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Objectives To explore the feasibility of using real-world data (RWD) with machine learning methods to simulate colorectal cancer (CRC) trials (i.e., 6 Phase III randomized clinical trials comparing other treatment regimens with FOLFIRI—an FDA-approved standard of care first line chemotherapy treatment in patients with metastatic CRC). Methods We used RWD from the OneFlorida Clinical Research Consortium, a clinical research network contributing to the national PCORnet with longitudinal linked electronic health records of ~15 million Floridians. We used the study protocols in the original trials, including the eligibility criteria, to define the various study populations. We focused on patients’ safety outcomes in terms of the occurrence of severe adverse events (SAEs) after the treatments; calculated SAE prevalence, mean SAEs per patient, and SAE event rates for each category defined in the CTCAE v5.0. We considered two scenarios: (1) only simulating the control arm (CA) (i.e., the FOLFIRI arm), and (2) simulating both the CA and experimental arm (EA) (e.g., Panitumumab + FOLFIRI) and calculating the relative risk of SAE between the 2 arms. Two sampling strategies were used to simulate study population: random sampling and proportional sampling with gender and race. Among the 6 trials, only 2 had sufficient patients in OneFlorida for the two-arm simulations. We used propensity score matching (PSM) on baseline characteristics such as age, gender, race, and comorbidities to simulate the randomization process. In addition to the traditional logistic regression (LR) model, we considered machine learning (ML) models for PSM (such as neural networks) as LR-based PSM assumes linearity of the underlying variables. Each trial was simulated 1,000 times. Results Consistent with the existing literature, the mean SAE and SAE event rates were higher in all CAs simulated through RWD from OneFlorida. The proportional sampling strategy provided estimates of SAE prevalence more comparable to rates reported by the original trials. In the two-arm simulations, no significant differences were observed in the matched case-control samples using LR or ML methods. As expected with patients treated in real-world settings, larger mean SAEs and SAE event rates (but similar SAE prevalence ) were observed in the simulations compared with the original trials. The risk ratios of having SAE obtained from simulations comparing CA vs. EA were very close to the ratios calculated from the original trials. Conclusion Our study showed feasibility of simulating cancer trials using RWD and obtained comparable estimates to the original trial in terms of patient safety outcomes. Despite more SAEs in RWD, ratios between CAs and EAs were similar to the previously published rigorously conducted trials. Future in-depth investigations are warranted and shall consider state-of-the-art AI methods such as deep learning and causal AI methods to help tackle issues with using RWD for cancer trial simulation (e.g., data bias, high-dimensionality). Citation Format: Zhaoyi Chen, Hansi Zhang, Thomas George, Mattia Prosperi, Yi Guo, Dejana Braithwaite, Elizabeth Shenkman, Jonathan Licht, Jiang Bian. Simulation of colorectal cancer clinical trials using real-world data and machine learning [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-071.

Few studies have examined cancer-related risk factors in relation to SES across the lifecourse in low to middle income countries. This analysis focuses on adult women in India, China, Mexico, Russia and South Africa, and examines the association between individual, parental and lifecourse SES with smoking, alcohol, BMI, nutrition and physical activity. Data on 22,283 women aged 18 years and older were obtained from the 2007 WHO Study on Global Aging and Adult Health (SAGE). Overall, 34% of women had no formal education, 73% had mothers with no formal education and 73% of women had low lifecourse SES. Low SES women were almost four times more likely to exceed alcohol use guidelines (OR: 3.86, 95% CI: 1.23-12.10), and 68% more likely to smoke (OR: 1.68, 95% CI: 1.01-2.80) compared with higher SES. Women with low SES mothers and fathers were more likely to have poor nutrition (Mothers OR: 1.59, 95% CI: 1.17-2.16; Fathers OR: 1.33, 95% CI: 1.11-1.59) and more likely to smoke (Mothers OR: 1.46, 95% CI: 1.15-1.87; Fathers OR: 2.17, 95% CI: 1.80-2.63) compared with those with high SES parents. Women with stable low lifecourse SES were more likely to smoke (OR: 2.55, 95% CI: 1.47-4.43), while those with declining lifecourse SES were more likely to exceed alcohol use guidelines (OR: 3.63, 95% CI: 1.07-12.34). Cancer-related risk factors varied significantly by lifecourse SES, suggesting that cancer prevention strategies will need to be tailored to specific sub-groups in order to be most effective.

In the U.S., guidelines recommend that women continue mammography screening until at least age 74, but recent evidence suggests declining screening rates in older women. We estimated adherence to screening mammography and multilevel factors associated with adherence in a longitudinal cohort of older women. Women aged 66–75 years receiving screening mammography within the Breast Cancer Surveillance Consortium were linked to Medicare claims (2005–2010). Claims data identified baseline adherence, defined as receiving subsequent mammography within approximately 2 years, and length of time adherent to guidelines. Characteristics associated with adherence were investigated using logistic and Cox proportional hazards regression models. Analyses were stratified by age to investigate variation in relationships between patient factors and adherence. Among 49,775 women, 89% were adherent at baseline. Among women 66–70 years, those with less than a high school education were more likely to be non-adherent at baseline (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.65–2.33) and remain adherent for less time (hazard ratio [HR] 1.41; 95% CI 1.11–1.80) compared to women with a college degree. Women with ≥ 1 versus no Charlson co-morbidities were more likely to be non-adherent at baseline (OR 1.46; 95% CI 1.31–1.62) and remain adherent for less time (HR 1.44; 95% CI 1.24–1.66). Women aged 71–75 had lower adherence overall, but factors associated with non-adherence were similar. In summary, adherence to guidelines is high among Medicare-enrolled women in the U.S. receiving screening mammography. Efforts are needed to ensure that vulnerable populations attain these same high levels of adherence.

A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients. We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000–2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14–4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74–3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29–1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90–11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68–5.29). comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

Breast cancer is a major cause of cancer-related deaths among older women, aged 65 years or older. Screening mammography has been shown to be effective in reducing breast cancer mortality in women aged 50-74 years but not among those aged 75 years or older. Given the large heterogeneity in comorbidity status and life expectancy among older women, controversy remains over screening mammography in this population. Diminished life expectancy with aging may decrease the potential screening benefit and increase the risk of harms. In this review, we summarize the evidence on screening mammography utilization, performance, and outcomes and highlight evidence gaps. Optimizing the screening strategy will involve separating older women who will benefit from screening from those who will not benefit by using information on comorbidity status and life expectancy. This review has identified areas related to screening mammography in older women that warrant additional research, including the need to evaluate emerging screening technologies, such as tomosynthesis among older women and precision cancer screening. In the absence of randomized controlled trials, the benefits and harms of continued screening mammography in older women need to be estimated using both population-based cohort data and simulation models.

