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

BACKGROUND: The National Cancer Institute's 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. METHODS: Stratified by ER and PR status, the frequency distributions of 112,588 breast cancer cases diagnosed between 1992--1997 in 11 SEER cancer registries were examined by age at diagnosis, stage at diagnosis, histologic grade, and tumor type for white, black, Hispanic, Japanese, Chinese, Filipino, Native Hawaiian, and American Indian and Alaska Native (AI/AN) females. RESULTS: For each racial/ethnic group, the percentage of ER positive (+)/PR+ was > ER-PR- > ER+PR- > ER-PR+ tumors. For the two major ER/PR groups, the ER+PR+ tumors were different from the ER-PR- tumors in several ways. For white females, there were differences in the age distributions, stage at diagnosis, and histologic grade. For black females, the differences involved the age distributions and tumor grades. For Hispanic and Japanese females, there were differences with regard to the age distributions and tumor grades. For Filipino, Chinese, and AI/AN females, the tumor stages and grades differed. For Native Hawaiians, the histologic tumor grades were different. CONCLUSIONS: For each racial/ethnic group, the ER/PR status appeared to divide breast cancer patients into two or more subgroups with unique tumor characteristics. In general, ER status appeared to have the greatest impact on delineating these subgroups, whereas in some cases, PR status was able to modify the subgroups further. It is hoped that reporting these tumor characteristics by ER/PR status for each racial/ethnic group will spur more investigation into the significance of ER/PR status in each racial/ethnic group.

The epidemiology of prostate cancer in the United States.

OBJECTIVES: To provide a review of prostate cancer epidemiology. DATA SOURCES: Journal articles and the Surveillance, Epidemiology, and End Results database. CONCLUSIONS: Numerous risk factors for prostate cancer have been identified. Incidence and mortality rates are higher in certain countries and among racial ethnic groups. Environmental and dietary influences are likely to be significant causes of prostate cancer. Distinguishing those cancers that are clinically significant from those that are not remains a central concern in prostate cancer research. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of epidemiologic patterns and trends will assist nurses in recognising persons at high risk for the development of prostate cancer and should result in tailored educational interventions.

The future of prostate cancer prevention.

The dramatic international variation in prostate cancer mortality rates suggest an environmental influence. This combined with a building understanding of the genetic mechanisms of carcinogenesis encourages a search for ways to prevent it. Androgenic stimulation over a period of time has been suggested a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. Decreasing androgenic stimulation of the prostate with 5-alpha-reductase inhibitors such as finasteride has been shown to decrease prostate size and may prevent prostate cancer. A large, long-term clinical trial is underway using finasteride to determine if it can prevent prostate cancer. Results are expected in 2004. Epidemiologic and laboratory studies also suggest that high selenium and vitamin E intake lowers risk of prostate cancer. Recent serendipitous findings of two randomized clinical trials support the hypothesis that selenium and vitamin administration will decrease prostate cancer risk. A study to assess these compounds is beginning. Other promising, but less developed, interventions in chemoprevention of prostate cancer include vitamin D supplementation and diet modification. All will need to be rigorously evaluated before they can be advocated for prostate cancer prevention.

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.

Cancer screening.

Especially in the emotionally charged field of cancer screening, which can have substantial public health implications for large numbers of healthy, asymptomatic people, it is important to achieve strong levels of evidence before promulgating new screening tools. This review of screening study methodology is intended to help the reader weigh such evidence and to evaluate reports which appear in the literature. It is an attempt to go beyond the often-stated intuition that early cancer detection finds cancers when they are easier to treat, at a time when survival is best. Examples tell us that sometimes this assumption has been true, sometimes not. A familiarity with the hidden biases in the supposition can be translated into everyday medical practice for screening tests in general. The practitioner can then match the strength of recommendation with the strength of the evidence behind the recommendation.

Prostate cancer prevention trials in the USA.

There is dramatic international variation in prostate cancer mortality rates. The variation suggests that the disease has an environmental cause and encourages the search for a way to prevent it. Androgenic stimulation over a period of time, perhaps due to a high fat diet, has been suggested as a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. 5-Alpha-reductase inhibition through drugs like finasteride have been shown to decrease androgenic stimulation of the prostate. A clinical trial is underway using finasteride to assess this hypothesis. Epidemiological and laboratory studies also suggest that those with high selenium and vitamin E intake have a lower risk of prostate cancer. Recent serendipitous findings of two randomised clinical trials support this. A study to assess these compounds is currently being designed. Other promising but less developed interventions in the chemoprevention of prostate cancer include vitamin D supplementation and diet modification.

Analysis of autopsy evaluations of ovarian cancer patients treated at the National Cancer Institute, 1972-1988.

