Andrew G Glass

Kaiser Permanente, Oakland, California, United States

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Publications (75)480.96 Total impact

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    ABSTRACT: The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies. We compared DNA methylation values of 1500 probes representing 807 genes in 148 population-based endometrial carcinoma samples and 23 benign endometrial tissues. Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform. Further replication was conducted in The Cancer Genome Atlas and in prospectively collected endometrial brushings from women with and without endometrial carcinomas. We identified 114 CpG sites showing methylation differences with p-values of ≤10(-7) between endometrial carcinoma and normal endometrium. Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY, and SOX1) were selected for further replication. Age-adjusted odds ratios for endometrial cancer ranged from 3.44 (95%-CI: 1.33-8.91) for ASCL2 to 18.61 (95%-CI: 5.50-62.97) for HTR1B. An area under the curve (AUC) of 0.93 was achieved for discriminating carcinoma from benign endometrium. Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the candidate markers. This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 03/2014; · 6.20 Impact Factor
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    ABSTRACT: The purpose of this paper is to document the use of intravenous (IV) bisphosphonates for prevention of skeletal-related events (SREs) in patients with bone metastases (BM) due to breast cancer (BC), lung cancer (LC), or prostate cancer (PC). Using data from two large US health systems, we identified all patients aged ≥18 years with primary BC, LC, or PC and newly diagnosed BM between 1/1/1995 and 12/31/2009. Starting with the diagnosis of BM, we reviewed medical and administrative records for evidence of receipt of IV bisphosphonates (zoledronic acid or pamidronate) and occurrence of SREs. Initiation of IV bisphosphonates prior to occurrence of an SRE was designated "primary prophylaxis"; use following an SRE was designated "secondary prophylaxis". We identified a total of 1,193 patients with newly diagnosed BM, including 400 with BC, 332 with LC, and 461 with PC. Use of IV bisphosphonates was substantially higher in BC (55.8 % of all patients) than in LC (14.8 %) or PC (20.2 %). Use of IV bisphosphonates was fairly evenly split between primary and secondary prophylaxis in BC (26.3 vs. 29.5 %, respectively) and PC (10.6 vs 9.5 %); in LC, however, primary prophylaxis was much less common than secondary prophylaxis (4.8 vs 9.9 %). Almost one half of all patients with BM due to BC, and substantially more with LC and PC, do not receive IV bisphosphonates. Among patients receiving such therapy, treatment often is not initiated until after the occurrence of an SRE. Our study suggests that IV bisphosphonates may be substantially underutilized in patients with BM due to these common cancers.
    Supportive Care in Cancer 01/2014; · 2.09 Impact Factor
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    ABSTRACT: To document the risk of skeletal complications in patients with bone metastases from breast cancer (BC), lung cancer (LC), or prostate cancer (PC) in routine clinical practice. We used data from two large US health systems to identify patients aged ≥18 years with primary BC, LC, or PC and newly diagnosed bone metastases between January 1, 1995 and December 31, 2009. Beginning with the date of diagnosis of bone metastasis, we estimated the cumulative incidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, radiation to bone, bone surgery), based on review of medical records, accounting for death as a competing risk. We identified a total of 621 BC, 477 LC, and 721 PC patients with newly diagnosed bone metastases. SREs were present at diagnosis of bone metastasis in 22.4, 22.4, and 10.0 % of BC, LC, and PC patients, respectively. Relatively few LC or PC patients received intravenous bisphosphonates (14.8 and 20.2 %, respectively); use was higher in patients with BC, however (55.8 %). In BC, cumulative incidence of SREs during follow-up was 38.7 % at 6 months, 45.4 % at 12 months, and 54.2 % at 24 months; in LC, it was 41.0, 45.4, and 47.7 %; and in PC, it was 21.5, 30.4, and 41.9 %. More than one half of patients with bone metastases had evidence of SREs (BC: 62.6 %; LC: 58.7 %; PC: 51.7 %), either at diagnosis of bone metastases or subsequently. SREs are a frequent complication in patients with solid tumors and bone metastases, and are much more common than previously recognized in women with BC.
