The significance of the rising incidence of breast cancer in the United States.
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Adolescent↗
Biomedical subjects
E J Feuer
Publications and source records attributed to E J Feuer.
The lifetime risk of developing breast cancer.
BACKGROUND: The lifetime risk of developing breast cancer in U.S. women, often quoted as one in nine, is a commonly cited cancer statistic. However, many estimates have used cancer rates derived from total rather than the cancer-free population and have not properly accounted for multiple cancers in the same individual. PURPOSE: Our purpose was to provide a revised method for calculating estimates of the lifetime risk of developing breast cancer and to aid in interpretation of the estimates. METHODS: A multiple decrement life table was derived by applying age-specific incidence and mortality rates from cross-sectional data to a hypothetical cohort of women. Incidence, mortality, and population data from 1975-1988 were used, representing the geographic areas of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The incidence rates reflected only the first breast primary cancer; mortality rates reflected causes other than breast cancer. The population denominator used in calculating incidence rates was adjusted to reflect only those women without previously diagnosed breast cancers in the hypothetical cohort. RESULTS: Our calculations showed an overall lifetime risk for developing invasive breast cancer of approximately one in eight with use of 1987-1988 SEER data, although up to age 85, it was still the commonly quoted one in nine. CONCLUSION: Our estimate was calculated assuming constant age-specific rates derived from 1987-1988 SEER data. Because incidence and mortality rates change over time, conditional risk estimates over the short term (10 or 20 years) may be more reliable. A large portion of the rise in the lifetime risk of breast cancer estimated using 1975-1977 data (one in 10.6) to an estimate using 1987-1988 data (one in eight) may be attributed to 1) early detection of prevalent cases due to increased use of mammographic screening and 2) lower mortality due to causes other than breast cancer. A common misperception is that the lifetime risk estimate assumes that all women live to a particular age (e.g., 85 or 95). In fact, the calculation assumes that women can die from causes other than breast cancer at any possible age. Cutting off the lifetime risk calculation at age 85 assumes that no women develop breast cancer after that age. While the lifetime risk of developing breast cancer rose over the period 1976-1977 to 1987-1988, the lifetime risk of dying of breast cancer increased from one in 30 to one in 28, reflecting generally flat mortality trends.
Adolescent↗
A statistical model validating triage for the peer review process: keeping the competitive applications in the review pipeline.
Triage of grant application at the National Institutes of Health (NIH) is a process whereby an initial screening of applications by a scientific peer review group eliminates applications that are not competitive for awards. The process of application triage has been limited to those applications submitted to the NIH in response to an RFA (Request for Applications). A hypergeometric model was developed to determine the extent to which five, six, seven, or eight member triage teams or subsets of 12-to-20 member full committees could provide a statistically defensible triage decision. Although the intent of triage is to remove from review those applications that are noncompetitive, the model was weighted in favor of the applicant to minimize the likelihood that highly competitive applications would be eliminated. Within the assumptions and rules developed, it was determined that there was little likelihood that the latter would occur. For example, in the worst case scenario, the greatest probability that a highly competitive application would be knocked out of competition is P < or = 0.014 in the case of a five-member triage subset of a 20-member committee. Using the latter case, the model was tested on a set of 73 applications that were submitted to the National Cancer Institute for action at the February 1993 National Cancer Advisory Board. The model selected for triage required that each application be assigned to five reviewers, that each reviewer be blinded to the review assignments of the other reviewers, and that four noncompetitive votes be registered to triage out an application. Each of 19 applications received four to five noncompetitive votes, and were triaged out of the review process. The remaining 54 applications were then reviewed according to the usual NIH review process. Four of the applications received three noncompetitive triage votes each and were either rated as not recommended for further consideration (NRF, n = 2)) or received priority scores > or = 250 (n = 2) (The smaller the priority score the better the technical merit). Thirteen of the 53 applications received two noncompetitive votes. Of the latter, two were not recommended for further consideration and the remaining 11 received priority scores between in excess of 200. The distribution of competitive applications was such that funding was limited to those applications with priority scores of less than 190. Thus, the data suggest that the conservative model is valid such that the likelihood of eliminating a highly competitive application from consideration for funding is remotely small.(ABSTRACT TRUNCATED AT 400 WORDS)
Competitive Bidding↗
How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilization? A dynamic population model approach.
