Age at diagnosis and social risks among Black cancer survivors: Results from the Detroit Research on Cancer Survivors cohort.

BACKGROUND: Social risks are common among cancer survivors who have the fewest financial resources; however, little is known about how prevalence differs by age at diagnosis, despite younger survivors' relatively low incomes and wealth. METHODS: The authors used data from 3703 participants in the Detroit Research on Cancer Survivors (ROCS) cohort of Black cancer survivors. Participants self-reported several forms of social risks, including food insecurity, housing instability, utility shut-offs, not getting care because of cost or lack of transportation, and feeling unsafe in their home neighborhood. Modified Poisson models were used to estimate prevalence ratios and 95% confidence intervals (CIs) of social risks by age at diagnosis, controlling for demographic, socioeconomic, and cancer-related factors. RESULTS: Overall, 35% of participants reported at least one social risk, and 17% reported two or more risks. Social risk prevalence was highest among young adults aged 20-39 years (47%) followed by those aged 40-54 years (43%), 55-64 years (38%), and 65 years and older (24%; p for trend < .001). Compared with survivors who were aged 65 years and older at diagnosis, adjusted prevalence ratios for any social risk were 1.75 (95% CI, 1.42-2.16) for survivors aged 20-39 years, 1.76 (95% CI, 1.52-2.03) for survivors aged 40-54 years, and 1.41 (95% CI, 1.23-1.60) for survivors aged 55-64 years at diagnosis. Similar associations were observed for individual social risks and experiencing two or more risks. CONCLUSIONS: In this population of Black cancer survivors, social risks were inversely associated with age at diagnosis. Diagnosis in young adulthood and middle age should be considered a risk factor for social risks and should be prioritized in work to reduce the financial effects of cancer on financially vulnerable cancer survivors.

Use of electronic cigarettes among African American cancer survivors.

BACKGROUND: The use of electronic cigarettes (e-cigarettes) is increasing rapidly in the United States, although the negative health outcomes associated with these products are still unknown. Emerging research has examined the use of e-cigarettes in the cancer survivor population as a whole, yet none has focused on e-cigarette use in the African American (AA) cancer survivor population. METHODS: The authors used data from the Detroit Research on Cancer Survivors cohort study, comprised of AA adult cancer survivors. Logistic regression models were used to evaluate factors potentially associated with e-cigarette ever use and current use. RESULTS: Of 4443 cancer survivors who completed a baseline interview, 8.3% (n = 370) reported ever using e-cigarettes, and 16.5% (n = 61) of those reporting ever use also reported current use of e-cigarettes. Ever users and current users were on average younger than those who did not use e-cigarettes (57.5 vs. 61.2 years; p < .001). Current cigarette smokers were >20 times more likely (odds ratio, 20.75; 95% confidence interval, 12.84-33.55) and former smokers were almost 10 times more likely (odds ratio, 9.50; 95% confidence interval, 6.03-14.97) to have ever used e-cigarettes than never-smokers. Preliminary data suggested that ever use of e-cigarettes is associated with later stage at diagnosis for breast and colorectal cancers. CONCLUSIONS: As the use of e-cigarettes increases in the general population, it is important to continue to monitor their use in cancer survivors and to gain more insight as it pertains to the AA cancer survivor population. Elucidation of the factors associated with e-cigarette use in this population may help inform comprehensive cancer survivorship recommendations and interventions.