Background: Early intervention with palliative care (PC) improves quality of life and increases survival among patients with advanced-stage non-small cell lung cancer (aNCSLC). However, PC is often offered late in the cancer care continuum and is underused. Few studies have examined racial disparities or evaluated the role of access to care in PC use among diverse aNCSLC patients. Objective: To determine the prevalence of PC use among aNSCLC patients by race/ethnicity and assess the role of healthcare access in PC disparities Methods: We used data from the 2004-2016 National Cancer Database, including adults aged 18-90 years with aNSCLC (stage 3 or 4 at diagnosis) who were deceased based on vital status on last contact (n=803,618). Based on the NCCN guidelines, PC includes surgery, radiation, chemotherapy, pain management or any combination with non-curative intent. We examined PC utilization rates by sociodemographic and health care access characteristics, and estimated adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) using logistic regression to evaluate the independent associations of race/ethnicity and health care access with PC. Covariate adjustment sets for racial disparities and health care access factor analyses varied by exposure determined using directed acyclic graphs. Results: Our population was 55% male and 77% NH-White, with a mean age of 68 years. Overall, 20% of aNSCLC patients received any PC, while 6% received pain management. Compared to non-Hispanic (NH)-White patients, NH-Black (aOR: 0.91, 95% CI: 0.90-0.93) and Hispanic patients (aOR: 0.80, 9%% CI: 0.77-0.83) were less likely to receive PC after adjustment for socio-demographic and clinical variables. However, American Indian/Alaskan Native (aOR: 1.12, 95% CI: 1.01-1.24) and Native Hawaiian/Pacific Islander (aOR: 2.04, 95% CI:1.79-2.33) were significantly more likely to receive PC. Overall, compared to privately insured patients, uninsured patients (aOR: 1.14, 95% CI: 1.10-1.17) and Medicaid patients (aOR: 1.16, 95% CI: 1.14-1.19) were more likely to receive PC, while patients treated at a community cancer program (aOR: 0.89, 95% CI: 0.87-0.91) were less likely to receive PC compared with those treated at Comprehensive Cancer programs. Treatment at an integrated network cancer program was associated with increased likelihood of PC use (aOR: 1.12, 95% CI: 1.11-1.14). When stratified by race/ethnicity, the associations between healthcare access and PC utilization was consistent across race/ethnic groups. Notably, Asian patients were more likely to receive PC at all types of cancer treatment facilities compared to NH-White patients. Conclusion: NH-Black and Hispanic patients with aNSCLC are less likely to receive palliative care, a disparity that may be associated with insurance type and type of cancer treatment facility. Strategies to enhance palliative care utilization among underserved patients with aNSCLC should be identified in order to improve quality of life and survival. Citation Format: Jessica Y. Islam, Dejana Braithwaite, Dongyu Zhang, Tina D. Tailor, Tomi Akinyemiju. Racial and health care access disparities in palliative care receipt among patients with advanced non-small cell lung cancer: An analysis of the 2016 National Cancer Database [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PR03.

PURPOSE Guatemala, a low- and middle-income country, has some of the poorest worldwide health indicators, including a high cancer incidence. We explored general cancer knowledge and breast and cervical cancer screening practices among Indigenous women in Lake Atitlán, Guatemala. METHODS We conducted 14 in-person, semistructured interviews and one focus group with 5 traditional midwives (comadronas). All participants were Mayan women from a rural community in Lake Atitlán (median age, 43.5 years; range, 18-72 years). The interviews and focus group were conducted in the participant’s preferred language, Spanish or Kaqchikel. Three coders analyzed the data using a process of inductive thematic analysis. RESULTS Participants had little knowledge and awareness about cancer in general, including screening and prevention. They associated the term cancer with death. Most had more knowledge about cervical cancer risk factors and screening compared with breast cancer. Participants voiced misinformation that breast cancer is caused by bad breast milk and that screenings for cervical cancer involve a hysterectomy. The terms uterine, ovarian, and cervical cancer were used interchangeably. None of the participants had ever been screened for breast cancer and all participants reported not knowing anyone who had been screened in the community. Some participants reported having received pap smears in the past. Major barriers reported include the cost and travel to health institutions and fear that the procedures may hurt. There was a strong preference for female doctors to conduct screenings given stigma. Participants reported experiencing discrimination and language barriers when attending hospitals. Participants mostly relied on family members and natural traditional medicine when they felt sick. Community and family support seemed to be key for health-seeking behaviors. CONCLUSION Findings highlight the lack of knowledge, limited screening practices, and numerous barriers among Mayan women in Guatemala. Efforts should focus on health promotion through educational workshops and increased accessibility to health services.

ObjectivePrevious studies identified several factors associated with cervical cancer screening. However, many of them used samples from the general population and limited studies focused on women with high-risk health behaviours. We aimed to disentangle the association of cervical cancer screening with healthcare access and HIV testing among women at a high risk of HIV infection.DesignNationwide cross-sectional survey in the USA.Setting2016 Behavioral Risk Factor Surveillance System.Participants3448 women with a history of high-risk behaviours associated with HIV infectionExposure and outcomeClinical check-up, having personal healthcare provider, health coverage and HIV testing history were treated as exposures. Appropriate cervical cancer screening, which was defined according to 2016 US Preventive Services Task Force guideline, was treated as the outcome of interest.Data analysisMultivariable logistic regression model was performed to evaluate associations of healthcare access and HIV testing with the uptake of cervical cancer screening; adjusted odds ratio (aOR) and 95% CI were reported. We further investigated if educational attainment modified associations identified in the primary multivariable model.ResultsA total of 2911 (84.4%) high-risk women in our sample underwent cervical cancer screening. In the multivariable model, delayed clinical check-up (≥5 years ago vs within the past year: aOR: 0.19, 95% CI: 0.14 to 0.26), having no health insurance (aOR: 0.60, 95% CI: 0.46 to 0.79) and no history of HIV testing (no testing vs testing within the past year: aOR: 0.46, 95% CI: 0.35 to 0.61) were inversely associated with cervical cancer screening utilisation.ConclusionFactors reflecting healthcare access, specifically clinical check-up and health coverage, as well as history of HIV testing were associated with cervical cancer screening in this population-based study of high-risk women. Targeted interventions are warranted to further increase cervical cancer screening among women at high risk of HIV infection.

The objective of this study was to investigate the association of metabolic syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes across race, menopause, and body mass index (BMI) groups. We examined the association of metabolic syndrome and its components with risk of invasive breast cancer among 94,555 female participants of the National Institute of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, accounting for ductal carcinoma in situ as a competing risk. Cox proportional hazard regression with the Fine and Gray method was used to generate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for baseline sociodemographic, behavioral, and clinical covariates. During a mean follow-up of 14 years, 5380 (5.7%) women developed breast cancer. Overall, MetS at baseline was associated with a 13% increased risk of breast cancer compared to women without MetS (HR: 1.13, 95% CI: 1.00, 1.27), similar estimates were obtained among postmenopausal women (HR: 1.14, 95% CI: 1.01, 1.29). MetS was associated with a slight but non-significantly increased risk of breast cancer among those with both normal weight and overweight/obesity, and those with estrogen receptor positive breast cancer subtype. In the NIH-AARP cohort, MetS was associated with an increased risk of breast cancer. Further studies are needed to definitively evaluate the association of MetS with triple negative breast cancer subtypes across all levels of BMI.

