bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testosterone Undecanoate Treatment Reduces Joint Morbidities Induced by Anastrozole Therapy in Postmenopausal Women with Breast Cancer: Results of a Double-Blind, Randomized Phase II Trial.
Authors: Birrell S. , Tilley W. 
Published: December 2010

Abstract
Background: Approximately 50% of women taking 3rd generation aromatase inhibitors (AI) for adjuvant breast cancer therapy develop arthralgia, tenosynovitis or arthritis. In many women, the morbidity is significant and affects therapy compliance. The pathology of AI-induced joint morbidity is poorly understood, but clinical features in severe cases mimic rheumatoid arthritis. Afflicted women are treated with anti-inflammatory medication, but this does not address the etiology, which appears to involve steroid hormone imbalance. Testosterone can be metabolised to estrogen or the more potent androgen, 5alpha-dihydrotestosterone (DHT). Androgen levels decrease with age and this may be exacerbated by chemotherapy and, paradoxically, aromatase inhibition. We hypothesise that AI-associated joint morbidities are the result of testosterone deficiency and that testosterone treatment during AI therapy will be beneficial. Testosterone replacement had been contraindicated in women with breast cancer until the advent of powerful 3rd generation aromatase inhibitors that are highly efficacious in blocking conversion of testosterone to estrogen, thus allowing the examination of combinations of drugs such as anastrozole and testosterone.Materials and Methods: 90 women taking Arimidex® 1mg daily and registering a visual analogue scale (VAS) pain or stiffness score of ≥ 40mm on a 100mm scale, were randomized into 3 equal arms: placebo, 40 mg or 80 mg testosterone undecanoate daily, with follow-up at 1 and 3 months. The primary efficacy endpoint was reduction in pain at 3 months and the primary safety endpoints were signs of androgen excess with secondary safety endpoints being serum hormone levels, serum lipids and bone absorption markers.Results: The VAS scores at 3 months fell for all groups, with a marked placebo effect of 35% compared with 43% and 70% for the 40 and 80mg treatment arms (p=0.06 and p=0.04, respectively). No significant androgenic side-effects (hirsutism, alopecia and acne) were observed and serum lipids remained unaltered. Serum total testosterone and free-testosterone levels stabilized at 3 months in a dose-dependent fashion into a physiological range. There was no elevation in serum estradiol in either treatment arm and the serum sex hormone binding globulin level fell significantly in the 80mg treatment group (p=0.03). There was no significant change in bone absorption markers in any of the patient groups.Discussion: This study has demonstrated for the first time that testosterone replacement may be a viable option in the management of AI-induced arthralgia, tenosynovitis and arthritis with good tolerability and safety, without adversely reducing aromatase inhibitor efficacy (as indicated by serum estradiol levels).This study was supported AstraZeneca (UK).
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 804.
Prospective Evaluation of Neurotoxicity in Breast Cancer Patients Treated with Adjuvant Paclitaxel.
Authors: Crew K. , Weimer L. , Brafman L. , Fuentes D. , Awad D. , Hershman D. 
Published: December 2010

