bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that SOM230 can prevent experimental mammary hyperplasia by blocking IGF-I and thus estrogen action in the mammary gland: preliminary evidence for an effect in humans.
Authors: Ruan W , Singh B , Smith J , Axelrod D , Kleinberg DL 
Published: December 2010

Abstract
Abstract #5084
Background: Antiestrogens or aromatase inhibitors are used for breast cancer chemoprevention, however, they are poorly tolerated. We have shown that IGF-I is required to permit estrogen and progesterone action in the mammary gland. A novel somatostatin analog, SOM230, which binds to several somatostatin subtype receptors (SSTR), prevents estrogen action by reducing pituitary growth hormone, and also by a direct IGF-I action inhibitory effect on the mammary gland. Menopausal symptoms have not been observed in acromegalic patients receiving SOM230. Material and Methods: Several approaches have been undertaken. 1) We developed a model of hyperplasia in hypophysectomized and oophorectomized female rats. Hyperplasia was induced by treatment with 600 mcg hGH and follicular phase concentrations of estradiol. 2) To assess translatability to humans we cell proliferation (Ki67) and apoptosis (TUNEL) were measured in normal human breast from reduction mammoplasty and in samples of proliferative fibrocystic change (FCC). 3) We also measured expression of SSTR in atypical ductal hyperplasia and DCIS, and 4) A proof of principal trial with SOM230 has begun accrual to determine whether SOM230 acts in human breast as in rats. Results: 1) hGH and E2 caused florid hyperplasia in rat mammary glands within a week. Twenty-six percent of gland structures exhibited hyperplasia with 50% of those showing florid hyperplasia. SOM230 reduced the number of areas of florid hyperplasia to 7.5 ±0.5 from 18.9±1.3 (p&lt;0.001). This was accomplished by a reduction in cell proliferation and an increase in apoptosis. Interestingly, co-administration with tamoxifen provided no additional benefit over that of SOM230. 2) Proliferative lesions from human breast had 8.09 % of cells stain for Ki67. 3) All 5 somatostatin subtype receptor (SSTR) were present in pathology samples of atypical hyperplasias and DCIS, but SSTR3 and 5 were present in highest concentrations. SSTR 3 is the receptor most likely to mediate the effect of SOM230 with SSTR5 being the next most likely. 4) In the first patient tested we found that SOM230 increased apoptosis and reduced cell proliferation (1000 cells counted).&#x2028; &#x2028; Discussion: Our data show that SSTR are present in ADH and DCIS and normal breast tissue. Our data also show that SOM230 can prevent cell proliferation and increase apoptosis both in rats and humans. Thus, further clinical trials will be important as SOM230 may have a role in breast cancer chemoprevention.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5084.
Characteristics of carpal-tunnel syndrome in the ATAC trial.
Authors: Sestak I , Cuzick J 
Published: December 2010

Abstract
Abstract #5085
Introduction: Carpal-tunnel syndrome (CTS) is a condition in which the median nerve is compressed leading to pain and muscle weakness in fingers and the hand. Oestrogen depletion has been shown to induce CTS, whereas the use of hormone replacement therapy is associated with a resolution of the symptom. Aromatase inhibitors lead to profound oestrogen suppression and therefore might induce CTS in postmenopausal women.&#x2028; Methods: The Arimidex Tamoxifen Alone or in Combination (ATAC) trial randomised 9,366 postmenopausal women to anastrozole (1mg/day), tamoxifen (20mg/day) or the combination. Analyses were based on the 100 month median follow-up data in women in the two monotherapy arms who started their allocated treatment (anastrozole=3,092; tamoxifen=3,094). Here, we retrospectively investigate the influence of anastrozole on CTS, clinical outcomes, the relative importance of a range of risk factors for CTS, and examine whether they act differently in the presence of anastrozole treatment.