    Supportive Care in Cancer 07/2013; · 2.09 Impact Factor
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    ABSTRACT: BACKGROUND: Although the effectiveness of cervical cancer screening has been firmly established in reproductive-age women, its usefulness in older women is unclear. We sought to evaluate the efficacy of cervical cancer screening in older women. METHODS: We conducted a case-control study within two integrated health care systems in the northwestern United States. Cases (n = 69) were women aged 55-79 years who were diagnosed with invasive cervical cancer during 1980-1999. Controls (n = 208) were women with an intact uterus and no diagnosis of cervical cancer, but otherwise similar to cases in terms of age and length of enrollment in the health plan. We reviewed medical records to ascertain screening history during the 7 years prior to reference date. RESULTS: Compared to cases, controls were more likely to have received a Pap test. After adjustment for age and current smoking status, screening prior to an estimated 1-year duration of the occult invasive phase of cervical cancer was associated with a substantial reduction in risk [odds ratio (OR) 0.23; 95 % CI 0.11-0.44]. Similar results were obtained using different estimates of the duration of the occult invasive phase. Analysis of the relative incidence of invasive cervical cancer in relation to the time following a negative screening test suggested a large reduction during the first year (OR 0.09; 95 % CI 0.03-0.24). The incidence remained low for several years thereafter, returning to the incidence among unscreened women after 5-7 years. CONCLUSIONS: Cervical cancer screening by means of cytology is highly efficacious in older women. Our findings also suggest that five-yearly screening is approximately as efficacious as more frequent screening.
    Cancer Causes and Control 06/2013; · 3.20 Impact Factor
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    ABSTRACT: To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction. Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated. A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap. HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older.
    Journal of Clinical Oncology 07/2012; 30(25):3044-50. · 18.04 Impact Factor
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    ABSTRACT: Obesity strongly increases the risk of endometrial cancer and is projected to increase current and future endometrial cancer incidence. In order to fully understand endometrial cancer incidence, one should also examine both hysterectomy, which eliminates future risk of endometrial cancer, and endometrial hyperplasia (EH), a precursor that prompts treatment (including hysterectomy). Hysterectomy and EH are more common than endometrial cancer, but data on simultaneous temporal trends of EH, hysterectomy and endometrial cancer are lacking. We used linked pathology, tumor registry, surgery and administrative datasets at the Kaiser Permanente Northwest Health Plan to calculate age-adjusted and age-specific rates, 1980-2003, of EH only (N = 5,990), EH plus hysterectomy (N = 904), hysterectomy without a diagnosis of EH or cancer (N = 14,926) and endometrial cancer (N = 1,208). Joinpoint regression identified inflection points and quantified annual percentage changes (APCs). The EH APCs were -5.3% (95% confidence interval [CI] = -7.4% to -3.2%) for 1980-1990, -12.9% (95% CI = -15.6% to -10.1%) for 1990-1999 and 2.4% (95% CI = -6.6% to 12.2%) for 1999-2003. The EH-plus-hysterectomy APCs were -8.6% (95% CI = -10.6% to -6.5%) for 1980-2000 and 24.5% (95% CI = -16.5% to 85.7%) for 2000-2003. Hysterectomy rates did not significantly change over time. The endometrial cancer APCs were -6.5% (95% CI = -10.3% to -2.6%) for 1980-1988 and 1.4% (95% CI = -0.2% to 3.0%) for 1988-2003. Hysterectomy rates were unchanged, but increased endometrial cancer incidence after 1988 and the reversal, in 1999, of the longstanding decline in EH incidence could reflect the influence of obesity on endometrial neoplasia.
