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B E Storer

Publications and source records attributed to B E Storer.

At least 19 recordsLinked to original sources

High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation.

This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood mononuclear cells (G-PBMC) (n = 116) or marrow (n = 14) transplantation after nonmyeloablative conditioning with 90 mg/m(2) fludarabine and 2 Gy TBI. The median number of CD34(+) cells transplanted was 6.5 x 10(6)/kg. Higher numbers of grafted CD14(+) (P = 0.0008), CD3(+) (P = 0.0007), CD4(+) (P = 0.001), CD8(+) (P = 0.004), CD3(-)CD56(+) (P = 0.003), and CD34(+) (P = 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14(+) (P = 0.01) and CD34(+) (P = 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8(+) (P = 0.005) and CD34(+) (P = 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34(+) cells were associated with higher levels of day 28 donor T-cell chimerism (P = 0.01), rapid achievement of complete donor T-cell chimerism (P = 0.02), and a trend for lower risk for graft rejection (P = 0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34(+) cells in unrelated grafts administered after nonmyeloablative conditioning.

Adolescent↗

Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after non-myeloablative conditioning.

We have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20, natural killer (NK; CD3(-)/CD56(+)), NKT (CD3(+)/CD56(+)), DC1, and DC2 cells] of granulocyte colony-stimulating factor mobilized peripheral blood stem cells (PBSC) on early T-cell chimaerism and later clinical outcomes in 125 patients with haematological malignancies who received human leucocyte antigen (HLA)-matched related grafts after non-myeloablative conditioning. Conditioning consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI preceded by either 90 mg/m(2) fludarabine (n = 62) or planned autologous haematopoietic cell transplantation (HCT) (n = 35). Post-transplant immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate analysis showed that higher numbers of grafted NK cells predicted higher early T-cell chimaerism (P = 0.03), while higher numbers of B cells were associated with better clinical outcomes and a higher risk for chronic graft-versus-host disease (P = 0.05). Higher numbers of CD14(+) cells were associated with worse overall survival (P = 0.03), while higher numbers of CD34(+) cells showed better survival (P = 0.03). The addition of fludarabine or autologous HCT predicted higher early T-cell chimaerism (P = 0.001), while advanced donor age predicted lower chimaerism (P < or = 0.02). Patients with aggressive diseases were at higher risk for relapse/disease progression, and shorter progression-free and overall survival (P < 0.01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post-HCT after non-myeloablative conditioning.

Adult↗

An evaluation of phase I clinical trial designs in the continuous dose-response setting.

Both traditional phase I designs and the increasingly popular continual reassessment method (CRM) designs select an estimate of maximum tolerable dose (MTD) from among a set of prespecified dose levels. Although CRM designs use an implied dose-response model to select the next dose level, in general it is neither assumed nor necessary that this model be tied to the actual dose of a drug. In contrast, in our two-stage design the fitting of a dose-response model after data have been collected is a necessary feature of the design, and the MTD is not constrained to be one of the prespecified dose levels. We conducted a simulation study to evaluate the performance of the two-stage design, two likelihood-based CRM designs, and two traditional designs in estimating the MTD in situations where one assumes that an explicit dose-response model exists. Under a wide variety of dose-response settings, we examined the bias and precision of estimates, and the fraction of estimates that were extremely high or low. We also studied the effect of adding a model fitting step at the end of a traditional design or a CRM design. The best performance was achieved using the two-stage and CRM designs. Although the CRM designs generally had smaller bias, the two-stage design yielded equal or somewhat smaller precision in some cases. The addition of a model-fitting step slightly improved the precision of the CRM estimates and decreased the percentage of extreme estimates. Allowing interpolation between doses for updating during CRM did not improve overall performance.

Bias↗

Fracture history and risk of breast and endometrial cancer.

Fractures in postmenopausal women may serve as a surrogate measure of bone density, reflecting long-term lower estrogen levels, and lower estrogen levels appear to be inversely associated with breast and endometrial cancer. Breast cancer cases aged 50-79 years (n = 5,559) and endometrial cancer cases aged 40-79 years (n = 739) were enrolled in a US case-control study in 1992-1994 to evaluate the relation between fractures and risk of breast and endometrial cancer. Controls for the breast cancer analysis (n = 5,829) and the endometrial cancer analysis (n = 2,334) were randomly selected from population lists (driver's license and Medicare files). Information on fracture history and other risk factors was obtained by telephone interview. Compared with women without a fracture in the past 5 years, the odds ratios for women with a history of fracture were 0.80 (95% confidence interval (CI): 0.68, 0.94) for breast cancer and 0.59 (95% CI: 0.40, 0.89) for endometrial cancer. Height loss (> or =2.5 cm) and recent fracture history were associated with the lowest risk of breast cancer (odds ratio = 0.62, 95% CI: 0.46, 0.83) and endometrial cancer (odds ratio = 0.15, 95% CI: 0.05, 0.43). These data suggest that the endogenous hormonal factors associated with increased fracture risk are also related to decreased breast cancer risk and, more strongly, to endometrial cancer risk.

