bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2-14-05: Racial Differences in the Use of Adjuvant Chemotherapy for Breast Cancer in a Large Urban Integrated Health System.
Authors: Simon MS , Lamerato L , Krajenta R , Booza J , Ruterbusch J , Kunz S , Schwartz K 
Published: June 2012

Abstract
Background: Despite improvements in breast cancer treatment, there continues to be a gap in survival between African American (AA) and White women with breast cancer, which may be due at least in part to racial differences in the patterns of care. In order to better understand breast cancer survival disparities, we evaluated racial differences in the receipt of adjuvant chemotherapy among women treated at a large integrated health care system in Southeastern Michigan. Materials and Methods: The study population included 2,234 women (33 % AA) with stage I through III breast cancer treated at the Henry Ford Health System (HFHS) from 1996 through 2005. Linked datasets from the HFHS, the Metropolitan Detroit Cancer Surveillance System (MDCSS) and the U.S. Census Bureau were used to obtain sociodemographic and clinical information. Co-morbidity was assessed by the Charlson co-morbidity index (CCI), and economic deprivation was categorized using a neighborhood deprivation index (DI). Results: AA women were significantly more likely than Whites to have larger tumors (40% vs. 31% &gt; 2 cm), as well as more aggressive tumors (29% vs 19% estrogen and progesterone negative). AA women were also significantly more likely than Whites to have other co-morbid conditions (15 % vs. 8% with a CCI of 2+) and to reside in a more economically deprived area (45% vs. 5% reside in the most deprived area). While AA women were more likely to receive adjuvant chemotherapy (47% vs. 43%, p=0.0278), they were also more likely to have a delay in initiation of treatment (57% vs 45% delayed beyond 60 days from diagnosis, p=0.0004). After multivariable adjustment for age, DI, CCI, insurance and surgery, there were no racial differences in treatment delay (Odds Ratio 1.20, 95% confidence interval, 0.82−1.77). Discussion: In a large urban integrated health care system, racial differences in the delay in receipt of adjuvant chemotherapy for breast cancer can be explained by clinical and socioeconomic characteristics.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-05.
P2-15-06: Breast Cancer Liver Metastases – Possibilities and Limits of Surgical Treatment.
Authors: Narsanska A , Treskova I , Treska V , Skalicky T , Sutnar A 
Published: June 2012

Abstract
Background
Breast cancer liver metastases (BCLM) are often considered as a sign of a systemic disease with little hope of therapeutic success. The aim of study was to assess the possibilities and determine the limits of the surgical treatment of BCLM.
Method: 646 patients were operated for malignant and benign lesions of the liver between 1999 and 2010. Liver surgery for BCLM was performed in 21 women of the average age of 48.5 years (33-71). The average time from the primary surgery for breast cancer till BCLM diagnosis was 4.7 years (2 months - 9 years). BCLM were solitary in 17 and in four cases multiple. Patient selection for liver surgery was based on sufficient future remnant liver volume, the absence of systemic non-resectable tumor dissemination and response to chemotherapy. The authors performed six right-sided hepatectomy, four segmentectomies, three left lobectomies, one metastasectomy, six radiofrequency ablations (RFA), one combined procedure -liver resection and RFA. Histological examination revealed ductal carcinoma in fourteen and lobular carcinoma in seven cases. All patients were treated with the curative adjuvant chemotherapy after surgery. The data were statistically evaluated by statistical software Statistica 9.0.
Results: 30 - days mortality rate was 0%. One patient had a complicated hepatectomy with iatrogenic bile duct injury. According to statistical analysis the probability of patients survival twelve, resp. thirty months after surgery was 100, resp. 66.7% and the probability of the tumor relapse anywhere in the body was at the same time intervals 0, resp. 71. 5%.
Conclusion: Liver surgery combined with the adjuvant chemotherapy are a therapeutic methods of choice for highly selected patients with metastases limited to the liver and objective response to neoadjuvant chemotherapy.
The study was supported by the research projects IGA MZ NS 9727 and IGA MZ NS 102 40.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-06.
P2-16-12: Skin Reducing Nipple Sparing Mastectomy – A Treatment Option for Patients with Significant Ptosis or Macromastia.
Authors: Ott Young A , Alizadeh K , Hodyl C , Pronovost M , Davenport T 
Published: June 2012

