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Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families.

Women from site-specific hereditary breast cancer families who carry a BRCA1 or BRCA2 mutation are at increased risk for ovarian cancer. It is less clear, however, whether individuals from hereditary breast cancer families who do not carry such a mutation are also at increased ovarian cancer risk. To determine whether women from BRCA mutation-negative hereditary breast cancer families are at increased risk for ovarian cancer, 199 probands from BRCA mutation-negative, site-specific breast cancer kindreds who consented to prospective follow-up at the time of genetic testing were identified. The incidence of new breast and ovarian cancers in probands and their families since receipt of their genetic test results was determined by questionnaire. The expected number of cancers and standardized incidence ratios (SIRs) were determined from age-specific cancer incidence rates from the Surveillance, Epidemiology, and End Results (SEER) program by using the method of Byar. All statistical tests were two-sided. During 2534 women-years of follow-up in 165 kindreds, 19 new cases of breast cancer were diagnosed, whereas only 6.07 were expected (SIR = 3.13, 95% confidence interval [CI] = 1.88 to 4.89; P < .001), and one case of ovarian cancer was diagnosed, whereas only 0.66 was expected (SIR = 1.52, 95% CI = 0.02 to 8.46; P = .48). These results suggest that women from BRCA mutation-negative, site-specific breast cancer families are not at increased risk for ovarian cancer.

Adult↗

Pediatric brain tumors in non-Hispanics, Hispanics, African Americans and Asians: differences in survival after diagnosis.

BACKGROUND: Racial differences in survival for children with brain tumors have not been well studied, particularly in Hispanics and Asians. The objective of this study was to assess racial differences in survival of children with brain tumors, focusing on Hispanics, African Americans and Asians compared to Non-Hispanics. METHODS: Subjects identified through the SEER Program were 2799 children, < or =19 years old at diagnosis, newly diagnosed between 1973 and 1996 with primary, malignant brain tumors. Chi-square tests were used to evaluate prognostic variables by race. Kaplan-Meier models and Cox proportional hazards models were used to assess racial differences in overall survival and in survival by histological type of tumor. RESULTS: The distribution histological type of tumor varied significantly by race. Overall survival was similar for Hispanics, African Americans, Asians compared to Non-Hispanics, although trends of increased risk of death for the minority groups were noted when stratifying by histological type of tumor. CONCLUSIONS: Racial differences in survival could exist by histological type of tumor, but further work is necessary for a more complete understanding of these differences.

Adolescent↗

The importance of histologic type on breast cancer survival.

Breast cancer is a morphologically and genetically heterogeneous disease. The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute provides the large number of cases necessary to study individual histologic types of female invasive breast cancer that for practical reasons are otherwise unattainable. Attention was specifically focused on 4082 cases of mucinous adenocarcinoma and 139,154 cases of infiltrating duct carcinoma identified for the years 1973-1990. Life table analyses were conducted to compare survival by histologic type using death due to breast cancer as the outcome; Cox proportional hazards analysis was used to adjust for important covariates. Findings were that women diagnosed with mucinous adenocarcinoma have a rate of mortality due to breast cancer that is 0.38 that of the rate of women diagnosed with infiltrating duct carcinoma (95% confidence interval 0.34-0.42). We conclude that histologic type is important to consider in the prognosis and treatment of women diagnosed with breast cancer.

Adenofibroma↗

Prostate cancer incidence, mortality, and survival trends in the United States: 1981-2001.

