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The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update.

BACKGROUND: The incidence of hepatocellular carcinoma was reported to be increasing in the United States. However, alternate explanations were diagnostic or reclassification bias and changes in the demographic features of the general population. OBJECTIVE: To examine the temporal trends in the incidence of hepatocellular carcinoma. DESIGN: Retrospective cohort study. SETTING: Information collected by population-based registries of the Surveillance, Epidemiology, and End Results (SEER) program. PATIENTS: Persons given a diagnosis of hepatocellular carcinoma between 1975 and 1998. MEASUREMENTS: Linear Poisson multivariate regression model, controlling for differences in age, sex, race or ethnicity, and geographic region among patients with hepatocellular carcinoma and in the underlying population. RESULTS: The overall age-adjusted incidence rates of hepatocellular carcinoma increased from 1.4 per 100 000 in 1975 to 1977 to 3.0 per 100 000 in 1996 to 1998. There was a 25% increase during the last 3 years of the study compared with the preceding 3 years (1993 to 1995). The increase affected most age groups above 40 years, with the greatest increase in the 45- to 49-year-old age group. White men had the greatest increase (31%) in the last time period (1996 to 1998) compared with 1993 to 1995. The Poisson regression model confirmed an almost 2-fold increase in the incidence rate ratio for hepatocellular carcinoma between 1975 to 1978 and 1996 to 1998. CONCLUSIONS: The incidence of hepatocellular carcinoma continues to increase rapidly in the United States, with rates increasing the fastest in white men 45 to 54 years of age. These findings are consistent with a true increase and could be explained by consequences of hepatitis C virus acquired during the 1960s and 1970s.

Adult↗

Distinct incidence patterns among in situ and invasive breast carcinomas,with possible etiologic implications.

BACKGROUND: Incidence patterns are well-established for invasive breast carcinoma (InvBC) overall and for InvBC defined by estrogen receptor (ER) expression, but are not as well-defined for breast carcinoma in situ (CIS). METHODS: We, therefore, examined and compared the incidence patterns for CIS and InvBC in the SEER program to define these patterns and to generate etiologic hypotheses. Data were stratified by age < 50 and > or =50 years to approximate menopause. RESULTS: During the years 1973-2000, annual age-adjusted incidence rates rose 660% for CIS and 36% for InvBC, with the most rapid increases occurring in women age > or =50 years. Age-specific incidence rate curves for CIS increased until age 50 years, and then flattened, irrespective of ER expression. On the other hand, rates for InvBC overall and for InvBC defined by ER-positive expression increased continuously with aging, whereas rates for InvBC defined by ER-negative expression flattened after 50 years. Age frequency distribution for CIS and for ER-negative InvBC demonstrated bimodal populations, with a predominant early onset peak incidence at age 50 years. Age frequency distribution for ER-positive InvBC showed bimodal populations with a predominant late-onset mode at age 71 years. CONCLUSION: Over the last three decades, age-adjusted incidence trends differed for CIS and InvBC in the United States, possibly due to screening mammography and/or etiologic diversity. Indeed, age-specific incidence patterns suggested that carcinogenic events operating early in reproductive life had greater impact upon CIS and InvBC defined by ER-negative expression than upon InvBC overall and InvBC defined by ER-positive expression.

Adult↗

Combinations of glutathione S-transferase genotypes and risk of early-onset lung cancer in Caucasians and African Americans: a population-based study.

Polymorphisms in GSTM1, GSTT1 and GSTP1 genes in humans are associated with the reduction of enzymatic activity toward several substrates, including those in tobacco smoke. To investigate the potential role these polymorphisms have, as modulators of early-onset lung cancer risk, a population-based case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 350 individuals diagnosed <50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 410 cases of age, race and sex-matched controls ascertained through random digit dialing. African Americans carrying at least one G allele at the GSTP1 locus were 2.9-fold more likely to have lung cancer compared with African Americans without a G allele after adjustment for age, sex, pack years of smoking and history of lung cancer in a first-degree relative (95% CI 1.29-6.20). African Americans with either one or two risk genotypes at the GSTM1 and GSTP1 loci were at increased risk of having lung cancer compared with those having fully functional GSTM1 and GSTP1 genes (OR = 2.8, 95% CI 1.1-7.2 and OR = 4.0, 95% CI 1.3-12.2, respectively). No significant single gene associations between GSTM1, GSTT1 or GSTP1 and early-onset lung cancer were identified in Caucasians, after adjusting for age, sex, pack years and family history of lung cancer. However, our results suggest that specific combinations of glutathione S-transferase polymorphisms increase the risk of early-onset of lung cancer. Joint analysis of these genotypes may identify individuals who are at a higher risk of developing early-onset lung cancer with a greater certainty than single gene studies.

