bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pleomorphic lobular breast carcinoma: A review of 35 cases at a single institution.
Authors: Cox J. A. , Eltorky M. A. , Wolski M. J. , Sturgeon J. D. , Joyner M. M. , Markowitz A. B. , Hatch S. S. 
Published: February 2017

175 Background: Pleomorphic lobular carcinoma (PL) is an aggressive subtype of invasive lobular carcinoma. A previous report of 52 patients showed an increase in development of metastases for pleomorphic lobular carcinoma patients. There are relatively few case series reporting on this aggressive form of breast cancer. This report features a descriptive and survivorship comparison of a large case series of PL reviewed by a single breast pathologist. Methods: From 1993-2010 we retrospectively reviewed 198 cases of invasive lobular carcinomas, 35 cases (34 patients with one patient presenting with 2 independent cancers) of PL and 163 cases of non-pleomorphic invasive lobular carcinoma (NPL). The pathology was reviewed by a single breast pathologist and classified as either PL or NPL according to WHO classification. Kaplan-Meier survivals were computed and compared with a log rank test using SPSS 18. Overall survival (OS) was computed from date of diagnosis to date of last update (02/01/11). Progression free survival (PFS) until either local or metastatic failure was also computed. Results: The median follow-up was 59.5 months and 73 months, for NPL and PL patients respectively. The median age of diagnosis was 55 (range 40-80) and 58.67 (range 36-89) for PL and NPL groups. Of the NPL group, 75.5% were post-menopausal as opposed to 67.6% in the PL group. PL cases were ER positive 87.1% vs. 90.1% of the NPL cases. Her-2/neu status was known in nearly 50% of cases with 17 positive NPL cases and 5 positive PL cases. Clinical stage at presentation was stage IIB or less in 67.6% of the PL patients and 80.1% of the NPL patients. Six patients presented (17.6%) with metastatic disease in the PL group and 12 patients (7.7%) in the NPL group. None of the descriptive comparisons above were significantly different by χ2 analysis. PFS at 5 years was 30% and 21% in PL and NPL patients, respectively (p=0.73). OS at 5 years was 68.5% for PL patients and 83.9% for NPL patients (p=0.031). Conclusions: In this large case series of PL cases reviewed by a single breast pathologist, PL patients showed a statistically significant decreased OS, but no significant difference in PFS, at 5 years from diagnosis.
Prevalence of BRCA1 mutations in women with triple-negative breast cancer: A systematic review.
Authors: Tun N. M. , Villani G. M. , Ong K. 
Published: February 2017

181 Background: We have reported a strong association between “triple-negative” breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative] and the risk of having BRCA1 mutations in a meta-analysis. We hereby present a systematic review of a larger pool of specific data investigating the overall prevalence of BRCA1 mutations in women with TNBC. Methods: A Medline search combining the MeSH terms “BRCA” and “triple” and “negative” yielded 37 articles. A similar search in ASCO abstracts yielded 18 relevant articles. Prevalence in each study population as well as the overall prevalence was calculated. Results: 13 eligible studies (from year 2006 to 2011) including 1075 women with TNBC were identified. Out of 13, 1 study each was carried out on Ashkenazi Jewish and Hong Kong Chinese women respectively. Overall prevalence of BRCA1 mutations in women with TNBC is 20.93% (225 out of 1075) (range = 4.8%–43%). Ashkenazi Jewish women with TNBC have a higher-than-average prevalence of BRCA1 mutations (29.2%) although it is lower than the prevalence rates of some study populations. A remarkably low prevalence rate of BRCA1 mutations (4.8%) is found in Chinese women with TNBC. Conclusions: In view of the overall high prevalence rate of BRCA1 mutations (20.93%) in women with TNBC, genetic testing should be discussed with patients with TNBC. Further studies are suggested to evaluate the molecular basis of interestingly low BRCA1 prevalence (4.8%) in Chinese patients with TNBC.
Single institution's data on triple-negative breast cancer in African-American women.
Authors: Abuelgasim Ahmed K. A. , Ghanem Z. Y. , Aggarwal A. 
Published: February 2017

