Search

Background: Most prior studies have reported cancer mortality trends across countries for specific cancer types. Herein, we examine recent patterns and trends in cancer mortality rates for the eight common forms of cancer in 47 countries across five continents (except Africa) based on the World Health Organization mortality database. Methods: Rates were age-standardized to the 1966 Segi-Doll world population, and trends in the age-standardized rates for the most recent 10 years of data were examined using Joinpoint regression. Results: Cancer-specific mortality rates vary substantially across countries, with rates of infection-related (cervix and stomach) and tobacco-related cancers (lung and esophagus) varying by 10-fold. Recent mortality rates for all major cancers decreased in most of the studied countries except lung cancer in females and liver cancer in males, where increasing rates were observed in most countries. Rates decreased or stabilized in all countries for lung cancer in men and stomach cancer in both sexes. Conclusions: The findings reinforce the importance of implementing and strengthening resource-stratified and targeted cancer prevention and control programs in all parts of the world to further reduce or halt the rising cancer burden. Impact: The results may inform cancer prevention and treatment strategies and in so doing, reduce the marked global cancer disparities observed today.

The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States.Data on new cancer diagnoses during 2001-2018 were obtained from the North American Association of Central Cancer Registries' Cancer in North America Incidence file, which is comprised of data from Centers for Disease Control and Prevention-funded and National Cancer Institute-funded, population-based cancer registry programs. Data on cancer deaths during 2001-2019 were obtained from the National Center for Health Statistics' National Vital Statistics System. Five-year average incidence and death rates along with trends for all cancers combined and for the leading cancer types are reported by sex, racial/ethnic group, and age.Overall cancer incidence rates were 497 per 100,000 among males (ranging from 306 among Asian/Pacific Islander males to 544 among Black males) and 431 per 100,000 among females (ranging from 309 among Asian/Pacific Islander females to 473 among American Indian/Alaska Native females) during 2014-2018. The trend during the corresponding period was stable among males and increased 0.2% on average per year among females, with differing trends by sex, racial/ethnic group, and cancer type. Among males, incidence rates increased for three cancers (including pancreas and kidney), were stable for seven cancers (including prostate), and decreased for eight (including lung and larynx) of the 18 most common cancers considered in this analysis. Among females, incidence rates increased for seven cancers (including melanoma, liver, and breast), were stable for four cancers (including uterus), and decreased for seven (including thyroid and ovary) of the 18 most common cancers. Overall cancer death rates decreased by 2.3% per year among males and by 1.9% per year among females during 2015-2019, with the sex-specific declining trend reflected in every major racial/ethnic group. During 2015-2019, death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, with the steepest declines (4% per year) reported for lung cancer and melanoma. Five-year survival for adenocarcinoma and neuroendocrine pancreatic cancer improved between 2001 and 2018; however, overall incidence (2001-2018) and mortality (2001-2019) continued to increase for this site. Among children (younger than 15 years), recent trends were stable for incidence and decreased for mortality; and among, adolescents and young adults (aged 15-39 years), recent trends increased for incidence and declined for mortality.Cancer death rates continued to decline overall, for children, and for adolescents and young adults, and treatment advances have led to accelerated declines in death rates for several sites, such as lung and melanoma. The increases in incidence rates for several common cancers in part reflect changes in risk factors, screening test use, and diagnostic practice. Racial/ethnic differences exist in cancer incidence and mortality, highlighting the need to understand and address inequities. Population-based incidence and mortality data inform prevention, early detection, and treatment efforts to help reduce the cancer burden in the United States.

This article is the American Cancer Society's update on female breast cancer statistics in the United States, including population-based data on incidence, mortality, survival, and mammography screening. Breast cancer incidence rates have risen in most of the past four decades; during the most recent data years (2010-2019), the rate increased by 0.5% annually, largely driven by localized-stage and hormone receptor-positive disease. In contrast, breast cancer mortality rates have declined steadily since their peak in 1989, albeit at a slower pace in recent years (1.3% annually from 2011 to 2020) than in the previous decade (1.9% annually from 2002 to 2011). In total, the death rate dropped by 43% during 1989-2020, translating to 460,000 fewer breast cancer deaths during that time. The death rate declined similarly for women of all racial/ethnic groups except American Indians/Alaska Natives, among whom the rates were stable. However, despite a lower incidence rate in Black versus White women (127.8 vs. 133.7 per 100,000), the racial disparity in breast cancer mortality remained unwavering, with the death rate 40% higher in Black women overall (27.6 vs. 19.7 deaths per 100,000 in 2016-2020) and two-fold higher among adult women younger than 50 years (12.1 vs. 6.5 deaths per 100,000). Black women have the lowest 5-year relative survival of any racial/ethnic group for every molecular subtype and stage of disease (except stage I), with the largest Black-White gaps in absolute terms for hormone receptor-positive/human epidermal growth factor receptor 2-negative disease (88% vs. 96%), hormone receptor-negative/human epidermal growth factor receptor 2-positive disease (78% vs. 86%), and stage III disease (64% vs. 77%). Progress against breast cancer mortality could be accelerated by mitigating racial disparities through increased access to high-quality screening and treatment via nationwide Medicaid expansion and partnerships between community stakeholders, advocacy organizations, and health systems.

Background:Most prior studies have reported cancer mortality trends across countries for specific cancer types. Herein, we examine recent patterns and trends in cancer mortality rates for the eight common forms of cancer in 47 countries across five continents (except Africa) based on the World Health Organization mortality database.Methods:Rates were age-standardized to the 1966 Segi-Doll world population, and trends in the age-standardized rates for the most recent 10 years of data were examined using Joinpoint regression.Results:Cancer-specific mortality rates vary substantially across countries, with rates of infection-related (cervix and stomach) and tobacco-related cancers (lung and esophagus) varying by 10-fold. Recent mortality rates for all major cancers decreased in most of the studied countries except lung cancer in females and liver cancer in males, where increasing rates were observed in most countries. Rates decreased or stabilized in all countries for lung cancer in men and stomach cancer in both sexes.Conclusions:The findings reinforce the importance of implementing and strengthening resource-stratified and targeted cancer prevention and control programs in all parts of the world to further reduce or halt the rising cancer burden.Impact:The results may inform cancer prevention and treatment strategies and in so doing, reduce the marked global cancer disparities observed today.

Supplementary Table 1. Country and time-period available for trend analysis of cancer mortality

Supplementary Table 2. Age-standardized mortality rate (ASR) per 100,000 person-years, 10-year average annual percent change (AAPC), and 5-year AAPC for 8 cancers by sex for 47 countries (bold font indicates statistically significant AAPC at p

Supplementary Figure 2. Age-standardized mortality rates per 100,000 person-years and ten-year average annual percent change in cervical cancer in 47 countries.

PDF file, 148KB, The previous studies on the serum levels of MMP-2 and breast cancer.

