patients undergoing screening for BCRL with a perometer at our institution (71 with left affected and 70 with right affected arms). Each patient had a baseline measurement prior to surgery and at least one post-surgical measurement. Median time of follow-up was 27.5 months and median standard deviation of longitudinal weight changes within patients during follow-up was 3%.
Results: Unilateral arm volume changes of the unaffected arm were correlated with weight changes at the last follow-up point (Kendall's tau=.58 and P&lt;.0001). Estimates of slope and intercept for median regression line between percent weight change and percent arm volume change evaluated for the unaffected arm at last follow-up are, respectively, .90 [95% CI] and .009 [95% CI]. Thus, percent weight change and percent arm volume change in the unaffected arm have an approximately linear relationship, such that the weight adjusted change (WAC) of affected unilateral arm volumes can be calculated according to the formula WAC=(A2*W1)/(W2*A1) — 1, where A1 is pre-surgical baseline arm volume on the affected side and A2 is post-surgical arm volume on the affected side, and W1, W2 are the patient's weights at these time points. Weight-adjusted change showed a strong correlation with RVC (RVC=(A2*U1)/(U2*A1) — 1), where A1, A2 are arm volumes on the side of the affected breast, and U1, U2 are volumes on the contralateral side at these time points (Kendall's tau=.41, P&lt;.0001).
Discussion: Unilateral arm volume changes can be quantified by adjusting for weight changes. We propose the weight-adjusted change (WAC) formula to calculate unilateral arm volume changes for detection and monitoring of BCRL in patients who undergo bilateral breast surgery. The validity of such a formula needs to be assessed in conjunction with clinically reported lymphedema.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-01.
P4-19-05: A Population-Based Study of Guideline-Based BRCA Screening in Male Breast Carcinoma.
Authors: Bradley KL , Nuk JE , Chia SK , Villa D , Speers CH , Woods R , Young S , Tyldesley S 
Published: June 2012

Abstract
Purpose: The British Columbia Cancer Agency (BCCA) Hereditary Cancer Program (HCP) is a publicly funded, centralized program that provides BRCA testing to patients with male breast cancer (MBC) who meet specified referral criteria (aimed at detecting a mutation in &gt; 10% of those tested). Criteria include: MBC with Ashkenazi heritage, MBC with one other family member with breast or ovarian cancer, MBC diagnosed at &lt; 35 years, Bilateral MBC with first diagnosed at &lt; 50 year. In this context, the purpose was to study referral patterns for hereditary counselling and outcomes of BRCA testing within a population-based study of male breast carcinoma.
Patients and Methods
Records of consecutive cases of invasive MBC diagnosed from 2000 to 2010 were reviewed. We documented any recorded personal and family history of cancer. For those meeting the HCP referral criteria we recorded whether a referral was made and the outcome of any genetic testing.
Results: Of 158 cases of MBC, 23 (14.6%) patients (21 met referral criteria; 2 did not) were seen for genetic counselling, of whom 21 were offered BRCA1/2 testing, and 19 accepted testing. Of 19 patients with BRCA1/2 genetic test results, 3 (16%) had a pathogenic mutation identified; one in the BRCA1 gene (c.1387_1390delinsGAAAG) and two in the BRCA2 gene (***c.755_758delACAG; c.1813dupA). In a further 4 cases (21%) an unclassified variant in BRCA1 was identified. In the remaining 12 cases (63%), testing was uninformative.
Conclusions: The BRCA1/2 mutation detection rate of 16% is in line with the expected rate of &gt;10% using established selection criteria. Expanding the criteria at this time to include all male breast cancers would be expected to decrease the detection rate below 10% with the potential to negatively impact on the publicly-funded and finite resources of the Hereditary Cancer Program and Cancer Genetics Laboratory.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-05.
P5-01-08: Immunocytochemistry Staining of Estrogen Receptor in Circulating Tumor Cells as Compared to Primary Tumor.
Authors: Mayer JA , Pham T , Wong KL , Bischoff FZ 
Published: June 2012

Abstract
Introduction: Estrogen receptor (ER) status in all breast cancer patients is recommended by immunohistochemistry (IHC) and is considered standard practice for selection of treatment options. However, the analytical sensitivity of IHC in detecting low levels of ER is often poor and likely due to methodological variation. Because biopsy is not often feasible in all patients presenting with recurrent and/or metastatic breast disease, circulating tumor cells (CTCs) offer an attractive alternative source of tumor tissue for determining ER status and can be monitored more readily to enable a more effective course of treatment.
Experimental Design: Twenty ml of peripheral blood was collected prospectively from # patients diagnosed with late stage metastatic/recurrent breast cancer. CTCs were isolated using the microfluidic OncoCEE™ platform. A cocktail of antibodies was utilized for CTC capture and detection with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER protein expression was assessed by immunocytochemistry (ICC) on the cells captured within the microchannels and compared to IHC performed on the primary tumor.
Results: CK+/CD45- cells were detected in 23 of 27 cases (85%). Among the 23 cases in which CK+ cells were detected, only moderate concordance (16/23; 70%) in ER status between primary tumor and CTCs was observed.
Conclusions: There is significant heterogeneity between ER protein expression in CTCs and primary tumor. ER ICC on CTCs from peripheral blood using the OncoCEE™ platform is shown to be feasible but the comparison likely compromised by lack of tumor staging at the time of blood draw. Given that IHC was in some cases performed 5–10 years pre-blood draw and that tumors have the potential to convert, ER status only moderately correlates to the IHC status in the primary tumor. The significance of heterogeneity at the ER protein level in CTCs ascertaining to the prognosis and predictive response to anti-estrogen therapy needs further evaluation in larger prospective clinical trials.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-08.
P5-06-05: Switching Addictions between HER2 and FGFR2 in HER2−Positive Breast Tumor Cells: FGFR2 as a Potential Target for Salvage after Lapatinib Failure.
Authors: Tsurutani J , Azuma K , Sakai K , Aaro T , Nishio K , Nakagawa K 
Published: June 2012