    International Journal of Cancer 01/2012; 131(8):1921-9. · 6.20 Impact Factor
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    ABSTRACT: To characterize healthcare resource utilization and costs in patients with metastatic lung cancer receiving chemotherapy in the US. Using data from a large private multi-payer health insurance claims database (2000-2006), we identified all patients beginning chemotherapy for metastatic lung cancer. Healthcare resource use (inpatient, outpatient, medications) and costs were tallied over time from date of therapy initiation ("index date") to date of disenrollment from the health plan (in most instances, presumably due to death) or the end of the study period, whichever occurred first. Healthcare utilization and costs were characterized using Kaplan-Meier sample average methods. The study population consisted of 4068 patients; mean (SD) age was 65 (11) years. Over a median follow-up of 334 days, study subjects averaged 1.5 hospital admissions, 8.9 total inpatient days, and 69 physician office and hospital outpatient visits. Mean (95% CI) cumulative total healthcare costs were $125,849 ($120,228, $131,231). Costs of outpatient medical services and inpatient care constituted 34% and 20% of total healthcare costs, respectively; corresponding estimates for outpatient chemotherapy and other medication were 22% and 24%. Our study sheds additional light on the burden of metastatic lung cancer among patients receiving chemotherapy, in terms of total cost thru end of life as well as component costs by setting and type of service, and may be useful in informing medical resource allocation in this patient population.
    BMC Health Services Research 11/2011; 11:305. · 1.77 Impact Factor
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    ABSTRACT: The economic costs of treating patients with metastatic breast cancer have been examined in several studies, but available estimates of economic burden are at least a decade old. In this study, we characterize healthcare utilization and costs in the US among women with metastatic breast cancer receiving chemotherapy as their principal treatment modality. Using a large private health insurance claims database (2000-2006), we identified all women initiating chemotherapy for metastatic breast cancer with no evidence of receipt of concomitant or subsequent hormonal therapy, or receipt of trastuzumab at anytime. Healthcare utilization and costs (inpatient, outpatient, medication) were estimated on a cumulative basis from date of chemotherapy initiation ("index date") to date of disenrollment from the health plan or the end of the study period, whichever occurred first. Study measures were cumulated over time using the Kaplan-Meier Sample Average (KMSA) method; 95% CIs were generated using nonparametric bootstrapping. Findings also were examined among the subgroup of patients with uncensored data. The study population consisted of 1444 women; mean (SD) age was 59.1 (12.1) years. Over a mean follow-up of 532 days (range: 3 to 2412), study subjects averaged 1.7 hospital admissions, 10.7 inpatient days, and 83.6 physician office and hospital outpatient visits. Mean (95% CI) cumulative total healthcare costs were $128,556 ($118,409, $137,644) per patient. Outpatient services accounted for 29% of total costs, followed by medication other than chemotherapy (26%), chemotherapy (25%), and inpatient care (20%). Healthcare costs-especially in the outpatient setting--are substantial among women with metastatic breast cancer for whom treatment options other than chemotherapy are limited.
    BMC Cancer 06/2011; 11:250. · 3.33 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (≥CIN3). Adding HPV testing to cytology is recommended for women ≥30 but long-term prospective studies of HPV testing are rare. Beginning in 1989-1990, ~20,000 women in a prepaid health maintenance organization (median age = 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan-Meier estimates of cumulative probability for ≥CIN3, up to 18 years of follow-up. We observed 47 cases of invasive cervical cancer during the study period, and 156 cases of CIN3. Predictive values and Kaplan-Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against ≥CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8-15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2-6.6). The risk for ≥CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7). CONCLUSION AND IMPACT: The data from this cohort study show the long-term predictive value of HPV testing, particularly in women ≥30, and a possible role for distinguishing particularly carcinogenic types like HPV16.
