-
Hui Shen,
Brooke L Fridley,
Honglin Song,
Kate Lawrenson,
Julie M Cunningham,
Susan J Ramus,
Mine S Cicek,
Jonathan Tyrer,
Douglas Stram,
Melissa C Larson, [......],
Joellen M Schildkraut,
Thomas A Sellers,
David Huntsman,
Andrew Berchuck,
Georgia Chenevix-Trench,
Simon A Gayther,
Paul D P Pharoah,
Peter W Laird,
Ellen L Goode,
Celeste Leigh Pearce
[show abstract]
[hide abstract]
ABSTRACT: HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
Nature Communications 03/2013; 4:1628. · 7.40 Impact Factor
-
Hui Shen,
Brooke L. Fridley,
Honglin Song,
Kate Lawrenson,
Julie M. Cunningham,
Susan J. Ramus,
Mine S. Cicek,
Jonathan Tyrer,
Douglas Stram,
Melissa C. Larson, [......],
Joellen M. Schildkraut,
Thomas A. Sellers,
David Huntsman,
Andrew Berchuck,
Georgia Chenevix-Trench,
Simon A. Gayther,
Paul D. P. Pharoah,
Peter W. Laird,
Ellen L. Goode,
Celeste Leigh Pearce
Nat Commun. 01/2013; 4:1628.
-
[show abstract]
[hide abstract]
ABSTRACT: The BRCAPRO model estimates carrier probabilities for the BRCA1 and BRCA2 genes, and was recently enhanced to use estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. No independent assessment of the added value of these markers exists. Moreover, earlier versions of BRCAPRO did not use human epidermal growth factor receptor 2 (Her-2/neu) status of breast cancer. Here, we incorporate Her-2/neu in BRCAPRO and validate all the markers. We trained the enhanced model on 406 germline tested individuals, and validated on a separate clinical cohort of 796 individuals for whom test results and family history are available. For model-building, we estimated joint probabilities of ER, PR, and Her-2/neu status for carriers and non-carriers of BRCA1/2 mutations. For validation, we obtained BRCAPRO predictions with and without markers. We calculated area under the receiver operating characteristic curve (AUC), sensitivity, specificity, predictive values, and correct reclassification rates. The AUC for predicting BRCA1 status among individuals who are carriers of at least one mutation improved when ER and PR were used. The AUC for predicting the presence of either mutation improved when Her-2/neu was added. Use of markers also produced highly significant correct reclassification improvements in both cases. Breast tumor markers are useful for prediction of BRCA1/2 mutation status. ER and PR improve discrimination between BRCA1 and BRCA2 mutation carriers while Her-2/neu helps discriminate between carriers and non-carriers, particularly among women who are ER positive and Her-2/neu negative. These results support the use of the enhanced version of BRCAPRO in clinical settings.
Breast Cancer Research and Treatment 01/2012; 133(1):347-55. · 4.43 Impact Factor
-
Jennifer K Litton,
Kaylene Ready,
Huiqin Chen,
Angelica Gutierrez-Barrera,
Carol J Etzel,
Funda Meric-Bernstam,
Ana M Gonzalez-Angulo,
Huong Le-Petross, Karen Lu,
Gabriel N Hortobagyi,
Banu K Arun
[show abstract]
[hide abstract]
ABSTRACT: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations.
Of the 132 BRCA-positive women with breast cancer who participated in a high-risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 106 women could be paired with a family member in the previous generation (Gen 1) who was diagnosed with a BRCA-related cancer (either breast cancer or ovarian cancer). Age at diagnosis, location of the mutation, and year of birth were recorded. A previously published parametric anticipation model was applied in these genetically predisposed families.
The median age of cancer diagnosis was 42 years (range, 28-55 years) in Gen 2 and 48 years (range, 30-72 years) in Gen 1 (P < .001). [corrected]. In the parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years (P < .0001). Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.
Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations. The authors concluded that patients who are younger at the onset of BRCA-related cancers should continue to be tracked to offer appropriate screening modalities at appropriate ages.
Cancer 09/2011; 118(2):321-5. · 4.77 Impact Factor
-
Steven J Skates,
Phuong Mai,
Nora K Horick,
Marion Piedmonte,
Charles W Drescher,
Claudine Isaacs,
Deborah K Armstrong,
Saundra S Buys,
Gustavo C Rodriguez,
Ira R Horowitz, [......],
Masoud Azodi,
Stacy Nerenstone,
Noah D Kauff,
Carol J Fabian,
Patrick M Sluss,
Susan G Nayfield,
Carol H Kasten,
Dianne M Finkelstein,
Mark H Greene, Karen Lu
[show abstract]
[hide abstract]
ABSTRACT: Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, whereas the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the National Cancer Institute-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this preplanned analysis. Because of the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points on the basis of 98th percentile. The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (50 for premenopausal women, 40 for premenopausal on OC, and 35 for postmenopausal women).
Cancer Prevention Research 09/2011; 4(9):1401-8. · 4.91 Impact Factor
-
The Breast Journal 02/2011; 17(2):210-2. · 1.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Background SULF1 (sulfatase 1) selectively removes the 6-O-sulphate group from heparan sulfate, changing the binding sites for extracellular growth factors. SULF1 expression has been reported to be decreased in various cancers, including ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) of SULF1 would impact clinicopathologic characteristics. Methods We genotyped five common (minor allele frequency>0.05) regulatory SNPs with predicted functionalities (rs2623047 G>A, rs13264163 A>G, rs6990375 G>A, rs3802278 G>A, and rs3087714 C>T) in 168 patients with primary epithelial ovarian cancer, using the polymerase chain reaction-restriction fragment length polymorphism method. Results We found that rs2623047 G>A was significantly associated with an early age of onset of ovarian cancer in the G allele dose-response manner (P = 0.027; Ptrend = 0.007) and that rs2623047 GG/GA genotypes were associated with longer progression-free survival; rs6990375 G>A was also associated with the early age of onset in the A allele dose-response manner (P = 0.013; Ptrend = 0.009). The significant differences in age of disease onset persisted among carriers of haplotypes of rs2623047 and rs6990375 (P = 0.014; Ptrend = 0.004). In luciferase reporter gene assays, rs2623047 G allele showed a slightly higher promoter activity than the A allele in the SKOV3 tumorigenic cell line. Conclusions These findings suggest that genetic variations in SULF1 may play a role in ovarian cancer onset and prognosis. Further studies with large sample sizes and of the mechanistic relevance of SULF1 SNPs are warranted.
Journal of Experimental & Clinical Cancer Research. 01/2011;
-
[show abstract]
[hide abstract]
ABSTRACT: Endometrial and colorectal cancers are the most common cancers in Lynch syndrome. Consensus guidelines recommend annual endometrial biopsy (EMB) and regular colonoscopies. We assessed the feasibility of concurrently performing EMB and colonoscopy and evaluated women's perception of pain, satisfaction, and acceptability.
From July 2002 to December 2009, women who had a gene mutation for Lynch syndrome, met the Amsterdam II criteria, or had a high-risk situation that required screening were prospectively enrolled. After conscious sedation, the procedures were sequentially performed. Patients completed pre- and postprocedure questionnaires assessing pain, level of satisfaction, and acceptability. The Wilcoxon rank test and Mann-Whitney test were used to compare pain scores.
Forty-two women completed the study. Median age was 37 years (range, 25 to 73). Nineteen had previously had an EMB in the office setting. Women reported significantly lower median levels of pain in the combined procedure compared with previous office setting biopsies (P < .001). Regardless of parity, women reported significantly less pain for an EMB as part of the combined screen compared with an office EMB (parous, P = .003; nulliparous, P = .026). Women also reported a high level of satisfaction and more convenience in the combined procedure. All participants preferred combined to separately scheduled procedures and would recommend the combined procedure to their relatives.
