bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-13-09: Sensitive liquid chromatography-tandem mass spectrometry method for serum estradiol and estrone assessment without derivatisation, overcoming cross reactivity with exemestane
Authors: Lintermans A , Pauwels S , Vermeersch P , Jans I , Billen J , Van Asten K , Vanderschueren D , Neven P 
Published: August 2014

Abstract
Objective Measuring serum estrogen levels in postmenopausal women on oral aromatase inhibitors is important but challenging. Direct immunoassays are the most widely used techniques for measuring serum estradiol (E2) in research and clinical laboratories. Unfortunately, commercially available immunoassays for E2 lack precision and accuracy in the low range (&lt;20 ng/l) and are susceptible to interference. In addition, particularly in exemestane users biochemical monitoring of E2 is problematic because exemestane metabolites cross react in most immunoassays for E2. We developed a sensitive, routinely applicable liquid chromatography-tandem mass spectrometry (LC-MSMS) method for E2 and estrone (E1) quantification in human serum without the need for derivatization or an extended extraction protocol.
Materials and methods Serum E2 levels, assessed with LC-MSMS and electrochemiluminescence estradiol assay (ECLIA) on Modular E170 from Roche Diagnostics, of 10 breast cancer patients treated with exemestane were compared. Limit of quantification (LOQ) was 1.3 ng/l for LC-MSMS (coefficient of variation &lt;20% and signal-to-noise ratio &gt; 10, own validation) and 5 pg/ml for ECLIA (Roche, according to manufacturer).
Results Patients treated with exemestane showed much higher E2 levels when measured by ECLIA compared to E2 levels determined by LC-MSMS (Table 1). All patients, but one, had E2 values below LOQ when assessed with LC-MSMS whereas ECLIA measurements showed higher levels with a large variety (mean: 16.5 ng/l; range: 7-33 ng/l).
Results for E2 via ECLIA and LC-MSMS for patients treated with exemestanePatientE2 LC-MSMS ng/lE2 ECLIA ng/l1&lt;1.3212&lt;1.373&lt;1.3124&lt;1.3335&lt;1.3156&lt;1.3227&lt;1.398&lt;1.32692.51010&lt;1.310
Conclusion E2 levels in exemestane users measured with ECLIA from Roche are overestimated, probably due to cross reactivity of its metabolites. Therefore, this assay can not be used in these patients. Here, we demonstrate that this hurdle can be overcome by assessment of estrogen values with LC-MSMS. Our group was able to develop such a sensitive method, without derivatization.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-09.
Abstract P1-13-13: Association between the serum concentrations of tamoxifen and its metabolites and age during steady state breast cancer treatment
Authors: Lien E , Søiland H , Lundgren S , Ås T , Steen VM , Mellgren G , Gjerde J 
Published: August 2014

Abstract
It has been suggested that the concentrations of tamoxifen and its demethylated metabolites increase with age. Here, we measured the serum concentrations of the active tamoxifen metabolites, 4OHtamoxifen (4OHtam), 4OHNdesmethyltamoxifen (4OHNDtam, Endoxifen), tamoxifen and its demethylated metabolites. Their relations to age were examined. 151 breast estrogen receptor and/or progesterone receptor positive cancer patients were included. Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Their serum concentrations were related to the age of the patients. The concentrations of 4OHNDtam, tamoxifen, NDtam (N-desmethyltamoxifen), and NDDtam (N-desdimethyltamoxifen) were positively correlated to age (n = 151, P = 0.017, 0.045, 0.011, and 0.001 respectively). Up to tenfold inter-patient variation in the serum concentrations was observed. The median (inter-patient range) of the concentrations 4OHNDtam in the age groups 30-49, 50-69 and &gt;69 years were 44 (65) ng/ml, 51 (116) ng/ml, and 54 (159) ng/ml, respectively. We conclude that the serum concentrations of 4OHNDtam (endoxifen), tamoxifen and its demethylated metabolites increase with age during steady state tamoxifen treatment. The observed high inter-patient range in serum concentrations of tamoxifen and its metabolites, especially in the highest age group, suggest that use of therapeutic monitoring of tamoxifen and its metabolites is warranted.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-13.
Abstract P1-13-16: Women commencing with anastrozole, letrozole or tamoxifen: The impact of comorbidity and demographics on initial choice
Authors: Boyle F , Kemp A , Preen DB , Saunders C , Bulsara M , Malacova E , Roughead EE 
Published: August 2014