    Cancer Epidemiology Biomarkers &amp Prevention 05/2011; 20(7):1398-409. · 4.56 Impact Factor
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    ABSTRACT: Mutations in the p53 tumor suppressor gene and accumulation of its protein in breast tissue are thought to play a role in breast carcinogenesis. However, few studies have prospectively investigated the association of p53 immunopositivity and/or p53 alterations in women with benign breast disease in relation to the subsequent risk of invasive breast cancer. We carried out a case-control study nested within a large cohort of women biopsied for benign breast disease in order to address this question. After exclusions, 491 breast cancer cases and 471 controls were available for analysis. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Neither p53 immunopositivity nor genetic alterations in p53 (either missense mutations or polymorphisms) was associated with altered risk of subsequent breast cancer. However, the combination of both p53 immunopositivity and any p53 nucleotide change was associated with an approximate 5-fold nonsignificant increase in risk (adjusted OR 4.79, 95% CI 0.28-82.31) but the confidence intervals were extremely wide. Our findings raise the possibility that the combination of p53 protein accumulation and the presence of genetic alterations may identify a group at increased risk of breast cancer.
    Journal of Oncology 01/2011; 2011:970804.
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    ABSTRACT: PURPOSE The severity of endometrial hyperplasia (EH)-simple (SH), complex (CH), or atypical (AH)-influences clinical management, but valid estimates of absolute risk of clinical progression to carcinoma are lacking. Materials and METHODS We conducted a case-control study nested in a cohort of 7,947 women diagnosed with EH (1970-2002) at one prepaid health plan who remained at risk for at least 1 year. Patient cases (N = 138) were diagnosed with carcinoma, on average, 6 years later (range, 1 to 24 years). Patient controls (N = 241) were matched to patient cases on age at EH, date of EH, and duration of follow-up, and they were counter-matched to patient cases on EH severity. After we independently reviewed original slides and medical records of patient controls and patient cases, we combined progression relative risks (AH v SH, CH, or disordered proliferative endometrium [ie, equivocal EH]) from the case-control analysis with clinical censoring information (ie, hysterectomy, death, or left the health plan) on all cohort members to estimate interval-specific (ie, 1 to 4, 5 to 9, and 10 to 19 years) and cumulative (ie, through 4, 9, and 19 years) progression risks. Results For nonatypical EH, cumulative progression risk increased from 1.2% (95% CI, 0.6% to 1.9%) through 4 years to 1.9% (95% CI, 1.2% to 2.6%) through 9 years to 4.6% (95% CI, 3.3% to 5.8%) through 19 years after EH diagnosis. For AH, cumulative risk increased from 8.2% (95% CI, 1.3% to 14.6%) through 4 years to 12.4% (95% CI, 3.0% to 20.8%) through 9 years to 27.5% (95% CI, 8.6% to 42.5%) through 19 years after AH. CONCLUSION Cumulative 20-year progression risk among women who remain at risk for at least 1 year is less than 5% for nonatypical EH but is 28% for AH.
    Journal of Clinical Oncology 02/2010; 28(5):788-92. · 18.04 Impact Factor
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    ABSTRACT: Women with a history of benign breast disease are at increased risk of subsequent breast cancer. However, few studies have examined whether established breast cancer risk factors other than histology are associated with an altered risk of breast cancer in women with benign breast disease. We used a nested case-control design within a large, multi-center cohort of women biopsied for benign breast disease (BBD) to estimate odds ratios for breast cancer in association with exposure to a range of personal and lifestyle factors. Cases were women biopsied for BBD who subsequently developed breast cancer; controls were individually matched to cases on center and age at diagnosis and were women biopsied for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After excluding women with prevalent breast cancer, 1357 records (661 case records and 696 records) were available for analysis. We used conditional logistic regression to obtain crude and multivariable-adjusted estimates of the association between specific factors and risk of breast cancer. In multivariable analyses age at first live birth, number of pregnancies, and postmenopausal status were inversely associated with risk of breast cancer. The odds ratio for women with age at first birth <25 years and >or=3 pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval 0.13-0.79, and that for postmenopausal women relative to premenopausal women was 0.60, 95% CI 0.37-0.99. Further study of personal factors influencing the risk of breast cancer in women with BBD may help to identify subgroups of the population at increased risk of invasive disease.