Background: Matrix metalloproteinase-2 (MMP-2) has been thought of as a predictor of recurrence or metastasis risk or prognostic markers in cancer. We evaluated whether preoperative serum levels of MMP-2 work as a prognostic biomarker in breast cancer prognosis.Methods: Preoperative serum levels of MMP-2 were measured with ELISA in 303 patients with histologically confirmed breast cancer. The median follow-up time for all patients was 4.24 years. The relationship of MMP-2 to survival was investigated using Cox proportional hazard regression model adjusted for the tumor–node–metastasis (TNM) stage and estrogen receptor (ER) status.Results: In the multivariate analysis, disease-free survival (DFS) was worse among patients with the third tertile of MMP-2 level than with the first tertile of MMP-2 level [hazard ratio, 1.80; 95% confidence interval (CI), 1.04–3.11; P = 0.04]. However, when the patients were stratified by age, ER status, histologic grade, and nuclear grade, inverse correlation was shown between serum MMP-2 levels and prognostic factors, and the associations between MMP-2 and DFS were only significant among patients with poor prognostic factors (HR, 2.75; 95% CI, 1.32–5.73 in ER-negative; HR, 2.90; 95% CI, 1.42–5.92 in histologic grade III; and HR, 2.61; 95% CI, 1.26–5.39 in nuclear grade III).Conclusions: Our results suggest that the preoperative serum levels of MMP-2 were associated with the survival in patients with breast cancer in ER-negative, higher histologic grade, or higher nuclear grade breast cancers.Impact: Our results indicate that serum levels of MMP-2 may play a role as prognostic biomarker in breast cancer survival. Cancer Epidemiol Biomarkers Prev; 21(8); 1371–80. ©2012 AACR.

Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer. Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined the association between genetic ancestry and TDLU involution in normal breast tissue donated by 2014 healthy women in the United States. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR]trend = 1.36, 95% confidence interval [CI] = 1.07 to 1.74), acini counts per TDLU (OR = 1.47, 95% CI = 1.06 to 2.03), and median TDLU span (ORtrend = 1.44, 95% CI = 1.08 to 1.91), indicating lower involution, whereas East Asian descendants were associated with decreased TDLU counts (ORtrend = 0.52, 95% CI = 0.35 to 0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of triple-negative breast cancer in the United States and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk.

Background The American Cancer Society, National Cancer Institute, Centers for Disease Control and Prevention, and North American Association of Central Cancer Registries provide annual information about cancer occurrence and trends in the United States. Part 1 of this annual report focuses on national cancer statistics. This study is part 2, which quantifies patient economic burden associated with cancer care. Methods We used complementary data sources, linked Surveillance, Epidemiology, and End Results-Medicare, and the Medical Expenditure Panel Survey to develop comprehensive estimates of patient economic burden, including out-of-pocket and patient time costs, associated with cancer care. The 2000-2013 Surveillance, Epidemiology, and End Results-Medicare data were used to estimate net patient out-of-pocket costs among adults aged 65 years and older for the initial, continuing, and end-of-life phases of care for all cancer sites combined and separately for the 21 most common cancer sites. The 2008-2017 Medical Expenditure Panel Survey data were used to calculate out-of-pocket costs and time costs associated with cancer among adults aged 18-64 years and 65 years and older. Results Across all cancer sites, annualized net out-of-pocket costs for medical services and prescriptions drugs covered through a pharmacy benefit among adults aged 65 years and older were highest in the initial ($2200 and $243, respectively) and end-of-life phases ($3823 and $448, respectively) and lowest in the continuing phase ($466 and $127, respectively), with substantial variation by cancer site. Out-of-pocket costs were generally higher for patients diagnosed with later-stage disease. Net annual time costs associated with cancer were $304.3 (95% confidence interval = $257.9 to $350.9) and $279.1 (95% confidence interval = $215.1 to $343.3) for adults aged 18-64 years and ≥65 years, respectively, with higher time costs among more recently diagnosed survivors. National patient economic burden, including out-of-pocket and time costs, associated with cancer care was projected to be $21.1 billion in 2019. Conclusions This comprehensive study found that the patient economic burden associated with cancer care is substantial in the United States at the national and patient levels.

Previous studies have reported on incidence and mortality patterns for individual genitourinary cancers in the USA. However, these studies addressed individual cancer types rather than genitourinary cancers overall.To comprehensively examine disparities and trends in the incidence and mortality for the four major genitourinary cancers (bladder, kidney, prostate, and testis) in the USA.We obtained incidence data from the National Cancer Institute 22-registry Surveillance, Epidemiology and End Results (SEER) database and the US Cancer Statistics database (Centers for Disease Control and Prevention) and mortality data from the National Center for Health Statistics to examine cross-sectional and temporal trends in incidence and death rates stratified by sex, race/ethnicity, and county.Age-adjusted incidence and death rates were calculated using SEER*Stat software. Temporal trends were analyzed using Joinpoint regression for a two-sided significance level of p 0.05.Incidence and mortality rates for bladder and kidney cancers were two to four times higher for men than for women. Among non-Hispanic White individuals, the highest incidence rates were found in the Northeast for bladder cancer and in Appalachia for kidney cancer, whereas the highest death rates for prostate cancer were found in the West. Incidence rates increased for cancers of the kidney and testis and for advanced-stage prostate cancer in almost all racial/ethnic populations and for bladder cancer in the American Indian/Alaska Native population. Death rates increased for testicular cancer in the Hispanic population and stabilized for prostate cancer among White and Asian American/Pacific Islander men after a steady decline since the early 1990s. Study limitations include misclassification of race/ethnicity on medical records and death certificates.We found persistent sociodemographic disparities and unfavorable trends in incidence or mortality for all four major genitourinary cancers. Future studies should elucidate the reasons for these patterns.In the USA, rates of cancer cases are increasing for kidney, testis, and advanced-stage prostate cancers in the overall population, and for bladder cancer in the American Indian/Alaska Native population. Differences in the rates by sex and race/ethnicity remain.

Background The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries collaborate to provide annual updates on cancer incidence and mortality and trends by cancer type, sex, age group, and racial/ethnic group in the United States. In this report, we also examine trends in stage-specific survival for melanoma of the skin (melanoma). Methods Incidence data for all cancers from 2001 through 2017 and survival data for melanoma cases diagnosed during 2001-2014 and followed-up through 2016 were obtained from the Centers for Disease Control and Prevention- and National Cancer Institute-funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries. Data on cancer deaths from 2001 to 2018 were obtained from the National Center for Health Statistics’ National Vital Statistics System. Trends in age-standardized incidence and death rates and 2-year relative survival were estimated by joinpoint analysis, and trends in incidence and mortality were expressed as average annual percent change (AAPC) during the most recent 5 years (2013-2017 for incidence and 2014-2018 for mortality). Results Overall cancer incidence rates (per 100 000 population) for all ages during 2013-2017 were 487.4 among males and 422.4 among females. During this period, incidence rates remained stable among males but slightly increased in females (AAPC = 0.2%, 95% confidence interval [CI] = 0.1% to 0.2%). Overall cancer death rates (per 100 000 population) during 2014-2018 were 185.5 among males and 133.5 among females. During this period, overall death rates decreased in both males (AAPC = −2.2%, 95% CI = −2.5% to −1.9%) and females (AAPC = −1.7%, 95% CI = −2.1% to −1.4%); death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, but increased for 5 cancers in each sex. During 2014-2018, the declines in death rates accelerated for lung cancer and melanoma, slowed down for colorectal and female breast cancers, and leveled off for prostate cancer. Among children younger than age 15 years and adolescents and young adults aged 15-39 years, cancer death rates continued to decrease in contrast to the increasing incidence rates. Two-year relative survival for distant-stage skin melanoma was stable for those diagnosed during 2001-2009 but increased by 3.1% (95% CI = 2.8% to 3.5%) per year for those diagnosed during 2009-2014, with comparable trends among males and females. Conclusions Cancer death rates in the United States continue to decline overall and for many cancer types, with the decline accelerated for lung cancer and melanoma. For several other major cancers, however, death rates continue to increase or previous declines in rates have slowed or ceased. Moreover, overall incidence rates continue to increase among females, children, and adolescents and young adults. These findings inform efforts related to prevention, early detection, and treatment and for broad and equitable implementation of effective interventions, especially among under resourced populations.