Abstract
Background: With new data showing the oncologic safety of nipple sparing mastectomy with immediate reconstruction - nipple sparing mastectomies are now offered to an increasing number of mastectomy patients. Unfortunately cosmetically acceptable reconstruction of nipple sparing mastectomies is technically limited to women with perfect breast anatomy - where the skin envelope shows no or little redundancy and where the nipple areolar complex is located in the perfect location on the breast mount. Especially in countries with a high incidence of obesity and associated macromastia only a small percentage of women fall into this category. A high percentahge of patients who would otherwise be good candidates for nipple sparing procedures are excluded based on their unfavorable breast anatomy. We describe a surgical technique that reduces the redundant mastectomy skin envelope in a breast reduction pattern and places the native nipple areolar complex as a free skin graft into proper anatomical position. This technique in conjunction with implant or autologous reconstruction combines the benefits of shorter better vascularized skin flaps with the cosmetic and emotional benefits of preserving the nipple areolar complex even in the anatomically difficult cases.
Methods: To investigate the safety and efficiency of this method we reviewed medical records of 40 patients who underwent 60 nipple preserving skin reducing mastectomies over the last 4 years. All procedures were performed by the senior author and follow up ranged from 4 weeks to 50 months.
The charts were analyzed for the occurrence of complications such as infection, seroma, hematoma, mastectomy flap necrosis, nipple-areolar loss and loco regional recurrence.
All patients were asked to rate their reconstruction on a scale of poor- good - excellent.
Results: In 60 reconstructed breasts we encountered one case of seroma, four cases of limited mastectomy flap necrosis treated with local wound care and one case of partial areolar necrosis treated with local excision. No loco regional recurrences, hematomas or infections were encountered. Out of the group of 40 patients, 31 patients rated their result as excellent, 8 as good, and one as poor.
Conclusion: Our results compare favorably with data published in the literature. Patient satisfaction rates are high and complication rates are low in a patient population that historically has been a challenge for the breast surgeon, as well as, the plastic surgeon. The use of a skin reducing mastectomy in conjunction with a free nipple graft enables the breast surgeon to offer nipple sparing procedures for all patients who are good oncological candidates regardless of their breast anatomy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-12.
P2-17-02: Increased Progression Free and Overall Survival in Breast Cancer Patients with Menopausal Symptoms or Arthralgia/Myalgia during Adjuvant Treatment with Exemestane or Tamoxifen – Results of the German TEAM Trial.
Authors: Hadji P , Kieback DG , Hasenburg A , Tams J , Ziller M 
Published: June 2012

Abstract
Background
Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response. We assessed if there was any correlation between treatment-emergent adverse events during exemestane or tamoxifen treatment and clinical response.
Methods: A retrospective analysis of the German cohort of the TEAM trial was performed to assess progression-free survival and overall survival in patients with and without menopausal symptoms or arthralgia/myalgia during adjuvant treatment with exemestane or tamoxifen.
Results: A total of 1502 patients were included in this analysis; 739 patients received tamoxifen and 763 received exemestane. Patients reporting menopausal symptoms and patients reporting arthralgia/myalgia during tamoxifen or exemestane treatment had significantly longer overall survival and progression-free survival. The effect on overall survival was irrespective of treatment. Progression-free survival was significantly improved in exemestane-treated patients reporting menopausal symptoms or those reporting arthralgia/myalgia versus those not reporting these adverse events. There was no significant difference in progression-free survival between tamoxifen-treated patients reporting these symptoms versus those who did not. A combined analysis of patients reporting either menopausal symptoms or arthralgia/myalgia showed that overall survival and progressionfree survival was significantly improved in patients reporting one of these symptoms versus those not reporting either symptom. In this analysis, the effect on overall survival and progression-free survival was irrespective of treatment.
Conclusions: Our results suggest that the occurrence of menopausal symptoms or arthralgia/myalgia during treatment with tamoxifen or exemestane is associated with significantly improved overall survival.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-17-02.
P2-17-03: Incomplete Uptake and Diminished Adherence to Endocrine Therapy in Women with Hormone Receptor Positive Breast Cancer 4 Years from Diagnosis: An Australian Cohort Study.
Authors: Bell RJ , Fradkin P , Schwarz M , Davis SR 
Published: June 2012