Abstract
Background: Australian clinical guidelines recommend post-surgical endocrine therapy for all women with early, hormone-dependent breast cancer. Guidelines specify tamoxifen as first-line therapy for pre-menopausal women, and either tamoxifen or an aromatase inhibitor for post-menopausal women depending on their risk of recurrence which is based on tumour size and other prognostic indicators. Tamoxifen and the aromatase inhibitors have different side effect profiles and therefore comorbidity may also influence choice of therapy. We examined comorbidities, and the clinical and demographic characteristics of women initiated on different endocrine therapies for breast cancer in Australian practice.
Method: We identified the first dispensing of tamoxifen, anastrozole or letrozole for women diagnosed with invasive breast cancer in the 45 and Up Study between January 2003 and December 2009 (n = 1383). Unit-level pharmacy and medical service claims, hospital separations, and Cancer Registry records were linked to self-reported data to determine menopause status at diagnosis, tumour size, age, change in subsidy restrictions, and specified comorbidities which may affect choice of therapy (i.e. arthritis, endometrial cancer, osteoporosis, thromboembolism). Chi-square tests and multivariate generalised linear models were used to compare the characteristics of post-menopausal women initiated on different therapies.
Results: The majority of pre-menopausal women commenced therapy with tamoxifen (93%). Tamoxifen was the predominant therapy for post-menopausal women with tumours ≤1cm (54%), and anastrozole most common for those with larger tumours (49%). Post-menopausal women with osteoporosis were less likely to commence an aromatase inhibitor compared with tamoxifen (anastrozole RR = 0.7, 95%CI = 0.5-0.9, P = 0.019; letrozole RR = 0.6, 95%CI = 0.3-0.9, P = 0.033) and those with arthritis were 1.6-times more likely to commence with letrozole than anastrozole (95%CI = 1.6-2.3, P = 0.004). Tamoxifen was more likely to be initiated in women with large tumours who also had comorbid arthritis or were aged ≥75 years. Changes in subsidy restrictions were associated with significant increases in the proportion of post-menopausal women commencing an aromatase inhibitor rather than tamoxifen (anastrozole RR = 7.0; letrozole RR = 18.5).
Conclusions: The findings show clinical guidelines regarding endocrine therapies are being followed in Australian practice, particularly in relation to menopause status and tumour size as a recurrence risk factor. The findings also indicate there is interplay of comorbidity and choice of therapy for older women and those with arthritis or osteoporosis.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-16.
Abstract P1-15-03: Preoperative endocrine treatment with letrozole ± triptorelin in patients with ER (estrogen receptor) and PgR (progesterone receptor) positive locally advanced breast cancer
Authors: Mazza M , Luini A , Veronesi P , Intra M , Bagnardi V , Sangalli F , Iorfida M , Munzone E , Colleoni M 
Published: August 2014

Abstract
Background: Neoadjuvant endocrine therapy demonstrated activity in endocrine responsive locally advanced breast cancer. Proper duration of neoadjuvant therapy has not yet established. We aimed to assess the efficacy and safety of longer duration of letrozole alone or combined with triptorelin in pre-or postmenopausal breast cancer patients.
Methods: Premenopausal and postmenopausal patients (pts) with ER and PgR-positive &gt; 50% of the cells, HER2-negative, T2-T4b breast cancer were considered eligible. Patients received letrozole 2,5 mg per day (plus triptorelin 3,75 mg/month in premenopausal pts) for 3-9 months. Tumor response was measured by caliper, ultrasound (US) and mammography. The primary endpoint was overall tumour response (ORR) (complete response plus partial response), during the neoadjuvant treatment period for the intention-to-treat population.
Results: Between 2009 and 2013, 54 pts were enrolled and 46 (34 pre- and 12 post-menopausal) pts were evaluable for ORR. Median age was 44 and 55 years, respectively. 44 patients are evaluable. The ORR was 77% in the premenopausal group and 67% in the postmenopausal group. One premenopausal patient had a pathological complete response (pCR). The mean time to complete/partial response was 4.9 months (95% CI: 3.8-6.0) in the premenopausal group and 3.6 months (95% CI: 0.8-6.4) in the postmenopausal group. Overall, 56% of premenopausal and 58% of postmenopausal pts underwent breast conservative surgery. Ki67-LI after surgery had a mean decrease of 33% (95% CI: 16%-50%, p-value = 0.0005) and 42% (95% CI: 18%-65%, p-value = 0.0030) in pre-and postmenopausal pts, respectively. Therapy was well tolerated in both groups with no grade 3/4 toxicity. The most common adverse events in both groups were hot flashes, fatigue, arthralgias/stiffness, and myalgias.
Conclusions: The results of this preliminary analysis support neoadjuvant endocrine therapy for a duration of up to 9 months. The combination of letrozole plus triptorelin might represent an alternative neoadjuvant treatment option for premenopausal women with early stage endocrine-responsive breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-15-03.
Abstract P1-16-01: Skeletal-related events (SRE) prevented in breast cancer patients with bone metastases in the United States (US)
Authors: Arellano J , Chen K , Halperin M , Danese M 
Published: August 2014