ImportanceThere are few data on state variation in racial and ethnic disparities in incidence of triple-negative breast cancer (TNBC) in the US, limiting the ability to inform state-level health policy developments toward breast cancer equity.ObjectiveTo quantify between and within racial and ethnic disparities in TNBC incidence rates (IRs) among US women across states.Design, Setting, and ParticipantsThis cohort study using population-based cancer registry data included data for all women with TNBC diagnosed from January 1, 2015, to December 31, 2019, identified in the US Cancer Statistics Public Use Research Database. Data were analyzed from July through November 2022.ExposuresState and race and ethnicity (Hispanic, non-Hispanic American Indian or Alaska Native, non-Hispanic Asian or Pacific Islander, non-Hispanic Black, or non-Hispanic White) abstracted from medical records.Main Outcomes and MeasuresThe main outcomes were diagnosis of TNBC, age-standardized IR per 100 000 women, state-specific incidence rate ratios (IRRs) using the rate among White women in each state as a reference for between-population disparities, and state-specific IRRs using the race and ethnicity–specific national rate as a reference for within-population disparities.ResultsThe study included data for 133 579 women; 768 (0.6%) were American Indian or Alaska Native; 4969 (3.7%), Asian or Pacific Islander; 28 710 (21.5%), Black; 12 937 (9.7%), Hispanic; and 86 195 (64.5%), White. The TNBC IR was highest among Black women (25.2 per 100 000 women), followed by White (12.9 per 100 000 women), American Indian or Alaska Native (11.2 per 100 000 women), Hispanic (11.1 per 100 000 women), and Asian or Pacific Islander (9.0 per 100 000 women) women. Racial and ethnic group–specific and state-specific rates substantially varied, ranging from less than 7 per 100 000 women among Asian or Pacific Islander women in Oregon and Pennsylvania to greater than 29 per 100 000 women among Black women in Delaware, Missouri, Louisiana, and Mississippi. Compared with White women, IRRs were statistically significantly higher in 38 of 38 states among Black women, ranging from 1.38 (95% CI, 1.10-1.70; IR, 17.4 per 100 000 women) in Colorado to 2.32 (95% CI, 1.90-2.81; IR, 32.0 per 100 000 women) in Delaware; lower in 22 of 22 states among Asian or Pacific Islander women, varying from 0.50 (95% CI, 0.34-0.70; IR, 5.7 per 100 000 women) in Oregon to 0.82 (95% CI, 0.75-0.90; IR, 10.5 per 100 000 women) in New York; and did not differ among Hispanic and American Indian or Alaska Native women in 22 of 35 states and 5 of 8 states, respectively. State variations within each racial and ethnic population were smaller but still substantial. For example, among White women, compared with the national rate, IRRs varied from 0.72 (95% CI, 0.66-0.78; IR, 9.2 per 100 000 women) in Utah to 1.18 (95% CI, 1.11-1.25; IR, 15.2 per 100 000 women) in Iowa, 1.15 (95% CI, 1.07-1.24; IR, 14.8 per 100 000 women) in Mississippi, and 1.15 (95% CI, 1.07-1.24; IR, 14.8 per 100 000 women) in West Virginia.Conclusions and RelevanceIn this cohort study, there were substantial state variations in racial and ethnic disparities in TNBC incidence, with Black women in Delaware, Missouri, Louisiana, and Mississippi having the highest rates among all states and racial and ethnic populations. The findings suggest that more research is needed to identify factors contributing to the substantial geographic variations in racial and ethnic disparities in TNBC incidence to develop effective preventive measures and that social determinants of health contribute to the geographic disparities in TNBC risk.

Background Second primary cancer (SPC) burden is increasing in the US, but few studies comprehensively examined survival in persons diagnosed with SPCs in relation to survivors’ antecedent cancer types. Methods Persons aged ≥20 years and diagnosed with one of the six most common SPCs (female breast, prostate, bladder, lung, colorectum, corpus uteri) from 2000-2013 were identified from 17 Surveillance, Epidemiology, and End Results registries (n=152,204). For comparison, persons diagnosed with same type cancers occurring as first primary cancers (FPCs) were also identified (n=2,131,953). For each cancer type, differences in the risk of cancer-specific or all-cause death between SPC and FPC were estimated using multivariable Cox proportional hazards models adjusted for potential confounders. Subgroup analyses were conducted to estimate the risk difference between SPC and FPC by antecedent cancer types of those with SPCs. Results During a median follow-up of 6.5 years (interquartile range, 1.8-10.6), cancer-type specific death occurred among 34% of persons with SPCs and among 32% of persons with FPCs. The corresponding proportions for all-cause death were 67% and 53%, respectively. In multivariable models, the risk of cancer-specific death was statistically significantly higher in persons with SPC than in persons with FPC for breast (hazard ratio [HR]=1.43; 95% confidence interval [CI]=1.40-1.48), bladder (HR=1.19; 1.09-1.29), corpus uteri (HR=1.10; 1.05-1.15), and colorectal (HR=1.05, 1.03-1.07) cancer, whereas it was lower for lung cancer (HR=0.78; 0.77-0.79). The risk did not vary between groups for prostate cancer (HR=0.92; 0.79-1.06). Subgroup analyses showed large variations in HRs across survivors by antecedent cancer types. In particular, the highest HR associated with SPC (vs FPC) was among ovarian cancer survivors for colorectal cancer (HR=1.31; 1.10-1.56), gallbladder cancer survivors for breast cancer (HR=1.78; 1.09-2.91), head and neck cancer survivors for uterine cancer (HR=1.69, 1.05-2.72), gallbladder cancer survivors for bladder cancer (HR=1.87; 1.06-3.22), while the lowest HR for lung cancer was among testicular cancer survivors (HR=0.54; 0.38-0.76). Associations were generally consistent across strata of diagnosis years, race/ethnicity, household income, and urbanicity. The risks of all-cause death were also higher among persons with SPC vs FPC, including prostate cancer. Persons with second primary prostate cancer were almost twice as likely to die from all causes as persons with first prostate cancer (HR=1.83; 1.80-1.87). Conclusion Persons with SPC generally have a higher risk of cancer-specific and all-cause death than those with FPC, suggesting that intensive SPC surveillance may benefit those at increased risk of developing SPC. Importantly, the risk difference substantially varied by survivors’ antecedent cancer type, highlighting a need for targeted strategies for treatment and survivorship care for persons with SPCs. Citation Format: Hyuna Sung, Lauren Nisotel, Ephrem Sedeta, Farhad Islami, Ahmedin Jemal. Survival of most commonly diagnosed second primary cancers among adult cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB129.