&#x2028; Results: During the entire active treatment period, 80 (2.6%) cases of CTS were reported in the anastrozole arm compared with 23 (0.7%) in the tamoxifen arm (OR=3.55 (2.22-5.65), P&lt;0.001). In both treatment arms, the majority of CTS were reported as of mild or moderate severity. Most reports of CTS in the anastrozole arm occurred within 18 months of treatment initiation, but incidence remained elevated compared to the tamoxifen arm for the entire treatment period. Median time to resolution of CTS was 8.4 months and none of the women stopped treatment medication due to this adverse event. 13 women underwent carpal-tunnel release surgery (11 anastrozole (1 in 300) vs. 2 tamoxifen (1 in 1500)). Reports of CTS were significantly increased for women who used prior hormone replacement therapy (HRT) (2.3% vs. 1.3%, OR=1.72 (1.16-2.54), P=0.007) or prior chemotherapy (2.5% vs. 1.4%, OR=1.73 (1.14-2.62)). Furthermore, women who were aged 60 years or younger at entry were at greater risk of CTS compared with those aged 61 years or older (2.5% vs. 1.2%, OR=0.48 (0.30-0.76), P=0.002). Body mass index (BMI), hormone receptor status, smoking status, and prior radiotherapy were not found to be risk factors for the development of CTS. When analyses were restricted to only women receiving anastrozole, the same risk factors were identified.&#x2028; Conclusions: Although the use of anastrozole is clearly associated with a greater incidence of CTS, it is rare and most cases were of mild severity and short duration and did not lead to treatment discontinuation or surgical intervention. Thus, while CTS can be quite debilitating for the few patients who have severe symptoms, this side effect has minimal impact on the overall risk-benefit ratio for the use of anastrozole in postmenopausal women.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5085.
Use of mastectomy in rural versus urban patients: the effects of medical community factors.
Authors: Jacobs LK , Detrani ME , Kelley KA , Rosson GD , Chang DC 
Published: December 2010

Abstract
Abstract #5089
Background: Disparity exists in surgical treatment of breast cancer patients living in rural versus urban counties. Past studies evaluating this used patient level data. We examine county-level medical community factors that potentially impact the geographic variation of mastectomy versus breast-conserving therapy.&#x2028; Methods: Data from 137,303 patients and 200 counties were analyzed combining the 2006 SEER and 2004 ARF (Area Resource File) databases. Inclusion criteria identified in SEER were: stage I, II, or III disease, female, diagnosis after 1992. Patients were linked to county level data from the ARF based on their county of residence. Medical community variables analyzed with ARF are seen in Table 1.&#x2028; Results: A total of 9.58% of the patients reside in a rural county, and 59.90% of these received a mastectomy, compared to 44.92% of the urban patients. Multivariate analysis of the medical community factors was calculated by both land area and population with calculation by population accounting for the disparity in mastectomy use (Table 1). Of the medical community factors in this analysis, the screening hospital density was highly significant, accounted for the difference in rural versus urban mastectomy rates, and resulted in an increased likelihood of receiving mastectomy (OR 1.009, 95% CI 1.004-1.014). Bivariate analysis also revealed a higher density of screening hospitals in rural counties (57.62) than in urban counties (18.22).&#x2028; Conclusions: Analysis using land area versus population to estimate availability of services suggests that disparity in the rural community is most affected by availability of providers and not to required travel distance. Density of screening hospitals was found to be the most important factor resulting in disparity between rural versus urban mastectomy rates. Rural counties have a higher density of screening facilities, yet they also have a higher mastectomy rate. This may represent a volume/quality issue that will require further investigation.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5089.
Multicentric study with neoadjuvant endocrine therapy for breast conserving surgery. Experience in Mexico.