Adult↗

Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) in the general population has markedly increased since the onset of the AIDS epidemic in 1981. However, during the 1990s, the dynamics of the AIDS epidemic changed, as human immunodeficiency virus (HIV) infection rates slowed and effective antiretroviral therapies were introduced. We examined the impact of these changes on the general population incidence of KS and NHL. METHODS: Age-standardized incidences for KS and NHL from 1973 through 1998 were obtained from nine population-based cancer registries that participate in the Surveillance, Epidemiology and End Results (SEER) program. RESULTS: During the mid-1990s, KS incidence declined sharply in all nine registries. Decreases in KS incidence were most evident in San Francisco, where KS rates among white men had risen from 0.5 per 100 000 people per year in 1973 to between 31.1 and 33.3 from 1987 through 1991 and then declined to 2.8 in 1998. With background NHL incidence in the general population being much higher than that for KS, changes in incidence related to the AIDS epidemic were most evident in subgroups at high risk of AIDS. In San Francisco, NHL rates among white men rose from 10.7 in 1973 to a peak of 31.4 in 1995 and then declined to 21.6 in 1998. NHL types that were most highly AIDS-associated declined most steeply, whereas the incidence of NHL types not associated with AIDS was either stable or increasing. CONCLUSION: Changes in KS and NHL incidence since the mid 1990s may reflect declines in the number of individuals with AIDS and improved immune function in such individuals following the introduction of effective antiretroviral therapies in the 1990s. Notably, non-AIDS-associated NHL incidence has continued to increase steadily through 1998.

Adult↗

Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973-1991.

OBJECT: The authors present population-based survival rate estimates for patients with malignant primary brain tumors based on an analysis of 18 years of data obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. METHODS: Estimates of survival rates at 2 and 5 years after diagnosis for patients with specific histological tumor types were categorized by patient's age at diagnosis (< or = 20 years, 21-64 years, and 65 years or older) and by the time period in which the patients were diagnosed (1973-1980, 1981-1985, 1986-1991). Where appropriate, survival estimates were adjusted for changing patterns in the mean age at diagnosis. CONCLUSIONS: The authors observed a pattern of declining survival rates in patients with increasing age of the patient at diagnosis for most histological groups and overall improvements in survival rates of patients across these time periods adjusting for age at diagnosis. There were improvements in 2- and 5-year survival rates over the three time periods for children and adults with medulloblastoma and for adults with astrocytoma and oligodendroglioma. Improvements in survival rates for pediatric patients with medulloblastoma have leveled off in the most recent time period, and gender differences in survival rates for patients with this tumor, which were present in the 1970s, have disappeared. Clinically significant improvements in survival rates were not apparent in patients aged 65 years and older. Changes in diagnostic and treatment procedures since the mid-1970s have resulted in improved survival rates for patients diagnosed as having medulloblastoma, oligodendroglioma, and astrocytoma, controlling for age at diagnosis. Glioblastoma multiforme continues to be the most intractable brain tumor.

Adult↗

Long-term survival probabilities for childhood rhabdomyosarcoma. A population-based evaluation.