Abstract
Background: Tamoxifen(T) and the aromatase inhibitors (AIs) are associated with side effects which impair adherence to therapy. Our aim was to investigate the uptake of, and adherence to, endocrine therapy (ET) in a cohort of women with invasive breast cancer (BC) nearly 4 years post-diagnosis.
Materials and Methods: The BUPA Health Foundation Health and Well being After Breast Cancer study is a prospective questionnaire-based cohort study of 1684 women with their first episode of invasive BC recruited between 2004 and 2006 through the Victorian Cancer Registry (VCR), Australia. An enrolment questionnaire (EQ) was completed within 12 months of diagnosis, with questionnaires every 12 months thereafter (FQ1-FQ3). Tumor pathology was provided by the VCR. FQ3 was completed on average 3.8 years from diagnosis. Active disease included a new primary BC, local recurrence or metastatic disease.
Results: Of 1684 recruits, 1370 were HR+. At diagnosis, average age was 58 years and 50% were stage 1. The table shows the number of HR+ women retained in the analysis at each questionnaire, the average time of each questionnaire from diagnosis and the proportions of women at each questionnaire on any ET on T, an AI or on no ET.

Switching of ET from T to an AI was predominantly a clinician decision. Cessation of T was patient initiated, mainly for vasomotor symptoms and vaginal bleeding. For the change from an AI to T, or cessation of an AI, the main reason was joint pain.
At FQ3, nearly 4 years from diagnosis, 215 (18%) women were not on any ET. Compared with women on ET at this time, these 215 women were more likely to have been stage 1 (rather than &gt; stage 1) at diagnosis, have active disease by FQ3, be seeing an alternative therapist (all p&lt;0.01) and were less likely to be seeing an oncologist (p&lt;0.001).
The 215 women not on ET nearly 4 years from diagnosis consisted of 117 previous users and 98 never-users. Compared with the 117 previous users, the 98 never-users were more likely to be stage 1 at diagnosis (p&lt;0.01) and be less likely to see an oncologist (p&lt;0.001). Compared with women on ET at FQ3, both previous- and never users were more likely to have active disease and see an alternative therapist (all p&lt;0.01).
Discussion: By nearly 4 years from diagnosis, an increasing proportion of women with HR+ BC are not on ET, despite the evidence for the benefit of therapy for at least 5 years. Differences between ET users and nonusers at this stage are not simply explained by previous users not continuing ET, with or without active disease. There is a small (8.2%) but important subgroup who appear to have never been on ET, which raises serious concerns.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-17-03.
P2-18-01: The Magnitude of Trastuzumab Benefit in HER2−Positive (HER2+) Lobular Breast Carcinoma (BC): Results of a HERA Trial Sub-Group Analysis.
Authors: Metzger O , Procter M , de Azambuja E , Viale G , Leyland-Jones B , Dowsett M , Gelber R , Gresko E , Loi S , Sotiriou C , Piccart M 
Published: June 2012

Abstract
Background: Invasive lobular carcinoma (ILC) represents the second most common BC subtype and is often characterized as hormone receptor positive and HER2−negative. However a small subset of ILC is found to be HER2+. Isolated case reports have demonstrated high responsiveness to trastuzumab in patients with advanced HER2+ ILC. The HERA trial compares 1 or 2 years of trastuzumab treatment with observation and 1 versus 2 years of trastuzumab treatment after standard chemotherapy in women with HER2+ breast cancer. We sought to evaluate the incidence of HER2+ ILC and the magnitude of trastuzumab benefit in HER2+ ILC in the context of the HERA trial. In addition, we sought to describe the pattern of hormone receptor positivity in the subsets of ILC and invasive ductal carcinoma (IDC) Methods: The database used in the analysis had a clinical cut-off date of 9th June 2008 and 4-year median follow-up (Gianni et al., 2011). Patients randomized to the 1-year trastuzumab and observation arms were included in the present analysis. Central assessment of hormone receptor status was considered. Histological BC subtype was assessed locally.
Results: Of the 1703 women randomized to one-year of trastuzumab and 1698 to observation, 5.5% (n=187) and 94.5% (n=3213) were diagnosed as HER2+ ILC and IDC, respectively. Central hormone receptor status was available in 88.3% (n = 2838) of IDC and 86.1% (n=161) of ILC. ER and/or PR positivity was more common in ILC than IDC (63.4% [102/161] vs. 46.3% [1314/2838]; p&lt;0.001). Allred scores for ER are shown in the table below. The DFS hazard ratios comparing one year of trastuzumab versus observation were 0.63 (95% CI 0.34−1.14) for ILC and 0.77 (95% CI 0.67−0.89) for IDC. There was no evidence of an interaction between histological subtype and trastuzumab benefit (interaction [subtype lobular and subtype ductal and not lobular] p=0.49).

