Breast cancer (BC) has been increasing globally, though it is unclear whether the increases are seen across all age groups and regions and whether changes in rates can be primarily attributed to decreasing fertility rates. We investigated age-specific trends in BC incidence and mortality from 1990 to 2017, worldwide and by region, and evaluated whether incidence trends are explained by decreases in fertility. We used country-level data to examine trends in BC incidence and mortality rates from 1990 to 2017 by region and age group. Linear mixed models were used to estimate age-specific rates from baseline models of year and were compared to fertility-adjusted models for incidence. The global BC mortality rate increased overall by 0.23% per year (95% CI=0.20, 0.25), with statistically significant increases in the under 50 and 70 and over age groups, and in 5 out of 7 regions. The global BC incidence rate increased overall by 1.44% per year (95% CI=1.42, 1.47), with statistically significant increases in all age groups, and in 6 out of 7 regions. After adjusting for fertility, the incidence annual percent change (APC) remained statistically significant (APC=0.84, 95% CI=0.81, 0.88), in all age groups, and in 6 of 7 regions. The global increase in BC mortality is seen in most age groups and regions. The global increase in BC incidence is seen in all age groups and is highest in women under 50; increases remained in most regions even after considering declining fertility rates. Breast Cancer Research Foundation and National Cancer Institute.

Background: For many childhood cancers, survival is lower among non‐Hispanic blacks and Hispanics in comparison with non‐Hispanic whites, and this may be attributed to underlying socioeconomic factors. However, prior childhood cancer survival studies have not formally tested for mediation by socioeconomic status (SES). This study applied mediation methods to quantify the role of SES in racial/ethnic differences in childhood cancer survival. Methods: This study used population‐based cancer survival data from the Surveillance, Epidemiology, and End Results 18 database for black, white, and Hispanic children who had been diagnosed at the ages of 0 to 19 years in 2000‐2011 (n = 31,866). Black‐white and Hispanic‐white mortality hazard ratios and 95% confidence intervals, adjusted for age, sex, and stage at diagnosis, were estimated. The inverse odds weighting method was used to test for mediation by SES, which was measured with a validated census‐tract composite index. Results: Whites had a significant survival advantage over blacks and Hispanics for several childhood cancers. SES significantly mediated the race/ethnicity–survival association for acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, and non‐Hodgkin lymphoma; SES reduced the original association between race/ethnicity and survival by 44%, 28%, 49%, and 34%, respectively, for blacks versus whites and by 31%, 73%, 48%, and 28%, respectively, for Hispanics versus whites ((log hazard ratio total effect – log hazard ratio direct effect)/log hazard ratio total effect). Conclusions: SES significantly mediates racial/ethnic childhood cancer survival disparities for several cancers. However, the proportion of the total race/ethnicity–survival association explained by SES varies between black‐white and Hispanic‐white comparisons for some cancers, and this suggests that mediation by other factors differs across groups.

Background: Studies have documented a temporal increase in incidence for several cancers in US young adults aged 25 to 39-years, including noncardia gastric cancer, colorectal cancer, and distant-stage breast cancer. To further characterize trends in young adults, we assessed age-specific and stage-specific incidence trends from 1975 to 2015, overall (all malignant cancers combined), and for 18 and 16 cancer sites in women and men, respectively. Methods: We used US population-based data from the Surveillance, Epidemiology, and End Results Program to obtain overall and site-specific cancer incidence rates by sex and age group. We individually analyzed cancer sites with an incidence rate of at least 5 per 100 000 in 2015, accounting for greater than 90% of all cancer diagnoses. We estimated annual percent changes (APCs) using segment log-linear regression performed with joinpoint software; multiple permutation testing was used to identify inflection points. We forecasted overall cancer incidence through 2030 using age-period-cohort regression models. Results: Based on trends occurring after the most recent joinpoint inflection point, overall cancer incidence increased by 1.15% (95% CI = 1.01% to 1.28%) per year in 25- to 39-year-old women and by 0.46% (95% CI = 0.17% to 0.75%) per year in 25- to 39-year-old men; APCs were of much lower magnitude in the older age groups (eg, 70- to 84-year-old women APC = −0.31%, 95% CI = −0.42% to −0.20%). We forecasted that overall cancer incidence will increase by an additional 11% by 2030 in 25- to 39-year-old women, and by an additional 12% in 25- to 39-year-old men. Ten of the 18 cancers assessed in 25- to 39-year-old women and 7 of the 16 cancers in 25- to 39-year-old men have been statistically significantly increasing over time. We found that the increase in incidence for young adults is stage specific for some cancers (eg, only nonlocalized breast cancer has increased in 25- to 39-year-old women). Conclusion: Cancer incidence is increasing in young adults, particularly in young women.