Importance First-degree family history is a strong risk factor for breast cancer, but controversy exists about the magnitude of the association among older women. Objective To determine whether first-degree family history is associated with increased risk of breast cancer among older women, and identify whether the association varies by breast density. Design, Setting, and Participants Prospective cohort study between 1996 and 2012 from 7 Breast Cancer Surveillance Consortium (BCSC) registries located in New Hampshire, North Carolina, San Francisco Bay area, western Washington state, New Mexico, Colorado, and Vermont. During a mean (SD) follow-up of 6.3 (3.2) years, 10 929 invasive breast cancers were diagnosed in a cohort of 403 268 women 65 years and older with data from 472 220 mammography examinations. We estimated the 5-year cumulative incidence of invasive breast cancer by first-degree family history, breast density, and age groups. Cox proportional hazards models were fit to estimate the association of first-degree family history with risk of invasive breast cancer (after adjustment for breast density, BCSC registry, race/ethnicity, body mass index, postmenopausal hormone therapy use, and benign breast disease for age groups 65 to 74 years and 75 years and older, separately). Data analyses were performed between June 2016 and June 2017. Exposure First-degree family history of breast cancer. Main Outcomes and Measures Incident breast cancer. Results In 403 268 women 65 years and older, first-degree family history was associated with an increased risk of breast cancer among women ages 65 to 74 years (hazard ratio [HR], 1.48; 95% CI, 1.35-1.61) and 75 years and older (HR, 1.44; 95% CI, 1.28-1.62). Estimates were similar for women 65 to 74 years with first-degree relative’s diagnosis age younger than 50 years (HR, 1.47; 95% CI, 1.25-1.73) vs 50 years and older (HR, 1.33; 95% CI, 1.17-1.51) and for women ages 75 years and older with the relative’s diagnosis age younger than 50 years (HR, 1.31; 95% CI, 1.05-1.63) vs 50 years and older (HR, 1.55; 95% CI, 1.33-1.81). Among women ages 65 to 74 years, the risk associated with first-degree family history was highest among those with fatty breasts (HR, 1.67; 95% CI, 1.27-2.21), whereas in women 75 years and older the risk associated with family history was highest among those with dense breasts (HR, 1.55; 95% CI, 1.29-1.87). Conclusions and Relevance First-degree family history was associated with increased risk of invasive breast cancer in all subgroups of older women irrespective of a relative’s age at diagnosis.

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults.

BACKGROUND Although healthy women aged 65 years have a life expectancy of 20 years, there is a paucity of data on the performance of digital screening mammography among these women. The authors examined the performance and outcomes of digital screening mammography among a national group of women aged ≥65 years. METHODS From Breast Cancer Surveillance Consortium data for the years 2005 to 2011, the authors included 296,496 full-field digital screening mammograms among 133,042 women ages ≥65 years without a history of breast cancer. Sensitivity, specificity, positive predictive value (PPV1), recall rates, and 95% confidence intervals (95% CIs) were calculated across the spectrum of age and breast density. Multivariate logistic regression was used to compare mammography accuracy, cancer-detection rates (CDRs), and tumor characteristics by age and breast density. RESULTS Multivariate analyses revealed a significant decrease in the recall rate with age (P for linear trend [Ptrend]

Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear. Methods: We studied the relationship of SEP to pubertal onset in a multiethnic cohort of 1,237 girls ages 6 to 8 years at baseline. Girls in three U.S. cities were followed for 5 to 8 years with annual clinical examinations from 2004 to 2012. SEP measures were examined for associations with pubertal onset, assessed by breast budding (thelarche) and pubic hair development (adrenarche). Analyses were conducted with accelerated failure time models using a Weibull distribution, with left, right, and interval censoring. Results: Higher body mass index percentage at entry to the study and black or Hispanic race/ethnicity were the strongest predictors of age at pubertal onset. An SEP index comprising household family income, mother's education, and home ownership was an independent predictor of thelarche in adjusted models for all girls together and for white and Latina, separately, but not black girls, and the relationship varied by study site. The SEP index was not related to adrenarche in adjusted models. Overall, girls from the lowest quintile of SEP entered puberty on average 6% earlier than girls from the highest quintile (time ratio = 0.94; 95% confidence interval 0.91–0.97) in adjusted models. Conclusions: Our results suggest that early-life SEP may influence the timing of pubertal development. Impact: Factors related to lower SEP in childhood can adversely affect early development in ways that may increase the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1714–21. ©2017 AACR.

OBJECTIVE: We conducted a systematic review of the literature relating early life socioeconomic position (SEP) to breast cancer incidence and mortality from a critical period and life course trajectory perspective. METHODS: PubMed, EMBASE and Web of Science were searched to identify cohort studies that evaluated the impact of early life SEP indicators on the incidence and/or mortality from breast cancer in adulthood. RESULTS: Nine distinct studies evaluated the relationship between early life SEP and breast cancer between 1990 and 2016. Five reports assessed breast cancer incidence and five assessed breast cancer mortality as outcomes; one study assessed both incidence and mortality. While lower early life SEP was associated with reduced breast cancer incidence and increased breast cancer mortality in the US, studies conducted in Europe were unable to establish a consistent association. CONCLUSIONS: We found moderate support for the association between early life SEP and incidence and mortality from breast cancer. The impact of early life SEP on breast cancer incidence and mortality appeared to vary between countries. We urge further investigation of the role of lifelong SEP trajectories in breast cancer outcomes.

Background The purpose of this review was to summarize the published literature on the association of childhood, adulthood and life course socio-economic status (SES) with obesity between January 1990 and June 2015. Methods The major medical electronic databases were searched to identify studies that examined SES over the life-course in relation to obesity. A total of 219 studies were identified through the initial search, and 35 qualified for full review. Of these, 14 publications met our inclusion criteria for the meta-analysis, all from developed or upper-middle income countries. Results There was a consistent association between lower life course SES and obesity among women (summary OR: 1.35, 95% CI: 1.04, 1.76), but not among men (summary OR: 0.92, 95% CI: 0.60, 1.40). Overall, mean BMI was higher among individuals with lower life course SES compared with those with higher life course SES (summary mean BMI difference: 0.65, 95% CI: 0.59, 0.71). Mean waist circumference (WC) was higher among women with lower life course SES compared with those with higher life course SES (summary mean WC: 4.67, 95% CI: 4.15, 5.20), but lower among men (summary mean WC difference: -0.10, 95% CI: -0.11, -0.08). Conclusion The inverse relationship between life course SES and obesity among women was consistent, based mostly on studies in developed countries. Nevertheless, critical information gaps remain in relation to the impact of childhood and life course SES on obesity in developing countries.

The International Agency for Research on Cancer estimates that over half of the new cancer cases and almost two-thirds of the cancer deaths in 2012 occurred in low and middle income countries. To discuss the challenges and opportunities to reducing the burden of cancer worldwide, the Molecular Epidemiology and the Environment and the International Issues in Cancer Special Interest Groups joined forces to hold a session during the 38th Annual Meeting of the American Society of Preventive Oncology (March 2014, Arlington, Virginia). The session highlighted three topics of particular interest to molecular cancer prevention researchers working internationally, specifically: 1) biomarkers in cancer research; 2) environmental exposures and cancer; and 3) molecular pathological epidemiology. A major factor for successful collaboration illuminated during the discussion was the need for strong, committed, and reliable international partners. A key element of establishing such relationships is to thoroughly involve individual international collaborators in the development of the research question; engaged international collaborators are particularly motivated to champion and shepherd the project through all necessary steps, including issues relating to institutional review boards, political sensitivity, laboratory-based assays, and tumor subtyping. Also essential is allotting time for the building, maintaining, and investing in such relationships so that successful international collaborations may take root and bloom. While there are many challenges inherent to international molecular cancer research, the opportunities for furthering the science and prevention of cancer worldwide are great, particularly at this time of increasing cancer incidence and prevalence in low and middle income countries. Cancer Epidemiol Biomarkers Prev; 23(11); 2613–7. ©2014 AACR.