Adult↗

Hormonal risk factors for endometrial cancer: modification by cigarette smoking (United States).

OBJECTIVES: To evaluate whether smoking modifies the risk of endometrial cancer associated with body mass index (BMI), postmenopausal hormone use, and other hormonal factors. METHODS: Using multivariate adjusted models we examined interview data from a population-based case-control study of Wisconsin women (n = 740 cases, n = 2,372 controls). RESULTS: The relative risk for endometrial cancer associated with current smoking was 0.8 (95% CI: 0.6-1.0) compared to never smokers. No clear dose-response relationship was evident for pack-years smoked. When examined according to smoking status the risk associated with the highest quartile of BMI seemed to be greater among non-smokers (OR = 3.6, 95% CI: 2.4-5.3) than among current smokers (OR = 2.8, 95% CI: 1.4-5.6). Among postmenopausal women the risk associated with current use of postmenopausal hormones appeared to be greater among non-smokers (OR = 3.3, 95% CI: 2.3-4.9) than among current smokers (OR = 2.7. 95% CI: 1.3-5.5). Risk for long-term use (10 or more years) compared with never users was 8.3 (95% CI: 4.6-15.1) among never smokers and 2.5 (95% CI: 0.8-7.9) among current smokers. The risk associated with non-insulin-dependent diabetes was greater among non-smokers (OR = 2.5, 95% CI: 1.7-3.6) than current smokers (OR = 1.1, 95% CI: 0.4-3.1). There was no modifying effect of smoking on the risk associated with parity. CONCLUSION: These results suggest that smoking moderates the risk associated with endometrial cancer among women at greatest risk, specifically women who are obese or who use postmenopausal hormones.

Aged↗

Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus.

BACKGROUND: The increased risk for esophageal adenocarcinoma associated with long-segment (> or =3 cm) Barrett esophagus is well recognized. Recent studies suggest that short-segment (<3 cm) Barrett esophagus is substantially more common; however, the risk for neoplastic progression in patients with this disorder is largely unknown. OBJECTIVE: To examine the relation between segment length and risk for aneuploidy and esophageal adenocarcinoma in patients with Barrett esophagus. DESIGN: Prospective cohort study. SETTING: University medical center in Seattle, Washington. PATIENTS: 309 patients with Barrett esophagus. MEASUREMENTS: Patients were monitored for progression to aneuploidy and adenocarcinoma by repeated endoscopy with biopsy for an average of 3.8 years. Cox proportional hazards analysis was used to calculate adjusted relative risks and 95% Cls. RESULTS: After adjustment for histologic diagnosis at study entry, segment length was not related to risk for cancer in the full cohort (P > 0.2 for trend). When patients with high-grade dysplasia at baseline were excluded, however, a nonsignificant trend was observed; based on a linear model, a 5-cm difference in segment length was associated with a 1.7-fold (95% CI, 0.8-fold to 3.8-fold) increase in cancer risk. Among all eligible patients, a 5-cm difference in segment length was associated with a small increase in the risk for aneuploidy (relative risk, 1.4 [CI, 1.0 to 2.1]; P = 0.06 for trend). A similar trend was observed among patients without high-grade dysplasia at baseline. CONCLUSIONS: The risk for esophageal adenocarcinoma in patients with short-segment Barrett esophagus was not substantially lower than that in patients with longer segments. Although our results suggest a small increase in risk for neoplastic progression with increasing segment length, additional follow-up is needed to determine whether the patterns of risk occurred by chance or represent true differences. Until more data are available, the frequency of endoscopic surveillance should be selected without regard to segment length.

Adenocarcinoma↗

Weight change and risk of postmenopausal breast cancer (United States).

OBJECTIVE: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case-control study of postmenopausal breast cancer. METHODS: Participants included women aged 50 79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (<45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84 0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95 1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06-1. 11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. CONCLUSIONS: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.

Aged↗

Risk factors for carcinoma in situ of the breast.

As more women obtain screening mammograms regularly and at younger ages, the diagnosis of breast carcinoma in situ becomes more frequent. To examine whether risk factors for carcinoma in situ correspond with risk factors for invasive breast cancer, we analyzed data from a population-based case-control study conducted in 1988-1990. We identified newly diagnosed cases of carcinoma in situ (n = 301) and invasive breast cancer (n = 3789) in women 18-74 years of age from Wisconsin's statewide tumor registry. Cases and population controls (n = 3999) completed structured telephone interviews. Overall, associations with risk of carcinoma in situ in relation to many reproductive life-style risk factors were similar to those associated with risk of invasive disease. Women who reported a family history of breast cancer had a 2-fold elevated risk of carcinoma in situ (odds ratio, 2.67; 95% confidence interval, 2.00-3.57). Personal history of benign biopsied breast disease also increased risk of carcinoma in situ (odds ratio, 2.19; 95% confidence interval, 1.62-2.95). Subgroup analysis suggested that high vitamin A intake and high alcohol intake may be associated with risk of ductal but not lobular carcinoma in situ. These data support the presence of common risk factors between in situ and invasive breast cancer.

