bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis of Metaplastic Breast Cancer: Poorer Than the Rest of Triple-Negative Breast Cancer.
Authors: Jung S. , Kim H. , Min S. , Lee S. , Park C. , Kwon Y. , Kim E. , Ko K. , Lee K. , Park I. , Shin K. , Lee S. , Kim S. , Kang H. , Ro J. 
Published: December 2010

Abstract
Background: The biologic behavior of metaplastic breast cancer (MBC) has not been well elucidated due to its rarity and heterogeneity. This study was designed to assess the clinical and tumor characteristics and outcomes of MBC patients as compared with invasive ductal carcinoma (IDC) in general and the triple-negative (TN) subtype.Materials and methods: This study included 35 MBC and 2,839 IDC patients diagnosed at the National Cancer Center, Korea between 2000 and 2008. We, retrospectively, reviewed the clinicopathologic characteristics and clinical outcomes.Results: The mean age was 47.4 years for MBC group and 48.3 years for IDC group. The MBC group presented with larger tumors (≥ T2, 78.8% vs 41.0%; P&lt;0.001), higher histologic grade (grade 3, 92.0% vs 44.6%; P&lt;0.001), fewer ER and PgR positivity (ER+, 14.3% vs 69.0% ; P&lt;0.001 and PgR+, 25.7% vs 66.1%; P&lt;0.001), higher Ki-67 expression (35.5%±26.2% vs 20.6% ±19.8%; P=0.024) and more TN subtypes (48.6% vs 11.9%; P&lt;0.001) than IDC group. Excluding de novo stage IV patients, 14 of 32 (43.7%) MBC patients and 260 of 2782 (9.4%) IDC patents developed disease recurrence with a median follow-up of 36.2 months (range, 4.9-117.8 months). MBC was a poor prognostic factor for disease recurrence in univariate and multivariate analysis (HR 5.19; 95% CI, 2.04-13.18; P=0.001). MBC patients demonstrated aggressive pathologic features and experienced more disease recurrence (HR 4.77; 95% CI, 1.99-11.44; P=0.001) even when compared with 330 patients with TN subtype.Conclusions:Patients with metaplastic breast carcinoma appeared to have inherent aggressive tumor biology with poorer clinical outcomes than those with IDC in general and TN subtype.Partly supported by NCC Grant No 0610240
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4057.
Prognostic Factors for Breast Cancer with 10 or More Lymph Nodes Metastasis.
Authors: Choi S. , Park H. , Lee J. , Park S. , Park B. 
Published: December 2010

Abstract
Background: Although the proportion of early breast cancer has been increased, advanced breast cancers of N3 stage still compose about 10% of all breast cancers. The purpose of this study was to investigate factors associated with prognosis of breast cancers with extensive nodal metastasis.Patients and method: Of 3912 invasive breast cancer patients who underwent surgery between April 1986 and May 2006 at Severance Hospital, patients who had 10 or more metastatic lymph nodes without distant metastasis were 304 (7.8%). With 55 months of median follow-up period, their clinicopathologic characteristics, follow-up of survival and the factors associated with disease free survival (DFS) and overall survival (OS) were analyzed.Result: Median age was 46.5 years and median number of positive lymph node was 16 with metastases to supraclavicular lymph nodes in 14 patients (4.6%). Median 5-year DFS rate were 42.4% and OS rate was 47.5%. In the Kaplan-Meier survival analysis, age less than 35 years (19.4% vs. 45.9%; p=0.001), the history of NAC (13.1% vs. 48.8%; p&lt;0.001), T4 stage (15.8% vs. 45.8%, excluding T4d; p&lt;0.001), 20 or more positive lymph nodes (27.0% vs. 50.2%; p&lt;0.001), lymphovascular invasion (20.2% vs. 48.4%; p=0.003), and negative progesterone receptor (32.8% vs. 49.3%; p=0.003) were significantly associated to poor 5-year DFS. For 5-year OS, age less than 35 years (43.8% vs. 59.7%; p=0.033), the history of NAC (28.0% VS. 63.8%; p&lt;0.001), T4 stage (21.1% vs. 61.0%, excluding T4d; p=0.001), 20 or more positive lymph nodes (48.9% vs. 63.8%; p&lt;0.001), and negative progesterone receptor (49.0% vs. 64.2%; p=0.013) were statistically significant. On the multivariate analysis, significant factors associated with poor DFS and OS were 20 or more metastatic lymph nodes (relative risk [RR] =1.598 and p=0.024 for DFS; RR=1.956 and p&lt;0.001 for OS), the history of neoadjuvant chemotherapy (RR=3.163 and p&lt;0.001 for DFS; RR=2.900 and p&lt;0.001 for OS). The contribution of lymphovascular invasion was significant only to DFS on the multivariate analysis.Conclusion: The patients with the same N3 stage show various prognosis. Clinical trial using new therapeutic agents should be applied in advanced breast cancers with high risk, which are predicted to be refractory to conventional adjuvant therapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4064.
Should Minors Be Offered BRCA1/2 Testing for Hereditary Breast Cancer? Opinions of Parents Who Have Undergone BRCA1/2 Testing.
Authors: Bradbury A. , Patrick-Miller L. , Li T. , Egleston B. , Sands C. , Schmidheiser H. , Hlubocky F. , Olopade O. , Daly M. , Daugherty C. 
Published: December 2010