    Cancer epidemiology. 02/2010; 34(1):34-9.
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    ABSTRACT: OBJECTIVE: We used a nested case-control design within a large, multi-center cohort of women who underwent a biopsy for benign breast disease (BBD) to assess the association of broad histologic groupings and specific histologic entities with risk of breast cancer. METHODS: Cases were all women who had a biopsy for BBD and who subsequently developed breast cancer; controls were individually matched to cases and were women with a biopsy for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After exclusions, 1,239 records (615 cases and 624 controls) were available for analysis. We used conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-proliferative BBD/normal pathology, the multivariable-adjusted odds ratio for proliferative lesions without atypia was 1.45 (95% CI 1.10-1.90), and that for atypical hyperplasia was 5.27 (95% CI 2.29-12.15). The presence of multiple foci of columnar cell hyperplasia and of complex fibroadenoma without atypia was associated with a non-significantly increased risk of breast cancer, whereas sclerosing adenosis, radial scar, and papilloma showed no association with risk. CONCLUSION: Our results indicate that, compared to women with normal pathology/non-proliferative disease, women with proliferative disease without atypia have a modestly increased risk of breast cancer, whereas women with atypical hyperplasia have a substantially increased risk.
    Cancer Causes and Control 01/2010; · 3.20 Impact Factor
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    ABSTRACT: Cervical infections by approximately 15 cancer-associated (carcinogenic) human papillomavirus (HPV) genotypes cause virtually all cervical cancer and its immediate precursor lesions worldwide. Prophylactic vaccines against human papillomavirus (HPV) types HPV16 and HP18, which cause 70% of cervical cancer worldwide, hold great promise for reducing the burden of cervical cancer worldwide. However, current HPV vaccines prevent future infections and related cervical abnormalities and do not treat pre-existing HPV infections. In the U.S., HPV vaccine introduction should be considered in the context of a very successful cervical cancer screening program that has reduced the rates of cervical cancer by 75% or more. Thus, HPV vaccines will only prevent an incremental number of additional cervical cancers in the U.S. The introduction of HPV vaccines can also prevent other HPV-related sequelae, most importantly cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), which precede the development of cervical cancer and require clinical follow-up and treatment. Examining data from 7 clinical centers in the U.S., the median age of CIN2/3 is typically between 25 and 30 years of age in 2007; if screen-detected CIN2/3 develops on average 5-10 years after the causal infection is acquired, HPV vaccination will only prevent a significant proportion of CIN2/3 if it is given to women before the age of 26 and more so if given to women 18 and younger. It is increasingly evident that prophylactic HPV vaccines will provide the greatest public health or population benefit only when delivered to adolescent, mostly HPV-naive women.
    Gynecologic Oncology 06/2009; 114(2):365-9. · 3.93 Impact Factor
  • Value in Health 01/2009; 12(3). · 2.19 Impact Factor
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    ABSTRACT: Histopathologic diagnosis of endometrial biopsies is used to estimate the risk of progression to carcinoma and guide clinical management. Problems with the widely used World Health Organization (WHO) system for classifying endometrial hyperplasia (EH) have prompted the development of an alternative system based on endometrial intraepithelial neoplasia (EIN). The authors estimated progression risk associated with EIN among endometrial biopsies in a nested case-control study of EH progression. Index biopsies with original community pathology diagnoses of disordered proliferative endometrium (DPEM) or EH that were independently confirmed by a panel of pathologists were independently reviewed and assigned EIN classifications (inadequate, benign, EIN, or cancer) by a second panel of pathologists. Cases (N = 138) progressed to carcinoma at least 1 year (median, 6 years) after their index biopsy. Controls (N = 241) also had EH, did not progress to carcinoma, and were individually matched to cases based on age at EH, date of EH, and length of follow-up. By using conditional logistic regression, the authors estimated relative risks (RRs) with 95% confidence intervals (95% CIs) for progression to carcinoma for EIN versus benign. In the EIN system, 71 (52.6%) cases and 159 (66.8%) controls were classified as benign and 42 (31.1%) cases and 65 (27.3%) controls were classified as EIN. The RR for EIN versus benign was 7.76 (95% CI, 3.36-17.91). In the WHO system, the RR for atypical hyperplasia (AH) versus DPEM, simple hyperplasia, or complex hyperplasia was 9.19 (95% CI, 3.87-21.83). Among women observed for at least 1 year after receiving a biopsy-based EH diagnosis, EIN and AH were both found to have similarly increased risks of progression to carcinoma.