The mission of the American Society for Preventive Oncology Special Interest Group in International Issues in Cancer is to serve as a worldwide cancer prevention resource. At the 2013 annual meeting, we presented three early career investigators who conducted research with international collaborators as part of postdoctoral studies. We present a synopsis of each of the scientific presentations. The investigators also highlight useful strategies to encourage a more successful international collaboration, including seeking out existing collaborations between colleagues and international researchers, maintaining awareness and sensitivity of cultural norms, establishing clear communication about investigator roles and expectations, and persevering in the face of potential challenges due to the nature of these collaborations. Incorporation of these key elements could prove useful for researchers interested in pursuing cross-country projects. Cancer Epidemiol Biomarkers Prev; 22(9); 1638–41. ©2013 AACR.

BACKGROUND Biennial screening mammography retains most of the benefits of annual breast cancer screening with reduced harms. Whether screening guidelines based on race/ethnicity and age would be more effective than age-based guidelines is unknown. METHODS Mammography data from the Breast Cancer Surveillance Consortium were linked to pathology and tumor databases. The authors identified women aged 40 to 74 years who underwent annual, biennial, or triennial screening mammography between 1994 and 2008. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of adverse tumor characteristics among 14,396 incident breast cancer cases and 10-year cumulative risks of false-positive recall and biopsy recommendation among 1,276,312 noncases. RESULTS No increased risk of adverse tumor characteristics associated with biennial versus annual screening were noted in white women, black women, Hispanic women aged 40 to 49 years, or Asian women aged 50 to 74 years. Hispanic women aged 50 to 74 years who screened biennially versus annually were found to have an increased risk of late-stage disease (OR, 1.6; 95% CI, 1.0-2.5) and large tumors (OR, 1.6; 95% CI, 1.1-2.4). Asian women aged 40 to 49 years who underwent biennial screening had an elevated risk of positive lymph nodes (OR, 3.1; 95% CI, 1.3-7.1). No elevated risks were associated with triennial versus biennial screening. Cumulative false-positive risks decreased markedly with a longer screening interval. CONCLUSIONS The authors found limited evidence of elevated risks of adverse tumor characteristics with biennial versus annual screening, whereas cumulative false-positive risks were lower. However, elevated risks of late-stage disease in Hispanic women and lymph node-positive disease in younger Asian women who screened less often than annually warrant consideration and replication. Cancer 2013;119:3959–3967. © 2013 American Cancer Society.

More than 50% of new invasive breast cancer cases diagnosed each year in the USA occur among women aged 65 years and older (hereafter referred to as ‘older’ women), and rates rise dramatically with advancing age [101]. With the increasing life expectancy and aging of women in the USA and worldwide, the absolute number of breast cancer cases among older women is expected to increase substantially over the coming decades. These dual demographic and epidemiologic forces, coupled with heterogeneity in health and the lack of direct evidence for screening effectiveness among older women, create a clinical and policy conundrum: what is the optimal upper age limit and screening frequency for which the balance of benefits and harms continues to favor ongoing screening? [1,2]. Apparent age-related differences in tumor biology, variations in women’s preferences for health outcomes associated with breast cancer screening, and increasing healthcare costs add to the challenge in answering this question [2,3].

Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risk of adverse tumor characteristics and false positive rates according to screening interval, age, and comorbidity. Methods From January 1999 to December 2006, data were collected prospectively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims. Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses. We used logistic regression analyses to calculate the odds of advanced (IIb, III, IV) stage, large (>20 millimeters) tumors, and 10-year cumulative probability of false-positive mammography by screening frequency (1 vs 2 years), age, and comorbidity score. The comorbidity score was derived using the Klabunde approximation of the Charlson score. All statistical tests were two-sided. Results Adverse tumor characteristics did not differ statistically significantly by comorbidity, age, or interval. Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48.0% (95% confidence interval [CI] = 46.1% to 49.9%) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0% (95% CI = 28.1% to 29.9%) of biennial screeners. Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity.

Objectives Socioeconomic differences in screening have been well documented in upper-income countries; however, few studies have examined socioeconomic status (SES) over the life-course in relation to cancer screening in lower-income and middle-income countries. Here, we examine individual, parental and life-course SES differences in breast and cervical cancer screening among women in India, China, Mexico, Russia and South Africa. Setting Data from the WHO9s Study on Global Ageing and Adult Health (SAGE) 2007–2008 data were used for survey-weighted multivariable regression analysis. We examined the association between individual, parental and life-course SES in relation to breast and cervical cancer screening using education-based and employment-based measures of SES. Participants 22 283 women aged 18–65 years, recruited from China, India, Mexico, Russia and South Africa. Results Having a college degree (OR 4.18; 95% CI 2.36 to 7.40) increased the odds of breast cancer screening compared with no formal education. Women with higher parental SES were almost 10 times more likely to receive breast cancer screening (OR 9.84; 95% CI 1.75 to 55.5) compared with women with low parental SES. Stable higher life-course (OR 3.07; 95% CI 1.96 to 4.79) increased breast cancer screening by threefold and increased cervical cancer screening by more than fourfold (OR 4.35; 95% CI 2.94 to 6.45); however, declining life-course SES was associated with reduced breast cancer screening (OR 0.26; 95% CI 0.08 to 0.79) compared to low life-course SES. Conclusions Higher individual, parental and life-course SES was positively associated with breast and cervical cancer screening, although education-based SES measures were stronger predictors of screening compared with employment-based measures. Improving knowledge of the benefits of cancer screening and integrating cancer screening into routine healthcare practice for low SES women are actionable strategies that may significantly improve screening rates in low-income and middle-income countries.

Low-grade chronic inflammation is a proposed mechanism linking excess body weight with cancer development. Adipocytes, particularly visceral fat cells, regularly release pro-inflammatory cytokines likely due to hypoxic and necrotic conditions in conglomerated fat tissue in obese individuals. C-reactive protein (CRP), a long-established acute-phase reactant, is triggered primarily by the cytokine Interleukin-6, as part of the innate immune system apparatus to resolve acute infection, injury, and inflammation. Some but not all epidemiologic studies suggest that low-grade circulating CRP levels predict cancer development, particularly for lung and colon cancers. Evidence as a prognostic factor, however, is more convincing, but whether or not elevated CRP reflects inflammation associated with large, aggressive neoplasms or solely serves as a general marker of mortality risk needs clarification.

Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density. Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1st-degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density. Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0–2.1 at age 40; RR, 1.5; 95% CI, 1.3–1.7 at age 50; RR, 1.4; 95% CI, 1.2–1.6 at age 60; RR, 1.3; 95% CI, 1.1–1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1–3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88–1.5 at age 70). Associations did not change substantially when adjusted for breast density. Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history. Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938–44. ©2017 AACR.