Background Cancer survivors have higher cardiovascular disease (CVD) mortality than the general population but comprehensive data by race and ethnicity are limited. Methods Data from 17 Surveillance, Epidemiology, and End Results (SEER) registries were used to identify adults diagnosed with invasive cancer at ages ≥20 years from 2000 to 2018. CVD mortality was calculated for five mutually exclusive race/ethnicity categories (non-Hispanic American Indian/Alaska Native [AIAN], non-Hispanic Asian or Pacific Islander [API], Hispanic, non-Hispanic Black [Black], and non-Hispanic White [White]). Standardized mortality ratios (SMR) were estimated to compare mortality rates in cancer survivors to their counterparts in the general population. Analyses were stratified by demographic factors, CVD subtype, and cancer site. Results During a mean follow up of 5.3 person-years among 5,786,876 survivors (20-64 years, 49.3%; men, 51.2%; White, 71.7%; Black, 10.1%; Hispanic, 10.9%; API, 7%, AIAN, 0.3%), 358,970 CVD deaths (cardiac death, 76.9%; cerebrovascular death, 15.9%) occurred. CVD mortality per 10,000 person-years was highest among survivors who were Black (122.9), followed by White (114.7), AIAN (86.7), API (78.6) and Hispanic (75.3). In contrast, SMRs were greatest among AIAN survivors (SMR=1.42, 95% CI=1.32-1.51), followed by API (SMR=1.39, 1.37-1.41), Hispanic (SMR=1.29, 1.27-1.30), Black (SMR=1.19, 1.17-1.20) and White (SMR=1.08, 1.07-1.08) survivors. Among survivors ages 20-64 years, Black survivors were approximately three times as likely to die from cardiac death as Hispanic or API survivors (46.7 vs. 14.5-17.6 per 10,000). SMR, however, was 1.47 among Hispanic survivors (95% CI=1.42-1.51) and 1.80 among API survivors (95% CI=1.42-1.51), greater than 1.25 among Black survivors (95% CI=1.22-1.27). Across cancer types, the highest SMR was among API survivors of pancreatic cancer (SMR=5.27, 3.83-7.08) and brain cancer (SMR=4.56, 3.10-6.48) in ages 20-64 years and among Hispanic (SMR=3.77, 3.09-4.56) and API survivors of brain cancer (SMR=3.24, 2.40-4.28) in ages ≥65 years. Conclusion Black survivors had the greatest CVD mortality of all groups, demonstrating that CVD health disparities in the general population extend to cancer survivors. Despite the lower absolute mortalities, relative risks compared to their counterparts in the general population were greatest among API and Hispanic survivors, implying a greater impact of cancer diagnosis on the risk of CVD death among survivors of these populations. Targeted primary care and cardio-oncologic intervention strategies are needed to improve CVD outcomes and achieve cardiovascular health equity among cancer survivors. Citation Format: Lauren Nisotel, Rebecca L. Siegel, Eric H. Yang, Ahmedin Jemal, Hyuna Sung. Cardiovascular disease mortality among cancer survivors by race and ethnicity in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB128.

Background: The burden of second primary cancers including secondary acute myeloid leukemia (sAML) is increasing in the United States; however, limited data exist regarding survival among individuals with sAML. This study aims to examine survival differences between sAML and AML arising de novo (dnAML) in relation to antecedent cancer types and the receipt of prior cancer treatment. Methods: Individuals aged ≥20 years and diagnosed with sAML or dnAML between 2001 and 2018 and followed for vital status through 2019 were identified from Surveillance, Epidemiology, and End Results 17 database, covering 27% of the US population. The differences in AML-specific survival between individuals with sAML and dnAML were examined using multivariable Cox proportional hazards regression. Trends in five-year age-standardized relative survival from 2001-2014 were assessed using Joinpoint survival model for sAML and dnAML, separately. Results: A total of 7,306 individuals diagnosed with sAML and 40,398 individuals with dnAML were included. During a median follow-up of 6 months, 78% of individuals with sAML died from AML compared to 71% of those with dnAML. In multivariable models, the risk of AML-specific mortality was 8% higher in individuals diagnosed with sAML than in those diagnosed with dnAML (hazard ratio [HR]=1.08, 95%CI=1.05-1.11), with the elevated risk more pronounced among those with younger ages at diagnosis (HR20-54 years=1.60, 95%CI=1.46-1.75 versus HR65+ years=0.99, 95%CI=0.96-1.03; Pinteraction Conclusion: Individuals with sAML had in general worse AML cause-specific survival compared with their dnAML counterparts, with the differences most pronounced among those diagnosed at younger ages and who received chemotherapy. The findings may inform targeted treatment and survivorship recommendations for cancer survivors who develop sAML. Citation Format: Ephrem Sedeta, Ahmedin Jemal, Lauren Nisotel, Hyuna Sung. Survival among adults diagnosed with secondary acute myeloid leukemia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4379.

Background: Triple-negative breast cancer (TNBC) (i.e., estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor type 2-negative) is an aggressive subtype of breast cancer, more frequently diagnosed among non-Hispanic Black women than other racial/ethnic groups in the United States. TNBC risk also varies by location, but limited data exist for state-level variation in the racial/ethnic disparities in TNBC risk. Methods: Data for TNBC diagnosed at all ages during 2015-2019 were obtained from the National Program of Cancer Registries and Surveillance, Epidemiology & End Results for racial/ethnic groups classified as non-Hispanic American Indian/Alaska Native (AIAN), non-Hispanic Asian or Pacific Islander (API), non-Hispanic Black (Black), Hispanic, or non-Hispanic White (White). State-specific incidence rates were available for 8, 23, and 36 states for AIAN, API, and Hispanic women, respectively, and 38 states and Washington, D.C. for Black women and 50 states and Washington, D.C. (hereafter referred to collectively as “states”) for White women. State-specific rates were compared within and between racial/ethnic groups using incidence rate ratios (IRR). Results: Nationally, the age-standardized incidence rate of TNBC was the highest among Black women (25.1 per 100,000), followed by White (12.9 per 100,000), AIAN (11.1 per 100,000), Hispanic (11.1 per 100,000), and API (9.0 per 100,000) women. The highest state-specific rates were found among Black women in Delaware, Missouri, and Louisiana (>30 per 100,000) and the lowest rates were among API women in Oregon and Pennsylvania (< 7 per 100,000). State variations within a population were relatively larger among AIAN (2.8-fold) and Hispanic (2.3-fold) women, and smaller among White women (1.65-fold). Compared with White women, Black women had a higher rate of TNBC in all 39/39 states with the greatest IRRs in Delaware (2.31, 95%CI=1.90-2.81), Missouri (2.28, 95%CI=2.08-2.50), and Louisiana (2.20, 95%CI=2.02-2.38) and the lowest IRRs in Minnesota (1.38, 95%CI=1.12-1.68) and Colorado (1.38, 95%CI=1.12-1.68). In contrast, API women had a lower rate than White women in 22/23 states, except for Nevada, with the lowest IRR in Oregon (0.50, 95%CI=0.34-0.70) and the highest IRR in New York (0.82, 95%CI=0.75-0.90). The rate among Hispanic compared with White women did not differ statistically significantly in 23/36 states but was lower in 12/36 states, with the lowest IRR in Ohio (0.57, 95%CI=0.43-0.74), and higher in Massachusetts (1.21, 95%CI=1.04-1.39). The rate among AIAN compared with White women did not differ in 5/8 states but was lower in Arizona (0.53, 95%CI=0.38-0.73) and North Carolina (0.68, 95%CI=0.46-0.96), and higher in Oklahoma (1.30, 95%CI=1.09-1.54). Conclusions: State variations in TNBC incidence rates both within and between populations are substantial, signifying the important role of potentially modifiable risk factors in determining the risk of TNBC by state and race/ethnicity. This finding highlights the need for more research to identify factors contributing to these variations to develop more effective preventive measures. Meanwhile, to mitigate the impact of the disproportionate burden of TNBC across states and racial/ethnic groups, universal access to screening modalities and timely, guideline-concordant treatments is essential. Citation Format: Hyuna Sung, Daniel Wiese, Ismail Jatoi, Ahmedin Jemal. State variation in racial and ethnic disparities in triple-negative breast cancer rates: NPCR-SEER incidence data, 2015-2019 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-24.