BACKGROUND: Evidence from clinical trials has documented improvements in event-free survival from childhood rhabdomyosarcoma (RMS) since the 1970s; however, the survival experience of children enrolled on cancer clinical trials may not reflect the full range of patients treated in community settings. The current study evaluated 5-year survival and 10-year conditional survival for RMS from U.S. population-based cancer registry data. METHODS: Public-use data from the Surveillance, Epidemiology, and End Results (SEER) program were used in life table and Cox regression analyses to evaluate RMS survival by patient age at diagnosis, gender, tumor histology, tumor site and stage, and major treatment eras among 848 children who were age < 20 years at the time of diagnosis, were a resident of 1 of 9 geographic reporting regions, and were diagnosed between 1973 and 2000. RESULTS: The 5-year survival probabilities were found to be highest for younger-age children (ages 1-4 years: 77%), patients with localized disease (83%), those whose tumors had an embryonal histology (67%), and patients with orbital (86%) and genitourinary (80%) tumor sites. Poor prognosis was associated with diagnosis during infancy (47%) and adolescence (48%); metastatic disease at the time of presentation (31%); alveolar histology (49%); and tumors of the extremities (50%), retroperitoneum (52%), and trunk (52%). Conditional 10-year survival probabilities among those who survived > or = 5 years were 85% or higher. The probability of survival by stage at the time of diagnosis increased with each successive treatment era, suggesting a stage shift phenomenon over time. CONCLUSIONS: Large variations in 5-year survival were evident depending on patient age and tumor characteristics. However, children who survived the first 5 years after diagnosis were found to have an excellent long-term prognosis. The patterns in RMS survival noted from the current population-based evaluation did not appear to differ substantially from those previously reported by major clinical trials.

Adolescent↗

The importance of sputum cytology in the diagnosis of lung cancer: a cost-effectiveness analysis.

STUDY OBJECTIVE: To assess the potential health and cost effects of initial testing with sputum cytology to diagnose lung cancer. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Surveillance Epidemiology and End Results (SEER) program; cost data from Northern California Kaiser Permanente Hospitals and Universities of Stanford and Iowa; National Center for Health Statistics; and a MEDLINE search. INTERVENTIONS: The use of sputum cytologies preceding other tests (ie, fine-needle aspiration, bronchoscopy, thoracoscopy) in patients with suspected lung cancer. MAIN OUTCOME MEASURES: Mortality associated with testing and initial surgical treatment (eg, performance of thoracoscopy to remove a local-stage, centrally located cancer), cost of testing and initial treatment, life expectancy, lifetime cost of medical care, and cost-effectiveness. RESULTS: In central lesions, sputum cytology as the first test was the dominant strategy because it both lowers medical-care costs ($2,516 per patient) and lowers the mortality risk (19 deaths in 100,000 patients) of the evaluation without adversely affecting long-term survival. In peripheral lesions, sputum cytology costs less then $25,000 per year of life saved if the pretest probability of cancer exceeds 50%. The estimated annual savings of adopting sputum cytology as the first test for diagnosing lung cancer in the United States is at least $30 million. CONCLUSIONS: Experience in regional centers indicates that sputum cytologic testing is infrequently ordered before implementing invasive diagnostic techniques, even in patients with central lung masses. The study findings suggest that sputum cytology as the first test in suspected lung cancer is likely to be cost saving without adversely affecting patient outcomes.

Biopsy, Needle↗

Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999.

OBJECTIVES: To determine the association of race with incidence, histology, treatment, and survival in women with uterine sarcoma during the period 1989-1999. METHODS: Uterine sarcomas were defined as leiomyosarcoma, carcinosarcoma, high-grade endometrial stromal sarcoma (HGESS), adenosarcoma, and sarcoma not otherwise specified (NOS). We used cases from Surveillance, Epidemiology, and End Results (SEER) program to compare uterine sarcoma among women >35 years of age. Using data from 1989 to 1999, we compared race-specific age-adjusted incidences, histological distributions, extent of disease at diagnosis, and race-specific survival. RESULTS: During the period of 1989-1999, 2677 women were diagnosed with uterine sarcoma, 2098 (78%) of whom were white and 420 (16%) of whom were black, and 159 (6%) of whom were of other races. The overall age-adjusted incidence for blacks was twice that of whites and more than twice that of women of other races (7/10(5) vs. 3.6/10(5) vs. 2.7/10(5), P < 0.0001). Racial differences in the incidence of uterine sarcoma existed for leiomyosarcoma (1.51/10(5) for blacks vs. 0.91/10(5) for whites, and 0.89 for women of other races, P < 0.01) and carcinosarcoma (4.3/10(5) for blacks, vs. 1.7/10(5) for whites, and 0.99 for women of other races, P < 0.001), but not for other histological types. Blacks with stage II disease were less likely to receive radiation in addition to surgery compared to whites (33% vs. 54%, P < 0.05). Five-year relative survival of patients with disease beyond the uterus was significantly longer for those that received radiation and surgery compared to those that received surgery alone. There were no racial differences in survival for women that received similar therapy. CONCLUSIONS: Adjuvant therapy improved survival for women with stage II-IV disease. Survival of black and white patients who received comparable treatment was similar.