Background Approximately half of new invasive breast cancer cases diagnosed each year in the United States occur among women aged 65 years and older. The increasing life expectancy coupled with the attendant rise in breast cancer incidence and elimination of out-of-pocket expenses for screening mammography as a result of the Affordable Care Act could lead to higher utilization rates of screening mammography. Although research indicates that life expectancy should be a strong consideration when making screening decisions among older women, the extent to which screening mammography utilization is tailored to comorbidity and life expectancy is not well established. Methods/design To identify relevant studies, a systematic search of the literature will be conducted using PubMed and EMBASE between January 1, 1991, and March 1, 2016. Additional studies will be found through citation review or by contacting experts in the field. The inclusion criteria will be any study design comprised of women aged 65 and older, assessing women’s comorbidity, functional impairments, and/or health status, and reporting outcome measures that addressed mammography utilization within the last 1–5 years. For each study, two authors will independently abstract data regarding study eligibility and outcomes to determine relevance. Quantitative results will be extracted from text and tables, choosing preferably those adjusted for important confounders. Discussion The review will provide evidence on the impact of comorbidity, functional limitations, and health status on screening mammography utilization in older women and inform decision aids in this area. Systematic review registration PROSPERO CRD42016032661 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0345-y) contains supplementary material, which is available to authorized users.

Objective To determine the association of prediagnostic alcohol consumption with long-term mortality from breast cancer and other causes in a cohort of women with breast cancer. Methods We studied a Michigan-based cohort of 939 women aged 40-84 years, who provided complete information about the type, amount and intensity of prediagnostic alcohol consumption. Associations of alcohol consumption, based on weekly volume of alcohol consumption during the year prior to breast cancer diagnosis, with mortality were evaluated in Cox proportional hazards models, with adjustment for sociodemographic factors, body mass index, smoking, comorbidity, tumor characteristics, and treatment. Differences among covariates were assessed with Pearson χ2 , Student t -tests and Wilcoxon Rank Sum tests. All statistical tests were two-sided. Results During a median follow-up of 11 years, 724 deaths occurred overall, with 303 from breast cancer. Fifty-five percent of the women were categorized as drinkers with volume of alcohol consumption ranging from 0.75 to 36.00 drinks/week. In multivariable models, a decreased risk of other-cause mortality was associated with low alcohol drinking (0.75-3.75 drinks/week; HR = 0.61, 95% CI = 0.47-0.78), moderate volume alcohol drinking (4.00-9.75 drinks/week; HR = 0.57, 95% CI = 0.39-0.85) and low frequency (0.75-3.75 drinks/week) beer and wine intake (HR = 0.69, 95% CI = 0.50-0.96 and HR = 0.68, 95% CI = 0.52-0.88 respectively). Although the risk of breast cancer-specific mortality was not statistically significantly associated with moderate (4.00-9.75 drinks/week) and high volume (10.00-36.00 drinks/week) alcohol drinking in the overall cohort (HR = 1.43, 95% CI = 95% 0.97-2.12 and HR = 1.53, 95% CI = 0.87-2.70 respectively), there was a positive association of alcohol consumption with breast cancer-specific mortality among current smokers (HR = 1.92, 95% CI = 1.03-3.57; Pinteraction = 0.04). Conclusion In this prospective cohort study, regular consumption of 0.75-36.00 alcoholic drinks per week during the year prior to breast cancer diagnosis was associated with a reduction in other-cause mortality and with an increase in breast cancer-specific mortality among current smokers, after taking into account clinical and sociodemographic factors.

Few studies have examined cancer-related risk factors in relation to SES across the lifecourse in low to middle income countries. This analysis focuses on adult women in India, China, Mexico, Russia and South Africa, and examines the association between individual, parental and lifecourse SES with smoking, alcohol, BMI, nutrition and physical activity. Data on 22,283 women aged 18 years and older were obtained from the 2007 WHO Study on Global Aging and Adult Health (SAGE). Overall, 34% of women had no formal education, 73% had mothers with no formal education and 73% of women had low lifecourse SES. Low SES women were almost four times more likely to exceed alcohol use guidelines (OR: 3.86, 95% CI: 1.23-12.10), and 68% more likely to smoke (OR: 1.68, 95% CI: 1.01-2.80) compared with higher SES. Women with low SES mothers and fathers were more likely to have poor nutrition (Mothers OR: 1.59, 95% CI: 1.17-2.16; Fathers OR: 1.33, 95% CI: 1.11-1.59) and more likely to smoke (Mothers OR: 1.46, 95% CI: 1.15-1.87; Fathers OR: 2.17, 95% CI: 1.80-2.63) compared with those with high SES parents. Women with stable low lifecourse SES were more likely to smoke (OR: 2.55, 95% CI: 1.47-4.43), while those with declining lifecourse SES were more likely to exceed alcohol use guidelines (OR: 3.63, 95% CI: 1.07-12.34). Cancer-related risk factors varied significantly by lifecourse SES, suggesting that cancer prevention strategies will need to be tailored to specific sub-groups in order to be most effective.

The association of smoking with outcomes following breast cancer prognosis is not well understood. In a cohort study called Life After Cancer Epidemiology (LACE), 2,265 women diagnosed with breast cancer were followed for a median of 12 years. We used multivariable proportional-hazards models to determine whether smoking, assessed approximately two years post-diagnosis, was associated with risk of death among these women. We also undertook a systematic review of all cohort studies to date that have examined the association between smoking and breast cancer mortality. Compared with never smokers, women who were current smokers had a twofold higher rate of dying from breast cancer [hazard ratio (HR) = 2.01, 95 % confidence interval (CI) 1.27-3.18] and an approximately fourfold higher rate of dying from competing (nonbreast cancer) causes (HR = 3.84, 95 % CI 2.50-5.89). Among seven studies that met the inclusion criteria in the systematic review, three studies and our own reported significantly increased risk of breast cancer death with current smoking. We found little evidence of an association between former smoking and breast cancer mortality (HR = 1.24, 95 % CI 0.94-1.64). Consistent with findings from our prospective observational study, the systematic review of seven additional studies indicates positive association of current smoking with breast cancer mortality, but weak association with former smoking. Women who smoke following breast cancer diagnosis and treatment are at higher risk of death both from breast cancer and other causes. © Springer Science+Business Media New York 2012.