Summary Background Breast cancer has distinct causes, prognoses, and outcomes and effects in patients at premenopausal and postmenopausal ages. We sought to assess the global burden and trends in breast cancer by menopausal status. Methods We did a population-based analysis of global breast cancer incidence and mortality among premenopausal and postmenopausal women. Menopausal status was defined using age as a proxy, whereby breast cancer cases or deaths at age 50 years or older were regarded as postmenopausal. Age-standardised breast cancer incidence and mortality in 2018 were calculated using GLOBOCAN data. Incidence trends for 1998–2012 were assessed in 44 populations from 41 countries using the Cancer in Five Continents plus database, by calculating the annual average percent change. Findings Approximately 645 000 premenopausal and 1·4 million postmenopausal breast cancer cases were diagnosed worldwide in 2018, with more than 130 000 and 490 000 deaths occurring in each menopausal group, respectively. Proportionally, countries with a low UNDP human development index (HDI) faced a greater burden of premenopausal breast cancer for both new cases and deaths compared with higher income countries. Countries with a very high HDI had the highest premenopausal and postmenopausal breast cancer incidence (30·6 and 253·6 cases per 100 000, respectively), whereas countries with low and medium HDI had the highest premenopausal and postmenopausal mortality, respectively (8·5 and 53·3 deaths per 100 000, respectively). When examining breast cancer trends, we noted significantly increasing age-standardised incidence rates (ASIRs) for premenopausal breast cancer in 20 of 44 populations and significantly increasing ASIRs for postmenopausal breast cancer in 24 of 44 populations. The growth exclusively at premenopausal ages largely occurred in high-income countries, whereas the increasing postmenopausal breast cancer burden was most notable in countries under transition. Interpretation We provide evidence of a rising burden of both premenopausal and postmenopausal breast cancer worldwide. Although early diagnosis and access to treatment remain crucial in low-income and middle-income countries, primary prevention efforts seeking to decrease exposure to known breast cancer risk factors are warranted in all world regions to curb the future breast cancer burden. Funding None.

High mammographic density (MD) is a strong risk factor for breast cancer; however, data on the association between MD and breast cancer subtypes has been inconsistent and most studies have been conducted using data from Western women. Studies have shown that Asian women, who in general have denser breasts compared with Western women, were more likely to develop luminal B and HER2-enriched tumors. We previously reported that higher MD, assessed using Breast Imaging Reporting and Data System (BI-RADS) categories, was associated with HER2-enriched tumors among Chinese breast cancer patients, which may at least partially explain the higher incidence of HER2-enriched tumors observed in Asian women. Since BI-RADS MD measurement is categorical and known to be subjective, in this study, we aimed to re-evaluate the MD-subtype association using an automated quantitative density metric. The analysis included 1,549 women with invasive breast cancer who were diagnosed and treated in a tertiary hospital in Beijing, China. Subtypes were defined as Luminal A (n=606): ER+ and PR+, HER2-, and low Ki-67 ( Citation Format: Xiaohong R Yang, Yuan Tian, Jennifer Guida, Hela Koka, Ariane Chan, Changyuan Guo, Erni Li, Eric Tang, Hyuna Sung, Ning Lu, Nan Hu, Gretchen Gierach, Jing Li. Association between quantitative mammographic density and breast cancer subtypes among Chinese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-20.

This cohort study compares current cancer mortality with that in 1971, 50 years after the National Cancer Act designated defeating cancer a national priority and allocated substantial resources to the National Cancer Institute.

Background A comprehensive examination of the incidence and mortality of subsequent primary cancers (SPCs) among adolescent and young adult (AYA) cancer survivors in the United States is lacking. Methods Cancer incidence and mortality among 170 404 cancer survivors of 5 or more years who were aged 15-39 years at first primary cancer diagnosis during 1975-2013 in 9 Surveillance, Epidemiology, and End Results registries were compared with those in the general population using standardized incidence ratio (SIR), absolute excess incidence (AEI), standardized mortality ratio (SMR), and absolute excess mortality (AEM). Results During a mean follow-up of 14.6 years, 13 420 SPC cases and 5008 SPC deaths occurred among survivors (excluding the same site as index cancer), corresponding to 25% higher incidence (95% confidence interval [CI] = 1.23 to 1.27, AEI = 10.8 per 10 000) and 84% higher mortality (95% CI = 1.79 to 1.89, AEM = 9.2 per 10 000) than that in the general population. Overall, SPC risk was statistically significantly higher for 20 of 29 index cancers for incidence and 26 for mortality, with the highest SIR among female Hodgkin lymphoma survivors (SIR = 3.05, 95% CI = 2.88 to 3.24, AEI = 73.0 per 10 000) and the highest SMR among small intestine cancer survivors (SMR = 6.97, 95% CI = 4.80 to 9.79, AEM = 64.1 per 10 000). Type-specific SPC risks varied substantially by index cancers; however, SPCs of the female breast, lung, and colorectum combined constituted 36% of all SPC cases and 39% of all SPC deaths, with lung cancer alone representing 11% and 24% of all cases and deaths, respectively. Conclusion AYA cancer survivors are almost twice as likely to die from a new primary cancer as the general population, highlighting the need for primary care clinicians to prioritize cancer prevention and targeted surveillance strategies in these individuals.

PURPOSE: Mammographic density (MD) is a strong risk factor for breast cancer, yet its relationship with tumor characteristics is not well established, particularly in Asian populations. METHODS: MD was assessed from a total of 2001 Chinese breast cancer patients using Breast Imaging Reporting and Data System (BI-RADS) categories. Molecular subtypes were defined using immunohistochemical status on ER, PR, HER2, and Ki-67, as well as tumor grade. Multinomial logistic regression was used to test associations between MD and molecular subtype (luminal A = reference) adjusting for age, body mass index (BMI), menopausal status, parity, and nodal status. RESULTS: The mean age at diagnosis was 51.7 years (SD = 10.7) and the average BMI was 24.7 kg/m(2) (SD = 3.8). The distribution of BI-RADS categories was 7.4% A = almost entirely fat, 24.2% B = scattered fibroglandular dense, 49.4% C = heterogeneously dense, and 19.0% D = extremely dense. Compared to women with BI-RADS = A/B, women with BI-RADS = D were more likely to have HER2-enriched tumors (OR = 1.81, 95% CI 1.08–3.06, p = 0.03), regardless of menopausal status. The association was only observed in women with normal (< 25 kg/m(2)) BMI (OR = 2.43, 95% CI 1.24–4.76, p < 0.01), but not among overweight/obese women (OR: 0.98, 95% CI 0.38–2.52, p = 0.96). CONCLUSIONS: Among Chinese women with normal BMI, higher breast density was associated with HER2-enriched tumors. The results may partially explain the higher proportion of HER2+ tumors previously reported in Asian women.