Combined colon and endometrial cancer screening is a patient-centered approach that is feasible, acceptable, and may improve adherence to Lynch syndrome screening recommendations.
Journal of Oncology Practice 01/2011; 7(1):43-7.
-
[show abstract]
[hide abstract]
ABSTRACT: The transforming growth factor-β (TGF-β) signaling pathway is involved in a diverse array of cellular processes responsible for tumorigenesis. In this case-control study, we applied a pathway-based approach to evaluate single-nucleotide polymorphisms (SNPs) in the TGF-β signaling pathway as predictors of ovarian cancer risk. We systematically genotyped 218 SNPs from 21 genes in the TGF-β signaling pathway in 417 ovarian cancer cases and 417 matched control subjects. We analyzed the associations of these SNPs with ovarian cancer risk, performed haplotype analysis and identified potential cumulative effects of genetic variants. We also performed analysis to identify higher-order gene-gene interactions influencing ovarian cancer risk. Individual SNP analysis showed that the most significant SNP was SMAD6: rs4147407, with an adjusted odds ratio (OR) of 1.60 (95% confidence interval [CI], 1.14-2.24, P = 0.0066). Cumulative genotype analysis of 13 SNPs with significant main effects exhibited a clear dose-response trend of escalating risk with increasing number of unfavorable genotypes. In gene-based analysis, SMAD6 was identified as the most significant gene associated with ovarian cancer risk. Haplotype analysis further revealed that two haplotype blocks within SMAD6 were significantly associated with decreased ovarian cancer risk, as compared to the most common haplotype. Gene-gene interaction analysis further categorized the study population into subgroups with different ovarian cancer risk. Our findings suggest that genetic variants in the TGF-β signaling pathway are associated with ovarian cancer risk and may facilitate the identification of high-risk subgroups in the general population.
PLoS ONE 01/2011; 6(9):e25559. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Risk-reducing salpingo-oophorectomy (RRSO) is the cornerstone of ovarian cancer prevention in BRCA1/2 mutation carriers. Occult fallopian tube and ovarian cancers have been reported in a small percentage of BRCA1/2 mutation carriers undergoing RRSO. Here, we review our single-institution experience with RRSO in BRCA1/2 mutation carriers to characterize cases of microscopic cancers in these patients. At the time of RRSO, 7.9% of BRCA1 mutation carriers were diagnosed with microscopic fallopian tube or ovarian cancers and no cases were diagnosed in BRCA2 mutation carriers. The majority of the microscopic cancers include cases that were confined to the fallopian tubes, although there were also cases involving ovaries only or peritoneal washings only. This suggests that the site of origin may be in the ovary, fallopian tube, or peritoneum for BRCA-associated serous cancers. However, an analysis of early-stage (stages I and II) ovarian and fallopian tube cancers diagnosed in BRCA1/2 mutation carriers confirms that the ovary is a preferred site for tumor growth with 11 of 14 early-stage cancers having a dominant ovarian mass. Overall, these data suggest that cancer initiation may occur in the ovary, fallopian tube, or peritoneum, but tumor growth and progression are favored in the ovary. We present an updated model for BRCA1/2 mutation-associated ovarian and fallopian tube carcinogenesis, which may aid in identifying improved prevention strategies for high-risk women who delay or decline RRSO.
