Second primary cancer risks according to race and ethnicity among U.S. breast cancer survivors.

Breast cancer survivors have an increased risk of developing second primary cancers, yet risks by race and ethnicity have not been comprehensively described. We evaluated second primary cancer risks among 717,335 women diagnosed with first primary breast cancer (aged 20-84 years and survived ≥1-year) in the SEER registries using standardized incidence ratios (SIRs; observed/expected). SIRs were estimated by race and ethnicity compared with the racial- and ethnic-matched general population, and further stratified by clinical characteristics of the index breast cancer. Poisson regression was used to test for heterogeneity by race and ethnicity. SIRs for second primary cancer differed by race and ethnicity with the highest risks observed among non-Hispanic/Latina Asian American, Native Hawaiian, or other Pacific Islander (AANHPI), non-Hispanic/Latina Black (Black), and Hispanic/Latina (Latina) survivors and attenuated risk among non-Hispanic/Latina White (White) survivors (SIRAANHPI = 1.49, 95% CI = 1.44-1.54; SIRBlack = 1.41, 95% CI = 1.37-1.45; SIRLatina = 1.45, 95% CI = 1.41-1.49; SIRWhite = 1.09, 95% CI = 1.08-1.10; p-heterogeneity<.001). SIRs were particularly elevated among AANHPI, Black, and Latina survivors diagnosed with an index breast cancer before age 50 (SIRs range = 1.88-2.19) or with estrogen receptor-negative tumors (SIRs range = 1.60-1.94). Heterogeneity by race and ethnicity was observed for 16/27 site-specific second cancers (all p-heterogeneity's < .05) with markedly elevated risks among AANHPI, Black, and Latina survivors for acute myeloid and acute non-lymphocytic leukemia (SIRs range = 2.68-3.15) and cancers of the contralateral breast (SIRs range = 2.60-3.01) and salivary gland (SIRs range = 2.03-3.96). We observed striking racial and ethnic differences in second cancer risk among breast cancer survivors. Additional research is needed to inform targeted approaches for early detection strategies and treatment to reduce these racial and ethnic disparities.

Endocrine therapy initiation among women diagnosed with ductal carcinoma in situ from 2001 to 2018.

PURPOSE: Trials demonstrating benefits of tamoxifen for women with ductal carcinoma in situ (DCIS) were published > 20 years ago; yet subsequent uptake of endocrine therapy was low. We estimated endocrine therapy initiation in women with DCIS between 2001 and 2018 in a community setting, reflecting more recent years of diagnosis than previous studies. METHODS: This retrospective cohort included adult females ≥ 20 years diagnosed with first primary DCIS between 2001 and 2018, followed through 2019, and enrolled in one of three U.S. integrated healthcare systems. We collected data on endocrine therapy dispensings (tamoxifen, aromatase inhibitors [AIs]) from electronic pharmacy records within 12 months after DCIS diagnosis. Using generalized linear models with a log link and Poisson distribution, we estimated endocrine therapy initiation rates over time and by patient, tumor (including estrogen receptor [ER] status), and treatment characteristics. RESULTS: Among 2020 women with DCIS, 587 (29%) initiated endocrine therapy within 12 months after diagnosis (36% among 1208 women with ER-positive DCIS). Among women who used endocrine therapy, 506 (86%) initiated tamoxifen and 81 (14%) initiated AIs. Age-adjusted endocrine therapy initiation declined from 34 to 21% between 2001 and 2017; between 2015 and 2018, AI use increased from 8 to 35%. Women less likely to initiate endocrine therapy were ER-negative or had borderline/unknown or no ER test results, ≥ 65 years at diagnosis, Black, and received no radiotherapy. CONCLUSION: One-third of women diagnosed with DCIS initiated endocrine therapy, and use decreased over time. Understanding why women eligible for endocrine therapy do not initiate is important to maximizing disease-free survival following DCIS diagnosis.

Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort.