Conclusion: HER2+ ILC accounts for 5.5% of patients included in a large population of over 3,000 HER2+ BC. While only a limited number of patients with ILC was enrolled, this analysis suggests an increased ER positivity in ILC compared to IDC. There was no suggestion that patients with HER2+ ILC derived a different magnitude of benefit from adjuvant trastuzumab when compared to the HER2+ IDC cohort. The lack of central pathology review for BC subtype assessment is a caveat of our study. Future research in the field of ILC and particularly in the HER2+ subset should be encouraged.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-01.
P3-01-02: EC 304: A Novel Progesterone Receptor (PR) Antagonist Inhibits Transcription and Induces Cell Cycle Arrest in T47D Breast Cancer Cells.
Authors: Bhaskaran SS , Kesavaram N , Nickisch KJ , VandeBerg JL , Nair HB 
Published: June 2012

Abstract
Progesterone receptor (PR) is a ligand activated transcription factor which plays a crucial role in female reproduction. PR antagonists have been shown to repress estrogen dependent proliferation in the uterus and mammary gland. Even though PR antagonists are potent therapeutic candidates for breast cancer, partial agonism towards glucocorticoid receptor (GR) and androgen receptor (AR) lead to undesirable side effects. Evestra's rational design and development approach in the synthesis of EC304 was aimed at minimizing these side effects as well as to deliver more potent and selective antiprogestins. We used select screen® (Invitrogen) to determine relative binding affinity of EC304 with AR,GR and PR. The binding affinity of EC304 showed strong antagonism towards PR with mild or negligible agonism with AR or GR. PR transactivation was inhibited by EC304 with IC50 of 0.04nM in the presence of progesterone (5nM).
EC304 showed superior cytotoxicity over known antiprogestins ZK230211, ORG33628, CDB2914, CDB4124 and RU486 in T47D cells. IC50 of EC304 was found to be 0.5nM in a 6-day cytotoxicity assay (MTT) in T47D cells stimulated with 1nM estrogen (E2). In a 21-day in vitro tumorigenicity assay, EC304 inhibited 80 and 100% of colony formation of T47D cells in the presence of E2 at 1 and 10 nM respectively. Further studies revealed that EC304 induced apoptosis and G1-phase arrest in cell cycle progression when co-incubated with E2 for 24 h. Treatment with EC304 down regulated PR target genes and up regulated cell cycle dependent kinase (CDK) inhibitor P21 in vitro. Ongoing studies address whether EC304 is specifically acting on PR-A or PR-B isoform at gene expression, protein levels and PR isoform specific knockdowns in T47D and other metastatic breast cancer cells. Considered together, these data indicate that EC304 might be a safer but efficacious novel antiprogestin for hormone sensitive postmenopausal breast cancer patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-02.
P3-01-06: NF-kB Inhibition Promotes Radiosensitivity of Breast Cancer Cells in Three-Dimensional Culture through Abating b1-Integrin Expression.
Authors: Ahmed KM , Zhang H , Park CC 
Published: June 2012