The increased use of prostate-specific antigen (PSA) in screening for preclinical disease after 1985 is thought to be a major determinant of the changing patterns in prostate cancer incidence; however, the long-term effect of screening on future trends in mortality and survival is uncertain. This article reviews the temporal trends (1981-1998) for prostate cancer incidence, mortality, and survival, and projects prostate cancer incidence and mortality rates for 1999 to 2001. Autoregressive, quadratic, time-series models were used to describe prostate cancer mortality rates in the US population and prostate cancer incidence rates derived from the National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) program. These models were based on data collected from 1979 through 1998, with forecasts produced for 1999 to 2001. Prostate cancer incidence increased steadily from 1981 to 1989, with a steep increase in the early 1990s, followed by a decline. Incidence rates were forecasted to remain stable through the year 2001. Mortality rates decreased steadily and were forecasted to continue to decrease concurrently with increasing 5- and 10-year relative survival rates. The incidence, mortality, and survival trends were comparable in US blacks, who exhibited on average 2-fold higher mortality and 50% higher incidence than whites. Decreasing prostate cancer mortality and increasing relative survival trends in the United States were described after the introduction of PSA screening. However, the exaggerated rate of increase in the early 1990s in prostate cancer incidence was transient and likely a result of increased detection of preclinical disease that was prevalent in the general population.

Black People↗

Therapy-related leukemia and myelodysplastic syndrome in chronic lymphocytic leukemia.

A retrospective analysis was performed to determine the incidence and clinical features of acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) developing in chronic lymphocytic leukemia (CLL) patients. AML/MDS occurred in 3/1374 CLL patients seen at a single institution between 1972 and 1992. The median follow-up exceeded 7 years and 72% of these patients had received prior alkylating agent therapy. The expected number of AML/MDS developing in a general population of the same size was 1.2 as calculated from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program data (observed-to-expected ratio = 2.49; 95% confidence interval = 0.9-7.3; p = 0.12). Although, not included in the incidence calculation, four patients with CLL were referred at the time of development of AML/MDS. CLL and AML/MDS were diagnosed concurrently in two patients. Three of the patients had received no prior alkylating agents. The median survival was 17 months in patients who had received no prior treatment, and 5 months in those who had received prior chemotherapy. Our results suggest that patients with CLL in whom AML/MDS develops have similar prognoses to other patients with AML/MDS. Furthermore, this analysis does not provide evidence for a heightened risk of AML/MDS in CLL patients, despite treatment with known leukemogenic agents.

Aged↗

Trends in the stage specific incidence of prostate carcinoma in the Detroit metropolitan area, 1973-1994.

BACKGROUND: Much of the recent increase in prostate carcinoma incidence has been attributed to screening with prostate specific antigen (PSA). Controversy exists as to whether this screening will ultimately impact prostate carcinoma mortality. Until adequate time elapses since PSA screening became widespread, or a randomized trial of PSA screening is completed, the effect of PSA screening on prostate carcinoma mortality cannot be determined. In the interim, stage specific prostate carcinoma incidence rates may provide an indication of the effect of PSA screening. METHODS: Annual stage specific age-adjusted prostate carcinoma incidence rates for the years 1973 through 1994 were obtained from the Metropolitan Detroit Cancer Surveillance System (MDCSS), a member of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. These incidence rates were analyzed for trends using Poisson regression analysis. RESULTS: There were 10,801 cases of prostate carcinoma in black men and 31,501 in white men during the 22-year period. Incidence rates for stages of local and regional prostate carcinoma reached a maximum in 1992 and 1993. Distant stage prostate carcinoma incidence has steadily declined since 1989 (P < 0.001), the year in which the increasing trend in the incidence rates for local and regional stage prostate carcinoma were first noted. CONCLUSIONS: These findings suggest that a substantial proportion of early stage prostate carcinoma detected by PSA is in fact clinically important and that early detection of these carcinomas has resulted in a continuous decline in the stage of metastatic prostate carcinoma since 1989.

Age Factors↗

Prognostic significance of in situ carcinoma associated with invasive breast carcinoma. A natural experiment in cancer immunology?

