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1.  Annual Report to the Nation on the Status of Cancer, 1975–2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State 
Background
The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data.
Methods
Population-based cancer trends and breast cancer incidence by molecular subtype were calculated. Breast cancer subtypes were classified using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression.
Results
Overall cancer incidence decreased for men by 1.8% annually from 2007 to 2011. Rates for women were stable from 1998 to 2011. Within these trends there was racial/ethnic variation, and some sites have increasing rates. Among children, incidence rates continued to increase by 0.8% per year over the past decade while, like adults, mortality declined. Overall mortality has been declining for both men and women since the early 1990’s and for children since the 1970’s. HR+/HER2− breast cancers, the subtype with the best prognosis, were the most common for all races/ethnicities with highest rates among non-Hispanic white women, local stage cases, and low poverty areas (92.7, 63.51, and 98.69 per 100 000 non-Hispanic white women, respectively). HR+/HER2− breast cancer incidence rates were strongly, positively correlated with mammography use, particularly for non-Hispanic white women (Pearson 0.57, two-sided P < .001). Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women (27.2 per 100 000 non-Hispanic black women), which is reflected in high rates in southeastern states.
Conclusions
Progress continues in reducing the burden of cancer in the United States. There are unique racial/ethnic-specific incidence patterns for breast cancer subtypes; likely because of both biologic and social risk factors, including variation in mammography use. Breast cancer subtype analysis confirms the capacity of cancer registries to adjust national collection standards to produce clinically relevant data based on evolving medical knowledge.
doi:10.1093/jnci/djv048
PMCID: PMC4603551  PMID: 25825511
2.  Providing Clinicians and Patients With Actual Prognosis: Cancer in the Context of Competing Causes of Death 
Background
To isolate progress against cancer from changes in competing causes of death, population cancer registries have traditionally reported cancer prognosis (net measures). But clinicians and cancer patients generally want to understand actual prognosis (crude measures): the chance of surviving, dying from the specific cancer and from competing causes of death in a given time period.
Objective
To compare cancer and actual prognosis in the United States for four leading cancers—lung, breast, prostate, and colon—by age, comorbidity, and cancer stage and to provide templates to help patients, clinicians, and researchers understand actual prognosis.
Method
Using population-based registry data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated cancer prognosis (relative survival) and actual prognosis (five-year overall survival and the “crude” probability of dying from cancer and competing causes) for three important prognostic determinants (age, comorbidity [Charlson-score from 2012 SEER-Medicare linkage dataset] and cancer stage at diagnosis).
Result
For younger, healthier, and earlier stage cancer patients, cancer and actual prognosis estimates were quite similar. For older and sicker patients, these prognosis estimates differed substantially. For example, the five-year overall survival for an 85-year-old patient with colorectal cancer is 54% (cancer prognosis) versus 22% (actual prognosis)—the difference reflecting the patient’s substantial chance of dying from competing causes. The corresponding five-year chances of dying from the patient’s cancer are 46% versus 37%. Although age and comorbidity lowered actual prognosis, stage at diagnosis was the most powerful factor: The five-year chance of colon cancer death was 10% for localized stage and 83% for distant stage.
Conclusion
Both cancer and actual prognosis measures are important. Cancer registries should routinely report both cancer and actual prognosis to help clinicians and researchers understand the difference between these measures and what question they can and cannot answer. We encourage them to use formats like the ones presented in this paper to communicate them clearly.
doi:10.1093/jncimonographs/lgu022
PMCID: PMC4841170  PMID: 25417239
3.  Cancer Survival: An Overview of Measures, Uses, and Interpretation 
Survival statistics are of great interest to patients, clinicians, researchers, and policy makers. Although seemingly simple, survival can be confusing: there are many different survival measures with a plethora of names and statistical methods developed to answer different questions. This paper aims to describe and disseminate different survival measures and their interpretation in less technical language. In addition, we introduce templates to summarize cancer survival statistic organized by their specific purpose: research and policy versus prognosis and clinical decision making.
doi:10.1093/jncimonographs/lgu024
PMCID: PMC4829054  PMID: 25417231
4.  US Incidence of Breast Cancer Subtypes Defined by Joint Hormone Receptor and HER2 Status 
Background
In 2010, Surveillance, Epidemiology, and End Results (SEER) registries began collecting human epidermal growth factor 2 (HER2) receptor status for breast cancer cases.
Methods
Breast cancer subtypes defined by joint hormone receptor (HR; estrogen receptor [ER] and progesterone receptor [PR]) and HER2 status were assessed across the 28% of the US population that is covered by SEER registries. Age-specific incidence rates by subtype were calculated for non-Hispanic (NH) white, NH black, NH Asian Pacific Islander (API), and Hispanic women. Joint HR/HER2 status distributions by age, race/ethnicity, county-level poverty, registry, stage, Bloom–Richardson grade, tumor size, and nodal status were evaluated using multivariable adjusted polytomous logistic regression. All statistical tests were two-sided.