Largely unexplained increases in breast cancer incidence of about 1% per year have been documented back to the 1940s. Since 1982, breast cancer incidence in women aged 40 years and above has been increasing at a faster rate than this long-term secular trend, especially in women aged 60 years and above. Increases in the use of mammography since 1982 (which have been documented in population surveys of women) provide the most plausible explanation for the incidence increase over the long-term secular trend. A study by White et al. (J Natl Cancer Inst 1990;82:1546-52) found that, for women aged 45-64 years, the increase in mammography utilization could explain the incidence increase, while for women aged 65-74 years, it could account for only half the increase. The authors have developed an alternative model to that of White et al. that incorporates estimates of differential lead time (time from screen detection to clinical detection in the absence of screening) by age group. Using this model, the authors show that if older women have longer lead times, than similar increases in mammography utilization across age groups will lead to a larger incidence increase in older women. Thus, the observed increases in mammography utilization are generally concordant with increases in incidence, even in the older age groups.
Adult↗
Breast cancer screening among women from 65 to 74 years of age in 1987-88 and 1991. NCI Breast Cancer Screening Consortium.
OBJECTIVE: To compare breast cancer screening rates from the 1991 survey with data from 1987-88 for women aged 65 to 74. DESIGN: Surveys of women from five communities. SETTINGS: Five control communities of the National Cancer Institute's Breast Cancer Screening Consortium. PARTICIPANTS: White, non-Hispanic women, ages 65 to 74; 499 in 1987-88 and 2156 in 1991. Response rates for the first survey wave ranged by area from 65% to 77% and for the second survey wave, from 62% to 85%. MAIN OUTCOME MEASURE: Mammogram and clinical breast examination during the past year and performance of monthly breast self examination, with the screening rates in wave 2 directly standardized to the income and education distribution of wave 1 in each area. RESULTS: Mammography use between waves increased significantly (P < 0.05 after adjusting for education, income, and age) in all but one area (from 19% to 33% in wave 1 to 35% to 59% in wave 2). Among women who had a mammogram, the percent who also had a clinical breast examination decreased between waves from 95% to 85% (P = 0.001). CONCLUSIONS: Mammography in older women increased dramatically over 3 years, although the use of clinical breast examination may be decreasing.
Aged↗
Stat Bite. Impact of combination chemotherapy for advanced testicular cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Graphical representation of survival curves associated with a binary non-reversible time dependent covariate.
The use of time dependent covariates has allowed for incorporation into analysis of survival data intervening events that are binary and non-reversible (for example, heart transplant, initial response to chemotherapy). We can represent this type of intervening event as a three-state stochastic process with a starting state (S), an intervening state (I), and an absorbing state (D), which usually represents death. In this paper we present three procedures for calculating survivorship functions which attempt to display the prognostic significance of the time dependent covariate. The first method compares survival from baseline for the two possible paths through the stochastic process; the second method compares overall survival to survival with state I removed from the process; and, the third method compares survival for those already in state I at a landmark time x to those in state S at time x who will never enter state I. We develop discrete hazard estimates for the survival curves associated with the three methods. Two examples illustrate how these methods can yield different results and in which situations one might employ each of the three methods. Extensions to applications with reversible binary time dependent covariates and models with both baseline and time dependent covariates are suggested.
Data Interpretation, Statistical↗
Trends in the surgical treatment of ductal carcinoma in situ of the breast.
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Breast Neoplasms↗
The increasing incidence of breast cancer since 1982: relevance of early detection.
Breast cancer incidence in the United States has been rising dramatically since 1982, as shown in data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. In women aged 50 and older, incidence rates for in situ and localized invasive tumors have increased over the period 1982-86, while rates for regional and distant tumors have remained stable. The incidence of localized tumors less than 1.0 cm, 1.0-1.9 cm, and 2.0-2.9 cm in size has increased more rapidly than that of tumors 3.0 cm or more in size among women over age 50. Survival rates also have improved among cases diagnosed over this time period. These data suggest that early detection may be playing a role in the recent increase in female breast cancer incidence, though other factors cannot be ruled out. Conclusions regarding improved cancer control await confirmation by reduced breast cancer mortality.
Breast Neoplasms↗
Number of helper T cells and phytohemagglutinin stimulation correlate in cancer patients.