The impact of the COVID-19 pandemic on African American cancer survivors.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had profound effects on population health to date. African American cancer survivors are particularly vulnerable to developing severe consequences; therefore, understanding the impact of the virus on this patient population is critical. METHODS: The Detroit Research on Cancer Survivors cohort is a unique effort to understand the determinants of poor outcomes in African American cancer survivors. To date, more than 4500 cancer survivors and nearly 950 primary caregivers have been enrolled; participation includes a survey and the collection of biospecimens, medical records, and tumor tissue. Beginning in the spring of 2020, a supplemental survey focusing on the impact of COVID-19 was offered to enrolled participants. The analysis included 890 survivors. RESULTS: Nearly all survivors (>99%) reported changes in their daily activities in an effort to reduce the risk of infection. More than 40% of the survivors reported some disruption in their access to medical care. A substantial proportion of the survivors (>40%) reported feeling anxious, depressed, and/or isolated during the COVID-19 pandemic. Approximately 40% of the patients reported changes in health behaviors shown to negatively affect survivorship outcomes (physical inactivity, smoking, and alcohol use) as a result of the pandemic. CONCLUSIONS: The influence of the COVID-19 pandemic on African American cancer survivors is substantial: it has affected both their physical and mental health. Coupled with changes in health behaviors, these factors will likely affect outcomes in this high-risk patient population, and this makes further study and interventions necessary to mitigate the long-term impact of the pandemic on cancer outcomes.

Social needs and health-related quality of life among African American cancer survivors: Results from the Detroit Research on Cancer Survivors study.

BACKGROUND: Social needs may affect cancer survivors' health-related quality of life (HRQOL) above and beyond sociodemographic and cancer-related factors. The purpose of this study was to estimate associations between social needs and HRQOL. METHODS: Results included data from 1754 participants in the Detroit Research on Cancer Survivors cohort, a population-based study of African American survivors of breast, colorectal, lung, and prostate cancer. Social needs included items related to food insecurity, utility shutoffs, housing instability, not getting health care because of cost or a lack of transportation, and perceptions of neighborhood safety. HRQOL was measured with the validated Functional Assessment of Cancer Therapy-General (FACT-G). Linear regression models controlled for demographic, socioeconomic, and cancer-related factors. RESULTS: More than one-third of the survivors (36.3%) reported social needs including 17.1% of survivors reported 2 or more. The prevalence of social needs ranged from 14.8% for food insecurity to 8.9% for utility shutoffs. FACT-G score differences associated with social needs were -12.2 (95% confidence interval [CI] to -15.2 to -9.3) for not getting care because of a lack of transportation, -11.3 (95% CI, -14.2 to -8.4) for housing instability, -10.1 (95% CI, -12.7 to -7.4) for food insecurity, -9.8 (95% CI, -12.7 to -6.9) for feeling unsafe in the neighborhood, -8.6 (95% CI, -11.7 to -5.4) for utility shutoffs, and -6.7 (95% CI, -9.2 to -4.1) for not getting care because of cost. CONCLUSIONS: Social needs were common in this cohort of African American cancer survivors and were associated with clinically significant differences in HRQOL. Clinical oncology care and survivorship care planning may present opportunities to screen for and address social needs to mitigate their impact on survivors' HRQOL.

The costs of treating and not treating patients with chronic myeloid leukemia with tyrosine kinase inhibitors among Medicare patients in the United States.

BACKGROUND: Patients with high cost-sharing of tyrosine kinase inhibitors (TKIs) experience delays in treatment for chronic myeloid leukemia (CML). To the authors' knowledge, the clinical outcomes among and costs for patients not receiving TKIs are not well defined. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors evaluated differences in TKI initiation, health care use, cost, and survival among patients with CML with continuous Medicare Parts A and B and Part D coverage who were diagnosed between 2007 and 2015. RESULTS: A total of 941 patients were included. Approximately 29% of all patients did not initiate treatment with TKIs within 6 months (non-TKI users), and had lower rates of BCR-ABL testing and more hospitalizations compared with TKI users. Approximately 21% were not found to have any TKI claims at any time. TKI initiation rates within 6 months of diagnosis increased for all patients over time (61% to 85%), with greater improvements observed in patients receiving subsidies (55% to 90%). Total Medicare costs were greater in patients treated with TKIs, with approximately 50% because of TKI costs. Non-TKI users had more inpatient costs compared with TKI users. Trends in cost remained significant when adjusting for age and comorbidities. The median overall survival was 40 months (95% confidence interval [95% CI], 34-48 months) compared with 86 months (95% CI, 73 months to not reached), respectively, for non-TKI users versus TKI users, a finding that remained consistent when adjusting for age, comorbidities, and subsidy status (hazard ratio, 2.23; 95% CI, 1.77-2.81). CONCLUSIONS: Approximately 21% of all patients with CML did not receive TKIs at any time. Cost-sharing subsidies consistently are found to be associated with higher initiation rates. Non-TKI users had higher inpatient costs and poorer survival outcomes. Interventions to lower TKI costs for all patients are desirable.