Abstract
Therapy-associated tumor resistance, giving rise to recurrence and mortality, is a critical issue in cancer therapy. The molecular mechanisms causing tumor resistnace to the therapeutic radiation remain elusive. Nuclear factor-KB (NF-KB), a stress-sensitive heterodimeric transcription factor in the regulation of the stress-responsive genes, has been shown to initiate prosurvival signaling pathways. The cooperative function of NF-KB with other key stress elements in radioresistance remains to be elucidated. We have previously reported that induction of α5β1-integrin is associated with the enhanced cell survival of breast cancer cells after exposure to high dose IR (ionizing radiation). Because a typical NF-KB binding site was located in human β1-integrin promoter region, β1-integrin-mediated resistance to radiation may be regulated by NF-KB. The aim of the present study was to reveal a connection between NF-KB and β1-integrin pathways in radioprotection of malignant T4-2 mammary epithelial cells in 3D ***lrECM (three-dimensional laminin-rich extracellular matrix). We show that the elevated NF-KB activity was correlated with enhanced clonogenic survival, and increased NF-KB heterodimer p50/p65 levels were associated with an increase in total and phosphorylated (Thr 788/789) β1-integrins. Inhibition of NF-KB activation significantly reduced clonogenic survival with the inhibition of β1-integrin. These results indicate that NF-KB-mediated induction of β1-integrin is associated with an increased radiation resistance. Treatment of T4-2 colonies, formed at day 4, with NF-KB activation inhibitor in 3D lrECM before exposure to IR (4-Gy X-ray) resulted in a reduction of the size of colonies. The surviving colonies were associated with a decrease in proliferation and increase in apoptosis, indicating a decrease of resistance to IR. Together, these results provide the first evidence that NF-KB-mediated β1-integrin expression is responsible for tumor radioresistance. The NF-KB/β1-integrin pathway may serve as an efficient drug target to re-sensitize radioresistant tumor cells.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-06.
P3-01-11: Increased Gene Copy Number of c-KIT and VEGFR2 at 4q12 in Primary Breast Cancer Is Related to an Aggressive Phenotype and Impaired Prognosis.
Authors: Rydén L , Johansson I , Ebbesson A , Grabau D , Wigerup C , Aaltonen KE , Hedenfalk I 
Published: June 2012

Abstract
Introduction: Triple-negative breast cancer (TNBC) accounts for approximately 15% of all female breast cancer and is associated with aggressive clinical behaviour. No targeted treatments are available for TNBC. Drugs inhibiting tyrosine kinases, such as vascular endothelial growth factor receptor 2 (VEGFR2) and c-KIT, have however shown some promising results for patients with TNBC. The aim of the present study was to investigate whether gains and/or amplifications of VEGFR2 and c-KIT occur in TNBC. These genes may constitute novel candidate biomarkers for selecting TNBC patients for treatment with tyrosine kinase inhibitors.
Material & Methods: Fluorescence in situ hybridization (FISH) was used to quantify gene copy numbers of VEGFR2 and c-KIT in 83 primary human breast cancers, of which 31 were classified as TNBC. Gains were defined as ≥4 gene copies in more than 40% of the cancer cells, while amplification was defined as gene copy/CEP ratio &gt;2 in more than 10% of the cancer cells. A tumour was considered FISH positive for c-KIT and/or VEGFR2 if it displayed copy number gain and/or amplification. Immunohistochemical (IHC) staining was performed for assessment of c-KIT protein expression.
Results: Ten (32%) of the TNBCs were VEGFR2 FISH positive and nine (29%) were c-KIT FISH positive, whereas non-TNBCs were FISH positive for VEGFR2 and c-KIT in nine (18%) cases for both genes. No significant difference in frequency between TNBCs and non-TNBCs was found. There was a correlation between FISH positivity for VEGFR2 and c-KIT (c2 test, P&lt;0.001), and VEGFR2 and c-KIT FISH positivity correlated to ER/PgR negativity and high Nottingham histological grade (NHG). A significantly worse breast cancer specific survival (BCSS) was seen for FISH positive cases in the whole cohort as well as among untreated patients and non-TNBCs, but not among TNBC cases.
Discussion: The high correlation between VEGFR2 and c-KIT FISH positivity suggests that the genes are co-amplified. Increased copy number of both genes was related to aggressive disease and a worse prognosis, and thus has the potential of functioning as a novel predictive biomarker for selected targeted therapy particularly in the difficult-to-treat TNBC patient category.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-11.