Abstract
Background: Professional societies recommend against the genetic testing of minors for hereditary cancer syndromes that present in adulthood. Yet, many adolescent specialists indicate that they would consider BRCA1/2 testing of minor children. We conducted interviews with parents who have had BRCA1/2 testing, to evaluate their opinions regarding the genetic testing of minors for BRCA1/2. Methods: 244 parents, including 67 BRCA1/2 mutation carriers (MCs), 140 parents with uninformative negative results (UN), 14 with true negative results (TN) & 23 with a variant of uncertain significance (VUS), from two cancer risk assessment programs completed semi-structured interviews. We used multiple logistic regressions to evaluate the associations among biomedical factors, demographic factors and support of testing minors. Wald tests and likelihood ratio tests were used to assess statistical significance for binary covariates and nominal covariates. Results: 38% of parents supported testing minors for BRCA1/2 in response to a dichotomous (Y/N) question. Support was greatest among parents with TN (64%) and UN (40%) results and lower among MCs (31%) and parents with a VUS (26%). In a multivariable analysis, support was greatest among parents who tested negative (p=0.02), were of minority race (p=0.06) and among fathers (&lt;0.01). Responses to open-ended questions suggest that 27% of parents unconditionally support testing of minors, and 25% support testing only in certain situations. Psychological risks, a lack of medical necessity and the insufficient maturity of minors, were frequent concerns of those opposed. The potential to positively impact minors' health behaviors was the most reported reason for supporting testing. Conclusions: Up to 52% of parents who have undergone BRCA1/2 testing support pediatric testing for BRCA1/2. Given willingness among general and pediatric practitioners and interest among parents, further research is necessary to formally evaluate the risks and benefits of providing genetic testing to minors for adult-onset hereditary cancer syndromes in order to inform clinical practice and public policy that will ensure optimal psychosocial and medical outcomes for all members of families at risk for hereditary cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4071.
Preliminary Results of the Mutational Analysis of the TP53 Gene in Women Diagnosed with Breast Cancer before the Age of 35 Years and Negative for BRCA1 and BRCA2 Mutations.
Authors: Balmaña J. , Ferro J. , Gutierrez-Enríquez S. , Masas M. , Gadea N. , Fortuny D. , Saura C. , Díez O. , Díez O. 
Published: December 2010

Abstract
Background: Early onset breast cancer is part of the tumor spectrum in the Li-Fraumeni syndrome (MIM 151623), which is associated with germ-line mutations in the TP53 gene. The aim of the study is to determine the presence of inherited mutations in TP53 in women with early onset breast cancer regardless of their family history and after having obtained a negative result for the BRCA1 and BRCA2 mutations. Patients and methods: We analyzed 41 women with breast cancer (BC) diagnosed before the age of 35 years and a negative result for the BRCA1 and BRCA2 genes (analyzed by direct sequencing and MLPA). Patients were classified according their family history in three groups: A) no family history of cancer (n=11); B) family history of breast/ovarian cancer (BC/OC) (n=22); C) family history of other neoplasms (pancreas, kidney, brain, leukemia) without fulfilling the classical Li-Fraumeni criteria (n=8). The analysis of the TP53 gene was carried out by PCR amplification and direct sequencing of the exons 4 to 10. Analysis of the remaining exons, the 5' and 3' UTR regions of the gene, and the detection of large rearrangements are in progress. Results: Among the 41 women we identified two (4.8%) deleterious mutations, and both were observed in group C (2/8, 25%): c.375G&gt;A in exon 4 (splicing mutation) and c.524G&gt;A in exon 5 (p.R175H). Conclusions: These preliminary results suggest that, after a negative result in the analysis of the BRCA1 and BRCA2 genes, TP53 mutations may play a relevant etiological role in the genetic predisposition of early onset BC, especially in those families with presence of different neoplasms
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4072.
Prevalence Rates of Pathogenic Mutations in the BRCA1 and BRCA2 Genes in Families with Different Disease Histories: Results from the German Consortium for Hereditary Breast and Ovarian Cancer.
Authors: Kast K. , Schmutzler R. , Distler W. , Arnold N. , Bartram C. , Bick U. , Froster U. , Grimm T. , Kreienberg R. , Naestle-Kraemling C. , Schlegelberger B. , Wieacker P. , Meindl A. , Engel C. 
Published: December 2010