Between 1972 and 1988, more than 500 women were treated for ovarian cancer at the National Cancer Institute in Bethesda, Maryland on approved experimental treatment protocols. Of these, 73 underwent autopsy evaluation on the National Cancer Institute campus. We have analyzed the autopsy reports of those individuals to determine the patterns of disease spread at death. By comparison with the literature, the demographics of the cohort did not differ from previously published reports, other than the extent of chemotherapy received antemortem. Median survival of the cohort was 15.6 months (range, 1.7-108.3 months), and median age at diagnosis was 55 years (range, 24-74 years). The median number of treatments regimens received was two (range, 1-6). The pattern of disease spread at autopsy was different from that in previously published work in that there was a higher proportion of patients with disease found in liver parenchyma, lung pleura, and the pericardium. Patients who received cisplatin as part of their initial treatment regimen had a higher incidence of metastases to the adrenal glands, thoracic nodes, bladder, and liver parenchyma, which was not explained by differences in survival. Median survival for patients who received cisplatin as part of their initial therapy was 15.6 months, compared with a median of 15.4 months for patients who did not. These data suggest a changing pattern of disease spread in patients with ovarian cancer receiving aggressive chemotherapy. This may be caused by some effect of platinum-based therapy on the metastatic potential of the tumor.

Association of Helicobacter pylori infection with gastric cancer.

BACKGROUND: Helicobacter pylori has generated public health interest since its identification in 1983. Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer. More recent studies support the conclusion that the association of H. pylori with gastric cancer is causal. The purpose of this article is to review the available evidence supporting the association of H. pylori with gastric cancer. METHODS: We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997. The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. RESULTS: H. pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of H. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer. CONCLUSIONS: New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed.

Breast cancer trends of black women compared with white women.

OBJECTIVE: To investigate why breast cancer mortality rates have decreased in the 1990's for white women but not for black women. DESIGN: Racial differences in breast cancer incidence, survival, and mortality rates were examined using regression methods and age-period-cohort models. SETTING: United States breast cancer mortality rates from 1970 through 1995, breast cancer incidence rates from 1980 through 1995, and 3-year survival rates from 1980 through 1993. The incidence and survival data are from the Surveillance, Epidemiology, and End Results Program, representing 11% of the US population, of the National Cancer Institute, Bethesda, Md. RESULTS: For both white and black women aged 30 to 39 years, breast cancer mortality rates began decreasing in 1987. For white women aged 40 to 79 years, breast cancer mortality rates declined after 1989, and for black women aged 40 to 69 years, mortality rates ceased increasing in the middle to late 1980s. Birth cohort trends were similar by race, but calendar period trends and survival rates differed. CONCLUSIONS: Declines in mortality rates in women younger than 40 years reflect a favorable birth cohort trend for women born after 1948 and likely reflect changes in risk factors. The increased early detection of breast cancer by mammography and improvements in breast cancer treatment appear to be contributing to the improving mortality trends in older women, although black women appear to have benefited less than white women from early detection and treatment advances. In addition, substantial increases in survival rates for white women with regional disease have contributed to their declining mortality rates and likely reflect an increasing use of beneficial adjuvant therapy.

Prostate cancer and black men.

Prostate cancer is a significant cause of death among men of all races in the United States, and it does disproportionately affect Black men. This disease poses a number of questions that desperately need answers. These questions involve not just the cause and prevention of the prostate cancer, but a very real and valid question is "does screening for and aggressive treatment of prostate cancer save lives." Almost all questions in prostate cancer are not questions unique to blacks or whites, or any specific population. These questions can only be answered through well-designed basic and clinical research studies. This research must be supported by both physician and patient participation. Conveying truthful, accurate information in this disease in which so much is unanswered is imperative. In American medical history, black men have often been misled or misinformed oftentimes by well-meaning paternalistic individuals. Physicians and laymen teaching about this disease must themselves realize and then truthfully convey "what is known, what is not known, and what is believed." This will allow the layman to make educated decisions regarding screening, treatment, and participation in clinical studies.

The epidemiology of prostate cancer part I: descriptive epidemiology.

The incidence and mortality of prostate cancer is highly varied among populations and especially among blacks and whites. The incidence rates of all American populations have dramatically changed over the past 25 years. The recent increase in incidence has been attributed to prostate cancer screening. Although the incidence has increased over the past 25 years, the mortality rates although vastly different between populations have remained rather stable within populations. Prostate cancer is still a disease that primarily afflicts older men. The median age at diagnosis is 71 years for whites and 69 years for blacks. More than 80% are over the age of 65 years. Screening for prostate cancer has dramatically increased the number of men with local disease at diagnosis, but it is unclear whether screening and aggressive treatment have caused a decrease in mortality.

Prostate cancer research and the National Cancer Institute.