Cancer Prevention Research 01/2011; 4(3):463-70. · 4.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs (miRNA) play important roles in tumorigenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the regulatory effect of miRNAs to their target genes, hence promoting tumorigenesis. This study analyzed 226 single nucleotide polymorphisms (SNP) in miRNA processing genes and miRNA binding sites in 339 ovarian cancer cases and 349 healthy controls to assess association with cancer risk, overall survival, and treatment response. Thirteen polymorphisms were found to have significant association with risk. The most significant were 2 linked SNPs (r(2) = 0.99), rs2740351 and rs7813 in GEMIN4 [odds ratio (OR) = 0.71; 95% confidence interval (CI), 0.57-0.87 and OR = 0.71; 95% CI, 0.57-0.88, respectively]. Unfavorable genotype analysis showed the cumulative effect of these 13 SNPs on risk (P for trend < 0.0001). Potential higher order gene-gene interactions were identified, which categorized patients into different risk groups according to their genotypic signatures. In the clinical outcome study, 24 SNPs exhibited significant association with overall survival and 17 SNPs with treatment response. Notably, patients carrying a rare homozygous genotype of rs1425486 in PDGFC had poorer overall survival [hazard ratio (HR) = 2.69; 95% CI, 1.67-4.33] and worse treatment response (OR = 3.38; 95% CI, 1.39-8.19), compared to carriers of common homozygous and heterozygous genotypes. Unfavorable genotype analyses also showed a strong gene-dosage effect with decreased survival and increased risk of treatment nonresponse in patients with greater number of unfavorable genotypes (P for trend < 0.0001). Taken together, miRNA-related genetic polymorphisms may impact ovarian cancer predisposition and clinical outcome both individually and jointly.
Cancer Research 12/2010; 70(23):9765-76. · 7.86 Impact Factor
-
Ellen L Goode,
Georgia Chenevix-Trench,
Honglin Song,
Susan J Ramus,
Maria Notaridou,
Kate Lawrenson,
Martin Widschwendter,
Robert A Vierkant,
Melissa C Larson,
Susanne K Kjaer, [......],
Natalia Bogdanova,
Arto Leminen,
Ralf Butzow,
Tuomas Heikkinen,
Kari Stefansson,
Patrick Sulem,
Sören Besenbacher,
Thomas A Sellers,
Simon A Gayther,
Paul D P Pharoah
[show abstract]
[hide abstract]
ABSTRACT: Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ≤ 10⁻⁴) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P ≤ 5 × 10⁻⁸ (8q24, P = 8.0 × 10⁻¹⁵ and 2q31, P = 3.8 × 10⁻¹⁴) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10⁻⁸ and 17q21, P = 1.4 × 10⁻⁷). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.
Nature Genetics 10/2010; 42(10):874-9. · 35.53 Impact Factor
-
Zoya Yurkovetsky,
Steven Skates,
Aleksey Lomakin,
Brian Nolen,
Trenton Pulsipher,
Francesmary Modugno,
Jeffrey Marks,
Andrew Godwin,
Elieser Gorelik,
Ian Jacobs,
Usha Menon, Karen Lu,
Donna Badgwell,
Robert C Bast,
Anna E Lokshin
[show abstract]
[hide abstract]
ABSTRACT: Early detection of ovarian cancer has great promise to improve clinical outcome.
Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data.
A training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer.
A panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer.
Journal of Clinical Oncology 04/2010; 28(13):2159-66. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Disseminated gynecologic cancers are usually fatal due to chemoresistance. Recently, rationally developed, targeted agents are entering the early clinical trials setting. We assessed patients with metastatic gynecologic cancers in a dedicated phase I clinical trials clinic in order to determine their outcome.
We reviewed records for 89 consecutive patients with gynecologic cancers referred to the Phase I Clinical Trials Program, 85 (96%) of whom were treated on > or = 1 trial.
Cancer diagnoses were ovarian (N=43), uterine (N=19), cervix (N=17), and other. Median age was 58 years; median number of prior cytotoxic regimens, five. Two patients (2.4%) achieved a CR; four (4.7%), a PR; and eight (9.4%), SD > or = 6 months (total CR/PR/SD > or = 6 months=16.5%) for the first phase I trial. Twenty-five patients enrolled on a second trial and three, on a third (N=113 trials total). Combining response data for all trials, of the 85 patients, two achieved CR (2.4%), nine achieved PR (10.6%), and 12 (14%) had SD for > or = 6 months. One-year survival was 30% (95% CI, 21% to 44%). There was no difference in time-to-treatment failure (TTF) on phase I versus the patient's last standard treatment.