BACKGROUND: Our previous studies indicate that the in situ phase of mammary carcinogenesis is characteristically associated with cell-mediated immunity (CMI against an immunogen shared by most breast carcinomas. Such reactivity is inversely correlated with stage and appears to impede in situ-to-invasive progression and lethality from invasive breast carcinoma. If in situ carcinomas are indeed associated with ambient, prognostically favorable immunity against such an immunogen, one would expect lethality from invasive breast carcinoma to be reduced in patients with a diagnosis of a prior, simultaneous, or subsequent in situ breast carcinoma. The present study provides a test of such relationships. METHODS: Patient survival was analyzed for 129,394 female patients with invasive breast carcinoma diagnosed in areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program based at the National Cancer Institute (NCI). Patients were classified according to whether they had a prior, simultaneous, or subsequent in situ breast carcinoma and survival was examined for up to 15 years subsequent to diagnosis using life tables and the Cox regression model. RESULTS: The findings indicate that patients with an invasive breast carcinoma who had a prior, simultaneous, or subsequent in situ breast carcinoma did experience significantly better survival than comparison groups of patients who either did not have an associated cancer of any type, had an associated invasive breast carcinoma, or had an in situ or invasive cancer of non-breast origin. CONCLUSIONS: Our prior and current observations warrant more direct studies of the prognostic, therapeutic, and prophylactic significance of the in situ carcinoma-associated type of specific CMI in breast cancer patients.

Aged↗

Epidemiology of nasopharyngeal carcinoma in the United States: improved survival of Chinese patients within the keratinizing squamous cell carcinoma histology.

BACKGROUND: This study examined potential survival differences among nasopharyngeal carcinoma (NPC) patients from various ethnicities in the United States. PATIENTS AND METHODS: A total of 2436 newly diagnosed NPC patients from 1992 to 2002 were analyzed from the population-based Surveillance, Epidemiology, and End Results (SEER) program. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. RESULTS: By multivariate analyses, early age of diagnosis, localized stage at presentation (versus distant, HR=0.35; P<0.0001), radiation therapy (versus none; HR=0.48; P<0.0001), undifferentiated non-keratinizing carcinoma (versus keratinizing squamous cell carcinoma; HR=0.67; P<0.0001), and Chinese ethnicity (versus Caucasian; HR=0.78; P=0.0010) were associated with improved survival. Within keratinizing squamous cell carcinoma histology, the survival advantage of Chinese patients remained even after adjustment for other prognostic factors. CONCLUSIONS: The significant survival advantage of Chinese NPC patients within the keratinizing squamous cell carcinoma histology contributed largely to Chinese ethnicity being an independent and favorable prognostic factor for survival in NPC.

Adolescent↗

Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer.

PURPOSE: A 1998 meta-analysis of postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC) found that PORT did not improve outcomes. Yet practice guidelines differ in their recommendations with regard to PORT use. We examine temporal trends in PORT use before and after the 1998 meta-analysis. METHODS AND MATERIALS: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we identified 22,953 patients with Stage I, II, or IIIA NSCLC who had resection between 1992 and 2002 in the United States and characterized each patient according to nodal status (N0, N1, or N2 disease). We measured use of PORT by calendar year. We examined the association between clinical and demographic characteristics and receipt of PORT using logistic regression. RESULTS: For N0, N1, and N2 NSCLC, PORT use has declined. The proportion of patients with N0 disease receiving PORT declined from 8% in 1992 to 4% in 2002. For patients with N1 disease, PORT use declined from 51% in 1992 to 19% in 2002; and for patients with N2 disease, PORT use declined from 65% in 1992 to 37% in 2002. CONCLUSION: In the context of uncertainty about what constitutes optimal adjuvant treatment for resected NSCLC, PORT use has substantially declined.

Adult↗

Mammographic breast density and the Gail model for breast cancer risk prediction in a screening population.