Adult↗

Impact of reporting delay and reporting error on cancer incidence rates and trends.

BACKGROUND: Cancer incidence rates and trends are a measure of the cancer burden in the general population. We studied the impact of reporting delay and reporting error on incidence rates and trends for cancers of the female breast, colorectal, lung/bronchus, prostate, and melanoma. METHODS: Based on statistical models, we obtained reporting-adjusted (i.e., adjusted for both reporting delay and reporting error) case counts for each diagnosis year beginning in 1981 using reporting information for patients diagnosed with cancer in 1981-1998 from nine cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Joinpoint linear regression was used for trend analysis. All statistical tests are two-sided. RESULTS: Initial incidence case counts (i.e., after the standard 2-year delay) accounted for only 88%-97% of the estimated final counts; it would take 4-17 years for 99% or more of the cancer cases to be reported. The percent change between reporting-adjusted and unadjusted cancer incidence rates for the 1998 diagnosis year ranged from 3% for colorectal cancers to 14% for melanoma in whites and for prostate cancer in black males. Reporting-adjusted current incidence trends for breast cancer and lung/bronchus cancer in white females showed statistically significant increases (estimated annual percent change [EAPC] = 0.6%, 95% confidence interval [CI] = 0.1% to 1.2%) and 1.2%, 95% CI = 0.7% to 1.6%, respectively), whereas trends for these cancers using unadjusted incidence rates were not statistically significantly different from zero (EAPC = 0.4%, 95% CI = -0.1% to 0.9% and 0.5%, 95% CI = -0.1% to 1.1%, respectively). Reporting-adjusted melanoma incidence rates for white males showed a statistically significant increase since 1981 (EAPC = 4.1%, 95% CI = 3.8% to 4.4%) in contrast to the unadjusted incidence rate, which was most consistent with a flat or downward trend (EAPC = -4.2%, 95% CI = -11.1% to 3.3%) after 1996. CONCLUSIONS: Reporting-adjusted cancer incidence rates are valuable in precisely determining current cancer incidence rates and trends and in monitoring the timeliness of data collection. Ignoring reporting delay and reporting error may produce downwardly biased cancer incidence trends, particularly in the most recent diagnosis years.

Adult↗

Inter- and intra-ethnic differences for female breast carcinoma incidence in the continental United States and in the state of Hawaii.

BACKGROUND: Ethnic diversity is well-documented for female breast carcinoma incidence in the continental US but is not so well-established in the state of Hawaii. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) program, we analyzed n=323,607 in situ and invasive female breast cancer cases for major ethnic groups in the continental US and in Hawaii, diagnosed during the years 1992-2002. RESULTS: In the continental US, age-specific incidence rate patterns and prognostic factor profiles were good-risk for Asian or Pacific Islanders (API), intermediate for Whites, and poor-risk for Blacks. For example, early age-at-onset, high nuclear grade, aggressive histopathologic subtypes, and hormone receptor negative expression was associated with Black race in the continental US. In Hawaii, age-specific rate and prognostic profiles were more favorable for API than for White women, albeit not so striking as in the continental US. CONCLUSION: We observed inter- and intra-ethnic differences for female breast carcinoma in the continental US and in the state of Hawaii. While inter-racial disparities were expected, intra-racial differences were somewhat unexpected and possibly due to variations in racial subgroup mixing and/or cultural assimilation. For example, API women with breast carcinoma in the continental US included 96.03% Asians and 2.4% Pacific Islanders. In contrast, API women with breast carcinoma in Hawaii included 76.52% Asians and 23.46% Pacific Islanders. Moreover, APIs were more likely to be first-generation migrants in the continental US ( approximately 92%) than in Hawaii ( approximately 34%). Future studies should attempt to disaggregate racial data to separately characterize epidemiological patterns for individual ethnic groups.