188 Background: Although African-American women (AAW) have lower incidence of breast cancer, they have higher breast cancer related mortality compared to Caucasian women (CW). The incidence of triple-negative breast cancer (TNBC) is as high as 20%-26% in AAW compared to 15% in CW. The incidence of TNBC is higher in women younger than age fifty, compared to non-triple-negative breast cancer (NTNBC). TNBC also presents at a more advanced stage. We studied the characteristics of TNBC in AAW diagnosed at Howard University Hospital. Methods: We identified all the newly diagnosed invasive breast cancer patients who had assessable data for ER, PR, and HER2/neu status from January 2004 to December of 2009, by reviewing our institution’s tumor registry. ER, PR positivity was determined if equal or more than 10% of the tumor cells tested positive by IHC stain. Her-2/neu was determined to be positive if the IHC stain was (3+). Tumors that tested equivocal (2+) were sent for FISH testing. Age and stage data was collected on all patients. Results: Between Jan 2004 and Dec of 2009, a total of 294 AAW were diagnosed with invasive breast cancer and had enough data for evaluation. Seventy four (25%) patients had TNBC. Among those, 22 patients (30%) were less than 50 years old at the time of diagnosis, compared to 57 patients (26%) of the NTNBC (P-value = 0.5). Fifty two (74%) patients with TNBC were diagnosed with early stage disease (stages 1 and 2), compared to 150 (73%) of the NTNBC (P-value = 1); with 4 patients with TNBC and 15 patients with NTNBC had missing staging. (See table.) Conclusions: The incidence of TNBC in our cohort of AAW is 25% which is the same as the incidence reported in the literature. Even though TNBC patients are known to have worse prognosis, this may not be attributed to the stage of the disease at presentation or the age of the patient since both group showed no statistically significant difference in both variables. [Table: see text]
Ethnic disparity of treatment initiation in women diagnosed with breast cancer.
Authors: Omaira M. , Mozayen M. , Mushtaq R. , Katato K. 
Published: February 2017

189 Background: Despite the major advances in early detection and treatment of breast cancer (BC), African American women, continued to have a higher mortality rates than Caucasians. Many studies have failed to identify a key factor to explain racial disparities in breast cancer outcome. These disparities persist even after controlling for insurance and socioeconomic settings. Data about delays in treatment initiation are limited and inconclusive. We intend to compare the time from diagnosis to the initiation of treatment between African American and Caucasian women diagnosed with BC in a single community-based cancer registry. Methods: Women aged 18 to 64 years with breast cancer were identified, between 1993 and 2009, using data from the Tumor Registry at Hurley Medical Center in Flint, Michigan. Patient’s characteristics obtained include age at diagnosis, race, stage, date of diagnosis, and date of treatment initiation. All patients were previously insured or became insured after diagnosis. Time from diagnosis to the initiation of treatment was calculated in days and compared between African American and Caucasian women using t-test. Results: A total of 1016 patients have been identified with diagnosis of BC. 23 patients were excluded due to missing data. 993 patients were analyzed. African Americans were 355 (36%), Caucasians 617 (62%), and other ethnicities 21 (2%). Mean age at diagnosis was (48.9) for African Americans versus (51.45) for Caucasians (p = 0.005). African American women were more likely to present with advanced stage (III, IV) than Caucasians (18% versus 12%, p = 0.009). African American women had significant delay in the treatment initiation of BC compared to Caucasians (31.11 versus 21.52 days, p < 0.0001). Conclusions: African American women were diagnosed with breast cancer at younger age and more advanced disease than Caucasians. African American women experienced significant delay in the initiation of therapy after diagnosis compared to Caucasians. However, the impact of an average delay of 10 days in treatment on overall survival is unknown. The exact explanation of this disparity is yet to be determined.
Microarray-based gene expression profiles to predict ELISA-derived uPA and PAI-1 levels in breast cancer biopsies: A comparison between fresh frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) samples.
Authors: Matuschek C. , Prisack H. B. , Boelke E. , Budach W. , Janni W. , Rezai M. , Bojar H. 
Published: February 2017