BACKGROUND: Breast cancer survivors are living longer due to early detection and advances in treatment and are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decades is lacking. METHODS: We identified 16,004 females diagnosed with a first primary stage I-III breast cancer between 1990 and 2016 (followed through 2017) and survived ≥ 1 year at Kaiser Permanente (KP) Colorado, Northwest, and Washington. Second cancer was defined as an invasive primary cancer diagnosed ≥ 12 months after the first primary breast cancer. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast cancer) using standardized incidence ratios (SIRs), and a competing risk approach for cumulative incidence and hazard ratios (HRs) adjusted for KP center, treatment, age, and year of first cancer diagnosis. RESULTS: Over a median follow-up of 6.2 years, 1,562 women developed second cancer. Breast cancer survivors had a 70% higher risk of any cancer (95%CI = 1.62-1.79) and 45% higher risk of non-breast cancer (95%CI = 1.37-1.54) compared with the general population. SIRs were highest for malignancies of the peritoneum (SIR = 3.44, 95%CI = 1.65-6.33), soft tissue (SIR = 3.32, 95%CI = 2.51-4.30), contralateral breast (SIR = 3.10, 95%CI = 2.82-3.40), and acute myeloid leukemia (SIR = 2.11, 95%CI = 1.18-3.48)/myelodysplastic syndrome (SIR = 3.25, 95%CI = 1.89-5.20). Women also had elevated risks for oral, colon, pancreas, lung, and uterine corpus cancer, melanoma, and non-Hodgkin lymphoma (SIR range = 1.31-1.97). Radiotherapy was associated with increased risk for all second cancers (HR = 1.13, 95%CI = 1.01-1.25) and soft tissue sarcoma (HR = 2.36, 95%CI = 1.17-4.78), chemotherapy with decreased risk for all second cancers (HR = 0.87, 95%CI = 0.78-0.98) and increased myelodysplastic syndrome risk (HR = 3.01, 95%CI = 1.01-8.94), and endocrine therapy with lower contralateral breast cancer risk (HR = 0.48, 95%CI = 0.38-0.60). Approximately 1 in 9 women who survived ≥ 1 year developed second cancer, 1 in 13 developed second non-breast cancer, and 1 in 30 developed contralateral breast cancer by 10 years. Trends in cumulative incidence declined for contralateral breast cancer but not for second non-breast cancers. CONCLUSIONS: Elevated risks of second cancer among breast cancer survivors treated in recent decades suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed.

Treatment-related thoracic soft tissue sarcomas in US breast cancer survivors: a retrospective cohort study.

BACKGROUND: Soft tissue sarcoma is a rare but serious side-effect of radiotherapy to treat breast cancer, and rates are increasing in the USA. We evaluated potential co-factors in two complimentary cohorts of US breast cancer survivors. METHODS: In this retrospective cohort study, we sourced data from the Kaiser Permanente (KP) cohort and the Surveillance, Epidemiology, and End Results (SEER) 13 registries cohort, both in the USA. The KP cohort included 15 940 women diagnosed with breast cancer from Jan 1, 1990, to Dec 31, 2016, in KP Colorado, KP Northwest (which serves Oregon and Southwest Washington state), or KP Washington, with detailed treatment data and comorbidities (including hypertension and diabetes at or before breast cancer diagnosis) from electronic medical records. The SEER cohort included 457 300 women diagnosed with breast cancer from Jan 1, 1992, to Dec 31, 2016, within the 13 SEER registries across the USA, with initial treatment data (yes vs no or unknown). Eligibility criteria in both cohorts were female breast cancer survivors (stage I-III) aged 20-84 years at diagnosis who had breast cancer surgery, and had survived at least 1 year after breast cancer diagnosis. The outcome of interest was any second thoracic soft tissue sarcoma (angiosarcomas and other subtypes) that developed at least 1 year after breast cancer diagnosis. Risk factors for thoracic soft tissue sarcoma were assessed using multivariable Poisson regression models. FINDINGS: In the KP cohort, median follow-up was 9·3 years (IQR 5·7-13·9) and 19 (0·1%) of 15 940 eligible, evaluable women developed a thoracic soft tissue sarcoma (11 angiosarcomas, eight other subtypes). Most (94·7%; 18 of 19) thoracic soft tissue sarcomas occurred in women treated with radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (relative risk [RR] 8·1 [95% CI 1·1-60·4]; p=0·0052), but there was no association with prescribed dose, fractionation, or boost. The RR of angiosarcoma after anthracyclines was 3·6 (95% CI 1·0-13·3; p=0·058). Alkylating agents were associated with an increased risk of developing other sarcomas (RR 7·7 [95% CI 1·2-150·8]; p=0·026). History of hypertension (RR 4·8 [95% CI 1·3-17·6]; p=0·017) and diabetes (5·3 [1·4-20·8]; p=0·036) were each associated with around a five-times increased risk of angiosarcoma. In the SEER cohort, 430 (0·1%) of 457 300 patients had subsequent thoracic soft tissue sarcomas (268 angiosarcomas and 162 other subtypes) after a median follow-up of 8·3 years (IQR 4·3-13·9). Most (77·9%; 335 of 430) cases occurred after radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (RR 3·0 [95% CI 2·4-3·8]; p<0·0001) and, for angiosarcomas, the RR for breast-conserving surgery plus radiotherapy versus mastectomy plus radiotherapy was 1·9 (1·1-3·3; p=0·012). By 10 years after radiotherapy, the cumulative incidence of thoracic soft tissue sarcoma was 0·21% (95% CI 0·12-0·34) in the KP cohort and 0·15% (95% CI 0·13-0·17) in SEER. INTERPRETATION: Radiotherapy was the strongest risk factor for thoracic soft tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance. FUNDING: US National Cancer Institute and National Institutes of Health.