Adolescent↗

Antibody immunity to prostate cancer associated antigens can be detected in the serum of patients with prostate cancer.

PURPOSE: Several immune based therapies targeting prostate cancer associated proteins are currently undergoing clinical investigation. In general, however, little is known about the immunogenicity of prostate cancer or which prostate cancer associated proteins elicit immune responses. We determine whether patients with prostate cancer have antibody immunity to known prostate cancer associated proteins, what the prevalence of this immunity is and whether immunity to individual proteins is associated with the stage of disease. MATERIALS AND METHODS: We evaluated the inherent humoral immune response against prostate specific antigen (PSA), prostatic acid phosphatase, p53 and HER-2/neu, all known prostate cancer associated proteins, in 200 patients with various stages of disease and male controls. RESULTS: Antibody immunity to PSA was significantly different between the patient (11%, 22 of 200) and control populations (1.5%, 3 of 100, p = 0.02), and titers 1:100 or greater were particularly prevalent in the subgroup of patients with androgen independent disease (11%, 6 of 56). Antibody immunity to prostatic acid phosphatase and p53 was detected (5.5%, 11 of 200 and 6%, 12 of 200), and was not different from the control population (4%, 4 of 100, p = 0.57 and 7%, 7 of 100, p = 0.74). Antibody immunity to HER-2/neu was significantly higher in patients with prostate cancer (15.5%, 31 of 200) compared to controls (2%, 2 of 100, p = 0.0004), and titers 1:100 or greater were most prevalent in the subgroup of patients with androgen independent disease (16%, 9 of 56). CONCLUSIONS: These findings suggest that prostate cancer is an immunogenic tumor. Moreover, for PSA and HER-2/neu the prevalence of antibody immunity was higher in patients with androgen independent disease, indicating that even patients with advanced stage prostate cancer can have an immune response to their tumor.

Acid Phosphatase↗

Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

A topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.

Confounding Factors, Epidemiologic↗

Usual consumption of plant foods containing phytoestrogens and sex hormone levels in postmenopausal women in Wisconsin.

Consumption of phytoestrogens may reduce hormone-dependent cancer risk through alterations in the actions or metabolism of steroid hormones. Studies in humans of phytoestrogen-hormone interactions have been limited and inconsistent. Relations between the consumption of phytoestrogen-containing foods and serum sex hormones and sex hormone-binding globulin were studied in a population-based sample of postmenopausal women who participated in the Nutritional Factors in Eye Disease Study of the Beaver Dam Eye Study. Information on phytoestrogen-containing foods (broccoli, carrots, cauliflower, chili, dark bread, peas, and dried beans) was collected by interviewer-administered food-frequency questionnaires. Estrone, sex hormone-binding globulin, dehydroepiandrosterone sulfate, and total and free testosterone were measured. Analyses included 246 postmenopausal women not taking hormone replacements. Partial correlations between hormones and intake of phytoestrogen-containing foods were computed, with adjustment for age, body mass index, years since menopause, and total energy intake. Number of standard servings per week of whole-grain products from the dark bread group was inversely associated with total testosterone (r = -0.20, p = 0.002). Although not statistically significant, other hormones displayed similar inverse associations with dark bread consistent with a common metabolic pathway. Although the magnitude of association was small, the data are consistent with the possibility that consumption of some phytoestrogen-containing foods may affect levels of testosterone in postmenopausal women.

Adult↗

Body size and risk of breast cancer.

The relation between body size and breast cancer remains uncertain, particularly with regard to differences between pre- and postmenopausal women. The authors examined whether height, weight, body mass index, and weight change were associated with breast cancer risk among pre- and postmenopausal women. This population-based case-control study included women aged 20-74 years (n = 6,548) who were diagnosed with invasive breast cancer during 1988-1991 in Maine, Massachusetts, New Hampshire, and Wisconsin. Similarly aged control women (n = 9,057) were selected at random from driver's license files and Health Care Financing Administration files. Height, weight, and information on other breast cancer risk factors were ascertained by telephone interview, and logistic regression was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. Among premenopausal women, the adjusted odds ratio for the upper quintile group of height relative to the lowest was 1.36 (95% confidence interval (CI) 1.05-1.76). The heaviest premenopausal women had a lower risk (odds ratio (OR) = 0.87, 95% CI 0.70-1.10). Among postmenopausal women, the adjusted odds ratios were higher for the upper quintile categories of both height (OR = 1.27, 95% CI 1.11-1.45) and weight (OR = 1.57, 95% CI 1.37-1.79). Weight gain since ages 18 and 35 years was associated with increased postmenopausal breast cancer risk, and risk was lower in women who had lost weight. These findings suggest that programs to avoid weight gain merit study as a means to reduce risk of postmenopausal breast cancer.

