Cancer-related disparities: weathering the perfect storm through comprehensive cancer control approaches.

During the last two decades extraordinary progress in developing and using effective cancer prevention strategies, early detection interventions, and cancer treatments has been made. This progress has resulted in an overall decline in mortality rates for all cancers combined. Nonetheless, cancer is the second most common cause of death in the United States. Although cancer is a diagnosis that many survive, cancer experiences across populations may vary considerably. These differences in cancer experiences have created an unequal disease burden that presents distinct professional and moral challenges to our nation. Many cancer control plans suggest specific strategies that prioritize eliminating cancer-related disparities. This article describes certain cancer-related disparities in the United States and gives several examples of how communities and disenfranchised populations are using comprehensive cancer control (CCC) approaches to eliminate these disparities. One or two interventions are highlighted in each example.

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.

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 Institute's 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.

Geographic variation in breast cancer mortality for white and black women: 1986-1995.

Breast cancer mortality rates have decreased during the last 20 years in the United States overall. However, declines in breast cancer mortality rates differ among individual states. This analysis ranked states from the highest to the lowest percentage change in mortality between 1986 to 1990 and 1991 to 1995. Data on white and black females were analyzed separately. Among white women, the 10 states showing the greatest percentage change in mortality during those two periods had the greatest baseline mortality in the 1986-to-1990 period. Similarly, the 10 states with the lowest percentage change in mortality had the lowest mortality rate in 1986 to 1990. In contrast, among black women, the top 10 states ranked by percentage change in mortality included either a decline or an increase. The disparities in mortality rates by state likely depend on the stage of disease at diagnoses, socioeconomic status, access to care, and adequacy of medical care.

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.

A Phase II study of high-dose tamoxifen in patients with hormone-refractory prostate cancer.

Micromolar concentrations of tamoxifen inhibit the activity of protein kinase C and were recently shown to inhibit prostate cancer cell growth in preclinical studies. Because micromolar concentrations can be attained with high-dose therapy, the clinical activity of high-dose tamoxifen was evaluated in patients with metastatic adenocarcinoma of the prostate. Between December 1993 and February 1997, 30 patients with hormone-refractory metastatic adenocarcinoma of the prostate were continuously administered tamoxifen at 160 mg/m2/day. Therapy was continued until disease progression. All study patients had failed prior treatment with combined androgen blockade, had castrate levels of testosterone, and were heavily pretreated, having received a median of three prior regimens. The average steady-state plasma concentration of tamoxifen was 2.96+/-1.32 microM (mean +/- SD). Grade 3 neurotoxicity was observed in 29% of patients and was rapidly reversible and readily managed with dose modification. Otherwise, grade 3 toxicities were rare. One partial response (80% decline in prostate-specific antigen) was observed (3.3%), whereas disease stabilization was observed in six patients (20%), for a combined partial response/stable disease response rate of 23%. Median time to progression was 2.1 months, and median survival time was 10.5 months. High-dose tamoxifen therapy was well tolerated and associated with micromolar concentrations of tamoxifen in human plasma, and it demonstrated activity, albeit limited, in a heavily pretreated patient cohort with hormone-refractory prostate cancer. These findings suggest that further investigation of the role of protein kinase C modulation in prostate cancer is warranted.

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.