Neighborhood walkability and body mass index in African American cancer survivors: The Detroit Research on Cancer Survivors study.

BACKGROUND: Extant evidence links neighborhood walkability with obesity-related health in the general population. This association likely exists in cancer survivors, but research is limited. Furthermore, a disproportionate obesity burden in African American cancer survivors warrants subgroup-specific analyses. METHODS: This study analyzed data from 2089 African American cancer survivors participating in the Detroit Research on Cancer Survivors (ROCS) cohort. On the basis of built environment data summarized within 1-km radial buffers around census block centroids, a multidimensional neighborhood walkability index (NWI) was constructed. Survivors' residential addresses at Detroit ROCS enrollment were geocoded, and addresses were linked to NWI scores via the census block of residence. At study enrollment, survivors reported height and weight; these data were used to calculate their body mass index (BMI). Associations between NWI quartiles and BMI overall and by cancer type, biological sex, and physical activity engagement were evaluated. RESULTS: BMI was found to be inversely associated with increasing NWI quartile (P for trend < .01). This inverse relationship was observed in men (P for trend < .01) and in survivors reporting any regular physical activity (P for trend < .01). CONCLUSIONS: This study's findings suggest that among African American cancer survivors, higher neighborhood walkability is associated with lower BMI. As health care systems in the United States increasingly consider the role of the neighborhood environment in their patients' health, these findings provide additional evidence supporting health systems' incorporation of neighborhood walkability as an obesity-related health indicator for this cancer survivor subgroup and potentially for cancer survivors from other vulnerable populations.

Cardiometabolic risk factors and survival after cancer in the Women's Health Initiative.

BACKGROUND: Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. METHODS: This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival. RESULTS: After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42). CONCLUSIONS: Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation. LAY SUMMARY: This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.

Physical activity and quality of life in African American cancer survivors: The Detroit Research on Cancer Survivors study.

BACKGROUND: The benefit of regular exercise in improving cancer outcomes is well established. The American Cancer Society (ACS) released a recommendation that cancer survivors should engage in at least 150 minutes of moderate to vigorous physical activity (PA) per week; however, few report meeting this recommendation. This study examined the patterns and correlates of meeting ACS PA recommendations in the Detroit Research on Cancer Survivors (ROCS) cohort of African American cancer survivors. METHODS: Detroit ROCS participants completed baseline and yearly follow-up surveys to update their health and health behaviors, including PA. This study examined participation in PA by select characteristics and reported health-related quality of life (HRQOL) as measured with the Functional Assessment of Cancer Therapy and Patient-Reported Outcomes Measurement Information System instruments. RESULTS: Among the first 1500 ROCS participants, 60% reported participating in regular PA, with 24% reporting ≥150 min/wk. Although there were no differences by sex, prostate cancer survivors were the most likely to report participating in regular PA, whereas lung cancer survivors were the least likely (P = .022). Survivors who reported participating in regular PA reported higher HRQOL (P < .001) and lower depression (P = .040). CONCLUSIONS: Just 24% of African American cancer survivors reported meeting the ACS guidelines for PA at the baseline, but it was encouraging to see increases in activity over time. Because of the established benefits of regular exercise observed in this study and others, identifying and reducing barriers to regular PA among African American cancer survivors are critical for improving outcomes and minimizing disparities.

