Trends in late mortality among adolescent and young adult cancer survivors

Background: Over the past several decades, treatment of cancer in adolescents and young adults (AYAs) has evolved substantially, leading to steady improvements in estimated 5-year survival at diagnosis. However, the impact on late mortality in this population is largely unexamined. We investigated temporal trends in mortality among 5-year AYA cancer survivors. Methods: The Surveillance, Epidemiology, and End Results database was used to identify AYAs (age 15-39 years) diagnosed with cancer during 1975-2011 who survived at least 5 years beyond diagnosis. Survival months were accrued from 5 years postdiagnosis until death or the end of 2016. Cumulative mortality from all causes, the primary cancer, other cancers, and noncancer or nonexternal causes (ie, excluding accidents, suicide, homicide) were estimated according to diagnosis era. Results: Among 282 969 five-year AYA cancer survivors, 5-year mortality (ie, from 5 through 10 years postdiagnosis) from all-causes decreased from 8.3% (95% confidence interval = 8.0% to 8.6%) among those diagnosed in 1975-1984 to 5.4% (95% confidence interval = 5.3% to 5.6%) among those diagnosed in 2005-2011. This was largely explained by decreases in mortality from the primary cancer (6.8% to 4.2%) between these periods. However, for specific cancer types, including colorectal, bone, sarcomas, cervical/uterine, and bladder, cumulative mortality curves demonstrated little improvement in primary cancer mortality over time. Some reduction in late mortality from noncancer or nonexternal causes was apparent for Hodgkin lymphoma, leukemia, kidney cancer, head and neck cancers, and trachea, lung, and bronchus cancers. Conclusion: Over the past four decades, all-cause and cancer-specific mortality have decreased among 5-year AYA cancer survivors overall, but several cancer types have not shared in these improvements

Enhancing Evidence for Preconception and Prenatal Counseling on Obstetrical Risks After Cancer

In this issue of the Journal, Zgardau and colleagues present a detailed assessment of obstetric and perinatal outcomes after childhood and adolescent cancer in Ontario, Canada. Included cancers were diagnosed at ages younger than 21years during 1985-2012. The majority cancer types were leukemias or lymphomas (47.5%), followed by central nervous system tumors (18.7%), and all other cancer types combined (33.9%). Using data from a single-payer insurance program, the investigators compared obstetric and perinatal outcomes between female cancer survivors and a comparison population of women without cancer, matched 5:1 on age and postal code, and within the survivor population

RE: Weight gain after breast cancer diagnosis and all-cause mortality: Systematic review and meta-Analysis

In the meta-analysis by Playdon et al. (1) in the Journal, the authors conclude

Trends in US Cancer and Heart Disease Mortality, 1999-2018

Since initial reports documenting an increase in midlife US mortality rates were first published, numerous studies have examined the resulting demographic, economic, and policy implications; however, fewer studies have examined trends for the 2 major drivers of US mortality: heart disease and cancer. Here, we used 2 decades (1999–2018) of death certificate data to further inform understanding of contemporary US cancer and heart disease mortality trends overall and by sex, race, ethnicity, and age group

Trends in the proportion of second or later primaries among all newly diagnosed malignant cancers

BACKGROUND: Improvements in cancer survival mean that an increasing number of survivors may live long enough beyond their initial cancer to be diagnosed with additional independent primary cancers. The proportion of newly diagnosed cancers that are second- or higher-order primaries and how this proportion has changed over the past several decades were examined. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program were used to identify incident malignant primaries diagnosed between 1975 and 2017. Using the SEER sequence number, the authors tabulated the proportion of all cancers in each calendar year that were second- or higher-order primaries. The average annual percent change (AAPC) was then calculated to assess how this proportion has changed over time. RESULTS: Analyses included nearly 4.9 million incident cancers diagnosed during 1975-2017. The proportion of all cancers that were second- or higher-order increased steadily from 9.77% during 1975-1984 to 21.03% during 2015-2017, reflecting an AAPC of 2.41% (95% CI, 2.16%-2.65%). In 2015-2017, second- or higher-order cancers were most prevalent among cancers of the bladder (28.79%), followed by lung and bronchus (28.07%), melanoma (27.88%), and leukemia (26.10%). The highest AAPCs over the study period were observed for melanoma (4.05%), leukemia (3.51%), and lung and bronchus (3.36%). CONCLUSIONS: The proportion of newly diagnosed cancers that are second- or higher-order has grown rapidly over the past several decades and currently exceeds 20%. Continued monitoring of second and later primaries will be critical for anticipating the future impact on cancer treatment and survivorship care