Abstract
Background: Taxanes are increasingly used in the treatment of early stage breast cancer (BC). Up to 30% of patients develop moderate-severe neurotoxicity during treatment. We recently reported that about 60% of BC patients complain of some neuropathy up to 2 years after completing adjuvant paclitaxel treatment. The prevalence, severity, and natural history of this syndrome have not been well described.Methods: Using a prospective cohort study design, women with stage I-III breast cancer undergoing adjuvant paclitaxel were enrolled. At baseline, 4 and 8 weeks during treatment, then 3, 6 and 12 months after finishing treatment, all patients completed the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) and quantitative neurosensory testing (touch perception and vibration threshold) was conducted. The FACT-Tax includes a 16-item subscale with components for neurotoxicity (11 items) and other taxane-related symptoms (5 questions), where lower scores represent worsening symptoms. Missing data was imputed. We used descriptive statistics, t-test and analysis of variance statistics.Results: A total of 50 patients enrolled, however only 41 are evaluable; median age: 47 (32-78); White/Hispanic/Black: 19/16/6; median BMI (kg/m2): 28 (21-44); stage I/II/III: 5/21/9. Mean self-reported scores on the Neurotoxicity component of the FACT-Tax decreased from 37.5 at baseline to a low of 24.8 at week 8 (p=0.0002). These scores remained lower than baseline at 6 and 12 months after completing paclitaxel treatment (32.0 and 32.4, respectively). Similar trends were seen with the Taxane component (P=0.001).The percentage of patients that reported any hand numbness increased from 14% at baseline to 57% at 8 weeks; while foot numbness increased from 20% to 72% in this timeframe. In both groups, 40% reported persistent symptoms at 12 months. Compared to baseline, there was a significant decrease in vibration sense at 8 weeks during active treatment in the great toe (p&lt;0.01), but only small, clinically insignificant changes in the fingers. No significant change from baseline was seen in touch perception.Discussion: The majority of BC patients receiving adjuvant taxanes develop moderate to severe self-reported numbness and discomfort during active treatment, which improves but remains below baseline up to 12 months later. Similar, but less impressive trends were seen with quantitative neurosensory testing. Taxane-based chemotherapy has been shown to improve survival, however, neurotoxicity is the main long-term side effect. Understanding the appropriate measures to be used in interventions to prevent and treat taxane-induced neuropathy are critical.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 807.
Breast Cancer Risk Single Nucleotide Polymorphism (SNP) Genotypes Do Not Correlate with Risk Estimates from Existing Prediction Models.
Authors: Comen E. , Balistreri L. , Kirchhoff T. , Gaudet M. , Dutra Clark A. , Hudis C. , Offit K. , Robson M. 
Published: December 2010

Abstract
Background:Breast cancer risk assessment professionals employ models to estimate individual probabilities of developing breast cancer. The Gail, Claus and BRCAPro models integrate personal, reproductive and family history variables to generate absolute risk estimates. A number of common DNA variants (single nucleotide polymorphisms, SNPs) are associated with modest elevations (relative risk &lt; 2) of breast cancer risk. We investigated the correlation between genotype at 18 published risk SNPs and model-derived breast cancer risk estimates.Methods:Subjects were 475 unaffected, BRCA mutation-negative women who were evaluated for a family history of breast or ovarian cancer. At the time of testing, subjects provided information that was used to estimate absolute breast cancer risk by Gail, Claus, and BRCAPro models. Subjects were genotyped by Sequenom iPLEX MassArray (Sequenom, Inc., San Diego, CA) at loci reported to be associated with elevations in breast cancer risk (1p11.2, 2q35, 5p12, 6q22.33, 8q24, CASP8, COX11, FGFR2, LSP1, MAP3K1, RAD51L1, SLC4A7, TNRC9). Kruskal-Wallis and Spearman correlation tests were used to compare risk estimates for individuals by genotype and number of risk alleles.Results:The median age at sample donation was 46 years (range 24-83). Most subjects (94.9%) were white, and 65.5% were of Ashkenazi Jewish (AJ) ancestry. Median breast cancer risk scores risk estimates were significantly lower from BRCAPro (5 yr: 1.1%, lifetime (LT): 11.6%) than those derived from Gail (5 yr: 1.8%, LT: 18.5%) or Claus (5 yr: 1.5%, LT: 11.8%) models. No significant differences (p&gt;0.05) in distribution of estimated breast cancer risk scores were found between women carrying 0, 1, or 2 risk alleles at any locus except 6q22.33, where AJ women homozygous for the risk allele rs2180341 were noted to have higher LT Claus (p=0.001) and BRCAPro (p=0.01) estimates. When comparing subjects with no risk alleles to those with 1-2 risk alleles for each SNP, no significant differences in distribution of estimated risk were noted at any loci, including 6q22.33. There was no significant correlation between the total number of risk alleles carried by a subject and her estimated lifetime Gail (ρ=-0.052, P=0.27), Claus (ρ=0.051, P=0.32), or BRCAPro (ρ=0.024, P=0.60) risk.Conclusions:In this analysis, risk allele genotype did not correlate with absolute breast cancer risk estimated by standard models. This suggests that the contribution to risk of genotype at these SNPs is insufficient to impact the modeled estimate. Further studies are necessary to evaluate whether incorporation of genotypic information can improve the calibration or discriminatory accuracy of existing models.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 901.
The Contribution of Founder Mutations to Early-Onset Breast Cancer in French-Canadian Women.
Authors: Ghadirian P. , Robidoux A. , Royer R. , Zhang P. , Akbari M. , Zhang S. , Fafard E. , Costa M. , Martin G. , Potvin C. , Patocskai E. , Larouche N. , Younan R. , Nassif E. , Giroux S. , Narod S. , Foulkes W. 
Published: December 2010

