bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-09-20: Response Prediction to Neoadjuvant Chemotherapy: Comparison between Pre-Therapeutic Gene Expression Profiles and In Vitro Chemosensitivity Assay
Authors: Singer CF , Klinglmueller F , Staudigl C , Fink-Retter A , Gschwantlerkaulich D , Helmy S , Pfeiler G , Dressler A-C , Sartori C , Bilban M. 
Published: April 2011

Abstract
Purpose: Although the use of (neo-)adjuvant chemotherapy in breast cancer patients has resulted in improved disease-free and overall survival, not all patients benefit equally. Nevertheless, chemotherapy is still applied empirically, since clinical tests for response prediction are not routinely available. We have evaluated the utility of an in vitro chemosensitivity assay (ATP-TCA) in predicting response to neoadjuvant chemotherapy. Methods: Pre-therapeutic tumor core biopsies were obtained from 65 breast cancer patients and subjected to a standardized ATP-based Epi/Doc tumor chemosensitivity assay (ATP-TCA). Of these, 30 breast cancer patients were also assigned to three cycles of neoadjuvant epirubicin 75 mg/m2 and docetaxel 75 mg/m2 (Epi/Doc) in a prospectively randomized clinical trial. Tumor response was evaluated by pre-and post-interventional ultrasound measurements of tumor diameter, and by differential Ki67 expression. Results: 3 Cycles of neoadjuvant Epi/Doc resulted in a clinical response according to RECIST criteria in 11/23 evaluable patients (48%), and in a profound reduction in tumor proliferation in 10/23 patients (43%). Similarly, in vitro treatment of tumor cell suspensions with Epi/Doc performed in 65 pre-treatment core-biopsies yielded chemosensitivity in comparable fraction of patients (30/65, 46%). When the differentail changes in tumor cell proliferation in response to 3 cycles Epi/Doc in 23 patients were compared with ATP-TCA results obtained from the pre-interventional tumor core-biopsies of the same individual patients, we found that the efficacy of Epi/Doc in vitro was significantly correlated with differential changes in tumor cell proliferation in response to 3 cycles Epi/Doc in vivo (p= 0.0011; r=0.73670, Spearman's rho), but did not predict for changes in tumor size when measured by ultrasound. Conclusion: This is the first prospective clinical trial to demonstrate the utility of a standardized in vitro chemosensitivity assay in predicting the individual response to chemotherapy in breast cancer patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-20.
Abstract P2-09-23: Investigating VAV3 Expression as a Novel Biomarker and Indicator of Chemosensitivity in Basal-Like Breast Cancer
Authors: Getz JE , Anderson EM , Balagurunathan Y , Black MA , Hedenfalk IA , Willis AL , Ramos P , Mancini CM , Cunliffe HE. 
Published: April 2011

Abstract
Background: Basal-like breast (BLB) cancer accounts for ∼15% of all breast cancers diagnosed. Patients with BLB cancer are typically younger, present with higher tumor grade and despite recent advances in therapy, still have a poor outcome. BLB cancers are the most proliferative breast tumor sub-type, are commonly triple-negative (ER-, PgR-, HER2/neu-), and often harbor mutations in TP53 and BRCA1. The biological drivers of disease progression in this tumor subtype remains poorly understood. Recently, VAV3, a guanine nucleotide exchange factor and a member of the of the Rho/Rac/Cdc42 GTPase superfamily, has been reported as overexpressed and oncogenic in ER+ breast cancer cells. Our preliminary studies using publicly available microarray data indicates a consistent lack of VAV3 in BLB cancer, particularly those patients with shorter survival time following chemotherapy. We therefore hypothesize that VAV3 is a novel biomarker of BLB cancer and potential predictor of chemosensitivity in this subtype.
Materials and Methods: Gene expression microarray technology, qRTPCR and western blotting was used to investigate relative expression of VAV3 in a panel of breast cancer cell lines and tumors. Array Comparative Genomic Hybridization and Fluorescence in Situ Hybridization were used to evaluate VAV3 gene copy number. BLB cancer cell lines stably overexpressing VAV3 were developed to evaluate the role of VAV3 in sensitivity to chemotherapy.
Results: Unsupervised hierarchical clustering revealed low VAV3 expression in BLB tumors compared to all other intrinsic subtypes. Consistently lower VAV3 mRNA and protein expression were observed in BLB cancer cell lines compared to luminal epithelial cell lines, consistent with our in silico observations. We confirmed that low VAV3 expression in the BLB cancer cell lines is not due to gene copy number loss. Ectopic expression of VAV3 in MDA-MB-231 BLB cancer cells significantly enhanced their sensitivity to cisplatin.
Discussion: A consistent lack of VAV3 gene expression is evident in BLB tumors, however the mechanism underlying this loss is yet to be elucidated. Our findings support a hypothesis that low VAV3 expression is a potential diagnostic biomarker of BLB cancer, and that VAV3 expression may be a predictor of response to chemotherapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-23.
Abstract P2-09-26: Circadian Clock Genes in Primary Breast Cancer: Strong Predictors of Pathologic Response on Neoadjuvant Chemotherapy
Authors: Iurisci I , Valet F , Giacchetti S , Pierga JY , André F , De Cremoux P , Asselain B , Delaloge S , de Thé H , Spyratos F , Brain E , Sigal-Zifrani B , Mignot L , Marty M , Levi F. 
Published: April 2011