Abstract
Introduction: In the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), a large number of families with different histories of breast and ovarian cancers was screened for pathogenic mutations in the tumor-suppressor genes BRCA1/2. We here aimed to analyse the prevalence rates of pathogenic mutations for various familial disease histories.Methods: From 1997-2009 more than 6,000 families were screened for pathogenic mutations in BRCA1/2. Mutation analysis was performed by DHPLC (denaturing high-performance liquid chromatography) pre-screening, direct sequencing of suspect fragments and MLPA (multiplex ligation-dependant probe amplification) in at least one index case of these families. Complete pedigree information over three generations was used for the analysis. All lineages within a pedigree were traced and checked for the presence of several predefined disease histories.Results: Detailed mutation prevalence rates have been determined for a variety of familial risk situations. The highest mutation prevalence rate (78%, 95%CI 67-87%) was seen in families with at least two relatives affected by pre-menopausal breast cancer and at least two affected by ovarian cancer at any age. Importantly, the presence of a single woman affected by breast and ovarian cancer or bilateral breast cancer with first breast cancer under the age of 41 was associated with a BRCA1/2 mutation prevalence of 53% (95%CI 48-59%) and 34% (95%CI 23-47%) respectively. Interestingly, low mutation prevalence rates of &lt;10% were found in families with only one case of male breast cancer (9%, 95%CI 4-19%), and in families with three or more cases of postmenopausal breast cancer (7%, 95%CI 4-14%), the former being only BRCA2 mutations. Overall, the mutation prevalence was 27% (95% CI 26-29%) in the whole cohort.Conclusion: We provide comprehensive estimates for BRCA1/2 mutation prevalence rates that are based on a large number of families with comprehensive pedigree information. Such estimates can be used to develop cost effective screening strategies for public health care providers.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4073.
Communicating Risk of Hereditary Breast/Ovarian Cancer among Underserved Women: Interim Findings from the CREdIT Study.
Authors: Braithwaite D. , Metrikin M. , Lee R. , Beattie M. , Luce J. 
Published: December 2010

Abstract
Purpose: With the support of the Avon Foundation, genetic counseling is available to underserved populations at the San Francisco General Hospital. One of the major challenges in providing genetic counseling for hereditary breast and ovarian cancer among these women is the lack of culturally appropriate educational tools.The purpose of this study is to evaluate the use of a Cancer Risk Educational Intervention (CREdIT), a novel audio-visual PowerPoint-based tool as an adjunct to genetic counseling. Methods: CREdIT took on average 15 minutes to view and was available in English and Spanish. It employed non-scientific images and language specifically designed for use by our target population. Participant questionnaires evaluating patient satisfaction, risk perception, knowledge of cancer genetics, and anxiety were administered before and after the intervention and at 1 year follow-up. For each of the continuous outcomes, differences from pre- to post-intervention were assessed with analyses of variance, while chi-squared tests were used to examine the differences among categorical variables. Results: A total of 52 women of diverse backgrounds who were on average 47 years old (range 27-69) took part in the study. Of these, 15% reported previous history of cancer, 58% were non-white and 59% had a below college education. Twenty-one percent viewed the presentation in Spanish. Following the presentation of CREdIT, we found an increase in the knowledge of BRCA inheritance and associated risk of malignancy, and options for risk reduction (all p &lt; .05). However, participants' perceived risk perception did not change from baseline to post-CREdIT (p=.73). Virtually all participants (98%) reported that CREdIT helped them learn more about cancer risk. Although patient anxiety decreased post-CREdIT (p=.02), 29% patients reported that CREdIT made them worry more about cancer. Among 32 participants who were interviewed at the long-term follow-up, we found that, compared to post-CREdIT, knowledge changed for only two of the seven questions (p&lt; .05). There were also no changes in anxiety or cancer worry compared to baseline (both p&lt; .05). Conclusions: These interim findings suggest that our intervention was successful at increasing knowledge regarding breast cancer genetics without increasing anxiety or cancer worry. Our long-term goal is to perform a large-scale evaluation among underserved women at risk of hereditary cancer across the Avon Foundation-supported clinics nationwide.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4074.
Prevalence of BRCA1/2 Mutations and Variants in a Southwest Hispanic Population.
Authors: Ballinger L. , Wallace A. , Dayao Z. , Royce M. 
Published: December 2010