Twenty-three of 85 patients (27%) with advanced, heavily pretreated, gynecologic cancers achieved CR/PR/SD > or = 6 months on a phase I trial, and overall TTF on phase I was comparable to that of last conventional therapy, suggesting that participation in a phase I trial is a reasonable option for these patients.
Gynecologic Oncology 03/2010; 117(3):467-72. · 3.89 Impact Factor
-
Shannon N Westin,
Russell R Broaddus,
Lei Deng,
Adrienne McCampbell, Karen H Lu,
Robin A Lacour,
Michael R Milam,
Diana L Urbauer,
Peter Mueller,
James H Pickar,
David S Loose
[show abstract]
[hide abstract]
ABSTRACT: Identification of biomarkers potentially provides prognostic information that can help guide clinical decision-making. Given the relationship between estrogen exposure and endometrial cancer, especially low grade endometrioid carcinoma, we hypothesized that high expression of genes induced by estrogen would identify low risk endometrioid endometrial cancers. cDNA microarray and qRT-PCR verification were used to identify six genes that are highly induced by estrogen in the endometrium. These estrogen-induced biomarkers were quantified in 72 endometrial carcinomas by qRT-PCR. Unsupervised cluster analysis was performed, with expression data correlated to tumor characteristics. Time to recurrence by cluster was analyzed using the Kaplan-Meier method. A receiver operating characteristic (ROC) curve was generated to determine the potential clinical utility of the biomarker panel to predict prognosis. Expression of all genes was higher in endometrioid carcinomas compared to non-endometrioid carcinomas. Unsupervised cluster analysis revealed two distinct groups based on gene expression. The high expression cluster was characterized by lower age, higher BMI, and low grade endometrioid histology. The low expression cluster had a recurrence rate 4.35 times higher than the high expression cluster. ROC analysis allowed for the prediction of stage and grade with a false negative rate of 4.8% based on level of gene expression in endometrioid tumors. We have therefore identified a panel of estrogen-induced genes that have potential utility in predicting endometrial cancer stage and recurrence risk. This proof-of-concept study demonstrates that biomarker analysis may play a role in clinical decision making for the therapy of women with endometrial cancer.
Cancer biology & therapy 11/2009; 8(22):2126-35. · 2.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine when, in reference to the course of their treatment, women with ovarian cancer are seen for genetic counseling, as well as to determine what factors influence this timing.
: Single institution retrospective chart review of patients with ovarian cancer who underwent BRCA1/BRCA2 genetic testing.
Thirty-three percent of our sample (n = 100) were seen for genetic counseling after ovarian cancer recurrence. In four cases, genetic test results were disclosed to next of kin. Thirty percent of women seen for genetic counseling after recurrence received their initial treatment elsewhere. Women with a history of breast cancer were significantly more likely to be seen for genetic counseling at an earlier phase of their treatment than women with no history of breast cancer.
We found that one third of patients with ovarian cancer who underwent genetic testing were seen for initial genetic counseling after disease recurrence. In some cases, genetic counseling took place during the end of life care, with genetic test results disclosed to next of kin. Given the poor prognosis of women with recurrent ovarian cancer, we advocate providing genetic counseling at the time of initial ovarian cancer treatment both in comprehensive cancer centers and in community oncology settings.
Genetics in medicine: official journal of the American College of Medical Genetics 08/2009; 11(9):624-8. · 3.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study aims to determine the prevalence of physical activity and obesity and their relationship to physical functioning (PF), fatigue, and pain in endometrial cancer survivors.
Surveys were mailed to 200 survivors of endometrial cancer diagnosed within the last 5 years; 61% were returned. Surveys assessed physical activity, height and weight, comorbid health problems, PF, fatigue, and pain.