Adenocarcinoma↗

Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients.

BACKGROUND: For many diseases, specialized care (i.e., care rendered by a specialist) has been associated with superior-quality care (i.e., better outcomes). We examined associations between physician specialty and outcomes in a population-based cohort of elderly ovarian cancer surgery patients. METHODS: We analyzed the Medicare claims, by physician specialty, of all women aged 65 years or older who underwent surgery for pathologically confirmed invasive epithelial ovarian cancer between January 1, 1992, and December 31, 1999, while living in an area monitored by the Surveillance, Epidemiology, and End Results (SEER) program to assess important care processes (i.e., the appropriate extent of surgery and use of adjuvant chemotherapy) and outcomes (i.e., surgical complications, ostomy rates, and survival). All statistical tests were two-sided. RESULTS: Among 3067 ovarian cancer patients who underwent surgery, 1017 patients (33%) were treated by a gynecologic oncologist, 1377 patients (45%) by a general gynecologist, and 673 patients (22%) by a general surgeon. Among patients with stage I or II disease, those treated by a gynecologic oncologist (60%) were more likely to undergo lymph node dissection than those treated by a general gynecologist (36%) or a general surgeon (16%). Patients with stage III or IV disease were more likely to undergo a debulking procedure if the initial surgery was performed by a gynecologic oncologist (58%) than by a general gynecologist (51%) or a general surgeon (40%; P < .001) and were more likely to receive postoperative chemotherapy when operated on by a gynecologic oncologist (79%) or a general gynecologist (76%) than by a general surgeon (62%, P < .001). Survival among patients operated on by gynecologic oncologists (hazard ratio [HR] of death from any cause = 0.85, 95% confidence interval [CI] = 0.76 to 0.95) or general gynecologists (HR = 0.86, 95% CI = 0.78 to 0.96) was better than that among patients operated on by general surgeons. CONCLUSIONS: Ovarian cancer patients treated by gynecologic oncologists had marginally better outcomes than those treated by general gynecologists and clearly superior outcomes compared with patients treated by general surgeons.

Aged↗

Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma.

BACKGROUND: Prior studies have demonstrated that women who receive adjuvant radiation therapy (RT) after mastectomy for breast carcinoma have an increased risk of a second primary lung carcinoma after 10 years, but, to the authors' knowledge, the risk associated with adjuvant RT after breast-conserving surgery (lumpectomy) has yet to be determined. The purpose of the current study was to confirm and extend earlier findings of the effects of postmastectomy RT on second primary lung carcinoma and to investigate the impact of postlumpectomy RT on second primary lung carcinoma in the same population and to compare the results. METHODS: The authors used data from the population-based Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute, encompassing approximately 10% of the U.S. population, from 1973 to 1998. Of the women with nonmetastatic invasive breast carcinoma, 194,981 had been treated with mastectomy and 65,560 were treated with lumpectomy. Cox regression analysis was used to estimate the relative risk (RR) of a second primary lung carcinoma among women treated with RT compared with those who received surgery alone as a function of time interval since treatment and laterality for both types of surgery. RESULTS: Although no statistically significant elevation in risk for second primary lung carcinoma prior to 10 years was observed, the authors estimated a RR of 2.06 (95% confidence interval [95% CI], 1.53-2.78) and 2.09 (95% CI, 1.50-2.90) for ipsilateral lung carcinoma at 10-14 years and 15+ years after postmastectomy RT, respectively, whereas no increased risk was observed for the contralateral lung. The excess risk of ipsilateral lung carcinoma after postmastectomy RT was found for all three major histologic subtypes of lung carcinoma (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). No increased risk of lung carcinoma was observed at 10-14 years after postlumpectomy RT for either lung. CONCLUSIONS: Postmastectomy RT was found to provide a moderate increase in risk for ipsilateral lung carcinoma starting 10 years after exposure; this increased risk is reported to persist to at least 20 years. Postlumpectomy RT does not appear to incur an increased risk. These findings should be reassuring to women treated with either type of RT, but the excess risk in the postmastectomy group should be considered in the choice between treatment options.