Authors: De la Garza JG , Bargallo E , Solorio C , Ramirez T , Salazar F , Sanchez J 
Published: December 2010

Abstract
Abstract #5119
Background: In patients with large, operable breast tumors who are ineligible for Breast-conserving surgery (BCS), neoadjuvant therapy is a useful option for reducing tumor size and for increasing the proportion of candidates to BCS. Neoadjuvant chemotherapy has been widely studied, but little has been published on neoadjuvant endocrine therapy. This study analyzes the use of neoadjuvant endocrine therapy with aromatase inhibitors in postmenopausal women with hormone receptor-positive locally advanced breast cancer (LABC).&#x2028; Material and Methods: The study was designed as a multicenter study and was conducted in four centers in Mexico between July 2005 and August 2006. Thirty six patients were assigned to receive letrozole 2.5 mg, daily, for 4 months prior to schedule surgery. This group was compared with a group of 36 patients who received conventional chemotherapy as neodjuvant treatment. At baseline none of these patients were considered to be candidates for BCS. Primary end points were response rate (ORR) defined as the percentage of patients with a complete response (CR) or partial response (PR) as determined by breast palpation and the percentage of patients who underwent BCS. Standard descriptive statistics were performed.&#x2028; Results: All patients were postmenopausal, median age was similar in both groups (64 (50 86) years vs. 59 (50 – 77) years; P = 0.1). At baseline 75% of tumors in endrocrine group were T2 (median (range) 4 (2 – 5) cm) while 25% were T3 (median (range) 7.6 (5.5 – 10) cm) and in chemotherapy group 83% were T2 (median (range) 3.9 (2 - 5) cm) and 17% T3 (median (range) 6.8 (5.5 – 9.5) cm). Clinical response was similar between groups. The ORR was 70% for endocrine group versus 80% for chemotherapy group (P = 0.3). In terms of clinical progression, 8% of patients in the endocrine group progressed vs. none in the chemotherapy group, while 22% of endocrine- and 19% of chemotherapy-treated patients had stable disease. The proportion of patients able to undergo BCS was significantly higher in the endocrine group than in the chemotherapy group (36% vs. 19%, respectively; P = 0.0008).&#x2028; Discussion: Over third of patients become BCS-eligible within 4 months of preoperative endocrine therapy. Neoadjuvant therapy with aromatase inhibitors could be an effective treatment option for highly selected postmenopausal women who are unwilling or unable to undergo BCS or preoperative chemotherapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5119.
A prospective nonrandomize study comparing electron intraoperative boost radiotherapy versus postoperative interstitional brachytherapy in patients having breast conserving surgery and adjuvant external beam radiotherapy.
Authors: van Dam PA , Weytjens R , DeMaeyer L , van Dam AM , Alberty J , Verstraeten H , Huget P , Verkinderen L , Prove A , Vermeulen P , Dirix LY 
Published: December 2010

Abstract
Abstract #5140
Purpose: to compare the surgery and radiotherapy related outcomes, toxicities and cosmesis of patients undergoing breast conserving surgery and adjuvant external beam radiotherapy having intraoperative electron boost radiotherapy (IEBR) versus postoperative boost interstitinal brachytherapy (PIB).&#x2028; Materials and methods: Between January 2007 and June 2008, 80 women with a diagnosis of early breast cancer ( pT1: 69, pT2: 11, pN0: 66, pN1: 14) were treated with lumpectomy, sentinel node biopsy, with (N=14) or without (N=66) axillary lymphadenectomy. During surgery an electron boost of 9 Gy (4-12 Mev) was administered to the tumor bed using a Mobetron (Intraop, USA). Adjuvant treatment was completed with whole breast external beam radiotherapy (WBEBR, 45 Gy in 25 fractions) and systemic therapy if necessary (group 1). The outcomes in these patients was compared propectively to 100 stage-matched patients treated in the same period having similar breast conserving surgery, systemic treatment and WBEBR, and receiving a boost by means of postoperative interstitional brachytherapy (192Iridium, 15 Gy, Nucletron Afterloader, USA) implanted under general anesthesia according to the Paris system (group 2)&#x2028; Results: Median netto (= incision to closure) and bruto (= total time spend in the operating theatre) time in the operating theatre at primary surgery was significantly higher in group 1 (respectively 96 vs 62 min, p &lt; 0.01, and 118 and 80 min, p &lt;0.01). Netto and bruto time to implant the iridium wires respectively was 27 and 50 min. This means that the total theatre time was comparable in both groups (netto 96 vs 89 minutes, and bruto 148 vs 130 minutes, NS). Perioperative morbidity was slightly higher in group 1 due to a higher amount of postoperative wound infections (9/80 vs 4/100, p&lt; 0.05). Median total surgery and radiotherapy related hospital stay for the entire treatment was 2.5 days in group 1 and 4.0 days in group 2 (p &lt; 0.01). Patient satisfaction was significantly higher in patients receiving IEBR. Acute skin toxicity at the end of the entire treatment was significantly lower in group 1. Out of 48 evaluable patients after 6 months there were no patients with grade 4 skin toxicity in group 1. No tumor recurrences were seen in both groups after a median follow-up 10 months.&#x2028; Conclusions: Intraoperative radiotherapy is feasible and well tolerated in selected patients with early breast cancer. Total hospital stay is lower and patient satisfaction is higher in women having IEBR compared to PIB. Our study suggest it may be considered to give patients undergoing IEBR prophylactic antibiotic treatment.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5140.