    Cancer 09/2008; 113(8):2073-81. · 5.20 Impact Factor
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    ABSTRACT: Identifying which categories in the World Health Organization classification of endometrial hyperplasia contribute to suboptimal reproducibility is clinically important. A 2-member panel reviewed 209 endometrial biopsy/curettage specimens originally diagnosed as incident endometrial hyperplasia as part of a progression study. Original diagnoses included the following: disordered proliferative endometrium, simple hyperplasia, complex hyperplasia, and atypical hyperplasia; panel diagnoses also included negative and carcinoma. We assessed percentage agreement and kappa statistics+/-standard errors (K+/-SE). Original and panel diagnoses (combining negative with disordered proliferative endometrium; atypical hyperplasia with carcinoma) agreed for 34.9% of biopsies (K-unweighted+/-SE=0.18+/-0.03; K-weighted+/-SE=0.27+/-0.04). Panelists' diagnoses agreed (using 6 categories) for 51.7% of biopsies, corresponding to K-unweighted+/-SE=0.37+/-0.03, improving with weighting to K-weighted+/-SE=0.63+/-0.05. Reproducibility based on a 2-tier classification ([negative, disordered proliferative endometrium, simple hyperplasia, or complex hyperplasia] versus [atypical hyperplasia or carcinoma]) increased agreement between original and panel diagnoses to 82.8%, K-unweighted+/-SE=0.37+/-0.06, and between panelists to 87.0%, K-unweighted+/-SE=0.63+/-0.07. Agreement between panelists at a cutpoint of complex hyperplasia and more severe versus simple hyperplasia or less severe was 88.0%, K-unweighted+/-SE=0.72+/-0.07. Developing and prospectively testing a binary system of classifying endometrial hyperplasia on endometrial biopsy may aid efforts to improve interobserver reproducibility.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 08/2008; 27(3):318-25. · 2.07 Impact Factor
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    ABSTRACT: Inactivation of PTEN tumor suppressor gene is common in endometrial carcinoma and its precursor, atypical endometrial hyperplasia (EH). We compared PTEN expression via immunohistochemistry in endometrial biopsies diagnosed as EH in 138 cases, who were diagnosed with EH and then endometrial carcinoma at least 1 year later (median, 6 years), and 241 individually matched controls, who were diagnosed with EH but did not progress to carcinoma during equivalent follow-up. We assessed PTEN status (normal versus null) in index biopsies containing EH to estimate the relative risk (RR) of developing endometrial carcinoma up to 25 years later. Analysis of 115 cases and 193 controls with satisfactory assays revealed PTEN-null glands in index biopsies of 44% of cases and 49% of controls [P = 0.85; RR, 1.51; 95% confidence interval (CI), 0.73-3.13]. For predicting progression to carcinoma, PTEN-null status had low sensitivity (44%; 95% CI, 45-54%) and specificity (51%; 95% CI, 44-58%). Among 105 cases with PTEN results for both index biopsy and carcinoma, 16% had a PTEN-null index biopsy, 23% had PTEN-null carcinoma, and 26% had both a PTEN-null index biopsy and carcinoma. Loss of PTEN expression in endometrial biopsies was neither associated with nor a sensitive and specific marker of subsequent progression to endometrial carcinoma.