Adult↗

Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status.

BACKGROUND: The current TNM classification system does not consider tumor length or the number of lymph nodes in the staging and classification scheme for patients with esophageal carcinoma. Using data from the National Cancer Institute SEER Program, the authors explored the effect of tumor length and number of positive lymph nodes on survival in patients with esophageal carcinoma. METHODS: Patients with esophageal adenocarcinoma or squamous cell carcinoma were subgrouped according to historic stage with localized, regional, or distant disease. Demographic factors (age at diagnosis, race, and gender) and tumor characteristics (morphology, histologic grade, tumor length, primary site, depth of invasion, number of positive lymph nodes, proportion of positive lymph nodes dissected, and distant metastatic sites) were examined. RESULTS: Overall factors that were associated with an increased mortality risk included increasing age at diagnosis, black race versus white race, histologic grade, primary tumor site in the lower esophagus and abdomen versus upper regions, and increasing depth of invasion. Among patients with regional disease, the number of positive lymph nodes (>/= 5 vs. < 5) was related to an increasing risk (hazard ratio [HR], 1.29; 95% confidence interval [95%CI], 1.06-1.56). The proportion of positive lymph nodes compared with the number of lymph nodes dissected conferred an increased risk (HR, 1.63; 95%CI, 1.26-2.11). Among patients with distant disease, sites other than distant lymph nodes implied an increased mortality risk (HR, 1.37; 95%CI, 1.37-1.65). Tumor length was an independent predictor of mortality when controlling for depth of invasion in patients with localized disease (HR, 1.15; 95%CI, 1.08-1.21). CONCLUSIONS: Tumor length, the number of involved lymph nodes, and the ratio of positive lymph nodes are important prognostic factors for survival in patients with esophageal carcinoma. A revised TNM classification system for patients with esophageal carcinoma might consider adding tumor length and number of positive lymph nodes as two important prognostic factors.

Adenocarcinoma↗

Stage at diagnosis and treatment patterns among older women with breast cancer: an HMO and fee-for-service comparison.

CONTEXT: Few studies have compared patterns of care in health maintenance organization (HMO) and fee-for-service (FFS) settings. OBJECTIVE: To examine breast cancer stage at diagnosis and, for those at an early stage, treatment patterns for elderly women in HMO and FFS settings. DESIGN: Cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare enrollment records. SETTINGS AND PARTICIPANTS: Women aged 65 years or older residing in 11 geographic areas who were newly diagnosed as having breast cancer between 1988 and 1993. MAIN OUTCOME MEASURES: Standardized percentage of cases diagnosed at late stages for HMO vs FFS; standardized percentage of early-stage cases undergoing initial treatment with breast-conserving surgery (BCS); and, among BCS cases, standardized percentage receiving adjuvant radiation therapy. Standardization was achieved through logistic regression, controlling for patient demographics, cancer history, county of residence, year of diagnosis, and educational attainment at the census tract level. Analyses of treatment patterns were controlled for stage at diagnosis and tumor size. RESULTS: The HMO enrollees were less likely to have breast cancer diagnosed at late stages than FFS patients (HMO, 7.6%; FFS, 10.8%; difference, -3.2% [95% confidence interval (CI), -4.2% to -2.2 %]). Among early-stage cases, the percentages undergoing BCS were similar in HMO and FFS settings overall (HMO, 38.4%; FFS, 36.8%; difference, 1.6% [95% CI, 0.0%-3.2%]); percentages varied markedly at the individual plan level. Among women undergoing BCS, HMO enrollees were significantly more likely to receive radiation therapy but, again, results varied by plan (HMO, 69.0%; FFS, 63.7%; difference, 5.3% [95% CI, 2.9%-7.7%]). In general, use of BCS and radiation therapy was substantially higher than that found in an earlier study examining cases diagnosed between 1985 and 1989. CONCLUSIONS: Treatment of early-stage breast cancer in HMOs often differs from local FFS patterns, but not in a consistent way. During the period of our study, elderly HMO enrollees did not appear to have systematic access problems with adjuvant radiation therapy following BCS compared with women in an FFS setting.