Due to an increasing comorbidity burden with aging, the margin of benefit from screening mammography in women ages ≥65 is highly variable. This study examined 10-year cumulative risk of non-breast cancer mortality and breast cancer by comorbidity and age in a screening population. Methods: We used prospective cohort data from the Breast Cancer Surveillance Consortium (BCSC), which included 198,362 women ages ≥65 years who have undergone at least one screening mammogram. We calculated cumulative incidence of non-breast cancer mortality and risk of breast cancer 10 years following the screening mammogram for women ages 65–74, 75–84 and ≥85 years stratified by the Charlson Comorbidity Index (CCI scores 0, 1 and ≥2). Results: During a median follow-up time of 8.1 years (interquartile range, 4.6 to 10 years), 34,768 died from non-breast cancer causes and 6,327 women were diagnosed with invasive breast cancer of whom 359 died from breast cancer and 942 from non-breast cancer causes. The 10-year cumulative risk of invasive breast cancer following a screening mammogram did not significantly decrease with elevating CCI score and age for women ages 65–74 [CCI 0 = 4.0% (95% CI, 3.9%–4.1%) vs. CCI ≥2 = 3.8% (95% CI, 3.3%–4.3%)], ages 75–84 [CCI 0 = 3.7% (95% CI, 3.5%–3.9%) vs. CCI ≥ 2 = 3.4% (95% CI, 2.8%–4.0%)], and ages ≥85 [CCI 0 = 2.7%, (95% CI, 2.3%–3.2%) vs. CCI ≥ 2 = 2.5% (95% CI, 1.4%–3.6%)]. Cumulative risk of non-breast cancer mortality significantly increased with increasing CCI and age for women ages 65–74 [CCI 0 = 11% (95% CI, 10%–11%] vs. CCI ≥ 2 = 45% (95% CI, [43%–46%)], ages 75–84 [CCI 0 = 29% (95% CI, 29%–30%) vs. CCI ≥2 = 62% (95% CI, 60%–63%)], and ages ≥85 [CCI 0 = 59%, (95% CI, 57%–60%) vs. CCI ≥2 = 84% (95% CI, 81%–86%)]. Conclusion: Risk of non-breast cancer mortality was high and significantly increased with rising comorbidity burden and age whereas breast cancer risk was low and non-significantly decreased with both. These results suggest that women with a CCI score of ≥2 or ages ≥75 years may experience minimal benefit from continuing routine screening mammography. Future research is needed to delineate the specific benefits and harms of screening mammography in subsets of older women defined by age and comorbidity burden.

This study examined whether breast density is associated with risk of breast cancer in women age ≥65 years undergoing screening mammography in community practice. Methods: We used prospective cohort data between 1996 and 2012 from the Breast Cancer Surveillance Consortium (BCSC). We calculated separate cumulative incidence models for breast cancer incidence according to Breast Imaging Reporting and Data System (BI-RADS) breast density for women ages 65–74 and ages ≥75. Multivariable Cox proportional hazards regression models were fitted to determine the risk of invasive breast cancer adjusted for BCSC registry, race/ethnicity, BMI, hormone therapy use and benign breast disease. Results: Among the 403,268 women included in the study, approximately 40% were ages ≥75. The annual incidence rate of invasive breast cancer increased with increasing breast density among women ages 65–74 [BI- RADS fatty breasts: 2.2% (95% CI, 2.1%–2.4%) vs. heterogeneously or extremely dense breasts: 4.7% (95% CI, 4.6%–4.9%)] and women ages 75+ [BI-RADS fatty breasts: 2.3% (95% CI, 2.1%–2.5%) vs. heterogeneously or extremely dense: 4.3% (95% CI, 4.1%–4.5%)]. Women with BI-RADS fatty breasts had a decreased risk of breast cancer among women ages 65–74 [HR: 0.66 (95% CI: 0.58%–0.78%) and women ages ≥75 [HR: 0.73 (95% CI: 0.62%–0.87%). Women with BI-RADS heterogeneously or extremely dense breasts were found to have increased risk of breast cancer among women ages 65–74 [HR: 1.39 (95% CI: 1.28%–1.51%)] and women ages ≥75 [HR: 1.23 (95% CI: 1.10%–1.37%)]. Conclusions: Older women with higher BI-RADS density had a significantly increased risk of breast cancer. These findings add further evidence that breast density continues to be associated with an increased risk of breast cancer, even among women age ≥75 years.

Purpose Adjuvant! Online ( www.adjuvantonline.org ) is a software model that predicts the benefit of adjuvant therapy for women with early-stage breast cancer. The model has been validated, is widely consulted, and has been shown to influence patient choices in the clinical setting. Adjuvant! requires the clinician to input patient age, tumor size, grade, hormone receptor status, number of positive lymph nodes, and comorbidity level. Because comorbidity is strongly and independently associated with survival, this study tested the hypothesis that Adjuvant! predictions would be sensitive to comorbidity inputs. Methods Investigators used single-variable deterministic sensitivity analysis to evaluate the effect of varying each input of the model independently for three representative case examples based on National Comprehensive Cancer Network guidelines (NCCN). The main outcome of interest was 10-year mortality prediction. Results The analyses show that Adjuvant!'s 10-year mortality predictions are most sensitive to patients’ comorbidity levels and the extent of nodal involvement for the cases, particularly among older women. Comorbidity was the most influential input except in younger women, aged 40 years. Conclusion The Adjuvant! model is sensitive to patient comorbidity, and impact on the model outputs are significant enough that they are likely to affect physician recommendations and patients’ treatment choices. For example, incorrect assessments of comorbidities could lead physicians to overtreat or undertreat a patient who is in a gray zone relative to the NCCN guidelines. These results point to the importance of accurately assessing comorbidities in patients with breast cancer when using Adjuvant! and highlight the need for a standardized process of comorbidity ascertainment.

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults.

We conducted a systematic review to assess the quality and limitations of published studies examining benefits and harms of screening mammography in relation to comorbidity and age. We searched MEDLINE and EMBASE from January 1980 through June 2013 for studies that examined benefits or harms of screening mammography in women aged 65 years or older in relation to comorbidity. For each study, we extracted data regarding setting, design, quality, screening schedule, measure of comorbidity, and estimates of benefits and/or harms. We reviewed 1760 titles, identifying 7 articles that met the inclusion criteria: prospective cohort (two studies), retrospective cohort (two studies), and decision analyses (three studies). No randomized controlled trials were identified. At least one measure of life expectancy or reduction in the risk of breast cancer death as a marker of benefit was examined in four studies, whereas three studies addressed the harms of screening mammography, including false-positive results. Both cohort studies and decision analyses showed that screening benefits decreased with increasing age and comorbidity burden. The limited evidence currently available suggests that, apart from older women with severe comorbidity, women 65 and older may experience improvements in life expectancy from screening. Given the potential for harm, it is unclear whether the magnitude of the benefit is sufficient to warrant regular screening. Women, clinicians and policymakers should consider these factors in deciding whether continue screening.

Background: Innovative technologies that enable the collection of family history information and the assessment of breast cancer risk have a potential to enhance the quality of preventive care. We developed a computerized tool that supports stratification of breast cancer risk, genetic risk assessment in the clinical environment (GRACE). Methods: In a preliminary evaluation of the tool's impact, we randomized women with a family history of breast cancer ( n =72) to either use the GRACE tool or undergo risk counseling by a nurse specialist. Results: There was no statistically significant differences between the GRACE and nurse counselling groups in risk perceptions ( F =.03, P >.05) and cancer-related worries ( F =.80, P >.05). However, patients reported more positive attitudes toward working with the nurse. Conclusion: It was feasible to use GRACE in a Clinic. Additional research is required to identify solutions for providing emotional support in conjunction with the tool.