Trends in heart disease mortality among breast cancer survivors in the US, 1975-2017.

PURPOSE: Heart disease is a significant concern among breast cancer survivors, in part due to cardiotoxic treatments including chemotherapy and radiotherapy. Long-term trends in heart disease mortality have not been well characterized. We examined heart disease mortality trends among US breast cancer survivors by treatment type. METHODS: We included first primary invasive breast cancer survivors diagnosed between 1975 and 2016 (aged 18-84; survived 12 + months; received initial chemotherapy, radiotherapy, or surgery) in the SEER-9 Database. Standardized mortality ratios (SMRs) and 10-year cumulative heart disease mortality estimates accounting for competing events were calculated by calendar year of diagnosis and initial treatment regimen. Ptrends were assessed using Poisson regression. All statistical tests were 2-sided. RESULTS: Of 516,916 breast cancer survivors, 40,812 died of heart disease through 2017. Heart disease SMRs declined overall from 1975-1979 to 2010-2016 (SMR 1.01 [95%CI: 0.98, 1.03] to 0.74 [0.69, 0.79], ptrend < 0.001). This decline was also observed for survivors treated with radiotherapy alone and chemotherapy plus radiotherapy. A sharper decline in heart disease SMRs was observed from 1975 to 1989 for left-sided radiotherapy, compared to right-sided. In contrast, there was a non-significant increasing trend in SMRs for chemotherapy alone, and significant by regional stage (ptrend = 0.036). Largest declines in 10-year cumulative mortality were observed from 1975-1984 to 2005-2016 among surgery only: 7.02% (95%CI: 6.80%, 7.23%) to 4.68% (95%CI: 4.39%, 4.99%) and radiotherapy alone: 6.35% (95%CI: 5.95%, 6.77%) to 2.94% (95%CI: 2.73%, 3.16%). CONCLUSIONS: We observed declining heart disease mortality trends by most treatment types yet increasing for regional stage patients treated with chemotherapy alone, highlighting a need for additional studies with detailed treatment data and cardiovascular management throughout cancer survivorship.

Endocrine therapy initiation among women with stage I-III invasive, hormone receptor-positive breast cancer from 2001-2016.