Results
Among case patients with known HR/HER2 status, 36810 (72.7%) were found to be HR+/HER2−, 6193 (12.2%) were triple-negative (HR−/HER2−), 5240 (10.3%) were HR+/HER2+, and 2328 (4.6%) were HR−/HER2+; 6912 (12%) had unknown HR/HER2 status. NH white women had the highest incidence rate of the HR+/HER2− subtype, and NH black women had the highest rate of the triple-negative subtype. Compared with women with the HR+/HER2− subtype, triple-negative patients were more likely to be NH black and Hispanic; HR+/HER2+ patients were more likely to be NH API; and HR−/HER2+ patients were more likely to be NH black, NH API, and Hispanic. Patients with triple-negative, HR+/HER2+, and HR−/HER2+ breast cancer were 10% to 30% less likely to be diagnosed at older ages compared with HR+/HER2− patients and 6.4-fold to 20.0-fold more likely to present with high-grade disease.
Conclusions
In the future, SEER data can be used to monitor clinical outcomes in women diagnosed with different molecular subtypes of breast cancer for a large portion (approximately 28%) of the US population.
doi:10.1093/jnci/dju055
PMCID: PMC4580552  PMID: 24777111
5.  Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State 
Background:
The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data.
Methods:
Population-based cancer trends and breast cancer incidence by molecular subtype were calculated. Breast cancer subtypes were classified using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression.
Results:
Overall cancer incidence decreased for men by 1.8% annually from 2007 to 2011. Rates for women were stable from 1998 to 2011. Within these trends there was racial/ethnic variation, and some sites have increasing rates. Among children, incidence rates continued to increase by 0.8% per year over the past decade while, like adults, mortality declined. Overall mortality has been declining for both men and women since the early 1990’s and for children since the 1970’s. HR+/HER2- breast cancers, the subtype with the best prognosis, were the most common for all races/ethnicities with highest rates among non-Hispanic white women, local stage cases, and low poverty areas (92.7, 63.51, and 98.69 per 100000 non-Hispanic white women, respectively). HR+/HER2- breast cancer incidence rates were strongly, positively correlated with mammography use, particularly for non-Hispanic white women (Pearson 0.57, two-sided P < .001). Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women (27.2 per 100000 non-Hispanic black women), which is reflected in high rates in southeastern states.
Conclusions:
Progress continues in reducing the burden of cancer in the United States. There are unique racial/ethnic-specific incidence patterns for breast cancer subtypes; likely because of both biologic and social risk factors, including variation in mammography use. Breast cancer subtype analysis confirms the capacity of cancer registries to adjust national collection standards to produce clinically relevant data based on evolving medical knowledge.
doi:10.1093/jnci/djv048
PMCID: PMC4603551  PMID: 25825511
6.  Use of Imputed Population-based Cancer Registry Data as a Method of Accounting for Missing Information: Application to Estrogen Receptor Status for Breast Cancer 
American Journal of Epidemiology  2012;176(4):347-356.
The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program provides a rich source of data stratified according to tumor biomarkers that play an important role in cancer surveillance research. These data are useful for analyzing trends in cancer incidence and survival. These tumor markers, however, are often prone to missing observations. To address the problem of missing data, the authors employed sequential regression multivariate imputation for breast cancer variables, with a particular focus on estrogen receptor status, using data from 13 SEER registries covering the period 1992–2007. In this paper, they present an approach to accounting for missing information through the creation of imputed data sets that can be analyzed using existing software (e.g., SEER*Stat) developed for analyzing cancer registry data. Bias in age-adjusted trends in female breast cancer incidence is shown graphically before and after imputation of estrogen receptor status, stratified by age and race. The imputed data set will be made available in SEER*Stat (http://seer.cancer.gov/analysis/index.html) to facilitate accurate estimation of breast cancer incidence trends. To ensure that the imputed data set is used correctly, the authors provide detailed, step-by-step instructions for conducting analyses. This is the first time that a nationally representative, population-based cancer registry data set has been imputed and made available to researchers for conducting a variety of analyses of breast cancer incidence trends.