Aged↗

Disparities in breast cancer treatment and survival for women with disabilities.

BACKGROUND: Breast-conserving surgery combined with axillary lymph node dissection and radiotherapy or mastectomy are definitive treatments for women with early-stage breast cancer. Little is known about breast cancer treatment for women with disabilities. OBJECTIVE: To compare initial treatment for early-stage breast cancer between women with and without disabilities and to examine the association of treatment differences and survival. DESIGN: Retrospective cohort study. SETTING: 11 Surveillance, Epidemiology, and End Results (SEER) Program tumor registries. PARTICIPANTS: 100,311 women who received a diagnosis of stage I to IIIA breast cancer at 21 to 64 years of age from 1988 to 1999. Women who qualified for Social Security Disability Insurance (SSDI) and Medicare at breast cancer diagnosis were considered disabled. MEASUREMENTS: Receipt of breast-conserving surgery versus mastectomy. For women who had breast-conserving surgery (n = 49 166), the authors examined receipt of radiotherapy and axillary lymph node dissection. Survival was measured from diagnosis until death or until 31 December 2001. RESULTS: Women with SSDI and Medicare coverage had lower rates of breast-conserving surgery than other women (43.2% vs. 49.2%; adjusted relative risk, 0.80 [95% CI, 0.76 to 0.84]). Among women who had breast-conserving surgery, women with SSDI and Medicare coverage were less likely than other women to receive radiotherapy (adjusted relative risk, 0.83 [CI, 0.77 to 0.90]) and axillary lymph node dissection (adjusted relative risk, 0.81 [CI, 0.74 to 0.90]). Women with SSDI and Medicare coverage had lower survival rates than those of other women in all-cause mortality (adjusted hazard ratio, 2.02 [CI, 1.88 to 2.16]) and breast cancer-specific mortality (adjusted hazard ratio, 1.31 [CI, 1.18 to 1.45]). Results were similar after adjustment for treatment differences. LIMITATIONS: Findings are limited to women who qualified for SSDI and Medicare. No data on adjuvant chemotherapy and hormonal therapy were available, and details about the underlying disability were lacking. CONCLUSIONS: Women with disabilities had higher breast cancer mortality rates and were less likely to undergo standard therapy after breast-conserving surgery than other women. Differences in treatment did not explain the differences in breast cancer mortality rates.

Adult↗

Ratios of involved nodes in early breast cancer.

INTRODUCTION: The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together. METHODS: The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1-T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R2 index (R2N). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform. RESULTS: In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986-0.997) and 1.150 (1.058-1.249), respectively, but without improving R2N. In node-positive cases the hazard ratios were 1.003-1.088 for the number of involved nodes, 0.966-1.005 for the number of excised nodes, 1.015-1.017 for the percentage, and 1.344-1.381 for the log odds. R2N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios). DISCUSSION: Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized to the number of nodes excised. In an extension to the study, ratios were validated in a comparison with categorized staging measures using blinded data from the San Jose-Monterey cancer registry. A ratio based prognostic index was also derived. It improved the Nottingham Prognostic Index without compromising on simplicity.

Adult↗

Risk of cardiac death after adjuvant radiotherapy for breast cancer.