BACKGROUND: Estimating an individual woman's absolute risk for breast cancer is essential for decision making about screening and preventive recommendations. Although the current standard, the Gail model, is well calibrated in populations, it performs poorly for individuals. Mammographic breast density (BD) may improve the predictive accuracy of the Gail model. METHODS: Prospective observational cohort of 81,777 women in the San Francisco Mammography Registry presenting for mammography during 1993 through 2002 who had no prior diagnosis of breast cancer. Breast density was rated by clinical radiologists using the Breast Imaging Reporting and Data System classification (almost entirely fat; scattered fibroglandular densities; heterogeneously dense; extremely dense). Breast cancer cases were identified through linkage to Northern California Surveillance Epidemiology End Results (SEER) program. We compared the predictive accuracy of models with Gail risk, breast density, and the combination. All models were adjusted for age and ethnicity. RESULTS: During 5.1 years of follow-up, 955 women were diagnosed with invasive breast cancer. The Gail model had modest predictive accuracy (concordance index (c-index) 0.67; 95% CI 0.65-0.68). Adding breast density to the model increased the predictive accuracy to 0.68 (95% CI .66-.70, p < 0.01 compared with the Gail model alone). The model containing only breast density adjusted for age and ethnicity had predictive accuracy equivalent to the Gail model (c-index 0.67, 95% CI 0.65-0.68). CONCLUSION: The addition of breast density measured by BI-RADS categories minimally improved the predictive accuracy of the Gail model. A model based on breast density alone adjusted for age and ethnicity was as accurate as the Gail model.

Adult↗

Treatment for breast cancer in patients with Alzheimer's disease.

OBJECTIVES: To report use of breast cancer treatment (surgery, radiation, and chemotherapy) by patients with Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: Surveillance, Epidemiology, and End Results (SEER) is a population-based cancer registry covering 14% of the U.S. population. PARTICIPANTS: Fifty thousand four hundred sixty breast cancer patients aged 65 and older, of whom 1,935 (3.8%) had a diagnosis of AD before or up to 6 months after cancer diagnosis. MEASUREMENTS: Diagnosis of AD was taken from International Classification of Diseases, Ninth Revision, diagnostic codes accompanying Medicare billing claims between 1992 and 1999. The SEER program reported surgery and radiation. Chemotherapy was taken from Medicare billing records. RESULTS: Subjects with AD were diagnosed with breast cancer at later stages, when tumors were larger and the likelihood of lymph node involvement had increased. Patients with AD had a lower likelihood of surgery (odds ratio (OR)=0.60, 95% confidence interval (CI)=0.46-0.81), radiation (OR=0.31, 95% CI=0.23-0.41), and chemotherapy (OR=0.44, 95% CI=0.34-0.58) than those without AD. CONCLUSION: Overall, AD patients receive less treatment for breast cancer than do comparable female Medicare beneficiaries. Chemotherapy and radiation are administered less frequently to women with AD than to other comparable patients. It is unclear whether suboptimal medical care has an effect on their survival. Further research on the effect of screening and treatment decision-making for these patients is warranted.

Aged↗

Racial differences in survival after diagnosis with primary malignant brain tumor.

BACKGROUND: Previous studies have shown that the overall incidence of primary malignant brain tumor is greatest in Caucasians, although survival is better in African Americans. The objective of this study was to examine racial differences in survival after diagnosis with primary malignant brain tumor in a population-based sample of patients while adjusting for prognostic variables that differ by race. METHODS: The authors analyzed 21,493 patients (20,493 Caucasians and 1000 African Americans) who were diagnosed with primary malignant brain tumors from 1973 to 1997 (with follow-up through 1999) from the population-based Surveillance, Epidemiology, and End Results (SEER) Program. Chi-square tests were used to determine statistical significance of prognostic variables and race (using two-sided P values). Kaplan-Meier and Cox proportional hazards models were used to assess survival differences by race. RESULTS: The univariable model for race showed no survival difference by race. The multivariable model demonstrated that African American patients were at a 13% increased risk of death from any cause compared with Caucasian patients. The racial difference was explained further by an interaction between race and surgery type in which there was an increased risk of death for African American patients who underwent subtotal resections or surgery not otherwise specified compared with Caucasian patients who underwent the same procedures. CONCLUSIONS: There was a significant difference in the risk of death due to any cause for Caucasian patients and African American patients who were diagnosed with first primary brain tumors.

Adult↗

Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?