194 Background: The urokinase plasminogen-activator (uPA) and its inhibitor (PAI-1) predict the benefit of node-negative breast cancer patients from chemotherapy. The determination of uPA and PAI-1 need(s) large amounts of tumor tissue. In contrast, microarray-based gene expression profiling (MGEP) requires only small quantities of FF tissue and is applicable to FFPE archival tissue. Identification of MPEG-derived surrogate markers for ELISA-based uPA/PAI-1 may facilitate their analysis together with MPEG-based predictive genes and metagenes. Methods: Three groups of breast cancer biopsies were analysed. Group A: 136 FF tissues from 2008-2009, group B: 85 FF tissues from 2010, group C: 20 independent FFPE tissues. Gene expression was assessed by Agilent 4x44K microarrays. Results: For group A a significant correlation between protein expression of uPA and uPA gene (PLAU) expression (r = 0.627 p < 0.001) and PAI-1 and PAI-1 genes (SERPINE1)(r = 0.281 p = 0.001) was found. Top sets of genes correlated with uPA/PAI-1 protein expression were extracted. For group B additional sets of top correlated genes were identified. The correlation of individual genes with uPA/PAI-1 protein expression was highest for their genes themselves (PLAU: r = 0.694 p < 0.001; SERPINE1 (r = 0.469 p < 0.001). Subsequently consensus gene sets were identified with a good performance for both biopsy sets. Only genes which were significantly correlated with their counterparts in group C were selected, resulting in a final 11-gene model (uPA metagene) and a 6-gene model (PAI-1 metagene). They significantly correlated with uPA/PAI-1 protein expression in all groups of biopsies (uPA: group A: r = 0.621, p < 0.001; group B: r = 0.771, p < 0.001; group C: r = 0.665, p = 0.005; for PAI-1: group A: r = 0.569, p < 0.001; group B: r = 0.687, p < 0.001; group C: r = 0.683, p = 0.008). Conclusions: Reliable MPEG-derived metagenes as surrogate markers for ELISA-based uPA/PAI-1 expression were identified.
Geographic disparity in the use of surgical management (SM) and radiotherapy (RT) for female breast cancer (BC) in Wisconsin (WI).
Authors: Ho A. , White J. R. , Owen J. B. , Trentham-Dietz A. , Wilson J. F. 
Published: February 2017

209 Background: The WICaRE Program is a part of the cross sectional Patterns of Care Study–Breast and Prostate (PoC-BP) that sought to evaluate the patterns of BC care in the state WI and to identify areas for potential improvement in data collection and factors associated with variation in care. This study was to examine the geographic disparities in SM and the use of RT in female BC patients diagnosed in WI in 2004. Methods: The Wisconsin Cancer Reporting System (WCRS) receives reports from 130+ facilities. Information of patient (disease status, sociodemographic, treatment, county of residence) was obtained from cancer registries and supplemental data was reabstracted from medical charts across 66 counties. Geographic regions were counties grouped by WI Dept. of Health Services (DHS) as Northeastern (NE), Northern (N), Southeastern (SE), Southern (S), Western (W). Results: A total of 1037 cases were reported. 25% age 20-49, 49% age 50-69, and 28% age 70+; Caucasian had 82%, black 10% and others 8%. 34% had T1 stage, 9% T2, 4% T3+, and 53% TX-T0/unknown stage. 46% had reported mild comorbidity, 9% had moderate or severe comorbidity. Majority (73%) lived in the Metropolitan Statistical Area (MSA). 29% patients from NE region, 10% from N, 36% SE, 17% S and 8% W. Patients in the S and W had significantly lower % who received RT (46 and 48% respectively) than those in NE (61%), N (62%) and SE (63%), p=0.01; % mastectomy (MA) by regions were 43% (NE), 42% (N), 33% (SE), 47% (S) and 35% (W), p=0.009. Multivariate models adjusting for disease status, comorbidity, and sociodemographic factors showed that patients in MSA region were more likely to have RT compared to those in non-MSA (odds ratio, OR=1.66, 95%CI=1.14-2.40), but those in S were less likely than those in SE (OR=0.59, 95%CI=0.38-0.91). Patients in MSA had a decreased likelihood of undergoing mastectomy. NE (OR=1.6, 95%CI=1.08-2.29) and S (OR= 2.04, 95%CI=1.31-3.17) had significantly higher odds of having MA than those in SE. Conclusions: This study showed evidence of geographic disparity in medical care for BC patients in Wisconsin. Identifying factors mediating this disparity will help in developing appropriate treatment options and improving outcomes.
Breast cancer treatment resources and guideline-concordant treatment in Appalachia.
Authors: Yao N. , Hillemeier M. M. , Anderson R. T. 
Published: February 2017