PURPOSE Although the family history is increasingly used for genetic risk assessment of common chronic diseases in primary care, evidence suggests that lay understanding about inheritance may confl ict with medical models. This study systematically reviewed and synthesized the qualitative literature exploring understanding about familial risk held by persons with a family history of cancer, coronary artery disease, and diabetes mellitus. METHODS Twenty-two qualitative articles were found after a comprehensive literature search and were critically appraised; 11 were included. A meta-ethnographic approach was used to translate the studies across each other, synthesize the translation, and express the synthesis. RESULTS A dynamic process emerged by which a personal sense of vulnerability included some features that mirror the medical factors used to assess risk, such as the number of affected relatives. Other features are more personal, such as experience of a relative’s disease, sudden or premature death, perceived patterns of illness relating to gender or age at death, and comparisons between a person and an affected relative. The developing vulnerability is interpreted using personal mental models, including models of disease causation, inheritance, and fatalism. A person’s sense of vulnerability affects how that person copes with, and attempts to control, any perceived familial risk. CONCLUSIONS Persons with a family history of a common chronic disease develop a personal sense of vulnerability that is informed by the salience of their family history and interpreted within their personal models of disease causation and inheritance. Features that give meaning to familial risk may be perceived differently by patients and professionals. This review identifi es key areas for health professionals to explore with patients that may improve the effectiveness of communication about disease risk and management.

Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with the age of menarche, which is inversely associated with risk of breast cancer, and to the age of pubertal onset, is less clear. We studied the relationship of SEP to pubertal onset in a multiethnic cohort of girls aged 6–8 years at baseline and followed for 5–8 years in the Breast Cancer and the Environment Research Program in three study sites across the United States that included annual clinical examinations performed from 2004 to 2012. Analyses were conducted with accelerated failure time models using a Weibull distribution, with left, right and interval censoring. Among 1059 girls, an index of SEP comprised of household family income, mother's education and whether the home was owned or rented was assessed for associations with pubertal onset, measured by breast budding (Tanner Stage B2) and pubic hair development (Tanner Stage PH2). Girl's BMI% at entry to the study and black or Hispanic race/ethnicity were the strongest predictors of age at pubertal onset by both measurements, but the SEP index was an independent predictor in adjusted models. Girls from the lowest quintile of SEP entered puberty on average 6% earlier (6.0–7.5 months) than girls from the highest quintile (time ratio = 0.94, 95% confidence interval 0.91–0.97) adjusted for BMI%, race/ethnicity and their interaction. The meaning of SEP in this relationship bears further study, but our results suggest that early life social circumstances beyond race/ethnicity and body size may influence the timing of pubertal development. The following are the 17 highest-scoring abstracts of those submitted for presentation at the 40th Annual ASPO meeting held March 13–15, 2016, in Columbus, OH.

BACKGROUND Computer decision support systems have been proposed as a suitable method to enable primary care practitioners to manage familial cancer and advise about other developments in clinical genetics. OBJECTIVE To investigate GPs' preferences, attitudes and intentions regarding the use of Genetic Risk Assessment on the Internet and Decision Support (GRAIDS) in clinical practice. METHODS GPs were recruited through a physician Internet portal for UK GPs (www.ukpractice.net). Electronic questionnaires assessed the respondents' current practice regarding family history taking and risk assessment, preferences about particular attributes of GRAIDS, intentions to use GRAIDS for familial cancer management and factors associated with these intentions. RESULTS Two hundred and sixty-eight GPs completed the electronic survey (adjusted response rate = 51.2%). Seventy-two GPs participated in a telephone survey of non-respondents (adjusted response rate = 63%). Ninety-two per cent of respondents in the electronic survey and 68% in the telephone survey stated that they would be either extremely or fairly likely to use GRAIDS. Intentions were associated with positive attitudes toward GRAIDS, beliefs that colleagues and patients would find the tool acceptable, perceived control and perceived confidence about conducting risk assessment and making appropriate decisions about patient management. Key attributes for the implementation of GRAIDS in practice were the authoritativeness of the guideline, easy user interface, the validity and reliability of risk estimation and specific advice about patient management. CONCLUSION GP users of the physician portal www.ukpractice.net value GRAIDS as an aid for the management of familial cancer in primary care. These Internet-literate GPs are likely to be early adopters of GRAIDS in clinical practice and could be important in promoting the use of such technology to support high quality advice about genetic issues in primary care.

This study aimed to identify factors predictive of intentions to participate in genetic testing for hereditary cancer. Measures of the psychosocial influences on intention were based on the theories of reasoned action (TRA) and planned behaviour (TPB) and a new measure of Attitude toward Uncertainty. The participants (the breast cancer sample, n = 124; the colon cancer sample, n = 168) were recruited via a general practitioner's patient database and asked to complete postal questionnaires. The overall response rate was 57.4% (54.7% in the colon cancer sample, 61.4% in the breast cancer sample). In the colon cancer sample, 72% of respondents stated that they would choose to participate in genetic testing for colon cancer susceptibility. In the breast cancer sample, 77% of respondents stated that they would choose to participate in genetic testing for breast cancer susceptibility. The TRA components (attitudes and subjective norms) and Attitude toward Uncertainty emerged as the strongest predictors of inten...

We examined the effect of smoking on long-term mortality from breast cancer and other causes among a cohort of women with breast cancer. A total of 975 women diagnosed with breast cancer and aged 40–84 years were followed for a median follow-up of 11 years in the U.S. Health and Functioning in Women (HFW) study. The impact of the individual smoking status and smoking intensity reported in the first few months following breast cancer diagnosis on the risk of mortality from breast cancer and other causes was examined using Cox proportional hazards models. In this study, former smoking was associated with increased risk of other-cause mortality (hazard ratio [HR] = 1.47, 95% confidence interval [CI]: 1.13–1.90), and the risk doubled with increased intensity (HR for

Given the relatively high prevalence of sickle cell trait and disease among African Americans and established racial disparities in cancer outcomes, we reviewed the literature regarding adverse events in cancer patients with these hematologic genotypes. Erythrocyte sickling can result from extreme hypoxia and other physiologic stressors, as might occur during cancer therapy. Further, tumoral hypoxia, a poor prognostic and predictive factor, could lead to a cycle of local sickling and increased hypoxia. A search of PubMed produced 150 publications, most of which were excluded because of incidental relevance. Eleven case reports of patients diagnosed from 1993 to 2013 were reviewed. Two reports of patients with sickle cell trait describe an abundance of sickled erythrocytes within tumors, and a third report describes sickling-related events requiring multiday hospitalization. Eight reports of patients with sickle cell disease delineated multiorgan failure, vaso-occlusive crises, and rapid renal deterioration. Hypothesized triggers are delayed clearance of anticancer agents attributable to baseline kidney damage, activation of vasoadherent neutrophils from treatment to counter chemotherapy-induced neutropenia, hypoxia from general anesthesia, and intratumoral hypoxia. Clinical implications include pretreatment genotyping for prophylaxis, dose adjustment, and enhanced patient monitoring. With the current lack of high-quality evidence, however, the scope of poor outcomes remains unknown. Genet Med 17 3, 237–241.

Objectives: We examined the association between comorbidity and long-term mortality from breast cancer and other causes among African-American and white women with breast cancer. Methods: A total of 170 African-American and 829 white women aged 40-84 years were followed for up to 28 years with median follow-up of 11.3 years in the Health and Functioning in Women (HFW) study. The impact of the Charlson Comorbidity Score (CCS) in the first few months following breast cancer diagnosis on the risk of mortality from breast cancer and other causes was examined using extended Cox models. Results: Median follow-up was significantly shorter for African-American women than their white counterparts (median 8.5 years vs. 12.3 years). Compared to white women, African-American women had significantly fewer years of education, greater body mass index, were more likely to have functional limitations and later stage at breast cancer diagnosis, and fewer had adequate financial resources (all P < 0.05). Proportionately more African-American women died of breast cancer than white women (37.1% vs. 31.4%, P = 0.15). A positive and statistically significant time-varying effect of the Charlson Comorbidity Score (CCS) on other-cause mortality persisted throughout the first 5 years of follow-up (P < 0.001) but not for its remainder. Conclusions: Higher CCS was associated with increased risk of other-cause mortality, but not breast cancer specific mortality; the association did not differ among African-American and white women. © 2014 Elsevier Inc. All rights reserved.