Abstract
Background: In an ethnically-homogeneous population, it is valuable to identify founder mutations in cancer-predisposing genes. Founder mutations have been found in four breast cancer predisposing genes in French-Canadian breast cancer families. The frequencies of the mutant alleles have not been measured in a large series of unselected breast cancer patients from Quebec, nor in healthy controls. These estimates are necessary to measure their contribution to the hereditary burden of breast cancer in Quebec and to help develop genetic screening policies which are appropriate for the province.Methods: We studied 564 French-Canadian women with early-onset invasive breast cancer who were treated at a single Montreal hospital. Patients had been diagnosed at age 50 or less, and were ascertained between 2004 and 2008. We screened all 564 patients for nine founder mutations; four in BRCA1, three in BRCA2 and one each in PALB2 and CHEK2. We also studied 6433 DNA samples from newborn infants from the Quebec City area to estimate the frequency of the nine variant alleles in the French-Canadian population.Results: We identified a mutation in 36 of the 564 breast cancer cases (6.4%) and in 35 of 6443 controls (0.5%). In the breast cancer patients, the majority of mutations were in BRCA2 (54%). However, in the general population (newborn infants), the majority of mutations were in CHEK2 (54%). The odds ratio for breast cancer to age 50, given a BRCA1 mutation was 10.1 (95% CI: 3.7 to 28) and given a BRCA2 mutation was 29.5 (95% CI: 12.9 – 67). The odds ratio for breast cancer to age 50, given a CHEK2 mutation was 3.6 (95% CI: 1.4 – 9.1). One-half of the women with a mutation had a first or second-degree relative diagnosed with breast or ovarian cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 902.
Breast Cancer Events Associated with Germline Mutations of the CDH1 Gene (Hereditary Diffuse Gastric Cancer).
Authors: Hebbard P. , MacMillan A. , McCarthy J. , Laing K. , Wadden N. , Green J. , Fernandez B. , Kwan A. , Wirtzfeld D. 
Published: December 2010

Abstract
Breast cancer events associated with germline mutations of the CDH1 gene (Hereditary Diffuse Gastric Cancer).Background: Mutations of the CDH1 (e-cadherin) gene are known to cause an autosomal dominant familial cancer syndrome, commonly referred to as hereditary diffuse gastric cancer. The lifetime risk of gastric cancer may be up to 80 percent. An associated risk of lobular breast cancer has been identified, but less well studied. Lifetime risk of breast cancer in affected women may be up to 50 percent.Method: We identified 17 women in our centre with known CDH1 mutations that have been offered genetic counseling for breast cancer risk. Counseling included discussion of prophylactic surgery, and breast screening via MRI/mammogram. We performed a chart review to identify breast cancer screening, prophylaxis, and treatment events in these patients.Results: 16 patients had adequate chart data to study. Of these, one patient had a breast cancer (T3N0M0) prior to mutation identification. 13 of 15 remaining patients entered into a high-risk breast-screening program with annual MRI and mammogram. Two breast cancers were identified in the first two years of patient screening; both were T1N0M0. Both women opted for bilateral mastectomy. No patient opted for prophylactic breast surgery prior to cancer detection, although several were in the process of prophylactic gastrectomy.Conclusion: To our knowledge, this is the first in-depth description of breast cancer events in patients with inherited CDH1 mutations. A majority of patients have opted for a breast-screening program, with successful early detection in two patients. Patients to date have not chosen primary prophylactic breast surgery, but two have chosen bilateral mastectomy upon detection of a malignancy. Further epidemiological studies are required to fully understand the breast cancer pattern and natural history that occurs in this genetic syndrome.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 904.
Local Therapy in BRCA1/2 Carriers with Operable Breast Cancer: Comparison of Breast Conservation and Mastectomy.
Authors: Pierce L. , Phillips K. , Griffith K. , Buys S. , Gaffney D. , Moran M. , Haffty B. , Ben-David M. , Garber J. , Merajver S. , Balmanya J. , Meirovitz A. , Domchek S. 
Published: December 2010