In all, 22% exercised in the past month at the level of current public health recommendations, 41% reported no physical activity, and 38% reported some activity. A total of 16% were overweight and 50% were obese. Both lower body mass index (BMI) and higher physical activity were related to better PF. Higher physical activity was related to less fatigue, primarily for patients of normal BMI.
Results suggest endometrial cancer survivors' obesity and inactivity contributes to poorer quality of life. This population could benefit from quality-of-life interventions incorporating physical activity.
American journal of obstetrics and gynecology 01/2009; 200(3):288.e1-8. · 3.28 Impact Factor
-
Susan J Ramus,
Karim Elmasry,
Zhiyuan Luo,
Alex Gammerman, Karen Lu,
Ayse Ayhan,
Naveena Singh,
W Glenn McCluggage,
Ian J Jacobs,
John C Whittaker,
Simon A Gayther
[show abstract]
[hide abstract]
ABSTRACT: Patients with synchronous ovarian and endometrial cancers may represent cases of a single primary tumor with metastasis (SPM) or dual primary tumors (DP). The diagnosis given will influence the patient's treatment and prognosis. Currently, a diagnosis of SPM or DP is made using histologic criteria, which are frequently unable to make a definitive diagnosis.
In this study, we used genetic profiling to make a genetic diagnosis of SPM or DP in 90 patients with synchronous ovarian/endometrial cancers. We compared genetic diagnoses in these patients with the original histologic diagnoses and evaluated the clinical outcome in this series of patients based on their diagnoses.
Combining genetic and histologic approaches, we were able make a diagnosis in 88 of 90 cases, whereas histology alone was able to make a diagnosis in only 64 cases. Patients diagnosed with SPM had a significantly worse survival than patients with DP (P = 0.002). Patients in which both tumors were of endometrioid histology survived longer than patients of other histologic subtypes (P = 0.025), and patients diagnosed with SPM had a worse survival if the mode of spread was from ovary to endometrium rather than from endometrium to ovary (P = 0.019).
Genetic analysis may represent a powerful tool for use in clinical practice for distinguishing between SPM and DP in patients with synchronous ovarian/endometrial cancer and predicting disease outcome. The data also suggest a hitherto uncharacterized level of heterogeneity in these cases, which, if accurately defined, could lead to improved treatment and survival.
Clinical Cancer Research 10/2008; 14(18):5840-8. · 7.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.4 and CA125 as potential markers in patients diagnosed with endometrioid adenocarcinoma of the uterus.
Pre-operative serum samples from surgically staged patients with endometrioid adenocarcinoma of the uterus were analyzed for levels of HE4, SMRP, CA72-4 and CA125. Control samples were obtained from healthy postmenopausal women. Logistic regression models and receiver operating characteristic (ROC) curves were constructed for each tumor marker and for all combinations, with cross-validation analyses to obtain average sensitivities at set specificities of 90%, 95%, and 98%.
Serum samples from 156 healthy subjects and 171 patients with endometrial cancer (122 stage I, 17 stage II, 26 stage III, and 6 stage IV) were analyzed. At a 95% specificity, the sensitivities for differentiating between healthy subjects and all stages of cancer were 45.5% for HE4 and 24.6% for CA125. For stage I disease, HE4 yielded a 17.1% improvement in sensitivity compared with CA125.
HE4 is elevated in all stages of endometrial can100cer and is more sensitive in early-stage endometrial cancer compared to CA125. Further investigation of HE4 as a marker for early detection of recurrent endometrial cancer and monitoring response to therapy is warranted.
Gynecologic Oncology 09/2008; 110(2):196-201. · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Defective DNA mismatch repair is one of the most common and best-characterized genetic defects detected in endometrial cancer. Defective DNA mismatch repair in endometrial cancer can be either inherited or acquired (sporadic). This article describes the clinical and pathologic significance of acquired and inherited defective DNA mismatch repair in endometrial cancer.
Obstetrics and Gynecology Clinics of North America 01/2008; 34(4):701-15, viii. · 1.70 Impact Factor