Tumor angiogenesis imaged by optical tomography can accurately diagnose early-stage invasive breast cancers.
Authors: Zhu Q , Kane M , Tannenbaum S , Cronin E , Hegde P , Iyers M , DeFusco P , Ardeshirpour Y , Xu C , Baccaro N , Kurtzman S , Deckers P 
Published: December 2010

Abstract
Abstract #52
Background: Our initial clinical results obtained from a novel ultrasound(US)-guided diffusive-wave optical tomography have shown that early-stage invasive breast cancers may be distinguished from benign lesions with an average of two-fold angiogenesis contrast. However, breast cancer is a heterogeneous disease with different growth and metabolic rates that result in a wide range of functional differences. In this report, we present a spectrum of breast lesion angiogenesis distributions from benign lesions, early-stage invasive cancers to advanced cancers. The objective is to investigate the feasibility of optical tomography with US localization in differentiating malignant from benign breast masses.&#x2028; Materials and Methods: 123 patients underwent US-guided biopsy and were imaged with a combined imager consisting of a commercially available US system and a near infrared (NIR) imager. A hand-held probe with a centrally located US transducer and NIR sensors surrounding it was used to simultaneously acquire co-registered US images and optical data. The lesion location provided by US was used to guide optical imaging reconstruction. Light absorption was measured at multiple wavelengths. From this, tumor angiogenesis was assessed based on calculated total hemoglobin concentration.&#x2028; Results: There were 23 stage I carcinomas, 21 stage II to IIII carcinomas, and 112 benign lesions. The mean maximum and average values of total hemoglobin concentration (tHb) of the stage I malignant group were 102.0 μ mol/liter (±30.7) and 72.3 μ mol/liter ( ±18.1), and the values of the state II to IIII malignant group were 114.4 μ mol/liter (±38.4) and 75.4 μ mol/liter (±25.2), respectively. The mean maximum and average values of the benign group were 54.0 μ mol/liter (±22.3) and 38.2 μ mol/liter (±14.8), respectively. Both maximum and average of tHb level were statistically significantly higher in the malignant groups than the benign group (P&lt;0.01). An example of a six mm stage I cancer imaged by US (Fig.1(a)) and the NIR imager (Fig.1(b) is given in Figure 1.&#x2028; &#x2028; The detection sensitivity and specificity of the stage I cancer group were 91% and 94%, and 76% and 94% for the stage II to IIII cancer group.&#x2028; Discussion: The tumor angiogenesis distributions are complex and the angiogenesis contrast holds great promise for distinguishing early-stage invasive breast cancers from benign lesions. For advanced cancers, the angiogenesis distribution is heterogeneous and often presents periphery enhancement and/or shadow effect which can be used to assist US diagnosis.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 52.
Risk of distant recurrence using oncotype DX in postmenopausal primary breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study.