Adult↗

Parental age in relation to risk of breast cancer.

Data from a population-based case-control study were analyzed to evaluate risk of breast cancer among women according to parental age at the time of subject birth. Between 1988-91, breast cancer cases (n = 1,253) were obtained from the statewide tumor registry in Wisconsin. Concurrently, population controls (n = 1,121) were randomly selected from driver's license lists (if under age 65) and Medicare beneficiary files (if 65-74 years). Information regarding parents' ages and breast cancer risk factors was obtained by telephone interview. Relative risk estimates were very slightly elevated with increasing maternal age, although no consistent trend of increasing risk was observed (P for trend = 0.38). No association between paternal age and breast cancer risk was observed (P for trend = 0.98). Older maternal or paternal age was not associated with risk among any of the subgroups examined, except for daughters who had late age at first birth. These findings are consistent with the majority of studies that have found little or no association between parental age and breast cancer risk.

Adult↗

Alcohol consumption in relation to endometrial cancer risk.

We analyzed data from a population-based case-control study of Wisconsin women to evaluate the relationship of alcohol consumption to endometrial cancer risk. Cases (n = 739) were identified from a statewide tumor registry; controls (n = 2313) were selected randomly from driver's license lists and Medicare beneficiary files. Alcohol consumption and other factors were ascertained by telephone interview. Compared with abstainers, the multivariable relative risk for recent consumption of two or more drinks per day was 1.27 [95% confidence interval (CI) 0.78-2.07]; increasing consumption was not associated with risk of disease (P for trend, 0.82). The relative risk for early adulthood consumption of two or more drinks per day was 1.00 (95% CI, 0.58-1.73), with no suggestion of a trend (P = 0.26). Although the sample size was limited, a significant inverse association was suggested in premenopausal women consuming one drink per day or more (0.20, 95% CI 0.06-0.71). Beverage-specific consumption was not associated with risk. This study suggests that, unlike breast cancer, endometrial cancer is not positively associated with alcohol intake.

Adult↗

Self-reported stress and risk of breast cancer.

BACKGROUND: Many women attribute the development of their breast cancer to psychosocial factors such as stress and depression. Yet investigations of the relationship between breast cancer and stressful life events have had inconsistent outcomes, due in part to studies with small sample sizes and reliance on hospital-based populations. METHODS: As part of a population-based, case-control study of breast cancer etiology, we evaluated the association between stressful life events and the risk of breast cancer among 258 breast cancer patients and 614 randomly selected population-based controls. Information on 11 stressful life events was collected in telephone interviews with women aged 50-79 who were participating in the ongoing study. RESULTS: Breast cancer patients and controls experienced the same number of stressful life events in the five years prior to diagnosis or an equivalent reference date (controls), averaging 2.4 and 2.6 events, respectively. After adjustment for known breast cancer risk factors, there was no association between weighted stressful life event scores and the risk of breast cancer (odds ratio [OR] = 0.90 per unit increase; 95% confidence interval [CI], 0.78-1.05). Only one life event, death of a close friend, was significantly more often reported by controls (OR = 0.72; 95% CI, 0.52-1.00). Other life events were inconsistently and nonsignificantly associated with breast cancer risk. CONCLUSIONS. The results of this retrospective study do not suggest any important associations between stressful life events and breast cancer risk.

Adult↗

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n = 6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n = 9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR] = 1.1, 95 percent confidence interval [CI] = 1.0-1.2). Total duration of use also was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI = 0.9-1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR = 2.0, CI = 1.1-3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m2) less than 20.4, RR = 1.7, CI = 1.1-2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.

Adult↗

The impact of co-morbidity on life expectancy among men with localized prostate cancer.

PURPOSE: We evaluated 3 indexes used to assess patient co-morbidities to determine whether they could predict mortality among men with clinically localized prostate cancer. MATERIALS AND METHODS: We measured the impact of co-morbidity classifications on all cause mortality using a parametric proportional hazards model based on a retrospective cohort analysis. RESULTS: Each index tested is a highly significant predictor of mortality for patients dying of nonprostate cancer related causes after adjusting for age and Gleason score. CONCLUSIONS: Each co-morbidity index provides significant, independent predictive information concerning patient mortality beyond that provided by age, Gleason score and clinical stage alone.

Aged↗