eHealth Activity among African American and White Cancer Survivors: A New Application of Theory.

eHealth is a promising resource for cancer survivors and may contribute to reducing racial disparities in cancer survivorship. This research applies the Unified Theory of Acceptance and Use of Technology (UTAUT) to examine eHealth activity among African American (AfAm) and White cancer survivors. In a population-based sample of AfAm and White survivors (n = 300), a Poisson regression tested whether UTAUT constructs (facilitating conditions, social influence, perceived ease of use, perceived usefulness) and beliefs about security/trustworthiness of eHealth were associated with the number of eHealth activities respondents had used. To test whether the effects varied across racial groups, interactions between each of these five facets and survivor race were included in the model. The model adjusted for demographic characteristics, cancer history, and internet access and use. Across racial groups, facilitating conditions (IRR = 1.44, 95%CI [1.17, 1.77]) and perceived usefulness (IRR = 1.16, 95%CI [1.08, 1.24]) were associated with increased eHealth activity. A marginally significant interaction between race and perceived ease of use (IRR = 1.17, 95%CI [0.99, 1.39]) indicated this perception was associated with decreased eHealth activity for White but not AfAm survivors. A significant interaction between race and perceived security/trustworthiness (IRR = 1.16, 95%CI [1.02, 1.32]) indicated this perception was associated with increased eHealth activity for AfAm but not White survivors. Social influence was not associated with eHealth use for either group (IRR = 1.07, 95%CI [0.98, 1.16]). Interventions targeting attitudes about eHealth may encourage its adoption and use. Furthermore, eHealth tools intended for use among AfAm cancer survivors should ensure they are secure and emphasize trustworthiness to intended users.

Real-world testing and treatment patterns in chronic lymphocytic leukemia: A SEER patterns of care analysis.

BACKGROUND: Laboratory testing and treatments for chronic lymphocytic leukemia (CLL) have changed dramatically within the last decade. The authors evaluated changes in patterns of real-world testing and treatment over time by comparing 2 population-based cohorts. METHODS: The National Cancer Institute-sponsored Patterns of Care study was conducted among patients with CLL who were sampled from 14 Surveillance, Epidemiology, and End Results (SEER) program registries. Demographics, testing, and treatment data were abstracted from medical records within 24 months of diagnosis. RESULTS: A total of 1008 patients diagnosed in 2008 and 1367 patients diagnosed in 2014 were included. There was a significant increase in fluorescence in situ hybridization (FISH) testing, immunoglobulin heavy-chain variable region gene (IgVH ) mutation analyses, and lymph node biopsies between 2008 and 2014. FISH testing was performed in the majority of, but not all, treated patients (53% in 2008, which increased to 62% in 2014). Some differences in the receipt of FISH testing by age and insurance status were observed over time (older patients and Medicare patients without private insurance were less likely to be tested in 2014). There were contrasting testing patterns noted by practice type and year, with nonteaching hospitals more likely to perform bone marrow biopsies in 2008, and teaching hospitals more likely to perform FISH and IgVH testing in 2014. There also were differences in treatments over time, with the use of bendamustine and rituximab being more common in 2014, at the expense of fludarabine, cyclophosphamide, and rituximab. CONCLUSIONS: There have been rapidly changing practices in the testing and treatment patterns of patients with CLL within the last decade.