The etiology of childhood cancers remains largely unknown, especially regarding environmental and behavioral risk factors. Unpacking the association between socioeconomic status (SES) and incidence may offer insight into such etiology. We tested associations between SES and childhood cancer incidence in a population-based case-cohort study (source cohort: Minnesota birth registry, 1989–2014). Cases, ages 0–14 years, were linked from the Minnesota Cancer Surveillance System to birth records through probabilistic record linkage. Controls were 4:1 frequency matched on birth year (2,947 cases and 11,907 controls). We tested associations of individual-level (maternal education) and neighborhood-level (census tract composite index) SES using logistic mixed models. In crude models, maternal education was positively associated with incidence of acute lymphoblastic leukemia (odds ratio (OR) = 1.10, 95% confidence interval (CI): 1.02, 1.19), central nervous system tumors (OR = 1.12, 95% CI: 1.04, 1.21), and neuroblastoma (OR = 1.15, 95% CI: 1.02, 1.30). Adjustment for established risk factors—including race/ethnicity, maternal age, and birth weight—substantially attenuated these positive associations. Similar patterns were observed for neighborhood-level SES. Conversely, higher maternal education was inversely associated with hepatoblastoma incidence (adjusted OR = 0.70, 95% CI: 0.51, 0.98). Overall, beyond the social patterning of established demographic and pregnancy-related exposures, SES is not strongly associated with childhood cancer incidence.

Although physical activity is associated with lower breast cancer risk for average-risk women, it is not known if this association applies to women at high familial/genetic risk. We examined the association of recreational physical activity (self-reported by questionnaire) with breast cancer risk using the Prospective Family Study Cohort, which is enriched with women who have a breast cancer family history (N = 15,550). We examined associations of adult and adolescent recreational physical activity (quintiles of age-adjusted total metabolic equivalents per week) with breast cancer risk using multivariable Cox proportional hazards regression, adjusted for demographics, lifestyle factors, and body mass index. We tested for multiplicative interactions of physical activity with predicted absolute breast cancer familial risk based on pedigree data and with BRCA1 and BRCA2 mutation status. Baseline recreational physical activity level in the highest four quintiles compared with the lowest quintile was associated with a 20% lower breast cancer risk (HR, 0.80; 95% confidence interval, 0.68–0.93). The association was not modified by familial risk or BRCA mutation status (P interactions >0.05). No overall association was found for adolescent recreational physical activity. Recreational physical activity in adulthood may lower breast cancer risk for women across the spectrum of familial risk. Significance: These findings suggest that physical activity might reduce breast cancer risk by about 20% for women across the risk continuum, including women at higher-than-average risk due to their family history or genetic susceptibility. See related commentary by Niehoff et al., p. 23

The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial or genetic risk. We examined the association between regular NSAID use and breast cancer risk using a large cohort of women selected for breast cancer family history, including 1054 BRCA1 or BRCA2 mutation carriers. We analyzed a prospective cohort (N = 5606) and a larger combined, retrospective and prospective, cohort (N = 8233) of women who were aged 18 to 79 years, enrolled before June 30, 2011, with follow-up questionnaire data on medication history. The prospective cohort was further restricted to women without breast cancer when medication history was asked by questionnaire. Women were recruited from seven study centers in the United States, Canada, and Australia. Associations were estimated using multivariable Cox proportional hazards regression models adjusted for demographics, lifestyle factors, family history, and other medication use. Women were classified as regular or non-regular users of aspirin, COX-2 inhibitors, ibuprofen and other NSAIDs, and acetaminophen (control) based on self-report at follow-up of ever using the medication for at least twice a week for ≥1 month prior to breast cancer diagnosis. The main outcome was incident invasive breast cancer, based on self- or relative-report (81% confirmed pathologically). From fully adjusted analyses, regular aspirin use was associated with a 39% and 37% reduced risk of breast cancer in the prospective (HR = 0.61; 95% CI = 0.33–1.14) and combined cohorts (HR = 0.63; 95% CI = 0.57–0.71), respectively. Regular use of COX-2 inhibitors was associated with a 61% and 71% reduced risk of breast cancer (prospective HR = 0.39; 95% CI = 0.15–0.97; combined HR = 0.29; 95% CI = 0.23–0.38). Other NSAIDs and acetaminophen were not associated with breast cancer risk in either cohort. Associations were not modified by familial risk, and consistent patterns were found by BRCA1 and BRCA2 carrier status, estrogen receptor status, and attained age. Regular use of aspirin and COX-2 inhibitors might reduce breast cancer risk for women at familial or genetic risk.