BACKGROUND/AIMS: The incidence of intrahepatic cholangiocarcinoma (ICC) has been reported to be increasing in the USA. The aim of this study is to examine whether this is a true increase or a reflection of improved detection or reclassification. METHODS: Using data from the Surveillance Epidemiology and End Results (SEER) program, incidence rates for ICC between 1975 and 1999 were calculated. We also calculated the proportions of cases with each tumor stage, microscopically confirmed cases, and the survival rates. RESULTS: A total of 2864 patients with ICC were identified. The incidence of ICC increased by 165% during the study period. Most of this increase occurred after 1985. There were no significant changes in the proportion of patients with unstaged cancer, localized cancer, microscopic confirmation, or with tumor size <5 cm during the period of the most significant increase. The 1-year survival rate increased significantly from 15.8% in 1975-1979 to 26.3% in 1995-1999, while 5-year survival rate remained essentially the same (2.6 vs. 3.5%). CONCLUSIONS: The incidence of ICC continues to rise in the USA. The stable proportions over time of patients with early stage disease, unstaged disease, tumor size <5 cm, and microscopic confirmation suggest a true increase of ICC.

Age Distribution↗

Effect of young age on prostate cancer survival: a population-based assessment (United States).

OBJECTIVE: To assess whether men diagnosed with prostate cancer at younger ages have a poorer prognosis. The influence of select factors (race, marital status, stage, histological grade, histology, presence of comorbid cancer, and time of diagnosis) on the relation between age at diagnosis and survival was considered. METHODS: Analyses were based on 289,809 men diagnosed with malignant prostate cancer, ages 40 years and older in the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 1997, actively followed for vital status through 31 December 1998. Cases diagnosed through autopsy or death certificate were excluded. Five-year relative survival and Cox proportional hazards were used for assessment. RESULTS: Five-year relative survival increased, leveled off, and then decreased over the age span. This pattern was most pronounced in men with advanced stage and poor grade tumors. Conditional death hazards that showed significantly higher hazard ratios in younger age groups (i.e. 40-44 and 45-49) represented local/regional stage and poorly differentiated/undifferentiated tumors, distant stage and moderately differentiated, poorly differentiated/ undifferentiated, or unknown grade, and unknown stage and unknown grade. The influence of young age on prostate cancer prognosis for advanced stage and poorly differentiated/undifferentiated cases was not significantly influenced by year of diagnosis or race. CONCLUSIONS: Younger age is a prognostic factor for prostate cancer survival. The relationship between young age at diagnosis and survival is significantly influenced by stage and histological grade at diagnosis.

Adult↗

Trends in the incidence of ocular melanoma in the United States, 1974-1998.

BACKGROUND: A recent report noted a fourfold risk of ocular melanoma associated with employment in occupations involving use of cellular telephones. METHODS: To aid interpretation of this finding, and clarify how subsite-specific temporal variation in incidence of ocular melanoma compares with that for cutaneous melanoma, we examined time trends in the incidence of melanoma among whites in the United States, based on data collected through the surveillance, Epidemiology, and End Results (SEER) program for 1974-1998. RESULTS: The incidence of ocular melanoma decreased over time in both sexes, with no indication of a recent increase during the 1990s. The annual percent change was -0.7% for males (95% confidence interval: -2.3, 0.9) and -1.2% for females (95% confidence interval: -2.5, 0.0). Time trends appeared to differ by subsite of ocular melanoma; rates were flat for the choroid, decreased for the ciliary body, and increased for the conjunctiva (among males only) beginning in the 1980s. In contrast, all subsites of cutaneous melanoma, including the face and adjacent areas, showed marked increases in incidence over the observation period. CONCLUSIONS: The dramatic increase in use of cellular telephones has not been accompanied by an increase in the incidence of ocular melanoma. Further study is required to explain the different time trends for subsites of ocular melanoma, and for ocular versus facial and other cutaneous melanomas.

Adolescent↗

Black-white differences in survival from late-stage prostate cancer.