Risk of incident claims for chemotherapy-induced peripheral neuropathy among women with breast cancer in a Medicare population.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling consequence of neurotoxic therapies, yet factors that modulate the development and clinical impact of CIPN are poorly understood. This epidemiological analysis identifies risk factors for the incidence of CIPN. METHODS: This retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data examined predictors of incident CIPN claims among 11,149 women aged 66 years or older with American Joint Commission on Cancer (AJCC) stage II to IV breast cancer (and no secondary cancer diagnosis or preexisting neuropathy) who received chemotherapy. RESULTS: Overall, new CIPN claims occurred for 8.3% of patients within 1 year of starting chemotherapy. Risk emerged approximately 3 months after the start of chemotherapy and increased throughout 1 year. Paclitaxel as part of first-line therapy increased CIPN risk 2.7-fold in comparison with nonneurotoxic agents (15.9% vs 5.0%), with lower incidence rates for carboplatin and paclitaxel (11.9%), carboplatin and docetaxel (9.3%), carboplatin alone (7.7%), and docetaxel alone (6.6%). The CIPN incidence rate was higher for women who at the time of their breast cancer diagnosis were relatively young (within this Medicare sample), were at AJCC stage II or III, were married or had an equivalent status, and had fewer comorbidities, but it did not differ by race/ethnicity or poverty level. CONCLUSIONS: These Medicare claims database findings indicate that women aged 66 years or older with breast cancer are susceptible to CIPN from taxane and/or platinum compounds, with risk emerging approximately 3 months into treatment. Prospective studies of symptom emergence and clinical response (eg, stopping chemotherapy and adjunctive treatments) are indicated to determine how best to inform patients of this risk and to manage CIPN in this population.

Biliary tract cancer incidence and trends in the United States by demographic group, 1999-2013.

BACKGROUND: Biliary tract cancers (BTCs) are rare but deadly cancers (gallbladder cancer [GBC], intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and ampulla of Vater cancer [AVC]). A recent US study reported increasing GBC incidence among people younger than 45 years and blacks; however, it did not examine trends for other biliary tract sites. METHODS: This study characterized demographic differences in BTC incidence rates and time trends by anatomic site. Population-based North American Association of Central Cancer Registries data were used to calculate age-adjusted incidence rates, incidence rate ratios (IRRs), and estimated annual percent changes (eAPCs) for 1999-2013 by site and demographic group. For sites with significant differences in eAPC by age group, IRRs were compared by age group. RESULTS: GBC incidence rates declined among women (eAPC, -0.5%/y; P = .01) and all racial/ethnic groups except for non-Hispanic blacks, among whom rates increased (1.8%/y; P < .0001). Although GBC rates increased among 18- to 44-year-olds (eAPC, 1.8%/y; P = .01), they decreased among people 45 years old or older (-0.4%/y; P = .009). Sex (P < .0001) and racial/ethnic differences (P = .003 to .02) in GBC incidence were larger for younger people than older people. During this period, ICC (eAPC, 3.2%/y; P < .0001) and ECC rates (1.8%/y; P = .001) steadily increased across sex and racial/ethnic groups. Although AVC incidence rates increased among younger adults (eAPC, 1.8%/y; P = .03) but not older adults (-0.20%/y; P = .30), sex and racial/ethnic IRRs did not differ by age. CONCLUSIONS: Differential patterns of BTC rates and temporal trends have been identified by anatomic site and demographic groups. These findings highlight the need for large pooling projects to evaluate BTC risk factors by anatomic site.

A study of circulating microRNAs identifies a new potential biomarker panel to distinguish aggressive prostate cancer.

Prostate cancer is one of the most common cancers in men worldwide. Currently available diagnostic and prognostic tools for this disease, such as prostate specific antigen, suffer from lack of specificity and sensitivity, resulting in over- and misdiagnosis. Hence, there is an urgent need for clinically relevant biomarkers capable of distinguishing between aggressive and nonaggressive forms of prostate cancer to aid in stratification, management and therapeutic decisions. To address this unmet need, we investigated the patterns of expression of a panel of 68 plasma-derived microRNAs (miRNAs) in a cohort of African American (AA) and European American (EA) prostate cancer patients (n = 114). miRNA qPCR results were analyzed using in-depth statistical methods, and a bioinformatics analysis was conducted to identify potential targets of the differentially expressed miRNAs. Our data demonstrate that a new previously unreported circulating miRNA signature consisting of a combination of interacting miRNAs (miR-17/miR-192) and an independent miRNA (miR-181a) are capable of segregating aggressive and nonaggressive prostate cancer in both AA and EA patients. The interacting miRNAs outperformed independent miRNAs in identifying aggressiveness. Our results suggest that these circulating miRNAs may constitute novel biomarkers of prostate cancer aggressiveness in both races and warrant further investigation.