TP53 is a well-known tumor suppressor gene and mutations in TP53 are the most frequent genomic event in most cancers including breast cancer. Recent studies have shown that the frequency, spectrum, timing, and clinical implications of TP53 mutations varied in different molecular subtypes of breast cancer. For example, the frequency of TP53 mutations is the highest in basal-like subtype and lowest in luminal A tumors. However, the evaluation of TP53 protein expression, as a surrogate for TP53 mutations, in large studies in the context of tumor subtypes is limited. In addition, the etiologic relevance of TP53 expression is yet to be investigated. The goal of this study is to evaluate the association of clinical and breast cancer risk factors with TP53 expression, measured using immunohistochemistry (IHC), in breast cancer molecular subtypes. The analysis included 7,226 women with invasive breast cancer who were diagnosed and treated in a tertiary hospital in Beijing, China. Subtypes were defined as Luminal A: ER+ and PR+, HER2–, and low grade (grades 1 or 2); luminal B/HER2–: ER+ and/or PR+, HER2–, and high grade (grade 3); luminal B/HER2+: ER+ and/or PR+, HER2+ (regardless of grade); HER2-enriched: ER–, PR–, and HER2+; Triple-negative (TN): ER–, PR–, and HER2–. As expected, positive TP53 staining showed the lowest frequency in the luminal A (46%) and highest in the TN (61%) and HER2-enriched (63%) subtypes (P-value Citation Format: Yang XR, Abubakar M, Guo C, Koka H, Sung H, Guida J, Deng J, Zhou B, Hu N, Lu N. TP53 expression in relation to clinical and etiologic factors in breast cancer subtypes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-12.

12075 Background: Cancer survivors have an elevated risk of death from cardiovascular disease (CVD). Whether the risk differs by race/ethnicity and cancer type has not been fully explored in the U.S. Methods: Data from survivors of top 23 cancers diagnosed at ages 20 to 64 years during 2000-2018 were obtained from 17 Surveillance, Epidemiology, and End Results registries. Risks for CVD death among survivors relative to the general population were calculated using standardized mortality ratios (SMRs) in each racial/ethnic group: Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, Non-Hispanic Asian or Pacific Islander (API), and Non-Hispanic American Indian (AI). Among survivors, the risks were compared by race/ethnicity using cause-specific proportional hazards models for competing risks, controlling for year of diagnosis, age at diagnosis, sex, stage (when appropriate), and the first course of treatment receipt (surgery, radiotherapy, chemotherapy). Results: Among 2,806,515 survivors (NHW, 68%; NHB, 13%; Hispanic, 12%; API, 7%; AI, 0.5%), 57,883 CVD deaths occurred during 6.4 person-years of mean follow-up (32 per 10,000). Cancer survivors overall were at increased risk of CVD death compared to their general population counterpart with an SMR of 1.76 among API (95% CI = 1.69-1.84; 8.7 excess deaths per 10,000), 1.49 among AI (95% CI = 1.33-1.68; 11.9 excess deaths per 10,000), 1.46 among Hispanic (95% CI = 1.41-1.50; 7.4 excess deaths per 10,000), 1.30 among NHB (95% CI = 1281-1.33; 14.9 excess deaths per 10,000), and 1.13 among NHW (95% CI = 1.12-1.14; 3.4 excess deaths per 10,000) survivors. Compared with NHW survivors, the adjusted hazard of CVD death was statistically significantly higher among NHB survivors for 23/23 cancers and among AI survivors for 9/18 cancers but was statistically significantly lower among Hispanic survivors for 5/23 cancers and among API survivors for 10/23 cancers, with no significant difference otherwise. The highest hazards ratios (HRs) were among NHB survivors of melanoma (HR = 3.19, 95% CI = 2.11-4.83); breast (HR = 2.73, 95% CI = 2.57-2.89); pancreatic (HR = 2.63, 95% CI = 2.19-3.16); and testicular (HR = 2.59, 95% CI = 1.62-4.14) cancers, whereas the lowest HRs were among API survivors of head and neck (HR = 0.53, 95% CI = 0.44-0.63) and cervical (HR = 0.57, 95% CI = 0.41-0.80) cancers and Hispanic survivors of cervical cancer (HR = 0.59, 95% CI = 0.46-0.75). Conclusions: The risk of CVD death differs considerably among cancer survivors by race/ethnicity and cancer types, highlighting the need for targeted prevention and surveillance in primary care. Future studies are needed to identify factors that contribute to this variation in order to inform efforts towards mitigating risk.

Background This study was aimed at examining the risks of subsequent primary cancers (SPCs) among breast cancer survivors by hormone receptor (HR) status and age at diagnosis. Methods Data from 12 Surveillance, Epidemiology, and End Results registries were used to identify 431,222 breast cancer survivors (at least 1 year) diagnosed between the ages of 20 and 84 years from 1992 to 2015. Risks of SPCs were measured as the standardized incidence ratio (SIR) and the excess absolute risk (EAR) per 10,000 person-years. Poisson regression was used to test the difference in SIRs by HR status. Results In comparison with the general population, the risk of new cancer diagnoses among survivors was 20% higher for those with HR-positive cancers (SIR, 1.20; 95% confidence interval [CI], 1.19-1.21; EAR, 23.3/10,000 person-years) and 44% higher for those with HR-negative cancers (SIR, 1.44; 95% CI, 1.41-1.47; EAR, 45.2/10,000 person-years), with the risk difference between HR statuses statistically significant. The higher risk after HR-negative cancer was driven by acute nonlymphocytic leukemia and breast, ovarian, peritoneal, and lung cancers. By age at diagnosis, the total EAR per 10,000 person-years ranged from 15.8 (95% CI, 14.1-17.5; SIR, 1.11) among late-onset (age, 50-84 years) HR-positive survivors to 69.4 (95% CI, 65.1-73.7; SIR, 2.24) among early-onset (age, 20-49 years) HR-negative survivors, with subsequent breast cancer representing 73% to 80% of the total EAR. After breast cancer, the greatest EARs were for ovarian cancer among early-onset HR-negative survivors, lung cancer among early- and late-onset HR-negative survivors, and uterine corpus cancer among late-onset HR-positive survivors. Conclusions Risks of SPCs after breast cancer differ substantially by subtype and age. This suggests that more targeted approaches for cancer prevention and early-detection strategies are needed in survivorship care planning.