The National Cancer Institute (NCI) is the largest funder of prostate cancer research in the United States and indeed the world. It is sponsoring a number of studies to answer the significant questions pertinent to prostate cancer and pertinent to black men. These include studies of epidemiology; cancer prevention, screening, and control; clinical treatment; and basic science. In addition, the NCI is charged with dissemination of research findings to physicians and the lay public. The following is a description of the NCI prostate cancer research portfolio including the scientific questions being addressed and how are they being addressed.

Prostate cancer treatment outcome in blacks and whites: a summary of the literature.

The disparate mortality rates of prostate cancer among populations have led to the question "Is therapy as effective in blacks versus whites." A review of the cancer literature that has assessed black-white outcomes supports the conclusion that equal treatment yields equal outcomes among equal patients. Although epidemiological studies demonstrate that blacks are disproportionately diagnosed with higher stage and higher grade disease, clinical studies show that equal treatment yields equal outcome regardless of race. Patterns-of-care studies demonstrate that there is not equal treatment in the United States among black and white patients.

The epidemiology of prostate cancer part II: the risk factors.

The epidemiology of prostate cancer gives us some clues that its etiology is likely both environmental and genetic. There is extreme country to country variability in prostate cancer mortality. Countries in which dietary fat intake is greater have been shown to have higher prostate cancer mortality rates leaving some to conclude that dietary fat causes prostate cancer. Migration studies show that men moving from Japan and China adopt increased risks of prostate cancer. Second- and third-generation Japanese Americans and Chinese Americans actually have risks of prostate cancer similar to white American men. This is highly suggestive that prostate cancer has an environmental influence. The differences in black-white mortality and newer data suggesting a higher mortality among Jamaican and Brazilian men of African descent suggest there may be a genetic predisposition to prostate cancer. Some have suggested certain polymorphisms increase prostate cancer risk, whereas others are searching for genetic mutations that may increase prostate cancer risk. Africans may have an increased prevalence of these genetic risk factors. Ultimately, the cause of prostate cancer is likely to be a combination of environmental and genetic factors.

Phase II study of suramin plus aminoglutethimide in two cohorts of patients with androgen-independent prostate cancer: simultaneous antiandrogen withdrawal and prior antiandrogen withdrawal.

Management of prostate cancer progression after failure of initial hormonal therapy is controversial. Recently, the activity of the simple discontinuation of antiandrogen therapy has been established by several groups, as well as the enhanced activity when combined with adrenal suppression (i.e., aminoglutethimide and hydrocortisone). Furthermore, suramin has generated considerable interest following reports of response rates ranging from 17 to 70%. More recently, suramin response rates of 18 and 22% have been reported when the potential confounding variables of flutamide withdrawal and hydrocortisone were prospectively controlled. On the basis of the activity of combining aminoglutethimide with flutamide withdrawal, we designed a protocol in which suramin was combined with aminoglutethimide in two cohorts of patients (those with simultaneous antiandrogen withdrawal compared to those who had previously discontinued antiandrogen therapy). Eighty-one evaluable patients were enrolled in this study between June 1992 and November 1994. Patients were a priori divided into two cohorts, those receiving prior antiandrogen withdrawal (n = 56) and those receiving simultaneous antiandrogen withdrawal (n = 25) at the time the patients were enrolled into the trial. For the group that discontinued antiandrogen prior to enrolling in therapy, the partial response rate (> 50% decline in PSA for > 4 weeks) was 14.2%, whereas the partial response was 44% for those patients who discontinued their antiandrogen at the time of starting suramin and aminoglutethimide. The median time to progression was 3.9 months in patients failing prior antiandrogen withdrawal and 5.5 months in those patients having concomitant antiandrogen withdrawal (P = 0.36 for the overall difference). The progression-free survival estimate at 1 year for patients having prior antiandrogen withdrawal was 19.8% [95% confidence interval (CI), 11-32.9%]. For those patients who experienced antiandrogen withdrawal simultaneous with the treatment, the progression-free survival estimates at 1 and 2 years were 27.1 (95% CI, 13.2-47.6%) and 4.5% (95% CI, 0.8-21.6%). The median survival time for those patients having prior antiandrogen withdrawal was 14.2 months, whereas the median survival was 21.9 months for those having concomitant antiandrogen withdrawal (P = 0.029 for the overall difference). In conclusion, the partial response rate of 44% for those who had concomitant flutamide withdrawal with adrenal suppression was consistent with that of other reports using a similar maneuver. Although this study was not randomized and thus we should not over-interpret the results, flutamide withdrawal plus adrenal suppression appears to have greater activity than flutamide withdrawal alone. Furthermore, these data suggest that suramin adds little to the response rate observed for other adrenal suppressive agents in the presence of antiandrogen withdrawal. This interpretation is in agreement with those studies controlling for adrenal suppression and flutamide withdrawal prior to suramin administration, which noted modest activity of short duration. Given that antiandrogen withdrawal is now accepted as an active maneuver for a subset of patients progressing after maximum androgen blockade, we propose that future trials attempting to maximize response rates incorporate this maneuver whenever possible into prospectively designed regimens.