OBJECTIVE: To examine differences between African Americans (Blacks) and non-Hispanic Whites in risk of death after diagnosis of later-stage prostate cancer in a large sample of patients from US population-based cancer registries. The theory that Black patients with advanced cancer have a lower survival rate compared to their White counterparts, based on a single clinical trial, was tested with large samples of patients. METHODS: The Cox proportional hazards regression model was used to compare survival rates among 24,136 non-Hispanic White, and 3,817 Black prostate cancer patients diagnosed between 1988 and 1997, whose cancer had spread beyond the prostate capsule, and who resided in 9 geographic areas covered by the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program of population-based cancer registries. Other analyses involved 5- and 10-year relative survival rates (RSRs) among non-Hispanic White and Black patients diagnosed with distant-stage prostate cancer from 1973 to 1994 (with almost all patients having had a chance to survive for at least 5 years). RESULTS: The risk of death from prostate cancer was only slightly higher for Blacks than for Whites (adjusted hazard rate ratio = 1.05), when age, extent of disease, tumor grade, marital status, and surgery were included in the Cox proportional hazards regression model. Five- and 10-year RSRs were about 2%-22% higher for Blacks and Whites in strata defined by extent of disease, or among patients with distant stage cancer, but differences were small among married patients. CONCLUSIONS: The findings do not indicate substantial Black-White differences in survival rates of later-stage prostate cancer patients, after adjusting for clinical characteristics and marital status.

Black or African American↗

Induced abortion and breast cancer risk.

Results from case-control studies suggest that induced abortion may be associated with a small increase in risk of breast cancer. While risk estimates from cohort studies have generally not observed such an association, these studies have had limited information regarding abortion and possible confounding variables. Therefore, we conducted a study among a cohort of post-menopausal women from whom detailed information regarding pregnancy outcomes as well as risk factors for breast cancer had been collected. The study sample included 37,247 Iowa Women's Health Study participants, 55-64 years of age at baseline in 1986, who reported no history of breast, or other, cancer (except non-melanoma skin cancer), and for whom information regarding pregnancy outcomes (that is, live birth, stillbirth, spontaneous abortion, ectopic pregnancy or induced abortion) was available. We used linkage with records of the State Health Registry of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, to estimate the incidence of breast cancer among cohort members through 1995. We calculated age-adjusted relative risks and 95% confidence intervals using Cox proportional hazards regression. Only 653 women (1.8%) reported an induced abortion. The age-adjusted relative risk of breast cancer among women with prior induced abortion compared with those without was 1.1 (95% CI = 0.8-1.6). Relative risks were higher among women whose age at first abortion was less than 20 or at least 30 years, for those whose abortion took place after their first birth or who never gave birth, and for those with early termination (0-2 months). These estimates varied from 1.3-1.7, but the confidence intervals around each were wide. Since most women in this cohort were beyond their reproductive years when abortion became legal in 1973, the low prevalence of induced abortion argues for a cautious interpretation.

Abortion, Induced↗

An international comparison of cancer survival: Toronto, Ontario, and Detroit, Michigan, metropolitan areas.

OBJECTIVES: This study examined whether socioeconomic status has a differential effect on the survival of adults diagnosed with cancer in Canada and the United States. METHODS: The Ontario Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program provided a total of 58,202 and 76,055 population-based primary malignant cancer cases for Toronto, Ontario, and Detroit, Mich, respectively. Socioeconomic data for each person's residence at time of diagnosis were taken from population censuses. RESULTS: In the US cohort, there was a significant association between socioeconomic status and survival for 12 of the 15 most common cancer sites; in the Canadian cohort, there was no such association for 12 of the 15 sites. Among residents of low-income areas, persons in Toronto experienced a survival advantage for 13 of 15 cancer sites at 1- and 5-year follow-up. No such between-country differentials were observed in the middle- or high-income groups. CONCLUSIONS: The consistent pattern of a survival advantage in Canada observed across various cancer sites and follow-up periods suggests that Canada's more equitable access to preventive and therapeutic health care services is responsible for the difference.

Health Services Accessibility↗