Abstract
Agents that target HER2 have improved the prognosis of patients with HER2−amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC50 of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2−targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2−positive breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-06-05.
P5-06-08: Mesenchymal Stem Cells and Carcinoma-Associated Fibroblasts Sensitize Breast Cancer Cells in 3D Cultures to Kinase Inhibitors.
Authors: Dittmer J , Dittmer A , Oerlecke I , Leyh B , Martens JWM , Thomssen C 
Published: June 2012

Abstract
Background: Bone-derived mesenchymal stem cells (MSCs) are attracted to cancer lesions and may differentiate to CAFs. By interacting with cancer cells, MSCs and CAFs may promote cancer progression and modulate drug sensitivity.
Material and Methods: To analyze ability of MSCs and CAFs to modulate drug response, we generated spheroids of MCF-7 or MDA-MB-231 breast cancer cells in the absence or presence of human (h) MSCs or hCAFs and tested the susceptibility of the breast cancer cells to three different kinase inhibitors (TKI258, RAD001 and RAF265) as used in cancer therapy.
Results: While MSCs and CAFs did not affect the response of either breast cancer cell line to PDGFR/FGFR/VEGFR inhibitor TKI258, they sensitized breast cancer cells to the mTOR inhibitor RAD001. In MCF-7 cells, this was accompanied by increased apoptosis. hMSCs and to a lesser extent hCAFs also enhanced the cytotoxic effect of RAF inhibitor RAF265 on MDA-MB-231 cells. Searching for the mechanism that underlies the effect of stromal cells on RAF265 response we found that stromal cells inhibited RAF265-induced increase in ERK1/2 phosphorylation, supported RAF265-dependent downregulation of PKCalpha (protein kinase Calpha) and prevented RAF265-induced conversion of LC3B, a marker of autophagy. To mimic the changes in ERK1/2 phosphorylation and PKCalpha expression in response to the stromal cells, we treated cells with MEK1 inhibitor U0126 or PKCalpha inhibitor Gö6976, respectively. U0126, but not Gö6976, was as effective as hMSCs in sensitizing MDA-MB-231 cells to RAF265.
Discussion: Our data suggest that hMSCs and hCAFs increased the cytotoxic effect of RAF265 on MDA-MB-231 cells by downregulating ERK1/2 phosphorylation. In summary, this study shows that hMSCs are able to render breast cancer cells more susceptible to kinase inhibitors and that, to the most part, hCAFs to which hMSCs can differentiate are able to mimic the drug-sensitizing effects of hMSCs.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-06-08.
P5-07-03: Modulation of Autophagic Activity by Extracellular pH.
Authors: Xu T , Su H , Ganapathy S , Yuan Z-M 
Published: June 2012

Abstract
Reprogramming energy metabolism from oxidative phosphorylation to aerobic glycolysis, a common feature of human cancer, results in a relative acidic tumor microenvironment which is further accentuated by hypoxia operating within most tumors. We report that alteration of extracellular pH induces marked and rapid changes of autophagic activity in a variety of cell lines including mammary non-transformed cells and breast cancer cells. Interestingly, acidic and basic conditions induce completely opposite effect on autophagy, with its activity suppressed at lower pH whereas stimulated at higher pH. Gene knockdown experiments indicate that pH induced-autophagy requires Beclin 1, Vps34 and ATG5, key components of the autophagy pathway. Of note, acidic condition not only inhibits the basal but also blocks starvation-induced autophagy activity. Significantly, examination of different areas of tumor mass reveals a lower autophagic activity within the inner region than the outer region. These findings have important implications on the connections between autophagy and cancer as well as a wide range of other physiological and pathological processes.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-03.
P5-08-03: How Reader's Training, Software, and Image Formats Impact Percent Dense Area Measures.
Authors: Fan B , Duewer F , Wu FF , Kerlikowske K , Vachon C , Shepherd JA 
Published: June 2012

Abstract
BACKGROUND: Mammographic percent dense area, the percent ratio of dense to total breast area in a mammogram, is one of the strongest measures of a woman's risk of breast cancer. However, systematic differences have been observed between readers and mammography technologies (film and digital) that could cause clinically inconsistent associations with risk. The purpose of this study was to evaluate inter- and intra-reproducibility of percent dense area between readers and between film and digital technologies.
METHODS: One hundred digitized film mammograms were randomly selected with 25 films in each of quartile of percent density and read by two readers at two different sites (Mayo Clinic and UCSF). The readers had extensive experience and were also jointly trained at university of Toronto using Cumulus software. After training, all films were read twice with at least one year between duplicate readings. The Mayo clinic reading used Cumulus while UCSF used custom semiautomatic software to estimate total and dense tissue area. In addition, digitized films and unprocessed full field digital mammograms of the same women were assessed by one reader. The time between the film and digital acquisitions ranged from nine to twenty-four months. Interclass correlation coefficient (ICC) was calculated for each comparison.
RESULTS: The intra- and inter-observer ICCs, consistency for film images, were 0.96 (UCSF) and 0.97 (Mayo), and 0.96 (UCSF vs. Mayo). We found ICC between film and digital mammograms for percent dense area was 0.88. The digital mammogram had 9% significantly higher total breast area and 5% significantly lower percent density area compared to film.
CONCLUSIONS: Similarly trained readers had a high reproducibility regardless of the software used. Our results suggest centralized reader training should enable pooling of film breast density results from different clinics. However, pooling film and digital results would need careful calibration due to lower measured percent dense areas than on film.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-08-03.