Abstract
Background: SREs are potentially debilitating consequences of bone metastases in advanced stage cancers. Bone-targeting agents (BTAs), including denosumab and intravenous zoledronic acid (ZA) are approved to prevent SREs. The purpose of this study was to estimate the annual number of SREs that might occur in US women with breast cancer without intervention, and to estimate the SREs that could be prevented with denosumab or with ZA.
Methods: A model was developed using US prevalence estimates (Li, et al. 2011), combined with 2012 Census projections to estimate the number of SREs in women with bone metastases from breast cancer in 2012. SREs were defined as fracture, radiation to bone, surgery to bone, or spinal cord compression. The SRE rate in untreated patients was estimated by pooling rates from 8 treatment groups in 4 trials (Lipton 2000; Rosen 2003; Kohno 2005; Stopeck 2010), applying the appropriate relative hazard (RH) of first and subsequent SRE from a network meta-analysis (NMA;Ford 2012), and weighting by the sample size. The denosumab and ZA SRE rates were derived from the pooled rate and the RH estimates from the NMA. Ineligibility was defined as one of the following: all uninsured patients (US Census) and patients discontinuing due to adverse events or non-compliance (ZA 4.6%, denosumab 3.7%; Stopeck 2010). Patients with kidney clearance &lt; 30 ml/min (1.3%; Launay-Vacher 2007) were considered ineligible to receive ZA. Using Monte Carlo sampling, we derived mean estimates and 95% simulation intervals (SI) based on 1,000 samples.
Results: Overall, we estimated 96,598 women with breast cancer had bone metastases at any given time in 2012. We estimated 164,673 (95% SI 110,153 to 220,770) SREs would have occurred in 2012 if no women were treated. Assuming all women eligible to receive ZA were treated with ZA (n = 83,870), the number of SREs would have been 108,233 (decline of 56,440, 95% SI 13,744 to 100,098); assuming all women eligible to received denosumab were treated with denosumab (n = 85,780), the number of SREs would have been 86,992 (decline of 77,681, 95% SI 38,327 to 120,521). The incremental difference between denosumab and ZA was 21,242 (95% SI 9,312 to 36,674).
Conclusions: The use of BTAs to reduce SRE risk, including denosumab, could result in reductions in the number of adverse skeletal complications in the US.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-16-01.
Abstract P1-17-02: Male breast carcinoma: A clinicopathological and immunohistochemical characterization study
Authors: Zhou R , Yu L , Yu B , Zhou S , Bi R , Shui R , Lu H , Cai X , Yang W 
Published: August 2014