doi:10.1093/aje/kwr512
PMCID: PMC3491971  PMID: 22842721
breast neoplasms; imputation; incidence; missing data; receptors, estrogen
7.  Use of Colony-Stimulating Factors With Chemotherapy: Opportunities for Cost Savings and Improved Outcomes 
Myeloid colony-stimulating factors (CSFs) decrease the risk of febrile neutropenia (FN) from high-risk chemotherapy regimens administered to patients at 20% or greater risk of FN, but little is known about their use in clinical practice. We evaluated CSF use in a multiregional population-based cohort of lung and colorectal cancer patients (N = 1849). Only 17% (95% confidence interval [CI] = 8% to 26%) patients treated with high-risk chemotherapy regimens received CSFs, compared with 18% (95% CI = 16% to 20%) and 10% (95% CI = 8% to 12%) of patients treated with intermediate- (10%–20% risk of FN) and low-risk (<10% risk of FN) chemotherapy regimens, respectively. Using a generalized estimating equation model, we found that enrollment in a health maintenance organization (HMO) was strongly associated with a lower adjusted odds of discretionary CSF use, compared with non-HMO patients (odds ratio = 0.44, 95% CI = 0.32 to 0.60, P < .001). All statistical tests were two-sided. Overall, 96% (95% CI = 93% to 98%) of CSFs were administered in scenarios where CSF therapy is not recommended by evidence-based guidelines. This finding suggests that policies to decrease CSF use in patients at lower or intermediate risk of FN may yield substantial cost savings without compromising patient outcomes.
doi:10.1093/jnci/djr152
PMCID: PMC3119647  PMID: 21670423
8.  Improved Estimates of Cancer-Specific Survival Rates From Population-Based Data 
Background
Accurate estimates of cancer survival are important for assessing optimal patient care and prognosis. Evaluation of these estimates via relative survival (a ratio of observed and expected survival rates) requires a population life table that is matched to the cancer population by age, sex, race and/or ethnicity, socioeconomic status, and ideally risk factors for the cancer under examination. Because life tables for all subgroups in a study may be unavailable, we investigated whether cause-specific survival could be used as an alternative for relative survival.
Methods
We used data from the Surveillance, Epidemiology, and End Results Program for 2 330 905 cancer patients from January 1, 1992, through December 31, 2004. We defined cancer-specific deaths according to the following variables: cause of death, only one tumor or the first of multiple tumors, site of the original cancer diagnosis, and comorbidities. Estimates of relative survival and cause-specific survival that were derived by use of an actuarial method were compared.
Results
Among breast cancer patients who were white, black, or of Asian or Pacific Islander descent and who were older than 65 years, estimates of 5-year relative survival (107.5%, 106.6%, and 103.0%, respectively) were higher than estimates of 5-year cause-specific survival (98.6%, 95% confidence interval [CI] = 98.4% to 98.8%; 97.4%, 95% CI = 96.2% to 98.2%; and 99.2%, 95% CI = 98.4%, 99.6%, respectively). Relative survival methods likely underestimated rates for cancers of the oral cavity and pharynx (eg, for white cancer patients aged ≥65 years, relative survival = 54.2%, 95% CI = 53.1% to 55.3%, and cause-specific survival = 60.1%, 95% CI = 59.1% to 60.9%) and the lung and bronchus (eg, for black cancer patients aged ≥65 years, relative survival = 10.5%, 95% CI = 9.9% to 11.2%, and cause-specific survival = 11.9%, 95% CI = 11.2 % to 12.6%), largely because of mismatches between the population with these diseases and the population used to derive the life table. Socioeconomic differences between groups with low and high status in relative survival estimates appeared to be inflated (eg, corpus and uterus socioeconomic status gradient was 13.3% by relative survival methods and 8.8% by cause-specific survival methods).
Conclusion
Although accuracy of the cause of death on a death certificate can be problematic for cause-specific survival estimates, cause-specific survival methods may be an alternative to relative survival methods when suitable life tables are not available.
doi:10.1093/jnci/djq366
PMCID: PMC2957430  PMID: 20937991
9.  The Impact of Underreported Veterans Affairs Data on National Cancer Statistics: Analysis Using Population-Based SEER Registries 
Reduced cancer reporting by the US Department of Veterans Affairs (VA) hospitals in 2007 (for patients diagnosed through 2005) impacted the most recent US cancer surveillance data. To quantify the impact of the reduced VA reporting on cancer incidence and trends produced by the Surveillance, Epidemiology, and End Results Program, we estimated numbers of missing VA patients in 2005 by sex, age, race, selected cancer sites, and registry and calculated adjustment factors to correct for the 2005 incidence rates and trends. Based on our adjustment factors, we estimated that as a result of the underreporting, the overall cancer burden was underestimated by 1.6% for males and 0.05% for females. For males, the percentage of patients missing ranged from 2.5% for liver cancer to 0.4% for melanoma of the skin. For age-adjusted male overall cancer incidence rates, the adjustment factors were 1.015, 1.012, and 1.035 for all races, white males, and black males, respectively. Modest changes in long-term incidence trends were observed, particularly in black males.
doi:10.1093/jnci/djn517
PMCID: PMC2720708  PMID: 19318639

Results 1-9 (9)