216 Background: Appalachia has poorer cancer outcomes, but little research has been done regarding availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This study 1) examines associations between radiation therapy resources and receipt of radiotherapy after BCS in counties within Kentucky - a SEER state; and 2) describes spatial patterning of breast cancer treatment resources in all 13 Appalachian states. Methods: For the Kentucky analyses, county-level data from the Area Resource File and SEER registry are analyzed. Bivariate analyses and spatial lag regression using a 6-nearest neighboring counties matrix are conducted. The sample includes stage I or II primary breast cancer patients age 18+ years diagnosed in Kentucky during 2000-2007. The dependent variable is the county-level percentage of patients received BCS without radiation; independent variables include density of radiation therapy providers and facilities and other socioeconomic covariates. For the analyses of entire Appalachian region, descriptive analyses and exploratory spatial data analysis are conducted including 420 Appalachian counties and 644 non-Appalachian counties in 13 states. Results: In Kentucky 16.44% of 17,227 early stage breast cancer patients received BCS without radiation therapy (21.08% in Appalachia versus 14.80% in non-Appalachia, p<0.001). Appalachian Kentucky had significantly fewer radiation oncologists and radiation therapy facilities per capita than non-Appalachian Kentucky. The number of radiation therapy facilities per capita is negatively associated with rates of BCS without radiation when controlling for covariates. Analysis of 13 Appalachian states shows that Appalachian counties, especially in the Central and Southern regions, had significant fewer physicians per capita in Surgery, Anesthesia, Clinical Pathology, and Radiation Oncology. Clustering of scarce breast cancer care resources was observed in Central Appalachia. Conclusions: Appalachian counties, especially in central Appalachia, have fewer breast cancer treatment resources than non-Appalachian counties, and resource availability is associated with cancer health disparities.
Predictive factors of adjuvant therapy-related amenorrhea for patients with breast cancer.
Authors: Tamura N. , Kato T. , Shimizu C. , Kinoshita T. , Fujiwara Y. 
Published: February 2017

217 Background: Reproductive age breast cancer patients often experience therapy-related amenorrhea so preserving fertility after treatment is a major concern. Anti-mullerian hormone (AMH) values have been reported useful in predicting menopause for infertility treatment patients, but published information is limited regarding breast cancer patients. If amenorrhea can be predicted before treatment, breast cancer patients hoping to have children in the future can consider this information in choosing treatment. Our aim was to predict patient fertility using AMH values. Methods: Forty breast cancer patients, 25-45 years of age (median, 35.5), who received adjuvant chemotherapy (CT) or endocrine therapy (ET), had AMH values retrospectively assayed from frozen serum before and after treatment. AMH values were then analyzed in relation to clinicopathological factors using logistic analysis. Of 19 adjuvant CT patients whose AMH values could be assayed, Cox’s proportional hazard model indicated a correlation in terms of amenorrhea and time to menses resumption between clinicolpathological factors and AMH values. Results: The mean pretreatment AMH value for all 40 patients was 21.4pM (range, 3-78) and a correlation was demonstrated with patient age, but not breast cancer intrinsic subtype or stage. AMH values decreased to the lower limit after treatment for all CT patients regardless of age, but there was a difference in degree depending on patient age for ET patients. Of the 19 CT patients, the mean AMH value was 25.6pM (3-78). These patients all underwent a regimen of anthracycline with 11 (58%) also receiving a regimen of taxiane. After starting CT, 17 patients (89%) experienced amenorrhea, but 11 (59%) resumed menstruation within one year of finishing CT and 15 (78%) resumed within two years. There were no significant differences among CT patients in age, pretreatment AMH value, intrinsic subtype or stage, but patients receiving taxiane demonstrated a noteworthy trend. Conclusions: Although we were unable to predict menopause directly using AMH values given the small number of patients in this study, we could estimate the risk of menopause as being either low or high for CT patients based on age and type of regimen.
A nonrandomized observational trial of short-term preoperative endocrine therapy in ER-positive breast cancer to investigate change in genomic expression using the 21-gene breast cancer assay.
Authors: Bleznak A. D. , Dellers E. A. , Glenn-Porter B. , Kimmel S. , Chung H. , Yoshizawa C. , Burke E. , Davison D. S. , Chao C. 
Published: February 2017

