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Background: Clinical trials have demonstrated that use of mammographic screening and advances in therapy can improve prognosis for women with breast cancer. Purpose: WE determined the trends in breast cancer mortality rates, as well as incidence and survival rates by extent of disease at diagnosis, for white women in the United States and considered whether these trends are consistent with widespread use of such beneficial medical interventions. Methods: We examined mortality data from the National Center for Health Statistics and incidence and survival data by extent of disease from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, all stratified by patient age, using statistical-regression techniques to determine changes in the slope of trends over time. Results: The age-adjusted breast cancer mortality rate for U.S. white females dropped 6.8% from 1989 through 1993. A significant decrease in the slope of the mortality trend of approximately 2% per year was observed in every decade of age from 40 to 79 years of age. Trends in incidence rates were also similar among these age groups: localized disease rates increased rapidly from 1982 through 1987 and stabilized or increased more slowly thereafter; regional disease rates decreased after 1987; and distant disease rates have remained level over the past 20 years. Three-year relative survival rates increased steadily and significantly for both localized and regional disease from 1980 through 1989 in all ages, with no evidence of an increase in slope in the late 1980s. Implications: The decrease in the diagnosis of regional disease in the late 1980s in women over the age of 40 years likely reflects the increased use of mammography earlier in the 1980s. The increase in survival rates, particularly for regional disease, likely reflects improvements in systemic adjuvant therapy. Statistical modeling indicates that the recent drop in breast cancer mortality is too rapid to be explained only by the increased use of=mammography; likewise, there has been no equivalent dramatic increase in survival rates that would implicate therapy alone. Thus, indications are that both are involved in the recent rapid decline in breast cancer mortality rates in the United States.

Background. The pattern of second cancers after treatment for cervical cancer provides important information on the risk of radiation-induced malignancies. Large numbers of women survive many years and can be studied for late effects. Methods. Incident second cancers in 86,193 patients with cervical cancer reported to 13 population-based cancer registries in 5 countries were evaluated to estimate the risk of second cancer among very long term survivors. Results. Overall, 7543 second cancers were observed versus 6015 cancers expected based on population rates (observed/expected = 1.2). Lung cancer accounted for nearly half of the excess cancers. Among the 49,828 women treated with radiation, 3750 survived 30 or more years and a two-fold risk of cancers of heavily irradiated organs was seen. Most of the excess cancers were of the rectum, vagina, vulva, ovary, and bladder. Patterns of risk over time since treatment were consistent with a radiation etiology. Significant increases of nonchronic lymphocytic leukemia and cancers of the bone and kidney were also linked to radiotherapy. Women treated surgically were also at significant risk of second cancers, in all likelihood related to cigarette smoking and risk factors similar to those of cervical cancer. Conclusions. Curative therapy for cervical cancer results in large numbers of long term survivors who develop second cancers very late in life. Radiation is an important cause of this increase and there is no evidence that risk returns to normal levels. Cancer 1995;76:442-52.

This supplement presents the study of various histologic types of cancers diagnosed in the populations covered by the Surveillance, Epidemiology, and End Results (SEER) Program. It describes the SEER program and the coding of histologic type by the International Classification of Diseases for Oncology. Each of the 19 articles deals with the histologic types of cancer found in major sites or with specific histologic types, such as lymphomas or melanomas. Histologic types have been grouped based on those developed by Dr. John Berg. Data presented in this supplement are based on more than one million microscopically proven invasive cancers and 98,000 in situ cancers diagnosed during the period 1973-1987 in areas covered by the SEER Program.

Background: Colorectal cancer mortality rates among U.S. white males remained relatively constant from 1950 through 1984 but declined sharply from 1985 through 1990. Those for U.S. white females decreased consistently from 1950 through 1984, with an acceleration of the decline from 1985 through 1990. Purpose: A study was planned to investigate patterns in incidence, survival, and mortality rates over time in order to examine possible reasons for the gender difference in mortality trends and for the decrease in the slope of the mortality trends for both males and females in the late 1980s. Methods: Incidence and survival data from the Connecticut Cancer Registry were examined to investigate the gender differences in mortality rates from 1950 through 1984. Incidence and survival data from the Surveillance, Epidemiology, and End Results (SEER) Program were investigated to examine reasons for the abrupt downturn in mortality rates for both white males and white females beginning around 1985. Results: During the period 1950 through 1984, the colorectal cancer incidence rates in Connecticut increased for males and declined slightly for females. Survival rates were similar for both sexes, increasing on average over 1% per year for both females and males from 1950 through 1984. Examination of SEER data from 1975 through 1990 revealed that for both males and females there were 1) declines in overall incidence and mortality rates beginning in the mid-1980s, 2) steady declines in distant disease incidence rates since 1975, 3) increases in regional disease incidence rates until the early 1980s followed by declines in the late 1980s, and 4) increases in local disease incidence rates until the mid-1980s followed by declines in the late 1980s. Age-period-cohort analyses of mortality rates indicated a statistically significant moderation of colorectal cancer risk with both advancing birth cohorts and recent calendar periods. Conclusions: The gender differences in colorectal cancer mortality rate trends observed from 1950 through 1984 are due to differences in incidence rate trends between males and females. Declining colorectal mortality rates in the late 1980s for males and females appear to reflect improved early detection. The peaking and subsequent decline of stage-specific incidence rates at later years for successively lower stage indicate sequential stage shifts as cancers are detected increasingly earlier over time. The increased use of sigmoidoscopy and fecal occult blood tests (triggering colonoscopy) appears to have played an important role in reducing colorectal cancer mortality. Improvements in birth cohort trends in risk for colorectal cancer for each sex suggest that lifestyle changes may have also contributed to the steady reductions in colorectal cancer mortality.