PURPOSE: This retrospective cohort study examined patterns of endocrine therapy initiation over time and by demographic, tumor, and treatment characteristics. METHODS: We included 7777 women from three U.S. integrated healthcare systems diagnosed with incident stage I-III hormone receptor-positive breast cancer between 2001 and 2016. We extracted endocrine therapy from pharmacy dispensings, defining initiation as dispensings within 12 months of diagnosis. Demographic, tumor, and treatment characteristics were collected from electronic health records. Using generalized linear models with a log link and Poisson distribution, we estimated initiation of any endocrine therapy, tamoxifen, and aromatase inhibitors (AI) over time with relative risks (RR) and 95% confidence intervals (CI) adjusted for age, tumor characteristics, diagnosis year, other treatment, and study site. RESULTS: Among women aged 20+ (mean 62 years), 6329 (81.4%) initiated any endocrine therapy, and 1448 (18.6%) did not initiate endocrine therapy. Tamoxifen initiation declined from 67 to 15% between 2001 and 2016. AI initiation increased from 6 to 69% between 2001 and 2016 in women aged ≥ 55 years. The proportion of women who did not initiate endocrine therapy decreased from 19 to 12% between 2002 and 2014 then increased to 17% by 2016. After adjustment, women least likely to initiate endocrine therapy were older (RR = 0.81, 95% CI 0.77-0.85 for age 75+ vs. 55-64), Black (RR = 0.93, 95% CI 0.87-1.00 vs. white), and had stage I disease (RR = 0.88, 95% CI 0.85-0.91 vs. stage III). CONCLUSIONS: Despite an increase in AI use over time, at least one in six eligible women did not initiate endocrine therapy, highlighting opportunities for improving endocrine therapy uptake in breast cancer survivors.

The influence of treatment on hormone receptor subgroups and breast cancer-specific mortality within US integrated healthcare systems.

PURPOSE: Estrogen receptor (ER) + /progesterone receptor (PR) - or ER-/PR + breast cancer prognosis has not been well-described outside of clinical trials. We evaluated the relationship between ER/PR (ER + /PR-, ER-/PR + , ER + /PR + , ER-/PR-) subgroups and breast cancer-specific mortality within a general community setting in the US. METHODS: A Retrospective cohort of 11,737 women diagnosed with breast cancer between 1990 and 2016 within US integrated healthcare systems (median follow-up = 7 years; 1,104 breast cancer-specific deaths) were included in this analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for site, demographic and clinicopathological characteristics, and treatment (surgery/radiotherapy, chemotherapy, endocrine therapy). RESULTS: Breast cancer-specific mortality was higher for those with ER + /PR- (n = 1,233) compared with ER + /PR + tumors (n = 8,439) before (HR = 1.43; 95% CI = 1.17-1.75) and after treatment adjustment (HR = 1.58; 95% CI = 1.27-1.97). ER + /PR- breast cancer-specific mortality remained higher than ER + /PR + tumors when stratified by treatment received. Breast cancer-specific mortality was similar in ER-/PR + (n = 161) compared with ER + /PR + tumors. CONCLUSION: Our findings suggest that ER + /PR- tumors may have worse breast cancer-specific mortality than ER + /PR + tumors in a community setting.

Excess heart age in young breast cancer survivors over 2-year follow-up.

BACKGROUND: Breast cancer survivors are at risk for developing cardiovascular disease due to cardiotoxic cancer treatment. Research on young breast cancer survivors (diagnosed < 45 years old) are limited. METHODS: Young breast cancer survivors diagnosed between age 30 and 44, stage I-III, and treated at the University of Alabama at Birmingham Hospital between 2012 and 2015 were included. Cardiovascular disease risk was estimated using excess heart age (calculated using age, systolic blood pressure, blood pressure medication, diabetes, smoking, body mass index) and examined at two time points: diagnosis and 2-year follow-up. Statistical analyses included within-group mean comparison tests and linear regression to examine predictors of excess heart age. RESULTS: A total of 152 young breast cancer survivors were included; 95 received anthracyclines and/or trastuzumab, and 57 did not. Overall excess heart age was 4.2 at diagnosis and 5.4 years at 2-year follow-up (p = 0.08). Change in excess heart age from diagnosis to 2-year follow-up among those receiving or not receiving anthracyclines and/or trastuzumab was 4.3-4.4 years, p = 0.93; and 4.0-7.1 years, p < 0.01; respectively. Factors that predicted excess heart age included endocrine therapy (p = 0.049) and change from premenopausal to postmenopausal status (p = 0.048). CONCLUSIONS: Anthracyclines and trastuzumab were not predictors of excess heart age. Subclinical changes undetected by heart age may still occur. Future research is needed to evaluate heart age over longer follow-up and to develop a modified heart age tool, that incorporates treatment risk, that facilitates identification of high-risk cancer patients for early intervention in cardiac risk prevention.

Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis.