Abstract
Background: Women with inherited germline BRCA1/2 mutations have a 55-85% cumulative risk of breast cancer (BC) by age 70. Thus, knowledge of expected outcomes following various treatments is needed to advise these patients should they be diagnosed with BC. It is unclear whether breast conservation (BCT) offers similar rates of tumor control as mastectomy (M) in BRCA1/2 carriers and it is doubtful whether a randomized trial comparing these options could be performed. Thus, this analysis compares the outcomes between similarly staged women with BRCA1/2 mutations treated with BCT vs. M.Methods: Women with deleterious BRCA1/2 mutations diagnosed with operable BC and who consented to longitudinal studies were identified at 10 institutions in the US, Australia, Spain and Israel. Patient, clinical and treatment characteristics were compared between those receiving BCT and those receiving M +/- RT. Time-to-event endpoints included first failure of treatment, diagnosis of contralateral breast cancer (CBC), and overall and BC-specific survival. Cox regression models were constructed to detect significant associations between patient and clinical characteristics and time-to-event endpoints.Results: Clinical characteristics and outcomes for 302 BCT and 353 M patients were compared. With a median F/U of 8.2 years for BCT patients and 8.9 years following M, 15-year local failure as first failure was significantly higher with BCT vs. M (23.5% vs. 5.5%, p&lt;0.0001). Multivariate analysis indicted choice of local therapy as the only factor significantly predicting local recurrence, with a 4.5-fold risk of local failure with BCT compared to M (p&lt;0.0001). Local failure analyses by cohort revealed the presence of a BRCA2 mutation (HR 2.8; p=0.024) and no use of adjuvant chemotherapy (HR 5.4; p=0.0001) as significant predictors within the BCT group; presence of invasive lobular cancer (HR 9.9; p=0.004) was the only significant predictor within the M cohort. No significant differences were seen in distant failure, BC-specific or overall survival by local therapy. 15-year estimates of CBC were 52.1% with BCT; 41.4% with M; and 37.9% with M+RT (p=0.44). Analyses of BCT vs. M +/- RT and surgery +/- RT did not reveal significant differences in CBC by cohort.Conclusions: The higher risk of local failure in BRCA1/2-associated BC treated with BCT compared to M did not translate into an increased risk of distant failure or mortality. RT did not result in a detectable increase in CBC at 15 years above baseline elevated rates. These results at both the involved and contralateral breasts should be discussed when patients with BRCA1/2-associated BC are considering local treatment options.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 959.
Are There Groups of Patients Who Don't Benefit from Chemotherapy?
Authors: Ravdin P. 
Published: December 2010

Abstract
The obvious answer to this question is: Yes. There are two reasons that a medical therapy would not be considered as of benefit to patients. The first of these is that the risks of toxicity or negative effects of a therapy outweigh the benefits. The second is that that therapy does not work: that it does not decrease the risk of negative outcome (for breast cancer that the risk of recurrence and/or death). Over the last 10 years there have been improvements in how we can assess patients for the appropriateness of chemotherapy: 1) We can better predict patients' prognoses without therapy, 2) in a modest way we can better assess their risk for toxicity and 3)we can better predict for individual patients the relative efficacy of a therapy. Over the last decade models to that integrate classical pathologic information to better predict the prognosis of patients have been refined. An advance beyond these models is the development of multi-gene assays either dependent on evaluation of mRNA or proteins that can stratify patients into prognostic groupings. These new methods can be integrated with classical pathologic information to evaluate prognosis. Work on predicting toxicity from chemotherapy has been more modest, but have important possible application. Models exist for some chemotherapeutic regimens for predicting the risk of clinically significant neutropenia or cardiac toxicity. In some instances the risk of particularly severe toxicity to specific agents such as 5FU can be tested for. Perhaps the greatest advance during this period is the better definition of predictors of response to chemotherapy. There has been a long recognition that the estrogen receptor status can stratify patients particularly likely to benefit from chemotherapy, but new predictors are able to identify patients within ER subgroups with particular chemosensitivity. The move toward more personalized therapy is taking place with improvements in prognostic assessment of patients, their risk of toxicity, and whether specific agents will (or will not) reduce the risk of recurrence or breast cancer related death. This review will show that there are certainly are patients who can be identified who do not benefit from chemotherapy, and will in its summary examine what current treatment guidelines say on this topic
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr CS1-1.
Advances in Preventive Therapy.
Authors: Cuzick J. 
Published: December 2010