Abstract
Background: There have been a limited number of studies of BRCA mutations in U.S. Hispanics. Of those previously published, two common mutations have been identified, and estimates of their prevalence vary, depending on the population studied. North American Hispanics are a heterogeneous population, consisting of Mexican, Caribbean, Central and South American descent. Furthermore, each of these groups has a significant admixture of other racial and ethnic groups. A limitation of most published studies is that they do not differentiate between these ethnically and genetically diverse Hispanics. In New Mexico, there is a large but relatively homogeneous Hispanic population. Since the University of New Mexico Cancer Center (UNMCC), sees a socially and economically diverse group of patients, the demographics of its Hispanic patients are similar to those of the whole state. Herein, we describe the prevalence of specific mutations and variants in Hispanics from a clinic-based population.Materials and Methods: A chart review of all patients evaluated for hereditary breast cancer risk from 1/1/2005 through 5/30/2009 was conducted. Data collected included patient age, self-reported ethnicity (including, if known, area of ancestral origin), cancer status, family history, BRCA testing status, including method (comprehensive analysis, Ashkenazi panel, single site, and/or comprehensive rearrangement testing), and what, if any, BRCA mutations or variants were found.Results: BRCA testing was performed on 312 patients, 70 of whom identified as NM Hispanic. Another 24 patients were of other Hispanic origins, mainly Mexican. Approximately 30% of those identified as NM Hispanic tested positive for mutations, and most mutations were found in BRCA1. All variants of uncertain significance in this group were found in BRCA2. Approximately 20% of other Hispanics tested positive for mutations, but variants of uncertain significance comprised a higher percentage of the results. In New Mexican Hispanics, 47% tested positive for BRCA1 187delAG, and another 19% tested positive for BRCA1 deletion of exons 9-12, both of which are previously described in the Hispanic populations from southern California and Colorado.Discussion: Although we found a large proportion of previously described mutations in our Hispanic population, 34% had other mutations. In this group, no mutation was seen more than once, indicating the need to offer these patients comprehensive BRCA testing or a combination of founder mutations testing followed by comprehensive sequencing. As most of our patients, even those identified as “Other Hispanic” have Colonial Spanish origins (via Mexico), this data is likely not applicable to Hispanics with other admixtures or historic arrival in the New World, such as Hispanics from the Caribbean.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4077.
A New Safer and More Effective Triphenylethylene Antiestrogen (SS1020) for the Treatment and Prevention of Breast Cancer.
Authors: Shibutani S. , Okamoto Y. , Suzuki N. , Liu X. , Kim H. , Laxmi Y. 
Published: December 2010