Authors: Dowsett M , Cuzick J , Wales C , Forbes J , Mallon L , Salter J , Quinn E , Bugarini R , Baehner FL , Shak S ,   on Behalf of the ATAC Trialists' Group
Published: December 2010

Abstract
Abstract #53
Background: The Recurrence Score (RS) has been validated for estimating residual risk of distant recurrence (DR) in ER+ node negative (N-) primary breast cancer patients receiving adjuvant tamoxifen. Aromatase inhibitors (AIs) are widely used for adjuvant treatment of ER+ disease in postmenopausal women. The RS has not been evaluated in patients treated with an AI.&#x2028; Method: Tumour blocks were collected retrospectively from patients in the monotherapy arms of the ATAC trial under the TransATAC protocol yielding 1308 hormone receptor positive (HR+) blocks in UK patients for analysis (1). Cox proportional hazards model was used to test the significance of adding RS to a clinical model (age, tumour size, grade, treatment) and to Adjuvant! Online.&#x2028; Results: 65 patients received chemotherapy, 4 were centrally HR negative and 8 did not start adjuvant therapy leaving 1231 evaluable patients of which 872, 306 and 53 were N-, N+ and N unknown in whom there were 72, 74 and 6 DRs, respectively. In the prospectively-defined primary multivariate analysis tumour size, grade and RS were each separately statistically significant in predicting time to DR in N- patients (p&lt;0.001, 0.003 and &lt;0.001, respectively). Similar results were seen in N+ patients. The 9-year rates of DR by nodal status for the pre-specified RS groups are shown in the table. RS showed statistically significant prognostic value beyond that provided by Adjuvant! Online in both N- (p&lt;0.001) and N+ patients (p=0.003).&#x2028; &#x2028; Conclusions: Oncotype DX RS is an independent predictor of the risk of distant recurrence in N- and N+ HR+ patients treated with anastrozole or tamoxifen. The data are not predictive of a differential benefit between anastrozole and tamoxifen.&#x2028; (1) Dowsett et al JCO 2008, 26, 1059.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 53.
Clinicopathological factors affected no 18FDG uptake in 18FDG-PET CT: only invasive ductal cancer.
Authors: Seo H , Bae Y , Park B 
Published: December 2010

Abstract
Abstract #6007
Background: Positron emission tomography with fluorine-18 fluoro deoxy-glucgose (18FDG-PET CT) recently used is suggested more useful tool for accurate, non-invasive imaging modality of the prediction of prognosis and staging of breast cancer. The aim of this study was to evaluate whether no enhanced 18FDG uptake would be associated with the biological non-aggressiveness of invasive ductal carcinoma and suggest limitation of using 18FDG-PET CT for preoperative evaluation.&#x2028; Materials and Methods: The patients were consisted of 124 female patients raging in age from 29-80 years (average 51.1 years) with primary invasive ductal carcinoma. All patients had histologically or cytologically proven invasive ductal carcinoma before performing 18FDG-PET CT sacn. All patients were examined with 18FDG-PET CT sacn before neoadjuvant chemotherapy. Patients undergoing excisional biopsy were excluded from this study.&#x2028; Results: 20 patients had primary tumor with no enhanced 18FDG uptake and 18FDG-PET CT showed hypermetabolic axillary foci in 25 patients. In these 25 patients, two was false positive findings. Histologic examination was confirmed 56 patients had axillary lymph node metastasis. The mean tumor diameter was 2.2 cm (range 0.4-6 cm). With regard to histopathologic grading, 117 were grade 1 and 2, and 7 were grade 3. It was correlation with no enhanced 18FDG uptake (p=0.003). No enhanced 18FDG uptake in invasive ductal carcinoma depended on presence of axillary lymph node metastases (p=0.014). Small tumor (&lt; 2.0cm) also was significantly correlated with no enhanced 18FDG uptake. The relationship between no enhanced 18FDG uptake and presence of lymphovascular invasion, necrosis and calcification was not significant. The immunohistochemical stain of ER/PR/p53/c-erbB2 did not correlate with no enhanced 18FDG uptake. Triple negative tumor also was not significant (p=0.072). 123 specimens were examined with Ki-67. Ki-67 positivity ranged from 0% to 60% (mean 15%). 67 specimens showed immunoreactivity to Ki-67 antigen in &lt; 10% of tumor cell. This revealed a significant correlation between no enhanced 18FDG uptake and Ki-67 (p=0.003). Logistic regression analysis between these factors was shown that histologic grade, status of axillary lymph node metastases and Ki-67 were correlated with no enhanced 18FDG uptake.&#x2028; Discussion: The our results demonstrated that an association exists between no 18FDG uptake and good prognostic factors in invasive ductal cancer, such as low histologic grade (1 & 2), no axillary lymph node metastases and low Ki-67 (&lt;10%). Although further studies are needed, 18FDG-PET CT may be suggested more useful tool for accurate, non-invasive imaging modality of the prediction of prognosis and we purpose the limitation of using 18FDG-PET CT for follow-up study in these patient.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6007.