The study of untreated syphilis in the negro male.

PURPOSE: The participation of minorities in clinical studies is the subject of much discussion and has even become the subject of Federal law. The project known as the Tuskegee Syphilis Study and officially titled "The Tuskegee Study of Untreated Syphilis in the Negro Male," is one of the great debacles of American medicine and a national shame. Despite the fact that its existence is well known, many do not know the historical facts of the study nor the context of the study. My purpose here is to recount the facts of the study and its historical context. METHODS: The history recounted here is taken from documents gathered during a U.S. Senate investigation of the study, original papers located in National Library of Medicine, and books about the trial. RESULTS: The trial began in 1931 as a survey of the natural history of untreated tertiary syphilis in Black men. This study enrolled 399 men with syphilis and 201 uninfected men to serve as controls. All were at least 25 years old at enrollment. The men were told they were in a study, but never educated about the implications. Later, men were not informed that there was a treatment for effective treatment for their disease--a treatment that was being withheld from them. This trial continued till 1972. CONCLUSION: Many of the issues that led to the study and caused it to continue for 40 years still exist. The lessons of the Public Health Study of Untreated Syphilis in the Untreated Negro include the dangers of paternalism, arrogance, blind loyalty, and misuse of science. "Those who do not appreciate history are condemned to repeat it" (Alfred North Whitehead).

National cancer clinical trials: children have equal access; adolescents do not.

PURPOSE: To determine whether adolescents with cancer, who in comparison to younger patients have a higher cancer incidence and lower mortality reduction, have equal access to national cancer clinical trials. METHODS: The ethnic/racial distribution of 29,859 subjects < 20 years of age entered onto National Cancer Institute-sponsored clinical trials between January 1, 1991, and June 30, 1994, was compared with the expected distribution of patients of the same age in the United States. RESULTS: The Children's Cancer Group and Pediatric Oncology Group had 29,134 (97.6%) of the total study entries among < 20-year-old subjects during the 3.5 years of surveillance. The adult cooperative groups accounted for < 3% of the clinical trials entries in the 15-19-year age range. When analyzed nationally by region, the under-representation of the older adolescent subjects was universal. From other analyses, the two pediatric cooperative groups were estimated to have registered > 94% of the children < 15 years of age who were expected to have been diagnosed to have cancer, but only 21% of the cancer patients in the 15-19-year age group. CONCLUSIONS: The national pediatric cancer cooperative groups allow the majority of American children < 15 years of age and their families equal opportunity to access clinical cancer trials, regardless of race or ethnicity. Among patients 15-19 years of age, however, > 75% are not being enrolled by any cooperative group sponsored by the National Cancer Institute. Thus, older adolescents are disadvantaged with respect to access to the national clinical trials, regardless of their race or ethnicity.

Prostate carcinoma incidence and patient mortality: the effects of screening and early detection.

BACKGROUND: Screening for and the aggressive treatment of prostate carcinoma are controversial, but they are nevertheless being practiced in the U.S. Current clinical studies of the effectiveness of screening will take years to complete. Meanwhile, screening for prostate carcinoma is already having an effect on society. METHODS: National and regional trends in prostate carcinoma incidence and data on patient mortality and survival from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute are described in this article. SEER is a population-based cancer data base comprised of nine discrete areas. Fundamental principles of screening are used in this article to explain the impact that prostate carcinoma screening has had in the U.S. RESULTS: According to the data in the SEER registries, overall prostate carcinoma incidence rates increased at a far greater pace than prostate carcinoma mortality rates during the period 1973-1994. During that period, there was a shift in stage at diagnosis characterized by an increase in local and regional disease, and a decline in distant disease at diagnosis. Overall 5-year survival rates for prostate carcinoma patients also increased. The increase in incidence rates, the shift in stage at diagnosis, and the increase in survival rates are all evidence of increasing early detection. However, these changes are consistent with lead-time bias, length bias, a decline in mortality, and all three could have occurred. In the geographic SEER registries, the prostate carcinoma incidence rates vary markedly. These variations in incidence rates are due to regional variations in practice patterns and screening efforts. On the other hand, the SEER registries have comparable mortality rates. This is evidence of both lead-time bias and length bias. CONCLUSIONS: Substantial regional variations in incidence were found, but regional mortality rates were similar. This is evidence that screening and early detection efforts are resulting in the diagnosis of prostate carcinoma in some men who do not need therapy; thus, prostate carcinoma screening can lead to unnecessary treatment for such men. Furthermore, epidemiologic data do not demonstrate that screening is decreasing mortality. The benefits of screening and early detection, although theoretically possible, are yet unproven, whereas the risks and harms of screening and resultant treatment are definite.