Mononuclear cells from 12 normal controls (co), 10 advanced untreated (c1), and 6 advanced treated cancer patients (c2) have been isolated. The numbers of mononuclear cells bearing Leu1, Leu2, Leu3, Leu2/HLA-DR and LeuM3 were measured with a fluorescence-activated cell sorter. Only the quantity of helper T cells (Leu3) was decreased in cancer patients (co: 0.89, cl: 0.32, c2: 0.44 x 10(9)/l). Expression of all other markers, including activated suppressor T cells (Leu2/HLA-DR), did not differ significantly from the control. The proliferation of the lymphocytes was determined in a phytohemagglutinin-culture assay. The cancer groups showed a significantly decreased response (co: 95.8 x 10(9), cl: 28.7 x 10(9), c2: 25.7 x 10(9) cpm). These values correlated with the number of helper T cells but not with the suppressor T cells. Monocytes of cancer patients absorbed significantly more immunoglobulins than the monocytes of controls. The addition of indomethacin or isoprinosine to phytohemagglutinin-culture assay increased the proliferation of lymphocytes from both the cancer patients and normal controls.
Adult↗
Projections of the breast cancer burden to U.S. women: 1990-2000.
Although breast cancer incidence rates in the United States have been climbing for the last 40 years, recent trends have shown a more dramatic increase since 1982. This recent rise has been the subject of much study, and it is likely due in part to increased mammographic screening. A mathematical model incorporating the long-term incidence trend estimated from the Connecticut Tumor Registry and recent increases in availability of dedicated mammography machines is described and used to project incidence rates. Projections of breast cancer incidence rates among U.S. women ages 50 and over from 1990 to the year 2000 are developed. It appears that breast cancer incidence rates will continue to rise until about 1990 and then decline as screening rates stabilize.
Adult↗
The impact of breakthrough clinical trials on survival in population based tumor registries.
Three statistical models are developed to study the impact that two breakthrough clinical trials (MOPP for Hodgkin's disease and PVB for disseminated testicular cancer) had on survival in the Connecticut tumor registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry program. A segmented regression model is used in conjunction with the Cox semi-parametric proportional hazards model, as well as the parametric Weibull and exponential cure models. These models allow us to determine approximately when survival first began to improve dramatically, indicating that improved treatments had become available, and how long it took for survival to level off again indicating that the full population survival impact had been realized. In addition, the degree to which the parametric models fit allows us to determine if the survival improvements occur within a parametric family. Results of the modelling indicate that dissemination took approximately 11 years in Hodgkin's disease while only 3 years in disseminated testicular cancer. In both disease sites survival first broke with prior trends between the time that the breakthrough trial started and its publication, indicating that earlier moderately successful 'precursor' trials with combination chemotherapy may have initiated the improved population survival trends. Reasons for the difference in dissemination time in the two cancer sites are examined in order to understand what factors may be responsible for the speed of dissemination and effective utilization of new therapies.
Antineoplastic Combined Chemotherapy Protocols↗
Adenocarcinoma of the cervical stump.
Sixteen women with adenocarcinoma of the cervical stump were treated over a 15-year period. The median survivals of 40 months for stage IB and 17 months for stages II and III were significantly worse compared with those for patients treated for cervical adenocarcinoma of the intact uterus or squamous carcinoma of the cervical stump. The poor results were due to both local and distant failure. Implications regarding tumor radiosensitivity and adjuvant therapy in these high-risk patients are discussed.
Adenocarcinoma↗
Adenocarcinoma of the uterine cervix: prognostic factors and patterns of recurrence.
Survival data, prognostic factors, and patterns of recurrence were analyzed for 70 women with adenocarcinoma of the uterine cervix treated between 1968 and 1982. The 5-year survival rates for stages I, II, and III-IV were 82, 90, and 38%, respectively. Control of pelvic tumor was achieved in 82, 80, and 12.5% of cases of stage I, II, and III-IV disease, respectively. When radiation therapy techniques alone were employed, pelvic control was achieved in 100% of stage I and 75% of stage II cases. Tumor grade was an important prognostic factor in stage I disease, with 92% of patients with grade 1 and 2 lesions surviving 5 years, in contrast to 68% of patients with grade 3 lesions (P less than 0.05, log rank test).
Adenocarcinoma↗
Test statistic and sample size for a two-sample McNemar test.
McNemar's (1947, Psychometrika 12, 153-157) test of marginal homogeneity is generalized to a two-sample situation where the hypothesis of interest is that the marginal changes in each of two independently sampled tables are equal. This situation is especially applicable to two cohorts (a control and an intervention cohort), each measured at baseline and after the intervention on a binary outcome variable. Some assumptions often realistic in this situation simplify the calculation of sample size. The calculation of sample size in a study designed to increase utilization of breast cancer screening is demonstrated.