Abstract
Background: Circadian clocks involve 15 specific genes, which control cell cycle, apoptosis, DNA repair and metabolism. Circadian disruption is associated with both an increased risk of breast cancer, and poor survival in patients (pts) with metastatic cancer (IARC#98; Innominato et al. Cancer Res 2009).
Objective: to provide first evidence of clinical relevance of clock genes expression for the therapeutic sensitivity of primary breast cancer. Method: Affymetrix Hgu133plus2 microarrays data were derived from 189 primary breast cancers. All the pts had non metastatic disease and were registered in multicenter Phase II trial of neoadjuvant chemotherapy with epirubicin-cyclophosphamide (4 courses) then docetaxel ± herceptin (4 courses). In this study, negative hormonal receptor status and limited tumor size predicted for pathological complete response rate (pCR) (Pierga JY, et al Breast Cancer Res Treat. 2010).The expression data of 15 core clock genes, within the whole tumor transcriptome, were related both to tumor mitotic index (MI) and estrogen receptors (ESR1), and to chemotherapy-induced pCR. Statistical validation involved T-test statistics, with corrections for multiple testing.
Results:
In the tumor biopsy obtained before treatment onset, both Per2 and Cry2 expressions correlated positively with ESR1 (r≥0.43; P&lt;0.001) and inversely with (MI (r≤−0.28; P&lt;0.007). In addition, a positive correlation was found for Dec 1 with ESR1 (r=0.65, P&lt;0.001). The mean expressions of Per2, Cry2 and Dec 1 before chemotherapy were lower in the 32 pts who subsequently achieved pathologic complete response (pCR) as compared to the 157 who did not (P&lt;0.001). No other clock gene expression was significantly related to pCR. The odds ratio confirmed the decreased chance of achieving pCR with increased expression of clock genes Per2, Cry2 or Dec1.
Clock gene expression and pCR
Conclusion: Low expressions of three core genes in the negative loop of the molecular circadian clock strongly predicted for the induction of a pathologic complete response of primary breast cancer with neoadjuvant chemotherapy. While circadian clock disruption seems to constitute a poor prognostic factor in cancer patients, our data suggest that the downregulation of core circadian genes in tumors significantly enhances susceptibility to chemotherapy.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-26.
Abstract P2-09-35: Differential Pathologic Response from Primary Systemic Chemotherapy across Breast Cancer Intrinsic Subtypes
Authors: Jinno H , Matsuda S , Takahashi M , Hayashida T , Sakata M , Mukai M , Kitagawa Y. 
Published: April 2011

