Kenneth C. Chu

Implications of Stage-specific Survival Rates in Assessing Recent Declines in Prostate Cancer Mortality Rates

It has been noted that the most important evidence for a benefit of early detection of prostate cancer using prostate-specific antigen (PSA) testing would be a decline in prostate cancer mortality rates to levels below those existing before diagnostic use of PSA testing. We document a decrease in U.S. prostate cancer mortality rates in white men less than 85 years of age to levels below those existing in 1986, the year use of PSA testing was approved. In fact, for men 60-79 years of age, prostate cancer mortality rates were lower in 1997 than in any year since 1950. Although it has been argued that the decrease in prostate cancer mortality rates began too soon to be explained by PSA testing, stage-specific survival rates indicate that a rapid decrease in mortality may be explained by the large number of high-grade prostate cancers detected before metastasis. If recent decreases in U.S. prostate cancer mortality rates are due to early detection using PSA testing, randomized clinical trials investigating PSA testing will show early evidence of a mortality benefit.

Tumor Variants by Hormone Receptor Expression in White Patients With Node-Negative Breast Cancer From the Surveillance, Epidemiology, and End Results Database

PURPOSE Hormone receptor expression (presence-positive or absence-negative) may reflect different stages of one disease or different breast cancer types. Determining whether hormone receptor expression represents one or more breast cancer phenotypes would have important paradigmatic and practical implications. METHODS Breast cancer records were obtained from the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) database. The study included 19,541 non-Hispanic white women with node-negative breast cancer. Standard tumor cell characteristics and breast cancer-specific survival were analyzed by independent estrogen receptor (ER+ and ER-), independent progesterone receptor (PR+ and PR-), and joint ERPR expression (ER+PR+, ER+PR-, ER-PR+, and ER-PR-). RESULTS Age frequency density plots by hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ phenotype were associated with smaller tumor sizes, better grade, and better cancer-specific survival than ER- and PR- breast cancer types. Joint ERPR phenotype exhibited biologic gradients for tumor size, grade, and cancer-specific survival, which ranked from good to worse for ER+PR+ to ER+PR- to ER-PR+ to ER-PR-. CONCLUSION Variations of standard tumor cell characteristics and breast cancer-specific survival by hormone receptor expression in white patients with node-negative breast cancer suggested two breast cancer phenotypes with overlapping etiologies and distinct clinical features.

Inflammatory Breast Carcinoma and Noninflammatory Locally Advanced Breast Carcinoma: Distinct Clinicopathologic Entities?

PURPOSE Inflammatory breast carcinoma (IBC) and noninflammatory locally advanced breast carcinoma (LABC) are both associated with poor prognosis; however, whether they are distinct clinicopathologic entities remains controversial. MATERIALS AND METHODS To determine whether IBC and LABC were different, we compared tumor characteristics, prognosis, and age-specific incidence rate patterns in the Surveillance, Epidemiology, and End-Results program. An age of 50 years served as a surrogate marker for menopause. RESULTS Younger age at diagnosis, poorer tumor grade, and negative estrogen receptors (ERs) were more predictive of IBC (n = 2,237) than of LABC (n = 7,985). Breast carcinoma survival was worse for patients with IBC than for those with LABC (log-rank test, P <.0001). Age-specific incidence rates for IBC increased until 50 years and then flattened, whereas rates for LABC increased for all ages. When rates for LABC were stratified by estrogen receptor-positive (ERP) and -negative (ERN) expression, rates for ERP and ERN diverged; that is, rates for ERP increased with advancing age, whereas rates for ERN flattened after 50 years. When rates for IBC were stratified by ER expression, rates for both ERP and ERN flattened after 50 years of age. CONCLUSION IBC and LABC seemed to be distinct biologic entities, as indicated by different prognostic factor profiles and age-specific incidence rate patterns. Rates that increased before 50 years and then stabilized, possibly indicated that premenopausal exposures had a greater effect on maintaining rates for IBC than for LABC.

Frequency distributions of breast cancer characteristics classified by estrogen receptor and progesterone receptor status for eight racial/ethnic groups

The National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) cancer registries have been collecting data regarding estrogen receptor (ER) and progesterone receptor (PR) status in breast cancer since 1990. The current study reports on some of these data for eight racial/ethnic groups.

Factors in the evaluation of 200 national cancer institute carcinogen bioassays

In determining the carcinogenicity of chemical tested in a National Cancer Institute (NCI) bioassay, the following criteria are considered: (1) the adequacy of the bioassay data, (2) the presence of significantly increased incidences of tumor, (3) the adequacy of the number of animals at risk of developing tumors, (4) the adequacy of the dose of chemical administered, (5) the etiology and pathogenesis of the lesions, and (6) other factors that may influence an evaluation, such as a shortened latency period for tumor formation in dosed animals or the stability of the chemical. A decision tree for evaluating these factors is presented. A summary of the results of 200 NCl carcinogen bioassays is also reported. These procedures are presented in the hope that they may serve as discussion points for future developments in the field.