Background. This national study of breast cancer incidence and mortality was conducted to determine whether patterns of change differ for black and white women, to evaluate patterns by extent of disease, and to determine whether recent patterns of breast cancer are consistent with results that one would expect due to increases in use of screening examinations by women. Methods. The study included 104,351 cases of in situ or invasive breast cancer diagnosed between 1983 and 1989 among women from the nine geographic areas participating in the National Cancer Institute Surveillance, Epidemiology, and End Results program. Breast cancer incidence patterns were examined by extent of disease for black and white women and by age at diagnosis. Results. Significant increases occurred in the incidence of all early-stage breast cancers. Concomitantly, significant decreases occurred in the incidence of the most advanced-stage breast cancers. Although both white and black women experienced significant increases in early-stage breast cancer, black women have substantially lower rates of the least extensive breast cancers. Conclusion. These results strongly suggest that a major explanation for the increase in breast cancer incidence in the 1980s may well be the increased prevalence of breast cancer screening among women in the United States. They also suggest a consistent benefit of screening across all age groups from 40 to 49 years through 70 years and older.

Background: Reports to date have provided widely divergent estimates of the risk of second malignant neoplasms in patients with chronic lymphocytic leukemia (CLL), ranging from cancer deFicits to excesses of twofold to threefold. Purpose: Our purpose was to estimate the risk of second primary cancers following CLL, utilizing population-based tumor registries, and to determine whether site-specific excesses might be associated with type of initial treatment for CLL. Methods: We analyzed data for 9456 patients diagnosed with CLL as a first primary cancer between 1973 and 1988, who were reported to one of nine tumor registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and who survived 2 or more months. SEER files were searched for invasive primary malignancies that developed at least 2 months after the initial CLL diagnosis. Results: Compared with the general population, CLL patients demonstrated a significantly increased risk of developing all second cancers (840 observed; observed-to-expected ratio [O/E] = 1.28; 95% confidence interval [CI] = 1.19-1.37). Significant excesses were noted for cancers of the lung (O/E = 1.90), brain (O/E = 1.98), and eye (intraocular melanoma) (O/E = 3.97) as well as malignant melanoma (O/E = 2.79) and Hodgkin's disease (O/E = 7.69). Cancer risk, which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis. Conclusion: CLL patients are at a significantly increased risk of developing a second malignant neoplasm. The pattern of cancer excesses suggests a susceptibility state permitting the development of selected second malignancies in patients with CLL, perhaps because of shared etiologic factors, immunologic impairment, and/or other influences. Although our results do not suggest a strong treatment effect, more detailed studies of second tumors in CLL are needed to investigate the role of radiation therapy and chemotherapy. [J Natl Cancer Inst 84:1422-1427, 1992]

Background: The objective of this study was to investigate the circumstances under which dissemination of prostate-specific antigen (PSA) testing, beginning in 1988, could plausibly explain the declines in prostate cancer mortality observed from 1992 through 1994. Methods: We developed a computer simulation model by use of information on population-based PSA testing patterns, cancer detection rates, average lead time (the time by which diagnosis is advanced by screening), and projected decreased risk of death associated with early diagnosis of prostate cancer through PSA testing. The model provides estimates of the number of deaths prevented by PSA testing for the 7-year period from 1988 through 1994 and projects what prostate cancer mortality for these years would have been in the absence of PSA testing. Results: Results were generated by assuming a level of screening efficacy similar to that hypothesized for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Under this assumption, the projected mortality in the absence of PSA testing continued the increasing trend observed before 1991 only when it was assumed that the mean lead time was 3 years or less. Projected mortality trends in the absence of PSA screening were not consistent with pre-1991 increasing trends for lead times of 5 years and 7 years. Conclusions: When screening is assumed to be at least as efficacious as hypothesized in the PLCO trial, it is unlikely that the entire decline in prostate cancer mortality can be explained by PSA testing based on current beliefs concerning lead time. Only very short lead times,would produce a decline in mortality of the magnitude that has been observed. [J Natl Cancer Inst 1999;91:1033-9]