Abstract
Purpose: This study's purpose was to evaluate the clinical utility of breast cancer intrinsic subtypes in the prediction of pathological complete response (pCR) in a cohort of breast cancer patients receiving primary systemic chemotherapy.
Patients and Methods: Patients with stage II/III breast cancer received 4 cycles of XT (capecitabine 1650 mg/m2 on days 1-14 and docetaxel 60 mg/m2 on day 8 every 3 weeks), followed by 4 cycles of FEC (fluorouracil 500 mg/m2, epirubicin 90 mg/m2, cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). Immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PgR), HER2, epidermal growth factor receptor (EGFR), cytokeratin (ck) 5/6, and Ki67 was performed in core needle biopsy samples at baseline. Tumors were classified as luminal A (ER+ and/or PgR+, and Ki67&lt;20%), luminal B(ER+ and PgR+, and Ki67≥20%), luminal-HER2 (ER+ and/or PgR+, and HER2+), HER2-enriched (ER-PgR-, and HER2+), or triple-negative (ER-, PgR-, and HER2-). Triple-negative tumors with and without EGFR+ and/or ck 5/6+ were further classified as basal-like and non-basal-like TN (NBTN), respectively. pCR was defined as no microscopic evidence of residual viable tumor cells, invasive or noninvasive, in all resected specimens of the breast. Results: Twenty-six (31.3%) patients were classified as luminal A, 12 (14.5%) were luminal B, 15 (18.1%) were luminal-HER2, 9 (10.8%) were HER2, 10 (12.0%) were basal-like, and 11 (13.3%) were NBTN. The overall response rate was 90.4%, including a complete response in 30 patients and a partial response in 45 patients. The overall pCR rate was 15.5% (12/83). The highest pCR rate (40.0%) was observed in patients with basal-like tumors. In triple-negative patients, basal-like patients showed significantly higher pCR rate than NBTN patients (40.0% vs. 9.1%, p=0.01). There were no cases with pCR in a cohort of luminal-HER2 subtype patients. A higher proportion of luminal B patients had pCR than luminal A patients (25.0% vs. 3.8%, p=0.01). With 33 months median follow-up, estimated 2-year disease-free survival for luminal A, luminal B, luminal-HER2, HER2, basal-like, and NBTN was 80.8%, 83.3%, 66.7%, 88.9%, 80.0%, and 81.8%, respectively.
Conclusions: Our data indicate that breast cancer subtypes are useful predictive biomarkers of pCR in breast cancer patients treated with primary systemic chemotherapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-35.
Abstract P2-10-06: Identification and Referral of Appropriate Patients for Genetic Services in the Community Setting: An innovative Approach
Authors: Sutphen R , Steenblock K , Carmany E , Trivedi A , Lewis K. 
Published: April 2011

Abstract
Although the U.S. Preventative Services Task Force, the HHS's Healthy People 2020 draft objectives and multiple professional medical societies recommend genetic counseling as the standard of care for women with family history suggesting increased risk for breast cancer, there is clear evidence that this standard is not being achieved. On the one hand, many women who are appropriate for genetic counseling are not receiving it, while on the other, many individuals are inappropriately undergoing BRCA testing. A number of factors have been identified as contributors to these poor public health outcomes, including lack of physician proficiency in genetics and lack of availability of genetic counseling services due to limited number of trained genetics professionals and their limited geographic distribution.
We report a novel systematic approach implemented through a large regional health plan (approximately 500,000 members, 14,000 network providers, 112 commercial hospitals, and 58 medicare hospitals) to address these issues, and present data regarding its performance. Components of the program include: 1) implementation of a model BRCA coverage policy that follows USPSTF guidelines recommending genetic counseling, 2) increased access to genetic counseling via telephone delivery and 3) removal of financial, language, convenience and other barriers to genetic counseling services.
The program was implemented in January, 2010 and data will be presented for January through September. Specific results include 1) changes in volume of BRCA testing (including by provider specialty), 2) decrease in rates of inappropriate BRCA test requests (i.e., requests not meeting national guidelines/clinical criteria for testing), 3) discrepancies in reported family history based on methods of data collection, 4) increased awareness and dissemination of genetic services in the community setting, and 5) cost-effectiveness estimates. This program may serve as a model for appropriate translation of genetic testing into public health benefit.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-10-06.
Abstract P2-12-01: Is Cancer-Specific Distress Correlated with Time to Definitive Surgery in Breast Cancer Patients?
Authors: Daup MB , Lush EL , Dedert E , McMasters KM , Sephton SE , Chagpar AB. 
Published: April 2011