Polypharmacy and medication use by cancer history in a nationally representative group of adults in the USA, 2003–2014

Purpose: This study examines polypharmacy and prescription drug use patterns in cancer survivors, a growing population at risk for cancer sequelae and side effects from treatment, which can arise months or even years following diagnosis. Survivors may experience greater medication burden than the general population, increasing concerns for polypharmacy and subsequent risks of drug interactions and non-adherence. Methods: Using the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2014, we examined the association between a cancer history and presence of polypharmacy (5+ medications). We estimated prevalence ratios and prevalence differences for polypharmacy comparing those with and without a cancer history using binomial regression models and propensity score (PS) weighting to account for baseline differences between groups. Results: We identified 32,238 adults aged 20 years or older; 1899 had cancer (excluding non-melanoma skin) at least 1 year before the survey. Overall, polypharmacy prevalence was 13% and 35% in those with and without a cancer history, respectively. After PS weighting, the polypharmacy prevalence was 1.26 times higher among those with versus without a cancer history (weighted prevalence ratio, 1.26; 95% CI, 1.18, 1.35). In sub-group analyses, the weighted prevalence ratio was largest for those 20–39 years old at survey (2.78; 95% CI, 1.71, 4.53), and the weighted prevalence difference was largest for those 40–64 years old at survey (9.35%; 95% CI, 5.70%, 13.01%). Conclusions/Implications for Cancer Survivors: Cancer survivors of all ages take more medications than those without cancer history and may benefit from discussions with providers about age-tailored medication use management

Comparison of 20-Year Obesity-Associated Cancer Mortality Trends with Heart Disease Mortality Trends in the US

Importance: Heart disease and cancer are the 2 major diseases associated with mortality risk in the United States. Four decades of improvements in heart disease mortality slowed after 2011; this slowing has been associated with the obesity epidemic. The same pattern has not been observed for total cancer mortality. However, trends in total cancer mortality may obscure patterns specific to obesity-associated cancers. Objective: To investigate whether trends in obesity-associated cancer mortality mirror the slowed mortality improvements observed for heart disease associated with the obesity epidemic. Design, Setting, and Participants: This cross-sectional study compared US mortality trends for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision-defined cancer (total cancer, obesity-associated cancer, and cancer not associated with obesity) and heart disease deaths from January 1, 1999, to December 31, 2018. Data were included on decedents with complete information on the underlying cause of death, age, sex, race, and ethnicity. Exposures: Changes in age-adjusted cause-specific mortality rates between 1999-2011 and 2011-2018 were compared. Main Outcomes and Measures: Annual relative rates of change in age-adjusted mortality rates (AAMRs) in the overall population and stratified by sex, race, and ethnicity were estimated using Poisson regression. Differences in AAMR annual relative rates of change before and after 2011 were evaluated using Wald tests. Results: A total of 50163483 decedents met the inclusion criteria (50.1% female decedents, 79.9% non-Hispanic White decedents, and 11.7% non-Hispanic Black decedents; mean [SD] age, 72.8 [18.5] years). In contrast with heart disease mortality, for which improvements slowed between 1999-2011 and 2011-2018, decreases in total cancer AAMR relative change accelerated between 1999-2011 (-1.48 [95% CI, -1.43 to -1.52]) and 2011-2018 (-1.77 [95% CI, -1.67 to -1.86]) (P <.001). For obesity-associated cancer mortality, which accounted for approximately 33% of total cancer deaths annually, decreases in annual AAMR relative change decelerated from -1.19 (95% CI, -1.13 to -1.26) in 1999-2011 to -0.83 (95% CI, -0.70 to -0.96) in 2011-2018 (P <.001). The largest decelerations in obesity-associated cancer mortality were observed for female decedents (-1.45 [95% CI, -1.36 to -1.53] in 1999-2011 and -0.91 [95% CI, -0.75 to -1.07] in 2011-2018; P <.001) and non-Hispanic White individuals (-1.16 [95% CI, -1.09 to -1.22] in 1999-2011 and -0.68 [95% CI, -0.55 to -0.81] in 2011-2018; P <.001). Conclusions and Relevance: Slowing improvements in obesity-associated cancer mortality were obscured when considering total cancer mortality. These findings potentially signal a changing profile of cancer-associated mortality that may parallel trends previously observed for heart disease as the consequences of the obesity epidemic are understood

Modifiable and non-modifiable risk factors for preterm delivery among adolescent and young adult cancer survivors