PURPOSE: Cardiotoxicity affects 5-16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. METHODS: A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran's Q test and the I2 test. RESULTS: Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27-0.78), p = 0.004, [Formula: see text] = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17-1.45), p = 0.20, [Formula: see text] = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75-9.52), p < 0.001, [Formula: see text] = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82-11.68, p = 0.024, [Formula: see text] = 80.9%]. We were unable to explore publication bias due to the small number of studies. CONCLUSION: This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: PROSPERO: CRD42020140352 on 7/6/2020.

Lessons Learned from the Young Breast Cancer Survivorship Network.

The Young Breast Cancer Survivors Network (Network) is an academic and community-based partnership dedicated to education, support, and networking. The Network used a multi-pronged approach via monthly support and networking, annual education seminars, website networking, and individual survivor consultation. Formative and summative evaluations were conducted using group survey and individual survivor interviews for monthly gatherings, annual education meetings, and individual consultation. Google Analytics was applied to evaluate website use. The Network began with 4 initial partnerships and grew to 38 in the period from 2011 to 2017. During this 5-year period, 5 annual meetings (598 attendees), 23 support and networking meetings (373), and 115 individual survivor consultations were conducted. The Network website had nearly 12,000 individual users and more than 25,000 page views. Lessons learned include active community engagement, survivor empowerment, capacity building, social media outreach, and network sustainability. The 5-year experiences with the Network demonstrated that a regional program dedicated to the education, support, networking, and needs of young breast cancer survivors and their families can become a vital part of cancer survivorship services in a community. Strong community support, engagement, and encouragement were vital components to sustain the program.

Speed of processing training in middle-aged and older breast cancer survivors (SOAR): results of a randomized controlled pilot.

PURPOSE: Cognitive changes are common among breast cancer survivors. There is limited evidence to guide management of cognitive changes. This randomized controlled pilot evaluated the preliminary efficacy of a speed of processing (SOP) training among middle-aged and older breast cancer survivors. METHODS: Sixty breast cancer survivors  with self-reported cognitive changes were recruited to the SOAR study. Participants were randomized to either a home-based SOP training (n = 30) or no-contact control group (n = 30). Primary outcomes were SOP (Useful Field of View Test®), and executive function (NIH Toolbox Cognition Battery). Neuropsychological assessments were completed at baseline, 6 weeks, and 6 months post study entry. Data were analyzed using repeated measures t tests, analysis of covariance, and sensitivity analyses. RESULTS: SOP training resulted in improvement in objective measures of SOP and executive function. Immediate (6 week) posttest and 6-month follow-up demonstrated large SOP training effects over time. Large representation of African American women (51.2%) and 96% retention in the SOAR study add to study strengths. CONCLUSION: Home-based SOP training shows promise for remediating cognitive changes following breast cancer treatment, particularly improved SOP, and executive function.

Engaging an Urban African American Community to Deliver Cognitive Health Education to Breast Cancer Survivors.

Little is known about cognitive changes among African American (AA) breast cancer survivors (BCS). Here, we report our experience with engagement of leaders of urban AA churches in Birmingham, Alabama to deliver and evaluate Think Well: Healthy Living to Improve Cognitive Function, an educational cognitive health program for BCS. The Think Well team engaged leaders of urban AA churches using a 7-step process: 1) identify leaders, 2) develop connection with leaders, 3) assess AA community preferences, 4) tailor for cultural relevance, 5) plan seminars, 6) deliver seminars, and 7) evaluate cultural relevance and overall program quality. Program evaluation was via a 22-item survey and sociodemographic questionnaire. Data from AA participants were analyzed using SPSS. The engagement process resulted in sustained partnerships with three urban AA churches and delivery of three Think Well seminars to 172 participants. Of the 172 participants, 138 (80%) AA participants (40 BCS, 98 co-survivors) returned the program survey. Respondents reported Think Well to be culturally relevant (90%) and of high quality (94%). Think Well was developed and evaluated with the collaboration of urban AA church leaders. Engaging church leaders facilitated reach of AA BCS. Partnership facilitated a culturally relevant, high quality program for AA BCS and co-survivors.

Association between diabetes and subsequent malignancy risk among older breast cancer survivors.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.

Survival of adult AML patients treated with chemotherapy in the U.S. population by age, race and ethnicity, sex, calendar-year period, and AML subgroup, 2001-2019.