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied

BackgroundStudies investigating associations between mammographic density (MD) and breast cancer subtypes have generated mixed results. We previously showed that having extremely dense breasts was associated with the human epidermal growth factor receptor-2 (HER2)-enriched subtype in Chinese breast cancer patients.MethodsIn this study, we reevaluated the MD-subtype association in 1549 Chinese breast cancer patients, using VolparaDensity software to obtain quantitative MD measures. All statistical tests were 2-sided.ResultsCompared with women with luminal A tumors, women with luminal B/HER2- (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.04 to 1.38; P = .01), luminal B/HER2+ (OR = 1.22, 95% CI = 1.03 to 1.46; P = .03), and HER2-enriched tumors (OR = 1.30, 95% CI = 1.06 to 1.59; P = .01) had higher fibroglandular dense volume. These associations were stronger in patients with smaller tumors (ConclusionAlthough biological mechanisms remain to be investigated, the associations for the HER2-enriched and luminal B subtypes with increasing MD may partially explain the higher prevalence of luminal B and HER2+ breast cancers previously reported in Asian women.

Background Recent studies have identified increases in cancer incidence among younger adults for some cancers. This study examined incidence trends for 28 cancers in Canada by age and birth cohort from 1983 to 2012. Methods Canadian incidence data for 20 to 84 year-olds were obtained from the Cancer Incidence in Five Continents Plus database. Age-period-cohort modeling was used to estimate the average annual percentage changes (AAPCs) and incidence rate ratios (IRRs) for 10-year birth cohorts (reference cohort, 1943) for 28 cancer types. Results Incidence increased for 13 cancer sites among adults younger than 50 years (1983-2012), with the largest increase occurring for rectal cancer (AAPC20-24 , 5.62; 95% confidence interval [CI], 3.77-7.51) and colon cancer (AAPC20-24 , 4.08; 95% CI, 2.89-5.29). Compared with the 1943 birth cohort, persons born circa 1988 had approximately 5- and 2-fold greater risks of rectal cancer (IRR, 4.98; 95% CI, 2.87-8.63) and colon cancer (IRR, 2.31; 95% CI, 1.62-3.30), respectively. Incidence decreased among younger adults for 9 sites (1983-2012), with the largest decreases observed for lung cancer (AAPC25-29 ,-2.29; 95% CI, -3.57 to -0.98), cervical cancer (AAPC25-29 , -1.29; 95% CI, -1.67 to -0.90), and melanoma (AAPC25-29 , -0.61; 95% CI, -0.97 to -0.24). Decreased risks in recent birth cohorts were observed for all sites with decreasing trends in younger adults. For example, the risk of lung cancer was 60% lower in the 1988 birth cohort than the 1943 birth cohort (IRR, 0.42; 95% CI, 0.23-0.78). Conclusions Incidence among young adults is increasing for some cancers associated with obesity but decreasing for many cancers associated with infections or smoking. Although further studies are needed to replicate these findings and understand the etiology of early-onset cancers, measures to promote healthy behaviors in young adults warranted.

Compared with white women, black women have higher incidence rates for triple-negative breast cancer but lower rates for hormone receptor (HR)–positive cancers in the United States. Whether similar racial difference occurs in male breast cancer is unclear. We examined racial differences in incidence rates of breast cancer subtypes defined by HR and human epidermal growth factor receptor 2 (HER2) by sex using nationwide data from 2010 to 2016. Among men, rates were higher in blacks than whites for all subtypes, with the black-to-white incidence rate ratios of 1.41 (95% confidence interval [CI ]= 1.32 to 1.50) for HR+/HER-, 1.65 (95% CI = 1.40 to 1.93) for HR+/HER2+, 2.62 (95% CI = 1.48 to 4.43) for HR-/HER2+, and 2.27 (95% CI = 1.67 to 3.03) for triple-negative subtype. Conversely, among women, rates in blacks were 21% lower for HR+/HER2- and comparable for HR+/HER2+ but 29% and 93% higher for HR-/HER2+ and triple-negative subtypes, respectively. Future studies are needed to identify contributing factors to the dissimilar racial patterns in breast cancer subtype incidence between men and women.

10604 Background: Adolescent and young adult (AYA) cancer survivors are at increased risk of subsequent primary cancer (SPC); however, a comprehensive examination of risk patterns across cancer types is lacking in the U.S. Methods: SPC incidence and mortality was calculated among >1-year cancer survivors aged 15 to 39 years at first primary cancer (FPC) diagnosis during 1992-2016 in 12 Surveillance, Epidemiology, and End Results registries. Rates were expressed as number of cases/deaths per 10,000 person-years and compared with those expected in the general population using standardized incidence (SIR) and standardized mortality ratios (SMR). Results: Among 202,440 survivors of AYA-onset cancers (mean age at FPC diagnosis, 31.8 years; 60.7% women), 6,675 SPC cases (34.3 per 10,000) and 3,786 SPC deaths (19.4 per 10,000) occurred during 1,955,119 person-years of follow-up (mean, 9.7 years), corresponding to an SIR of 1.58 (95%CI = 1.54-1.62) and SMR of 4.19 (95%CI = 4.06-4.33. In men, overall incidence and mortality SPC rates were statistically significantly higher for each of 21 FPC types compared with risks in the general population, except for thyroid cancer mortality. In women, risk was statistically significantly higher for 14/23 FPC types for incidence and 19/23 FPC types for mortality. SIRs were highest in survivors of pancreatic cancer (SIR = 5.68, 95% CI = 2.94-9.93; 84 per 10,000), Kaposi sarcoma (SIR = 5.15, 95%CI = 4.62-5.73; 116 per 10,000) and liver cancer (SIR = 4.97, 95%CI = 2.57-8.68; 68.4 per 10,000) in men, and acute lymphoid leukemia (SIR, 3.27, 95% CI = 2.22-4.64; 49.5 per 10,000), Hodgkin lymphoma (SIR = 2.47, 95% CI = 2.22-2.73; 51.6 per 10,000), and bone sarcoma (SIR = 2.41, 95%CI = 1.80-3.16; 47.6 per 10,000) in women. SMRs were highest in survivors of pancreatic cancer, acute lymphoid leukemia, and stomach cancer in men, and liver cancer, acute lymphoid leukemia, and soft tissue sarcoma in women. Conclusions: Overall and type-specific risk patterns of SPCs among AYA cancer survivors differ considerably across FPC type, highlighting the need for targeted approaches for cancer prevention and surveillance in survivorship care planning.

Eleven high-evidence single-nucleotide polymorphisms (SNPs) at nine loci for gastric cancer (GC) risk were reported, but their associations with survival remain unknown. In this study, we examined associations between SNP and GC survival by anatomic location and histology among 1147 incident cases from the Shanxi Upper Gastrointestinal Genetics Project. We further examined whether SNPs were expression quantitative trait loci in normal and tumor gastric tissues, and whether tumor versus normal somatic mRNA differences in 126 cases were associated with survival. No SNPs were associated with GC survival overall. However, subtype-specific associations were observed for gastric cardia adenocarcinomas at MUC1/TRIM46/1q22 rs2070803 [HRAA versus GA+GG = 2.16; 95% confidence interval (CI) = 1.24-3.78; P = 0.0068] and LTA/TNF/6p21.33 rs1799724 (HRTT+CT versus CC = 1.30; 95% CI = 1.07-1.57; P = 0.0077), and for diffuse-type GC at PSCA/8q24.3 rs2294008 (HRTT versus CT+CC = 1.99; 95% CI = 1.33-2.97; P = 7.8E-04). Rs2294008T was a cis-expression quantitative trait loci for PSCA, upregulating mRNA in normal gastric (β = 0.60; P = 5.7E-21) and GC (β = 0.30; P = 0.0089) tissues. Cases in the highest quartile (the smallest downregulation of tumor PSCA) had shortest survival than cases with the most downregulated PSCA (median survival of 0.47 years in the highest quartile versus 3.73 years in the lowest quartile; hazard ratio = 9.70; 95% CI = 2.46-38.4; P = 0.0012). Less striking effects for mRNA levels were observed for MTX1 at 1q22 in gastric cardia adenocarcinoma and for JRK at 8q24.3 in diffuse GC. Our results suggest three high-evidence GC risk loci have prognostic importance in GC subtypes. Future studies in well-characterized independent populations are warranted to validate our findings and further investigate the clinical utility of these variants in predicting GC prognosis.