Despite steady decreases in the cancer burden in industrialized countries, its rapid increase in the developing world means that the number of cancer cases and deaths will likely more than double worldwide over the next two decades ([1][1]). Already a leading cause of death around the globe, cancer

Objectives: We examined the impact of functional limitations and functional decline during the first year following breast cancer diagnosis on the risk of mortality from breast cancer and other causes among African-American and white women, respectively. Design: The Health and Functioning in Women (HFW) cohort study. Setting: Detroit, Michigan, USA. Participants: A total of 162 African-American and 813 white women aged 40-84 years with newly diagnosed breast cancer identified through the Metropolitan Detroit Cancer Surveillance System over a 7-month period between 1984 and 1985 and followed for up to 28 years (median 11 years). Outcome measures: Risk of mortality from breast cancer and other causes. Results: Statistically significant increases in the risk of other-cause mortality were found for each unit increase in the number of self-reported functional limitations (HR=1.08, 95% CI 1.03 to 1.14), 0 vs ≥1 functional limitations (HR=1.47, 95% CI 1.13 to 1.91), difficulty in pushing or pulling large objects (HR=1.34, 95% CI 1.04 to 1.73), writing or handling small objects (HR=1.56, 95% CI 1.00 to 2.44), and walking half a mile (HR=1.60, 95% CI 1.19 to 2.14). Functional limitations and functional decline did not explain racial disparities in the survival of this cohort. Functional decline was associated with increased risk of other-cause mortality in women with regional and remote disease but not in women with localised disease. Whereas measures of functional limitation were not associated with breast cancer-specific mortality, each unit of functional decline (HR=1.17, 95% CI 1.05 to 1.31) and decline in the ability to sit ≥1 h (HR=2.06, 95% CI 1.13 to 3.76) were associated with increased risk of breast cancer-specific mortality. Measures of functional decline were associated with increased risk of breast cancer mortality in overweight and obese women, but not in women of normal weight. Conclusions: Whereas functional limitations were associated with increased risk of other-cause mortality, functional decline was associated with increased risk of breast cancer mortality.

Importance Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age. Objective To compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use. Design Prospective cohort. Setting Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries. Participants Data were collected prospectively on 11 474 women with breast cancer and 922 624 without breast cancer who underwent mammography at facilities that participate in the BCSC. Main Outcomes and Measures We used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (>20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval. Results Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women's breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively). Conclusions and Relevance Women aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high.

Background Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS. Objectives To evaluate the efficacy and safety of rituximab for MS treatment. Data collection Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies. Main results Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events. Author’s conclusion Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal.

Controversy remains regarding the frequency of screening mammography. Women with different risks for developing breast cancer because of body mass index (BMI) may benefit from tailored recommendations.To determine the impact of mammography screening interval for women who are normal weight (BMI25), overweight (BMI 25-29.9), or obese (BMI ≥ 30), stratified by menopausal status.Two cohorts selected from the Breast Cancer Surveillance Consortium. Patient and mammography data were linked to pathology databases and tumor registries.The cohort included 4,432 women aged 40-74 with breast cancer; the false-positive analysis included a cohort of 553,343 women aged 40-74 without breast cancer.Stage, tumor size and lymph node status by BMI and screening interval (biennial vs. annual). Cumulative probability of false-positive recall or biopsy by BMI and screening interval. Analyses were stratified by menopausal status.Premenopausal obese women undergoing biennial screening had a non-significantly increased odds of a tumor size20 mm relative to annual screeners (odds ratio [OR] = 2.07; 95 % confidence interval [CI] 0.997 to 4.30). Across all BMI categories from normal to obese, postmenopausal women with breast cancer did not present with higher stage, larger tumor size or node positive tumors if they received biennial rather than annual screening. False-positive recall and biopsy recommendations were more common among annually screened women.The only negative outcome identified for biennial vs. annual screening was a larger tumor size (20 mm) among obese premenopausal women. Since annual mammography does not improve stage at diagnosis compared to biennial screening and false-positive recall/biopsy rates are higher with annual screening, women and their primary care providers should weigh the harms and benefits when deciding on annual versus biennial screening.

Background: Little is known about the long-term impact of comorbidity among women with breast cancer. Methods: We studied a prospective cohort of 2,272 women with breast cancer, who were recruited following initial breast cancer treatment. Associations of the Charlson comorbidity index (CCI) and hypertension with survival were evaluated in delayed entry Cox proportional hazards models. Results: During a median follow-up of nine years, higher CCI scores were independently associated with an increased risk of death from all causes [HR, 1.32; 95% confidence interval (CI), 1.13–1.54] and from nonbreast cancer causes (HR, 1.55; 95% CI, 1.19–2.02), but not from breast cancer (HR, 1.14; 95% CI, 0.93–1.41). Hypertension was independently associated with an increased risk of death from all causes (HR, 1.55; 95% CI, 1.20–1.99), from nonbreast cancer causes (HR, 1.67; 95% CI, 1.10–2.54), and from breast cancer (HR, 1.47; 95% CI, 1.03–2.09), but these associations were no longer significant after adjustment for antihypertensive medication. The relationship between the CCI and overall survival was the strongest among women with stage I disease (stage I, HR, 1.65; 95% CI, 1.26–2.16 vs. stage III, HR, 0.53; 95% CI, 0.23–1.25). Conclusion: The CCI was independently associated with lower overall and nonbreast cancer survival, but not with breast cancer–specific survival. Impact: Comorbidity may play an important role in breast cancer outcomes. Cancer Epidemiol Biomarkers Prev; 21(7); 1115–25. ©2012 AACR.

As cancer incidence and mortality rates increase in low- and middle-income countries, the need for cancer prevention and control research directed to these countries becomes increasingly important. The American Society of Preventive Oncology (ASPO) is a community of professionals in cancer prevention and control whose mission is to “foster the continuing development of investigators and the exchange and translation of scientific information to reduce the cancer burden.” In the session presented at the ASPO 36th Annual Meeting in Washington, DC in March 2012, chaired by Drs. Frank Meyskens and Dejana Braithwaite, Dr. Paolo Boffetta discussed some of the achievements in global cancer prevention and suggested that future efforts focus on three major causes of cancer: tobacco-use, infections, and overweight/obesity. Dr. Timothy Rebbeck presented an overview of prostate cancer research in sub-Saharan Africa and highlighted how the complex nature of prostate cancer etiology and outcomes can be addressed through capacity-building research partnerships. Cancer is an emerging public health challenge in developing countries because of the aging and expansion of the population and increased prevalence of cancer risk factors such as smoking, obesity, physical inactivity, and reproductive factors. There are opportunities to reduce the growing cancer burden through the development of research capacity and the application of resource-appropriate interventions. Cancer Epidemiol Biomarkers Prev; 21(9); 1606–10. ©2012 AACR.