Purpose: A cancer diagnosis in adolescence and young adulthood (AYA, ages 15–39) may affect future pregnancy outcomes. Previous studies have reported an increased risk of preterm delivery (< 37 weeks of gestation) after maternal cancer treatment. In this analysis, we evaluated whether non-cancer characteristics modify the association between an AYA cancer history and preterm birth. Methods: North Carolina Central Cancer Registry records (2000–2013) were linked to state birth certificate files (2000–2014) to identify births to AYA cancer survivors (n = 1,980). A comparison cohort of births to women without a cancer diagnosis was selected from birth certificate files (n = 11,860). Log-binomial regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for preterm delivery. Effect modification by early prenatal care (1st trimester; yes/no), race/ethnicity (white/black/other), previous live births (0/1+), maternal age (< 25/25–29/30–34/35+), smoking during pregnancy (any/none), and education (high school or less/some college/Bachelor’s degree or higher) was evaluated using likelihood ratio tests (LRT). Results: Overall, preterm births were more common among AYA survivors than the comparison group (RR = 1.24, CI 1.07–1.43). The association was stronger among those who did not receive early prenatal care (RR = 1.73, CI 1.26–2.37) than among those who did (RR = 1.15, CI 0.98–1.35; LRT p = 0.03). Maternal age < 25 was also associated with a greater increase in preterm birth (< 25: RR = 1.80, CI 1.27–2.54; LRT p = 0.07). Associations did not vary strongly by other factors evaluated. Conclusions: An AYA cancer diagnosis may be associated with an increased risk of preterm birth, particularly among women who are younger and receive late or no prenatal care

Suicide rates among patients with cancers of the digestive system

Objective: Previous studies have suggested that suicide rates are elevated among cancer patients relative to the general population. In this analysis, we comprehensively evaluated characteristics associated with higher suicide rates among patients with cancers of the digestive system. Methods: Using the United States Surveillance, Epidemiology, and End Results database, we identified all patients diagnosed with digestive system cancers during 2000 to 2014. Patients were classified as having died of suicide if their cause of death in Surveillance, Epidemiology, and End Results was listed as “suicide and self-inflicted injury.” Suicide rates were compared to age-, sex-, and race-adjusted rates in the general population. Results: A total of 881 suicides were identified among 856 293 patients diagnosed with digestive system cancers. The suicide rate in this population was 32.8 per 100 000 person-years and was nearly twice that in the general population (standardized mortality ratio [SMR] = 1.91; 95% CI, 1.79-2.04). Suicide rates were significantly elevated for all cancer sites but were highest for esophageal (SMR = 5.03), pancreatic (SMR = 5.28), stomach (SMR = 2.84), and liver (SMR = 2.14) cancers. Standardized mortality ratios for suicide were highest within the first 5 years of diagnosis and increased with age at diagnosis for all sites except colon and stomach. Conclusions: Patients with cancers of the digestive system have a higher incidence of suicide than the general population. Suicide rates among esophageal and pancreatic cancer patients are more than 5 times general population rates. The involvement of psychiatrists and other mental health professionals may be a critical component of cancer care for these high-risk patient subgroups

Risk versus Benefit of Chemoprevention among Raloxifene and Tamoxifen Users with a Family History of Breast Cancer

Tamoxifen and raloxifene have been approved for the primary prevention of breast cancer in high-risk women, but are associated with an increased risk of serious side effects. Few studies have characterized risk–benefit profiles for chemoprevention among women who initiate tamoxifen or raloxifene outside of a clinical trial setting. Use of raloxifene and tamoxifen for chemoprevention was self-reported in 2014 to 2016 by participants in The Sister Study, a prospective cohort of women with a sister who had been diagnosed with breast cancer. After exclusions, 432 current raloxifene users and 96 current tamoxifen users were matched to 4,307 and 953 nonusers, respectively, on age and year of cohort enrollment. Conditional logistic regression was used to evaluate characteristics associated with chemoprevention use. Risk–benefit profiles were examined using published indices that assess the level of evidence (none, moderate, strong) that the benefits of chemoprevention outweigh the risk of serious side effects. Among current chemoprevention users, 44% of tamoxifen users and 5% of raloxifene users had no evidence of a net benefit. In analyses of factors associated with chemoprevention use, having strong evidence of benefit was a significant predictor of raloxifene use, but not of tamoxifen use. In our sample of women with a first-degree family history of breast cancer, raloxifene was more commonly used for breast cancer prevention than tamoxifen. Most raloxifene users, but <60% of tamoxifen users, were likely to benefit. Use of risk–benefit tables can help women and their healthcare providers make an informed decision about breast cancer chemoprevention