    Cancer Research 07/2008; 68(14):6014-20. · 8.65 Impact Factor
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    ABSTRACT: Cost of neutropenic complications of myelosuppressive chemotherapy has been reported to be substantial. Prior research, however, has focused on initial hospitalization only and has failed to account for follow-on care. Using a US health-care claims database, all adult cancer patients who received a course of chemotherapy were identified. For each such patient, each unique cycle of chemotherapy within the course and each occurrence of neutropenic complications within these cycles were characterized. Patients developing neutropenic complications in a given cycle (neutropenia patients), starting with the first, were matched (1:1) to those who did not develop neutropenic complications in that cycle (comparison patients), and health-care costs (i.e. expenditures) were tallied for each matched pair. Neutropenia patients (n = 373) and comparison patients were similar in terms of baseline characteristics. Costs of neutropenia-related care were $12,397 (95% confidence interval $10,274-$14,754) higher for neutropenia versus comparison patients [$14,407 ($12,357-$16,743) versus $2010 ($1490-$2553)]. Among neutropenia patients, mean cost of initial hospitalization for neutropenic complications was $7813 ($6537-$9379); cost of all subsequent neutropenia-related care averaged $6594 ($5217-$8272). Neutropenic complications of myelosuppressive chemotherapy are costly. Prior research focusing on initial hospitalization only may have underestimated the cost of these complications by as much as 40%.
    Annals of Oncology 04/2008; 19(3):454-60. · 7.38 Impact Factor
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    ABSTRACT: Classifying endometrial hyperplasia (EH) according to the severity of glandular crowding (simple hyperplasia (SH) vs complex hyperplasia (CH)) and nuclear atypia (simple atypical hyperplasia (SAH) vs complex atypical hyperplasia (CAH)) should predict subsequent endometrial carcinoma risk, but data on progression are lacking. Our nested case-control study of EH progression included 138 cases, who were diagnosed with EH and then with carcinoma (1970-2003) at least 1 year (median, 6.5 years) later, and 241 controls, who were individually matched on age, date, and follow-up duration and counter-matched on EH classification. After centralised pathology panel and medical record review, we generated rate ratios (RRs) and 95% confidence intervals (CIs), adjusted for treatment and repeat biopsies. With disordered proliferative endometrium (DPEM) as the referent, AH significantly increased carcinoma risk (RR=14, 95% CI, 5-38). Risk was highest 1-5 years after AH (RR=48, 95% CI, 8-294), but remained elevated 5 or more years after AH (RR=3.5, 95% CI, 1.0-9.6). Progression risks for SH (RR=2.0, 95% CI, 0.9-4.5) and CH (RR=2.8, 95% CI, 1.0-7.9) were substantially lower and only slightly higher than the progression risk for DPEM. The higher progression risks for AH could foster management guidelines based on markedly different progression risks for atypical vs non-atypical EH.
    British Journal of Cancer 02/2008; 98(1):45-53. · 5.08 Impact Factor

Publication Stats

4k Citations
480.96 Total Impact Points

Institutions

  • 1989–2014
    • Kaiser Permanente
      • Center for Health Research (Oregon, Hawaii, and Georgia)
      Oakland, California, United States
  • 1999–2012
    • National Cancer Institute (USA)
      • • Hormonal and Reproductive Epidemiology
      • • Division of Cancer Epidemiology and Genetics
      Maryland, United States
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, MD, United States
  • 2010–2011
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
  • 2007
    • County of Los Angeles Public Health
      Los Angeles, California, United States
    • Merck
      Whitehouse Station, New Jersey, United States
  • 2006
    • Policy Analysis Inc.
      Brookline, Massachusetts, United States
  • 2004
    • University of Washington Seattle
      • Department of Epidemiology
      Seattle, WA, United States
    • University of Wisconsin, Madison
      • Department of Population Health Sciences
      Madison, MS, United States
  • 2003
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
  • 2001
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, PA, United States