221 Background: Preoperative systemic treatment is commonly employed for women with locally advanced breast cancer. Women with early-stage breast cancer, whose resections may be delayed for 30 to 60 days while they undergo preoperative evaluation, may benefit from receiving preoperative endocrine therapy while awaiting surgery. One rationale for not initiating such treatment is that the cancer may be rendered less chemosensitive. The 21-gene assay is a proven predictor of chemotherapy responsiveness. The objective of this study is to examine the association between recurrence score (RS) and ER, PR, and HER2 RT-PCR values in core biopsy and surgical specimens from patients treated with short term pre-operative endocrine therapy. Methods: Pre- and postmenopausal women with clinical T1-N0-M0, sonographically visible, ER-positive, HER2-negative breast cancer were eligible. Patients were treated with 4-8 weeks of preoperative endocrine therapy; letrozole if postmenopausal or tamoxifen if premenopausal. Clinical breast examination and ultrasound were conducted every two weeks, with the final ultrasound immediately prior to surgery. Tumor blocks from the core biopsy and surgical excision were submitted to Genomic Health, Inc., where RS, ER, PR, and HER2 results were obtained from each of the paired specimens. Results: Nineteen matching core biopsy and surgical specimens were available for analysis. Pearson correlation coefficients between core biopsy and excisional sample results were 0.89 for RS, 0.87 for ER, 0.72 for PR, and 0.77 for HER2. On average, small but statistically significant increases in RS and decreases in ER and PR were observed (all p < 0.005 from paired t-test). No obvious associations between these markers and clinical response were observed. Conclusions: In this small, hypothesis-generating study, paired RS and RT-PCR for ER/PR/HER2 remained correlated after short-term preoperative endocrine therapy. This study provides no suggestion of decreasing chemosensitivity during preoperative endocrine therapy, but additional research is warranted to explore these findings further.
Molecular markers for circulating tumor cells in breast cancer.
Authors: Zeillinger R. , Obermayr E. , Fink-Retter A. , Heinze G. , Reinthaller A. , Horvat R. , Castillo-Tong D. C. 
Published: February 2017

223 Background: Recently, we identified a six gene panel (CCNE2, DKFZp762E1312, EMP2, MAL2, PPIC, and SLC6A8) for the RT-qPCR based detection of circulating tumor cells (CTC) in breast cancer patients. The aim of the present study was to evaluate the gene panel in further blood samples. Methods: Blood samples were taken from breast cancer patients with metastatic disease (MBC, N=10) or with no evidence of disease (NED, N=30). Putative CTC were enriched by Oncoquick density gradient centrifugation. Total RNA was isolated with RNeasy Micro Kit (QIAgen). Template cDNA was generated with M-MLV Reverse Transcriptase, RNase H Minus (Promega) and random nonamers as primers. RT-qPCR was performed in duplicate reactions using TaqMan Assays (Applied Biosystems) with default thermal cycling parameters. Raw data were analyzed with the AB7900 Sequence Detection Software version 2.2.2 using automatic baseline correction and manual cycle threshold setting. Gene expression was normalized to GAPDH expression. A threshold value TX for each gene X was set at two standard deviations above the mean dCtX value in the healthy control group. A patient was defined as CTC-positive, if at least one gene marker was over-expressed compared to the defined threshold. Results: The gene panel consisting of CCNE2, DKFZp762E1312, EMP2, MAL2, PPIC, and SLC6A8 identified 4/11 MBC but only 5/27 NED patients as CTC positive (p=0.163). By adding known CTC markers (SCGB2A2, TFF1, FXYD3, AGR2, S100A18, and EPCAM) to the panel, 7/11 MBC but only 6/27 NED patients were CTC positive (p=0.018). The presence of CTC in NED patients correlated with pN staging (p=0.026). Only one out of the six CTC positive NED patients relapsed within the observation period (median 35 months, range 25-39 months from blood sampling). We observed no correlation of CTC positivity and recurrence in NED patients. Conclusions: The sensitivity of the RT-qPCR based CTC detection in breast cancer patients may be enhanced by adding known CTC markers (SCGB2A2, TFF1, FXYD3, AGR2, S100A18, and EPCAM) to the six gene panel (CCNE2, DKFZp762E1312, EMP2, MAL2, PPIC, and SLC6A8). Longer follow-up times are needed to evaluate the predictive value of the gene markers on survival.