Background: Population-based survival studies of adult acute myeloid leukemia (AML) have not simultaneously evaluated age at diagnosis, race and ethnicity, sex, calendar period or AML subtypes/subgroups among chemotherapy-treated patients. Methods: For 28,473 chemotherapy-treated AML patients diagnosed at ages ≥20 years in population-based cancer registry areas of the Surveillance, Epidemiology, and End Results Program (2001-2018, followed through 2019), we evaluated 1-month through 5-year relative survival (RS) and 95% confidence intervals (95% CI) using the actuarial method in the SEER∗Stat Survival Session and overall survival (OS) using multivariable Cox regression to estimate proportional hazard ratios (HR) and 95% CI. Findings: RS decreased with increasing age (20-39, 40-59, 60-74, 75-84, ≥85 years) at AML diagnosis. RS declined substantially within the first month and, except for acute promyelocytic leukemia, decreasing patterns continued thereafter for core binding factor AML, AML with antecedent condition/therapy, and all other AML. For all ages, acute promyelocytic leukemia RS stabilized after the first year. For total AML the hazard of death was significantly increased for non-Hispanic (NH)-Black (HR = 1.18, 95% CI = 1.12-1.24) and NH-Pacific Islander patients (HR = 1.31, 95% CI = 1.11-1.55) compared with NH-White patients. In contrast, NH-Asian and Hispanic patients had similar OS to NH-White patients across all ages and most AML subgroups. Males had significantly inferior survival to females with some exceptions. Compared to 2001-2006, in 2013-2018 OS improved for all age and AML subgroups. Interpretation: Chemotherapy-treated U.S. adults with AML have notable differences in survival by age, race and ethnicity, sex, calendar-year period, and AML subgroup. Despite survival gains over time, our findings highlight the need for improving early outcomes across all AML subgroups, older ages, and Black and Pacific Islander patients and long-term outcomes among most treated groups. Funding: Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology.

Association of cancer treatment with excess heart age among five-year young breast cancer survivors.

PURPOSE: Data evaluating cardiovascular disease (CVD) risk by cancer treatment among young women (≤ 40 years) with breast cancer are limited. METHODS: Among 372 five-year breast cancer survivors aged 30-40 years from the Young Women's Breast Cancer Study, we assessed the association of cancer treatments (anthracyclines, trastuzumab, radiation/laterality, endocrine therapy) and excess heart age (difference between predicted 10-year CVD risk as assessed by adapted Framingham Risk Score and chronological age), prevalent elevated excess heart age (≥ 2 years), and worsening excess heart age (change of ≥ 2 excess heart age years) at breast cancer diagnosis and two- and five-year follow-up using multivariable linear and logistic regressions. RESULTS: Most women had stage I or II (79%), ER + (71%), or PR + (65%) breast cancer. At diagnosis, women had little excess heart age by treatment receipt (range of means = -0.52,0.91 years). Left-sided radiation (ß = 2.49,SE = 0.96,p = 0.01) was associated with higher excess heart age at five-year follow-up. For prevalent elevated excess heart age (two-year = 26%;five-year = 27%), women treated with right-sided radiation had increased risk at two-years (OR = 2.17,95%CI = 1.12-4.19), yet at five-years, associations were observed after any radiation (OR = 1.92,95%CI = 1.09-3.41), especially after left-sided (OR = 2.13,95%CI = 1.09-3.41) radiation. No associations were observed between systemic treatments and prevalent elevated excess heart age or any treatments with worsening excess heart age. CONCLUSIONS: Among young breast cancer survivors, radiation, but not other cancer treatments, was associated with elevated excess heart age. IMPLICATIONS FOR CANCER SURVIVORS: CVD risk tools that incorporate cancer treatment, such as radiation, are needed to identify high risk young breast cancer survivors given the long survivorship and long latency of cardiovascular disease.

Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in US breast cancer survivors.