Rare germline mutations in African American men diagnosed with early-onset prostate cancer.

BACKGROUND: African Americans have both a higher incidence of prostate cancer and greater disease-specific mortality compared with non-Hispanic whites. Historically, the investigation of the contribution of rare genetic variants to prostate cancer in African American men has been hampered by low participation in large genetic studies, particularly those focused on early-onset and familial disease. METHODS: We sequenced 160 genes purported to be involved in carcinogenic pathways in germline DNA samples collected from 96 African American men diagnosed with early-onset prostate cancer (≤55 years at diagnosis). REVEL software was used to determine the pathogenic potential of observed missense variants. RESULTS: We observed three protein-truncating mutations, one in BRCA2 and two in BRIP1 in three African American men diagnosed with early-onset prostate cancer. Furthermore, we observed five rare, mostly private, missense variants among four genes (BRCA1, BRCA2, PMS2, and ATM) that were predicted to be deleterious and hence likely pathogenic in our patient sample. CONCLUSIONS: Protein-truncating mutations in BRCA2 and BRIP1 were discovered in African American men diagnosed with early-onset prostate cancer. Further study is necessary to determine the role of rare, missense variants to prostate cancer incidence, and progression in this group of high-risk men.

Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States.

BACKGROUND: The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. METHODS: Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease. RESULTS: There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease. CONCLUSIONS: Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018;124:2104-14. © 2018 American Cancer Society.

Cardiometabolic risk factors and survival after breast cancer in the Women's Health Initiative.

BACKGROUND: Few studies have examined the relationship between cardiometabolic risk factors linked to metabolic syndrome and mortality among women with breast cancer. METHODS: We used the Women's Health Initiative to evaluate the relationship between cardiometabolic risk factors, including waist circumference (WC), blood pressure, cholesterol level, and presence of type 2 diabetes, and their relation with death from breast cancer, cardiovascular disease (CVD), and other causes among 8641 women with local or regional stage invasive breast cancer. Cox proportional hazards models were used to estimate hazard ratios, and 95% confidence intervals, adjusted for important predictors of survival. RESULTS: After a median of 11.3 years, there were 2181 total deaths, 619 (28.4%) of which were due to breast cancer. Most participants (55.7%) had at least 2 cardiometabolic risk factors, and 4.9% had 3 or 4. Having a larger number of risk factors was associated with higher risk of CVD and other-cause mortality (P trend < .001 for both), but not with breast cancer mortality (P trend = .86). Increased WC was associated with a higher risk of CVD (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.05-1.57) and other-cause mortality (HR, 1.32; 95% CI, 1.16-1.49) and only with a small and nonsignificant higher risk of breast cancer mortality (HR, 1.19; 95% CI, 0.93-1.52). The results did not differ in analyses stratified by race, hormone receptor status, or after an analysis of cases diagnosed within 5 years after baseline. CONCLUSIONS: Among women with early stage breast cancer, cardiometabolic risk factors are significantly associated with cardiovascular and other-cause mortality, but not breast cancer mortality. Cancer 2018;124:1798-807. © 2018 American Cancer Society.

The effect of genetic variants on the relationship between statins and breast cancer in postmenopausal women in the Women's Health Initiative observational study.