Abstract
AIM Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were also evaluated.
METHODS Clinical and pathological data on 73 cases of male breast carcinoma were collected and microscopic pathological features were examined. Immunostaining for ER, PR, HER2, Ki-67, CK5/6, EGFR, GCDFP15, MGB, AR and FOXP1 was performed and the molecular subtype was classified.
RESULTS Invasive carcinoma of no special type was the major histological type in our study group (71.2%, 52/73). Except for 4 cases of carcinoma in situ, forty-two male invasive carcinomas (42/69, 60.9%) were classified as luminal A subtype while 24 cases (24/69, 34.8%) were classified as luminal B subtype. Only 2 cases of basal-like subtype and 1 case of HER2 positive subtype were identified in this group. Nuclear immunostaining of AR and FOXP1 could be observed in 82.4% (48/57) and 71.9% (41/57) of the cases respectively. Cases of luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than those of luminal B subtype (34.8%, 8/23 and 43.5%, 10/23, respectively).
CONCLUSIONS Invasive carcinoma of no special type was the most common histological type in male breast carcinoma. Our study revealed that luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 were highly expressed in male breast cancer. Luminal A subtype tends to express GCDFP15 and MGB more frequently than luminal B subtype.
KEYWORDS: breast carcinoma, male, molecular subtype, immunohistochemistry.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-17-02.
Abstract P2-01-05: Mammographic microcalcifications and breast cancer tumorigenesis: A radiologic-pathologic analysis
Authors: Naseem M , Murray J , Hilton JF , Manoharan AS , Polenz CK , Han D , Hogeveen S , Heersink RL , Bookwala A , Muradali D , Karamchandani J , Bell D , Brezden-Masley CB 
Published: August 2014

Abstract
Background: Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. They serve as key diagnostic radiological features for localization of malignancy. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their role in breast cancer tumorigenesis is currently unknown. The purpose of this study was to investigate the relationship between mammographic MCs and breast cancer pathology.
Methods: A retrospective chart review was performed for 1015 women treated for breast cancer between 2000-2012 at St. Michael's Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 overexpression and presence of MCs were collected for breast cancer patients. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All tests were two-sided and p-values less than 0.05 were considered statistically significant.
Results: A total of 1015 patient charts were included; 78 (7.7%) patients had metastatic carcinoma and were excluded from analysis. About 38.3% (287/1015) of the patients presented with mammographic MCs. Patients were more likely to have MCs if they were HER-2 positive (52.9%) as opposed to being HER-2 negative (33.8%) (p&lt;0.001). There was a significant association between MCs and having heterogeneous breast density (p = 0.031) and having multifocal disease (p = 0.044). Patients with invasive ductal carcinomas (40.9%) were more likely to present with MCs than were patients with other tumor histology (p = 0.001). There was a positive correlation between MCs and tumor grade (p = 0.057), with grade III tumors presenting with the most MCs (41.3%), followed by grade II (39.8%) and grade I (30.7%). There was no significant association between mean age, mean tumor size, ER and PR status with the presence of MCs.
Conclusion: This is the largest study analyzing data over a 12 year period, suggesting that the appearance of MCs on mammograms is strongly associated with HER-2 overexpression, invasive ductal carcinoma, heterogeneous breast density and multifocal breast cancers. Since HER-2 is implicated in mediating aggressive tumor growth and metastasis, future studies should investigate the molecular pathways connecting HER-2 overexpression and MC development. This would help better understand the role of MCs in breast cancer tumorigenesis.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-01-05.
Abstract P2-01-06: How much agreement can we expect on BI-RADS mammographic findings? Observer agreement among 10 expert mammographers
Authors: Wisner DJ , Feig S , Joe B , Hargreaves J , Ojeda-Fournier H , Bassett L , Aminololama-Shakeri S , DeGuzman JQ , Flowers CI , Campbell JE , Elson S , Retallack H , Wells C 
Published: August 2014