Biometry↗
Augmentation of activity of cis-diamminedichloroplatinum(II) and mitomycin C by interferon in human malignant mesothelioma xenografts in nude mice.
Two human mesothelioma xenograft lines, BG and ES, serially passaged in athymic mice, were studied to determine the efficacy of alpha-interferon in this type of tumor. Treatment began after progressive tumor growth was established. Recombinant human alpha-interferon-2a (Roferon- A) was given by s.c. injection, at a site distant from the tumor, at a dose of 2 x 10(5) IU 5 days per wk for 5 wk. Mild inhibitory activity was noted in both lines with interferon alone. cis-Diamminedichloroplatinum(II) (CDDP) (4 mg/kg) weekly x 5 was effective in line BG, while mitomycin C (1.5 mg/kg) weekly x 3 was effective in line ES. CDDP was not as effective in line ES. The moderate activity of CDDP in line BG and of mitomycin C in line ES was markedly increased by the addition of alpha-interferon. The combination of mitomycin C and alpha-interferon was as effective as mitomycin C and CDDP. No additional toxicity was noted by the addition of alpha-interferon. The combination of recombinant human alpha-interferon-2a and active chemotherapeutic agents is effective in mesothelioma xenografts.
Animals↗
Effects of etoposide-induced blood-brain barrier disruption on brain water, intracranial pressure, and cerebral vasomotor tone.
This study investigated the effects of hypertension and water loading on etoposide-induced, reversible blood-brain barrier disruption in a rat model. Twenty-nine animals were divided into four groups: group 1--intracarotid (i.c.) injection of saline followed in 1 h by 5 ml i.c. water; group 2--i.c. etoposide followed by i.c. water; group 3--i.c. saline followed by i.v. metaraminol to increase systemic blood pressure; group 4--i.c. etoposide followed by i.v. metaraminol. Systemic blood pressure and intracranial pressure were monitored continuously. Evans blue staining of the brain was used as a monitor of blood-brain barrier disruption. Animals were killed 1 h after either aramine or water infusion, and the brains removed and inspected for the degree of disruption. After dehydration, brain water was calculated for each hemisphere. Two-thirds of the animals infused with etoposide had evidence of barrier disruption, whereas none of the control animals infused with saline were disrupted. Neither control groups 1 or 3 showed significant change in intracranial pressure after water loading or augmentation of systemic blood pressure, respectively. Group 4 animals failed to demonstrate any significant change in intracranial pressure despite marked barrier disruption and acute hypertension (within the limits of normal autoregulation). A small but statistically significant increase in intracranial pressure was noted in group 2 animals with the greatest degree of barrier disruption. A significant increase in brain water was observed ipsilateral to etoposide infusion in only those animals with the most marked barrier disruption. These results indicate that etoposide-induced blood-brain barrier disruption caused significant increases in brain water without significant alteration of cerebral vasomotor tone or increases in intracranial pressure after water loading except in the most severe disruption. The classic untoward consequences of vasogenic edema were not encountered in the present model.
Animals↗
Fecal alpha 1-antitrypsin as a measure of Crohn's disease activity. The effect of therapy and anatomical extent of disease.
Random fecal alpha 1-antitrypsin levels, determined in 35 patients with Crohn's disease, showed a strong correlation with clinical activity (Spearman r = 0.44, p = 0.01). In 85% of the patients, both clinical and fecal measurements of Crohn's disease activity agreed (kappa = 0.368, p = 0.011). Similar agreement occurred in those with colitis (kappa = 0.385, p = 0.035) or ileitis (binomial, p less than 0.001) and those with (binomial, p = 0.006) or without (kappa = 0.492, p = 0.01) prior surgery. There was a reduction in the mean clinical score and fecal levels among all patient groups after treatment. There was good agreement between both disease activity measurements after medical therapy. However, even after apparent surgical "cure," fecal protein levels generally remained at values consistent with diffuse occult intestinal disease. When surgical removal of all diseased bowel was not possible, fecal measurements again appeared superior to clinical assessment in reflecting the residual disease. A good correlation existed between the anatomical extent of disease and fecal levels (r = 0.606, p = 0.028), in contrast to the relationship between extent and clinical score (r = 0.14, p = 0.64). Random fecal alpha 1-antitrypsin determinations provide a measure of the intestinal activity and extent of Crohn's disease. They may be useful in monitoring the response to therapy and the presence of residual disease after surgery.
Adult↗