Abstract
INTRODUCTION: A number of studies have investigated factors influencing delay in seeking medical care for self-detected breast symptoms. Few, however, have sought to understand factors that are correlated with the time interval between diagnostic imaging and definitive surgery. We sought to determine factors that may influence this time interval. METHODS: From May 2005 to January 2009, a prospective study of 59 breast cancer patients was performed in which patients’ cancer-related distress was evaluated using the Impact of Events Scale (IES). After patients undergoing neoadjuvant chemotherapy and those who did not have imaging or surgery were excluded, the remaining 43 patients formed the cohort of interest for this analysis. The effect of clinicopathologic and psychological factors on the time between diagnostic imaging and definitive surgery was evaluated using non-parametric statistics (SPSS, Version 18.0).
RESULTS: The median time between diagnostic imaging and definitive surgery in this cohort was 43 days (range; 4-200). In 25 patients (58.1%), this interval was less than 45 days. Patient age, largest tumor size on imaging, and previous history of breast or other cancers did not appear to be related to time to surgery. Similarly, race, marital status, education, income and insurance status were not significant predictors of time to surgery. Patients who had a longer time interval between imaging and surgery scored higher on the avoidance and total distress subscales of the IES (median 19.5 vs. 12.0, p=0.016 and 37.0 vs. 29.0, p=0.028, respectively). In particular, patients with a longer time between imaging and surgery were more likely to report that they “tried not to think about it” (p= 0.040), “tried not to talk about it” (p=0.039) and “stayed away from reminders of it” (p=0.001).
CONCLUSION: Psychological distress associated with a diagnosis of cancer is significantly correlated with the time to definitive surgery in breast cancer patients. Avoidance behaviors tend to be associated with a delay in surgery. Early psychosocial support aimed at reducing such distress may shorten time to definitive treatment in such patients; alternatively, shorter times to surgery may reduce cancer-specific distress.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-12-01.
Abstract P2-13-03: Osteonecrosis of the Jaw: Dental Outcomes in Metastatic Breast Cancer Patients Treated with Bisphosphonates with/without Bevacizumab at Roswell Park Cancer Institute
Authors: Ngamphaiboon N , Frustino JL , Kossoff EB , Sullivan MA , O'Connor TL. 
Published: April 2011

Abstract
Background: The etiology, optimal management, and long term outcome of osteonecrosis of the jaw (ONJ) is not well understood. Large trials have suggested that the combination of bevacizumab and bisphosphonates (BPs) does not significantly increase the incidence of ONJ. Because healing after mucosal trauma or dental surgery requires revascularization, it is possible that bevacizumab use could influence dental outcomes. Theoretically, the combination of bevacizumab and BPs may affect the time to development of ONJ and/or the response to dental therapy. Dental management of ONJ has not changed over time in our center, but increased recognition and screening may impact the dental outcome.
Methods: We reviewed all cases of ONJ in metastatic breast cancer patients treated with BPs and with or without bevacizumab at Roswell Park Cancer Institute between October 2002 and April 2010. All patients diagnosed with ONJ discontinued BP therapy, while 3/7 (42%) continued bevacizumab until breast cancer progression. Type of BP, duration of treatment, total dose of BPs and bevacizumab dosing were recorded. All patients were treated in the department of dentistry with a combination of antibiotics, debridement, and chlorhexidine scrub. We evaluated the time to diagnosis of ONJ after the initiation of BP therapy, total dose of BP and dental treatment outcomes. Statistical analysis was performed using t-test and log-rank analysis. Results: See tables. 27 ONJ patients with a median age of 57 years (range 40-68) were analyzed. Patients were treated with zoledronic acid (95%), pamidronate (20%), or both (15%). 2 patients were excluded from dental response analysis due to lost follow up. Overall median time to ONJ treatment response was 5.0 months (range 1.3-67.5). Conclusions: The addition of bevacizumab to BP treatment did not significantly alter the time to the development of ONJ, the number of BP doses administered prior to diagnosis, or the response to dental treatment. However, ONJ response rates (complete and partial) to dental therapy have improved from 38% prior to 2007 to 58% after 2007, likely reflecting improved recognition and earlier treatment.
Table.1 Time to ONJ and number of BP doses
Table 2 ONJ response to dental treatments

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-13-03.
Abstract P2-14-01: A Prospective Controlled Analysis of Fertility Preservation by Oocyte and Embryo Cryopreservation Using an Aromatase Inhibitor-Gonadotropin Protocol: Treatment Outcomes and Safety in Young Women with Breast Cancer
Authors: Oktay K , Lee SH , Moy F 
Published: April 2011