BACKGROUND: Women with breast cancer who are treated with adjuvant radiation have a decreased risk of local recurrence but an increased risk of mortality from ischemic heart disease. Patients with left-sided breast tumors receive a higher dose of radiation to the heart than patients with right-sided tumors. Because radiation techniques have improved over time, we investigated whether the risk of death from ischemic heart disease after adjuvant breast radiotherapy decreased over time. METHODS: We used the 12-registry 1973-2000 dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Women (n = 27,283) treated with adjuvant radiation for breast cancer diagnosed in 1973-1989 were included in the study. Ischemic heart disease mortality was calculated at 15 years and compared for women diagnosed during 1973-1979, 1980-1984, and 1985-1989. Cox proportional hazards models were used to calculate the hazard of death from ischemic heart disease for women diagnosed 1973-1988 and censored at 12 years. All statistical tests were two-sided. RESULTS: There were no differences in age, race/ethnicity, disease stage, or follow-up time between the 13 998 women with left-sided and 13 285 with right-sided cancer. For women diagnosed in 1973-1979, there was a statistically significant difference in 15-year mortality from ischemic heart disease between patients with left-sided (13.1%, 95% confidence interval [CI] = 11.6 to 14.6) and those with right-sided (10.2%, 95% CI = 8.9 to 11.5) breast cancer (P = .02); no such difference was found for women diagnosed in 1980-1984 (9.4%, [95% CI = 8.1 to 10.6] versus 8.7% [95% CI = 7.4 to 10.0], respectively, P = .64) or 1985-1989 (5.8% [95% CI = 4.8 to 6.8] versus 5.2% [95% CI = 4.4 to 5.9], respectively, P = .98). In the Cox model, the hazard ratio [HR] for ischemic heart disease mortality for women with left-sided versus women with right-sided disease was 1.50 (95% CI = 1.19 to 1.87) in 1979. With each succeeding year after 1979, the hazard of death from ischemic heart disease for women with left-sided versus those with right-sided disease declined by 6% (HR = 0.94, 95% CI = 0.91 to 0.98). CONCLUSIONS: Risk of death from ischemic heart disease associated with radiation for breast cancer has substantially decreased over time.

Adult↗

Recent cancer trends in the United States.

BACKGROUND: Cancer incidence rates have been reported to be increasing in the United States, although trends vary according to form of cancer. PURPOSE: We identify the cancers accounting for the rising incidence, quantify the changes that have occurred from the mid-1970s to the early 1990s, and contrast incidence and mortality trends to provide clues to the determinants of the temporal patterns. METHODS: Sex-, race-, and age-specific and age-adjusted incidence rates for the 5-year periods 1987-1991 versus 1975-1979 were calculated for 28 cancers among men and 30 cancers among women using data from the Surveillance, Epidemiology, and End Results (SEER) Program of cancer registration covering about 10% of the U.S. population. Similar rates were computed using national mortality data. Cancers were ranked according to the change in incidence rates over the two periods. RESULTS: Age-adjusted incidence rates for all cancers combined increased by 18.6% among males and 12.4% among females from 1975-1979 to 1987-1991, due largely to rising rates for prostate cancer among men and for breast and lung cancers among women. National mortality rates for all cancers combined rose less steeply, 3% and 6% among men and women, respectively, driven mostly by continuing increases in lung cancer mortality, while death rates for the majority of the cancers were steady or declining. Total cancer incidence rose at all ages, but with different tumors responsible for the increases at different ages: leukemia and brain/nervous system cancer among children; testicular cancer, nonmelanoma skin cancer (largely Kaposi's sarcoma), non-Hodgkin's lymphoma, and melanoma among young and middle-aged adults; and prostate, breast, and lung cancers among older individuals. In contrast, mortality rates for all cancers combined declined among both males and females under age 55 years, increasing only among older persons. CONCLUSIONS: Trends in cancer incidence and mortality differ. For most cancers, incidence rates are rising, while mortality rates are generally stable or declining. IMPLICATIONS: Much of the recent increase in cancer incidence can be explained by known factors. Improved detection appears to account for most of the increases in breast cancer among women and prostate cancer among men. On the other hand, cigarette smoking is the major determinant of the rise in lung cancer among women, acquired immunodeficiency syndrome has led to increases in non-Hodgkin's lymphoma and Kaposi's sarcoma among young and middle-aged men, and sunlight exposure patterns have affected the trends in melanoma. Some trends remain unexplained, however, and may reflect changing exposures to carcinogens yet to be identified and clarified.

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