PURPOSE: Statins have been postulated to have chemopreventive activity against breast cancer. We evaluated whether germline genetic polymorphisms modified the relationship between statins and breast cancer risk using data from the Women's Health Initiative. We evaluated these interactions using both candidate gene and agnostic genome-wide approaches. METHODS: To identify candidate gene-statin interactions, we tested interactions between 22 SNPS in nine candidate genes implicated in the effect of statins on lipid metabolism in 1687 cases and 1687 controls. We then evaluated statin use interaction with the remaining 30,380 SNPs available in this sample from the CGEMS GWAS study. RESULTS: After adjusting for multiple comparisons, no SNP interactions with statin usage and risk of breast cancer were statistically significant in either the candidate genes or genome-wide approaches. CONCLUSIONS: We found no evidence of SNP interactions with statin usage for breast cancer risk in a population of 3374 individuals. These results suggest that genome-wide common genetic variants do not moderate the association between statin usage and breast cancer in the population of women in the Women's Health Initiative.

Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

BACKGROUND: Evidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated. METHODS: Analyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White). RESULTS: Of 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54). CONCLUSIONS: Our findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers.

Antioxidant micronutrients and the risk of renal cell carcinoma in the Women's Health Initiative cohort.

BACKGROUND: Renal cell carcinoma (RCC) is the eighth leading cancer among women in incidence and commonly is diagnosed at a more advanced stage. Oxidative stress has been considered to play an important role in the pathogenesis of RCC. Various dietary micronutrients have antioxidant properties, including carotenoids and vitamins C and E; thus, diets rich in these nutrients have been evaluated in relation to RCC prevention. The objective of this study was to explore the correlation between antioxidant micronutrients and the risk of RCC. METHODS: In total, 96,196 postmenopausal women who enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and were followed through July 2013 were included in this analysis. Dietary micronutrient intake was estimated from the baseline WHI food frequency questionnaire, and data on supplement use were collected using an interview-based inventory procedure. RCC cases were ascertained from follow-up surveys and were centrally adjudicated. The risks for RCC associated with intake of α-carotene, ß-carotene, ß-cryptoxanthin, lutein plus zeaxanthin, lycopene, vitamin C, and vitamin E were analyzed using Cox proportional hazards regression adjusted for confounders. RESULTS: Two hundred forty women with RCC were identified during follow-up. Lycopene intake was inversely associated with RCC risk (P = .015); compared with the lowest quartile of lycopene intake, the highest quartile of intake was associated with a 39% lower risk of RCC (hazard ratio, 0.61; 95% confidence interval, 0.39-0.97). No other micronutrient was significantly associated with RCC risk. CONCLUSIONS: The current results suggest that further investigation into the correlation between lycopene intake and the risk of RCC is warranted.

Familial clustering of breast and prostate cancer and risk of postmenopausal breast cancer in the Women's Health Initiative Study.

BACKGROUND: Evidence suggests that the risk of breast and prostate cancer is increased among those with a family history of the same disease and particularly among first-degree relatives. However, less is known about the relationship between breast and prostate cancer within families and particularly among minority populations. METHODS: Analyses of participants in the Women's Health Initiative observational cohort who were free of breast cancer at the time of their baseline examination were conducted. Subjects were followed for breast cancer through August 31, 2009. A Cox proportional hazards regression modeling approach was used to estimate the risk of breast cancer associated with a family history of prostate cancer, breast cancer, and both among first-degree relatives. RESULTS: There were 78,171 eligible participants, and 3506 breast cancer cases were diagnosed during the study period. A family history of prostate cancer was associated with a modest increase in breast cancer risk after adjustments for confounders (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.02-1.26). In a separate analysis examining the joint impact of both cancers, a family history of both breast and prostate cancer was associated with a 78% increase in breast cancer risk (aHR, 1.78; 95% CI, 1.45-2.19). Risk estimates associated with a family history of both breast and prostate cancer were higher among African American women (aHR, 2.34; 95% CI, 1.09-5.02) versus white women (aHR, 1.66; 95% CI, 1.33-2.08). CONCLUSIONS: These findings suggest that prostate cancer diagnosed among first-degree family members increases a woman's risk of developing breast cancer. Future studies are needed to determine the relative contributions of genes and a shared environment to the risk for both cancers.