Abstract
Background: Tamoxifen (TAM) is widely used as a first-line endocrine therapy for breast cancer patients and as a prophylactic agent for women at high risk of developing this disease. Besides the significant benefit, long-term administration of TAM has serious side effects, including endometrial cancer. These side-effects are due to the DNA damaging and/or estrogenic action of the drug. Raloxifene (RAL) approved as a chemopreventive agent for postmenopausal women at high risk for invasive breast cancer retains an estrogenic action. RAL has a poor bioavailability. This makes it difficult to achieve adequate bioavailability by oral administration in humans. High doses are required to obtain an efficacy quivalent to that achieved with TAM. Several other antiestrogens were dropped out from the clinical trials due to their undesirable effects on the uterus. Therefore, development of new antiestrogen alternatives, but free of genotoxic and estrogenic potential, having significant antitumor potential beyond TAM and RAL is urgently required for breast cancer therapy and prevention.Results: SS1020 was developed as a new triphenylethylene antiestrogen in our laboratory. Although TAM is a hepatic carcinogen and produces a high level of DNA damage in rats, SS1020 did not produce such DNA damage. Unlike TAM and RAL, SS1020 had no detectable uterotrophic activity in OVX-rats even treated with a high dose (10 mg/kg). These indicate that SS1020 is free of genotoxic and estrogenic activities. The antitumor potential of SS1020 against 7,12-dimethyl-benz(a)anthracene (DMBA)-induced mammary carcinoma in rats and human MCF-7 breast cancer xenograft in athymic nude mice was superior to that of TAM and RAL. In addition, the development of estrogen-induced mammary tumor in rats was completed inhibited by dietary intake of SS1020, indicating that this compound has preventive potential. The bioavailability of SS1020 was approximately 35 times higher than that of RAL. The maximum blood concentration (493 ng/ml serum) of SS1020 was observed at 2 hour after the oral treatment while that of RAL (15.6 ng/ml) was at 6 hours, indicating that SS1020 is absorbed rapidly into the body. SS1020 has a much higher bioavailability than RAL, endowing it with higher antitumor potential than RAL.Conclusion: Taken together, SS1020 lacking genotoxic and estrogenic actions has anti-breast cancer activity superior to that of TAM and RAL and has a preventive potential. SS1020 is a safer and more effective antiestrogen candidate for breast cancer therapy and prevention.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4085.
A Phase II Study (FINDER 2) Comparing Three Dosing Regimens of Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Advanced Breast Cancer.
Authors: Pritchard K. , Rolski J. , Pápai Z. , Mauriac L. , Cardoso F. , Fukase K. , Lindemann J. , Macpherson M. , Neven P. 
Published: December 2010

Abstract
Background: The Faslodex Investigation of Dose evaluation in Estrogen Receptor-positive (ER+) advanced breast cancer (FINDER) 2 study investigated the efficacy, safety, and pharmacokinetic (PK) profile of 3 fulvestrant dosing regimens in postmenopausal women with ER+ advanced breast cancer, recurring/progressing after prior endocrine therapy.Objectives: Primary: to evaluate the objective response rate (ORR). Secondary included assessment of: time to progression (TTP), clinical benefit rate (CBR), duration of response (DOR), tolerability, and PK parameters.Methods: This randomized, double-blind, parallel-group, multicenter, Phase II study, evaluated patients (pts) randomized 1:1:1 to different doses of fulvestrant: 250 mg (approved dose [AD]; given on Days 0, 28 and every 28 days thereafter), 250 mg plus loading dose (LD; 500 mg on Day 0, then 250 mg on Days 14, 28 and every 28 days thereafter), and 500 mg (high dose [HD]; Days 0, 14 and 28 and every 28 days thereafter). Treatment continued until disease progression, or until any other criterion for discontinuation was met.Results: In total, 144 pts were randomized from 34 centers in 8 countries and 143 received treatment: fulvestrant AD (n=47); LD (n=50); HD (n=46). ORRs were: 8.5% (95% confidence interval [CI] 2.4-20.4%), 5.9% (1.2-16.2%), and 15.2% (6.3-28.9%) in the AD, LD, and HD arms, respectively. CBRs were: 31.9% (95% CI 19.1-47.1%), 47.1% (32.9-61.5%), and 47.8% (32.9-63.1%) for the AD, LD, and HD arms, respectively. Median TTP was numerically longer for the HD (6.0 months) and LD (6.1 months) arms vs the AD arm (3.1 months). The low number of responders in all treatment arms prevented DOR assessment. The incidence of adverse events (AEs) was similar in all groups (76.6% AD, 72.0% LD, 69.6% HD); few pts experienced serious AEs (4 pts AD, 9 LD, 4 HD) with no clustering of event type. AEs with an incidence of ≥10% (in any arm) were back pain, arthralgia, fatigue, injection-site pain, nausea, dyspnea, cough, and hot flash. Concentrations in the AD arm approached steady state in the 3rd month of dosing and within the 1st month for LD and HD. Exposure (AUC, Cmin and Cmax) appeared to be linear across the dose range studied and, for the 250mg arms, similar to that previously reported in Western populations (Studies 9238IL/0020 & 0021).Conclusion: No statistically significant differences in efficacy could be proven between AD, LD and HD given the widely overlapping CIs for median TTP. The tolerability profile was similar across the three dosing regimens. Steady-state concentrations were achieved earlier with LD and HD. A parallel study in Japanese pts will be used for comparisons of fulvestrant efficacy and tolerability in Japanese and non-Japanese pts.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4095.