Abstract
Recent evidence on the chemoprevention of breast cancer has come from a number of sources: 1) Recent data on a new SERM – lasofoxifene – suggests this might be an attractive option, but further details are needed to fully evaluate its role. 2) Update on the tamoxifen and raloxifene preventive trials have shown a continued benefit after treatment completion, and an overview is ongoing to combine all the post-treatment data on risks and benefits. 3) Simple biomarkers for the preventive effect of tamoxifen have been reported. These include both genetic markers such as 2D6 polymorphisms and the observation that 12-18 month changes in breast density are predicative of the subsequent preventive benefit of this drug. A report from the ATAC trial indicating that the occurrence of endocrine symptoms predicts response to both tamoxifen and anastrozole may also have relevance in the preventive setting. 4) Long term follow-up of the adjuvant trials using aromatase trials has provided new evidence on the duration of a potential preventive effect by looking at isolated new contralateral tumours. This has been an excellent model for tamoxifen and may well also be so for the AIs. 5) New data confirm the long term protective effect of aspirin on breast cancer, but suggests it needs to be taken for at least 10 years to get a benefit. Mixed data have appeared for the statins. These issues will be reviewed and discussed.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr ES2-1.
Overview of Gene Expression Profiling and Novel Translational Technologies in Breast Cancer.
Authors: Perou C. 
Published: December 2010

Abstract
Gene expression profiling has had an enormous impact on many aspects of breast cancer, including elucidation of the basic mechanisms of carcinogenesis and mammary development, prediction of outcome and response to treatment, and identification of new subtypes of disease. Importantly, gene expression profiling in breast cancer has allowed the development of biomarkers that are being used in the clinic and/or will become part of routine clinical care in the near future. Genomic profiling is accomplished nowadays by using genome-wide DNA microarray assays, which evaluate thousands of genes with relatively low sensitivity, or qRT-PCR assays, which evaluate small numbers of genes with high sensitivity. The majority of these assays focus on mRNA molecules; however, in recent years, DNA microarrays evaluating other functionally important classes of RNA molecules, such as microRNAs and non-coding RNAs, have been developed and will likely have an impact on our understanding of breast cancer biology. Nonetheless, DNA microarrays and qRT-PCR assays based on mRNA have provided robust platforms for the investigation of breast cancer transcriptomes, and each has resulted in the development of clinically useful prognostic tests (i.e. OncotypeDX and Mammaprint). However, as with all technologies, new methods and platforms are constantly being developed, offering higher speed, lower cost and increased accuracy. Importantly, many of these promising new technologies are compatible with RNA derived from archival formalin-fixed paraffin embedded materials. Therefore, it is likely that gene expression-based assays will continue to play a critical role in the development of novel biomarkers, and the discovery of new targets. In this session, we will cover the basics of DNA microarrays and microarray statistics, and discuss the next generation of technologies to further study the gene expression patterns of breast cancers.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr ES3-1.
Sequencing of Breast Cancer Genomes.
Authors: Stratton M. 
Published: December 2010

Abstract
All cancer genomes carry somatic mutations. The recent advent of second generation sequencing technologies has brought closer the prospect of sequencing large numbers of cancer genomes. Early studies in breast cancer have investigated the prevalence and nature of rearrangements. These studies have shown that there are many more rearrangements in breast cancer than have previously been appreciated, some of which have distinctive patterns suggesting underlying DNA repair defects. These studies are now leading into the sequencing of complete breast cancer genomes which aim to generate comprehensive catalogues of somatic mutations. These will include point mutations, rearrangements and copy number changes and most of the driver and passenger mutations operative in individual cancers.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr ES3-2.