BACKGROUND: Although breast cancer survivors are at risk for cardiovascular disease (CVD) from treatment late effects, evidence to inform long-term and age-specific cardiovascular surveillance recommendations is lacking. METHODS: We conducted a retrospective cohort study of 10 211 women diagnosed with first primary unilateral breast cancer in Kaiser Permanente Washington or Colorado (aged 20 years and older, survived ≥1 year). We estimated multivariable adjusted hazard ratios (HRs) for associations between initial chemotherapy regimen type (anthracycline and/or trastuzumab, other chemotherapies, no chemotherapy [referent]) and CVD risk, adjusted for patient characteristics, other treatments, and CVD risk factors. Cumulative incidence was calculated considering competing events. RESULTS: After 5.79 median years, 14.67% of women developed CVD (cardiomyopathy and/or heart failure [HF], ischemic heart disease, stroke). Women treated with anthracyclines and/or trastuzumab had a higher risk of CVD compared with no chemotherapy (adjusted HR = 1.53, 95% confidence interval [CI] = 1.31 to 1.79), persisting at least 5 years postdiagnosis (adjusted HR5-<10 years = 1.85, 95% CI = 1.44 to 2.39; adjusted HR≥10 years = 1.83, 95% CI = 1.34 to 2.49). Cardiomyopathy and/or HF risks were elevated among women treated with anthracyclines and/or trastuzumab compared with no chemotherapy, especially for those aged younger than 65 years (adjusted HR20-54years = 2.97, 95% CI = 1.72 to 5.12; adjusted HR55-64years = 2.21, 95% CI = 1.52 to 3.21), differing for older women (adjusted HR≥65 years = 1.32, 95% CI = 0.97 to 1.78), and at least 5 years postdiagnosis (adjusted HR5-<10years = 1.89, 95% CI = 1.35 to 2.64; adjusted HR≥10 years = 2.21, 95% CI = 1.52 to 3.20). Anthracyclines and/or trastuzumab receipt was associated with increased ischemic heart disease risks after 5 or more years (adjusted HR5-<10years = 1.51, 95% CI = 1.06 to 2.14; adjusted HR≥10 years = 1.86, 95% CI = 1.18 to 2.93) with no clear age effects, and stroke risk (adjusted HR = 1.33, 95% CI = 1.05 to 1.69), which did not vary by time or age. There was some evidence of long-term cardiomyopathy and/or HF and ischemic heart disease risks with other chemotherapies. Among women aged younger than 65 treated with anthracyclines and/or trastuzumab, up to 16% developed CVD by 10 years (20-54 years = 6.91%; 55-64 years = 16.00%), driven by cardiomyopathy and/or HF (20-54 years = 3.90%; 55-64 years = 9.78%). CONCLUSIONS: We found increased long-term risks of cardiomyopathy and/or HF and ischemic heart disease among breast cancer survivors treated with anthracyclines and/or trastuzumab and increased cardiomyopathy and/or HF risk among women aged younger than 65 years.

Racial Disparities among Asian American, Native Hawaiian, and Other Pacific Islander Patients with Cancer Who Refuse Recommended Radiation Therapy or Surgery.

Despite radiation therapy (RT) and surgery being the curative treatments, prior work demonstrated that the aggregated Asian American (AA) and Native Hawaiian and Other Pacific Islanders (NHPI) population refuse RT and surgery at a higher rates than other races. Given that AA and NHPI are distinct groups, data disaggregation is necessary to understand racial and ethnic disparities for treatment refusal. We aimed to (1) compare RT and surgery refusal rates between AA and NHPI populations, (2) assess RT and surgery refusal on overall mortality, and (3) determine predictors of refusing RT and surgery using the United States (U.S.) National Cancer Database. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) for treatment refusal were calculated using logistic regression. Adjusted hazard ratios (aHR) were calculated for overall survival using Cox proportional hazard models among propensity score-matched groups. The overall rate of RT refusal was 4.8% and surgery refusal was 0.8%. Compared to East AA patients, NHPI patients had the highest risk of both RT refusal (aOR = 1.38, 95%CI = 1.21-1.61) and surgery refusal (aOR = 1.28, 95%CI = 1.00-1.61). RT refusal significantly predicted higher mortality (aHR = 1.17, 95%CI = 1.08-1.27), whereas surgery refusal did not. Predictors of RT and surgery refusal were older patient age, high comorbidity index, and cancer diagnosis between 2011-2017. The results show heterogenous treatment refusal patterns among AA and NHPI populations, suggesting areas for targeted intervention.