Abstract
Purpose: To determine the agreement between expert readers on mammographic findings and calcification patterns.
Materials and Methods: Ten academic radiologists from 5 centers reviewed 250 de-identified mammographic cases without prior exams which were previously assessed as BI-RADS 4 or 5 with subsequent pathologic diagnosis by percutaneous or surgical biopsy. For benign cases diagnosed by percutaneous biopsy, 1 year of benign or negative imaging follow-up was required. Using standardized forms, each radiologist assessed the presence of any suspicious mammographic findings (microcalcifications, asymmetry (1-vew), focal asymmetry (2-view), architectural distortion), and the morphology (none, round/punctate, amorphous, coarse heterogeneous, fine pleomorphic, fine linear branching) and distribution (none, diffuse, regional, grouped, linear, segmental) of any identified microcalcifications. Agreement between radiologists for presence/absence of findings, morphology, and distribution of calcifications was determined by calculating the Kappa (k) coefficient with 95% confidence interval (95% CI). The kappa coefficient proposed strength of agreement is ≤0 = poor, .01-.20 = slight, .21-.40 = fair, .41-.60 = moderate, .61-.80 = substantial, and .81-1 = almost perfect, as established by Landis and Koch.1
Results: Of the 250 lesions, 156 (62%) were benign and 94 (38%) malignant. Agreement among the 10 expert readers was strongest for recognizing the presence/absence of calcifications (k = 0.82, 95% CI: 0.80-84), “almost perfect”). There was substantial agreement among the readers for the identification of a mass (k = 0.67, 95% CI: 0.66-69), whereas agreement was fair for the presence of a focal (2-view) asymmetry (k = 0.21, 95% CI: 0.1900.23) or architectural distortion (k = 0.28, 95%CI: 0.26-0.30). Agreement for asymmetries (1-view) was slight (k = 0.09, 95%CI: 0.08-0.11). Among the 6 categories of microcalcification distribution and morphology, reader agreement was moderate (distribution k = 0.60, 95%CI:0.59-0.61; morphology k = 0.51, 95%CI: 0.50-0.52).
Conclusion: When asked to characterize suspicious mammographic findings, this sampling of 10 expert academic breast imagers across 5 centers revealed varying strength of agreement for different findings, ranging from slight to almost perfect. Strongest agreement (“almost perfect”) was found for identifying the presence or absence of microcalcifications, although agreement drops to moderate when readers are asked to specify microcalcification morphology and distribution.
1 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics.1977;33:159-174.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-01-06.
Abstract P2-01-07: Analysis of the relationship between breast cancer risk-related gene polymorphisms, ESR1/6q25.1-rs2046210 and mammographic breast density
Authors: Nogami T , Taira N , Mizoo T , Nishiyama K , Iwamoto T , Motoki T , Shien T , Matsuoka J , Doihara H , Ishihara S , Kawai H , Kawasaki K , Ogasawara Y , Ishibe Y 
Published: August 2014

Abstract
Background: Based on the results of a case-control study performed in Japan (Okayama and Kagawa), it was revealed that gene polymorphisms of the estrogen receptor (single nucleotide polymorphisms, SNPs), ESR1/6q25.1-rs2046210 and rs3757318, were closely related to breast cancer risk in Japanese women, and that the odds ratios per allele of individual SNPs were 1.37 [95% CI: 1.1 - 1.7] and 1.33 [1.04 - 1.7], respectively (San Antonio Breast Cancer Symposium 2012, Mizoo et al.). To examine the effects of these SNPs on the pathogenic mechanism of breast cancer, we analyzed the relationship of SNPs with reproductive/physiological factors (age of menarche and number of births), physical factors (height and Body Mass Index [BMI]), family history and mammographic breast density.
Methods: Among the patients enrolled in the case-control study, the patients who could be evaluated regarding their lifestyle, SNPs and mammographic breast density were divided into the case group (N = 394) and the control group (N = 511) as the dataset for the study. SNPs were analyzed using the TaqMan genotyping assay® for blood samples. In the analysis of the relationship between SNPs and breast cancer risk, the odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using logistic regression analysis. For the analysis of the relationship between SNPs and the factors, t-test and chi-square test were used.
Results: In our dataset, the age-adjusted OR [95% CI] of ESR1/6q25.1-rs2046210 and rs3757318 were 2.22 [1.41 - 3.55] (AA vs. GG) and 2.12 [1.2 - 3.8] (AA vs. GG), respectively, suggesting that they would be significant risk factors. As a result of analyzing the relationship between SNPs and other factors, a significantly lower BMI was observed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.014, t-test). Regarding the mammographic breast density, a significantly higher proportion of mammary glands with high density was confirmed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.0389, chi-square test). The tendency towards a high mammographic breast density in the rs2046210 risk allele AA/AG was also confirmed based upon a stratified analysis of the case and control groups before and after menopause, and a significant correlation was observed, especially before menopause (p = 0.026, chi-square test).
Conclusion: Mammographic high breast density is generally considered as one of the breast cancer risks, and it was suggested that gene polymorphisms of ESR1/6q25.1-rs2046210 might affect mammographic breast density.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-01-07.