Rates for breast cancer characteristics by estrogen and progesterone receptor status in the major racial/ethnic groups

It has been reported that age-specific breast cancer rates vary by estrogen receptor and progesterone receptor status. We report breast cancer rates for age-at-diagnosis, stage-at-diagnosis, histological grade and type by estrogen (ER) and progesterone (PgR) receptor status in six major racial/ethnic groups. The average annual age-adjusted rates for breast cancers with estrogen receptor positive (ER+), ER−, progesterone receptor positive (PgR+), PgR−, ER+PgR+, ER+PgR−, ER−PgR+ and ER−PgR− are determined from 123,732 breast cancers with known ER status, diagnosed from 1992 to 1998 from 11 Surveillance, Epidemiology, and End Results (SEER) cancer registries. For each racial/ethnic group, their ER+ (ER+PgR+ and ER+PgR−) age-specific rates increased with age (but at a slower pace after ages 50–54) while their ER− (ER− PgR+ and ER−PgR−) age-specific rates did not increase after ages 50–54. The rank orders of the rates among the racial/ethnic groups varied by ER/PgR status. The stage I rates were greater than the stage II rates for the ER/PgR groups except for ER− and ER−PgR− cancers. The grade 2 (moderately differentiated) rates were greater than the grades 3 and 4 (poorly differentiated and undifferentiated cancers) rates for ER+ cancers, but not for ER− cancers. These results suggest that although breast cancer is a disease with enormous heterogeneity, the multiple types of breast cancer can be separated into distinct subgroups by their ER status, and perhaps by their ER/PgR status, and their cancer characteristics may be important in understanding the multiple nature of breast cancer.

The greater impact of menopause on ER- than ER+ breast cancer incidence: a possible explanation (United States)

Objective: Analysis of 3359 Danish breast cancer cases indicated that menopause exerted a greater protective effect on estrogen- receptor negative (ER–) breast cancer than on estrogen- receptor positive (ER+) breast cancer. We examined US age-specific breast cancer rates by hormone receptor status in white and black women and men to investigate this unexpected result. Methods: Age-specific breast cancer incidence rates from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were analyzed by joint estrogen receptor and progesterone receptor (ER/PR) status of 101,140 white female and 8870 black female cases and by ER status in 706 white male and black male cases diagnosed from 1992 to 1998. Changes in the rate of increase in rates with age were identified using Poisson regression analyses. Results: For both white women and black women the age-specific rates of ER– breast cancer cease increasing after 50 years of age, but age-specific rates of ER+ breast cancer continue to increase after 50 years of age. For men the incidence of ER– cancers may increase at a slower rate than incidence of ER+ cancers in older ages. In women the black rates of ER+ cancers are greater than white rates only until age 35, but black rates of ER– cancers are greater than white rates for all ages. Conclusions: Differences in age-specific breast cancer incidence patterns by hormone receptor status are similar for black women and white women. The incidence pattern for ER– cancers is consistent with a paracrine model for hormone-stimulated growth in normal breast tissue. The continued increase in ER+ cancers after menopause may be explained by both the paracrine growth model and an increase in the proliferation rate of ER+ cells with age.

A method for partitioning cancer mortality trends by factors associated with diagnosis: An application to female breat cancer

U.S. cancer mortality data derived from information recorded on death certificates are frequently relied upon as an indicator of progress against cancer. A limitation of this measure is the lack of information pertaining to the onset of disease, such as year-of-diagnosis, age-at-diagnosis, stage of disease at diagnosis and histology of lesions. However, population-based cancer registries collect these types of data and allow the calculation of an incidence-file based mortality rate. This incidence-based mortality rate allows a partitioning of mortality by variables associated with the cancer onset. Breast cancer incidence-based mortality measures are created and compared to mortality rates based on death certificates over a comparable time period. Novel mortality measures, such as mortality rates by stage-at-diagnosis, age-at-diagnosis and year-of-diagnosis, are used to illustrate the value of this approach.

Annual cancer incidence rates for hispanics in the United States

The expansion of the Surveillance, Epidemiology, and End Results (SEER) program and the determination of annual population estimates by county level for different racial/ethnic groups since 1990 allow the calculation of annual cancer incidence rates for Hispanics.

Representation of Asian Americans in clinical cancer trials.

PURPOSE The objectives of this study are to analyze the accrual of Asian Americans to National Cancer Institute (NCI)-supported prevention, screening/diagnosis, and treatment trials and to determine if there is proportional ethnic representation. METHODS Data were obtained on all participants accrued to ongoing prevention and screening/ diagnosis trials and on all patients accrued to treatment trials from 1994 to mid-1998. In the analysis, the percentage of Asian Americans to the total number of trial participants is calculated. For treatment trials, participants were stratified into five age groups: 0-20 years, 21-44 years, 45-54 years, 55-64 years, and 65 or more years. RESULTS Asian Americans represented 4.8% of subjects accrued in screening/diagnosis trials, 1.8 to 2.2% of subjects in treatment trials, and 0.9% of subjects in prevention trials. Comparison of treatment trial age groups revealed that younger Asian Americans participate significantly more in treatment trials than older Asian Americans. CONCLUSIONS Asian American accrual in NCI-supported trials is representative of the cancer burden of Asian Americans in the United States. However, Asian Americans 65+ years are underrepresented. Their full participation in cancer trials is justified.