Recent studies from high-risk countries such as the US, Denmark and Ireland have shown rising incidence rates of hormone receptor (HR)-positive and falling rates of HR-negative breast cancers (BC). However, it remains unclear whether a similar pattern occurs in low-risk countries. Detailed clinical and risk factor data were collected from 2,977 female invasive BC patients (≥20 years) in Sarawak General Hospital, Malaysia, representing 93% of the population. The population-at-risk was obtained from the Department of Statistics Malaysia. Secular trends in age-standardized incidence rates were assessed using estimated average annual percent changes. Associations between established BC risk factors and tumor subtypes defined by HR or joint human epidermal growth factor receptor 2 (HR/HER2) status were examined by case-case comparisons using logistic regression. From 2006 to 2015, incidence rates increased for HR-positive cancers by 4.46%/year (95% CI = 2.19-6.78) and decreased for HR-negative cancers by 2.29%/year (95% CI = -4.31 to -0.24). When further stratified by HER2, the most contrasting difference in linear trends was observed between HR+/HER2- and HR-/HER2- subtypes. After controlling for potential confounders, cases with excess body weight (ORoverweight vs. normal = 0.82; 95% CI = 0.69-0.98; ORobese vs. normal = 0.62; 95% CI = 0.48-0.80), later age at first birth (OR≥26 years vs.

TP53 mutations are common in breast cancer and are typically associated with more aggressive tumor characteristics, but little is known about the clinicopathological and epidemiological relevance of p53 protein expression, a TP53 mutation surrogate, in breast cancer subtypes. In this study of 7226 Chinese women with invasive breast cancer, we defined breast cancer subtypes using immunohistochemical (IHC) measures of hormone receptors and HER2 in conjunction with histologic grade. p53 expression status was then used to further stratify subtypes into p53-positive and p53-negative. Odds ratios (ORs) and 95% confidence intervals (CIs) in case-only logistic regression analyses were used to examine heterogeneity across different subtypes. The frequency of p53 protein expression varied by breast cancer subtype, being lowest in the luminal A-like and highest in the triple-negative and HER2-enriched subtypes (P-value parous vs. nulliparous = 2.67 (1.60, 4.51); P-value ever vs. never = 1.38 (1.03, 1.85); P-value = 0.03]. p53 positivity was not associated with examined clinical and risk factors in other tumor subtypes. Overall, these findings suggest that p53 expression, which is readily available in many settings, can be used to identify phenotypes of luminal A-like breast cancer with distinct clinical and epidemiological implications.

Background: Recent studies have identified significant increases in cancer incidence among younger adults for some cancers. We examined incidence trends of 27 cancer sites in Canada by age and birth cohort between 1983 and 2012. Methods: Canadian incidence data for 20-84 year-olds was obtained from the Cancer in Five Continents plus database. The average annual percentage change (AAPC) was calculated, and age-period-cohort modeling was used to estimate incidence rate ratios for 10-year birth cohorts. Results: Incidence significantly increased in 12 cancer sites among adults

Background: Breast cancer has distinct etiologies, prognoses, and patient impact at pre- and post-menopausal ages. We sought to assess the global burden and trends in breast cancer by menopausal status. Methods: Menopausal status was defined using age as a proxy, where breast cancer cases/deaths at >50 years were considered as post-menopausal. Age-standardized breast cancer incidence and mortality rates in 2018 were calculated using GLOBOCAN data. Incidence trends for 1998-2012 were assessed in 44 populations from 41 countries using CI5plus data by calculating the annual average percent change. Findings: Approximately 645,000 pre-menopausal and 1.4 million post-menopausal breast cancer cases were diagnosed in 2018, with approximately 130,000 and 490,000 deaths occurring in each menopausal group, respectively. Proportionally, Low Human Development Index (HDI) countries faced a greater burden of pre-menopausal breast cancer for both incidence and mortality compared to more developed countries. Very High HDI countries had the highest pre- and post-menopausal breast cancer incidence rates (30·6 and 253·6 per 100,000 respectively), while Low and Medium HDI countries had the highest pre-menopausal and post-menopausal mortality rates respectively (8·5 and 53·3 per 100,000 respectively). When examining incidence trends, we observed significantly increasing rates of pre-menopausal breast cancer in 20/44 populations, and significantly increasing rates of post-menopausal breast cancer in 24/44 populations. The increases exclusively at pre-menopausal ages largely occurred in the most developed countries, while the increasing post-menopausal breast cancer burden was most notable in countries under transition. Interpretation: We provide evidence of a rising burden of both pre- and post-menopausal breast cancer worldwide, and wide inequities in breast cancer care. Although early diagnosis and access to treatment remain crucial in developing countries, primary prevention efforts seeking to decrease obesity and alcohol consumption, and increase physical activity and breastfeeding, are warranted in all world regions to curb the future breast cancer burden. Funding Statement: This study was undertaken without any funding. Declaration of Interests: All authors declare no conflicts of interests. Ethics Approval Statement: Not required.

Extensive mammographic density (MD), a well-established breast cancer risk factor, is a radiological representation of stromal and epithelial breast tissue content. In studies conducted predominantly among Caucasian women, histologic measures of reduced terminal duct lobular unit (TDLU) involution have been correlated with extensive MD, but independently associated with breast cancer risk. We therefore examined associations between TDLU measures and MD among Chinese women, a low-risk population but with high prevalence of dense breasts. Diagnostic pre-treatment digital mammograms were obtained from 144 breast cancer cases at a tertiary hospital in Beijing and scored using the Breast Imaging Reporting and Data System (BI-RADS) density classification. TDLU features were assessed using three standardized measures (count/100 mm2 , span [μm], and acini count/TDLU) in benign tissues. Associations between each of TDLU measures and MD were examined using generalized linear models for TDLU count and span and polytomous logistic regression for acini count with adjustment for potential confounders stratified by age. Among women ≥50 years, 63% had dense breasts; cases with dense breasts (BI-RADS, c-d) had greater TDLU count (21.1 [SE = 2.70] vs. 9.0 [SE = 1.83]; p = 0.0004), longer span (480.6 μm [SE = 24.6] vs. 393.8 μm [SE = 31.8]; p = 0.03), and greater acini count (ORtrend = 16.1; 95%CI = 4.08-63.1; ptrend < 0.0001) compared to those with non-dense breasts (BI-RADS, a-b). Among women