Abstract
Objective: Breast Cancer (BCa) is the most common malignancy in reproductive age women and letrozole, an aromatase inhibitor, has been used to reduce estrogen exposure in women undergoing embryo/oocyte cryopreservation prior to chemotherapy. Our aim was to determine the long-term outcomes and safety of letrozole-FSH protocol. Design: Prospective
Materials and Methods: Women with stage 0-3 BCa underwent ovarian stimulation with letrozole 5-mg starting menstrual cycle day (CD)-2 and gonadotropins 150-450 IU, starting CD-4. Oocyte maturation was triggered either with human chorionic gonadotropin (hCG) or a Gonadoropin Releasing Hormone Agonist (GnRHa).
Results: Of the 129 women with mean age of 35.2±4.6, 13 vs. 91 underwent oocyte vs. embryo freezing, and 9 underwent both. Ovarian trigger with GnRHa (n=37/115, 32.2%) resulted in higher number of mature oocytes (10.9±6.6 vs. 8.4±6.0, p=0.045,). Of those, 21 underwent 25 frozen embryo transfers (mean age 35.5±4.5) with a clinical pregnancy (CP) rate of 68% and y per ET. CP rates were similar between the self-transfer and gestational carrier groups (7/9 vs. 10/16, p=0.37). No birth defects are encountered. Relapse rates were compared to a similar group of women with BCa (n=141, mean age 35.7±4.7, similar projected 10-year relapse rate at the outset by! adjuvant online) who elected to not to undergo ovarian stimulation. After a mean follow up of 2.4±1.6 vs. 2.9±1.7 years (range 8 mo - 5.6y vs. 4m-6.8y) women who had undergone ovarian stimulation with letrozole and FSH had a significantly lower recurrence rate [2.0% vs. 25.0%, Hazard ratio 0.08, 95%C.I. (0.06, 0.48), p=0.01]. Conclusions: This long term follow up of LF protocol for up to 7 years indicates that the protocol is safe, efficient and is associated with age-appropriate pregnancy success rates. Whether pretreatment with letrozole improves BCa treatment outcomes should be further investigated. Women with BCa can be safely offered this protocol when undergoing fertility preservation prior to chemotherapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-01.
Abstract P2-14-02: A Pilot Study of Vascular Endothelial Growth Factor Inhibition with Pazopanib in Patients (pts) with Lymphedema Following Breast Cancer Treatment
Authors: Miller KD , Brown C , Perkins SM , Schneider BP , Storniolo A , Sledge GW. 
Published: April 2011

Abstract
Purpose: Lymphedema is a significant long-term complication of primary therapy for breast cancer. VEGF has a major impact on vascular permeability and lymphangiogenesis. In a prior case control study, we found a significant increase in serum VEGF-C (median 6895 vs. 5349 pg/mL, p=0.0016) in women with lymphedema compared to women without lymphedema suggesting inhibition of VEGF-C as a potential therapeutic strategy.
Methods: Pts with significant unilateral lymphedema were treated with pazopanib 800 mg/day continuously. Baseline assessments include arm volume, interstitial fluid pressure (IFP), extracellular fluid volume by lymphometer (ECF), quality of life (QOL) and plasma VEGF-C,-D, and R3. IFP was measured serially for 24 hours after the first treatment; arm volume, ECF, QOL, and plasma VEGF-C/D/R3 are assessed every 4 weeks.
Results: Ten pts were enrolled. Median duration of lymphedema was 3.5 years (0.7-8.2) Median time since surgery was 5.1 years (1.0-14.2); median time since radiation (n=9) was 4.7 years (0.4-8.8). Complete IFP data are available in 7 pts. Baseline IFP was significantly higher in the affected compared to unaffected arm (mean 5.73 vs. -1.78 mmHg; p=0.0005). Mean IFP in the affected arm decreased an average of 76% 24 hours after initiation of pazopanib (5.73 vs. 1.56 mmHg; p=0.0061). Toxicity was greater than anticipated with grade 3 fatigue (n=3), arthralgia (n=2), and anorexia (n=1); three pts discontinued therapy prior to the first post-treatment assessment. Five pts met the definition of response with a ≥25% reduction in excess arm volume four weeks after initiating treatment. ECF significantly (p=0.014) decreased as well though the mean difference in excess arm volume did not significantly change (p=0.06). Conclusions: Preliminary data supports the hypothesis that VEGF plays a role in the development and/or persistence of lymphedema after local therapy for breast cancer. Pazopanib acutely decreases IFP, leading to a decrease in ECF and modest improvement in arm volume but results in significant toxicity at the dose used on this study. Subsequent studies will explore a lower dose of pazopanib in this population. This study was supported by the Breast Cancer Research Foundation with pazopanib supplied by GSK.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-02.