Causes & Control

Cost-effectiveness of patient navigation for breast cancer screening in the National Breast and Cervical Cancer Early Detection Program Abstract Objectives Patient navigation (PN) services have been shown to improve cancer screening in disparate populations. This study estimates the cost-effectiveness of implementing PN services within the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Methods We adapted a breast cancer simulation model to estimate a population cohort of women aged 40–64 years from the NBCCEDP through their lifetime. We incorporated their screening frequency and screening and diagnostic costs. Results Within the NBCCEDP, Program with PN (vs. No PN) resulted in a greater number of mammograms per woman (4.23 vs. 4.14), lower lifetime mortality from breast cancer (3.53% vs. 3.61%), and fewer missed diagnostic resolution per woman (0.017 vs. 0.025). The estimated incremental cost-effectiveness ratios for a Program with PN was $32,531 per quality-adjusted life-years relative to Program with No PN. Conclusions Incorporating PN services within the NBCCEDP may be a cost-effective way of improving adherence to screening and diagnostic resolution for women who have abnormal results from screening mammography. Our study highlights the value of supportive services such as PN in improving the quality of care offered within the NBCCEDP.

Dose–risk relationships between cigarette smoking and ovarian cancer histotypes: a comprehensive meta-analysis Abstract Purpose Although smoking has not been associated with overall ovarian cancer risk, a different impact on various histotypes has been reported. Our aim is to provide an accurate, up-to-date estimate of the dose–risk relationships between cigarette smoking and epithelial ovarian cancer, overall and by histotypes. Methods Using an innovative approach for the identification of original study publications, we conducted a systematic review and meta-analysis of epidemiological studies published on the topic until September 2018. Summary relative risks (RR) for cigarette smoking were estimated using random-effects models; dose–risk relationships were evaluated using one-stage random-effects models with restricted cubic splines. Results Thirty-seven studies were considered in the meta-analysis. The summary RRs for current versus never smokers were 1.05 (95% confidence interval CI 0.95–1.16) for overall ovarian cancer, 1.78 (95% CI 1.52–2.07) for mucinous, 0.77 (95% CI 0.65–0.93) for clear cell, 0.81 (95% CI 0.73–0.91) for endometrioid, and 1.05 (95% CI 0.94; 1.17) for serous cancer. The risk of borderline mucinous (RR 2.09) and serous (RR 1.16) tumors was higher than for invasive cancers (RR 1.44 and 0.95, respectively). For mucinous cancer, risk was noticeably higher with smoking intensity and duration (RR 2.35 for 20 cigarettes/day, and 2.11 for 20 years of smoking). A non-significant linear relation was found with smoking intensity, duration, and time since quitting for overall ovarian cancer and other histotypes. Conclusions This uniquely large and comprehensive meta-analysis confirms that although cigarette smoking does not appear to be a risk factor for ovarian cancer, and it is even slightly protective for some rare histotypes, there is a strong dose–risk relationship with mucinous ovarian cancer.

The association between colorectal sessile serrated adenomas/polyps and subsequent advanced colorectal neoplasia Abstract Purpose Colorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia. Methods This case–control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review. Subsequent pathology reports and biopsies through 1/1/2013 were reviewed for advanced colorectal neoplasia. We linked to the Seattle-Puget Sound Surveillance Epidemiology and End Results (SEER) registry to identify additional CRC cases. We used generalized estimating equations with a logit link to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing those with SSA/Ps to those with HPs. Results There were 161 individuals with index SSA/Ps, 548 with HPs, and 918 subsequent endoscopies included in analyses. Of those with index SSA/Ps, 19 had subsequent advanced colorectal neoplasia; 39 with HPs had subsequent advanced colorectal neoplasia. Compared to those with HPs, those with SSA/Ps were not statistically significantly more likely to have subsequent advanced colorectal neoplasia (adjusted OR 1.79; CI 0.98–3.28). Polyp size ≥ 10 mm, right colon location, and the presence of multiple serrated polyps were also not associated with advanced colorectal neoplasia. Conclusions Our results suggest that there is not a strong association between SSA/Ps and subsequent advanced colorectal neoplasia during the 5 years following SSA/P removal.

Socioenvironmental adversity and risk of prostate cancer in non-Hispanic black and white men Abstract Non-Hispanic black (NHB) men experience higher risk of prostate cancer than other racial/ethnic groups, and it is possible that socioenvironmental (SE) adversity and resulting stress may contribute to this disparity. Data from the Southern Community Cohort Study were used to evaluate associations between SE adversity and perceived stress in relation to prostate cancer risk, overall and by race/ethnicity and grade. Between 2002 and 2009, 26,741 men completed a questionnaire, from which an 8-item SE adversity composite was created (covering socioeconomic status, residential environment, and social support/buffers). Two items from the Perceived Stress Scale were assessed. With follow-up through 2011, 527 prostate cancer cases were diagnosed. In multivariable models, each one-unit increase in the SE adversity composite was associated with increased prostate cancer risk among non-Hispanic white (NHW) men (HR 1.23; 95% CI 1.02–1.48) and reduced risk among NHB men (HR 0.89; 95% CI 0.82–0.95) (p interaction: 0.001). This pattern held for low grade, but not high grade, cancers although power was limited for the latter. Perceived stress variables were associated with increased risk of prostate cancer among NHW men, but not among NHB men. Results do not support the hypothesis that SE adversity my underlay the racial disparity in prostate cancer, over and above that of covariates, including healthcare utilization.

Patterns of comorbidities in women with breast cancer: a Canadian population-based study Abstract Purpose Improving the understanding of co-existing chronic diseases prior to and after the diagnosis of cancer may help to facilitate therapeutic decision making in clinical practice. This study aims to examine patterns of comorbidities in Canadian women with breast cancer. Methods We conducted a retrospective cohort study using provincial linked administrative health datasets from British Columbia, Canada, between 2000 and 2013. Women diagnosed with breast cancer between 2005 and 2009 were identified. The index date was defined as the date of diagnosis of breast cancer. Subsets of the breast cancer cohort were identified based on the absence of individual type of comorbidity of interest within 5 years prior to breast cancer diagnosis. For each subset, cases were then individually matched by year of birth at 1:2 ratios with controls without a history of cancer and the individual type of comorbidity of interest within 5 years prior to the assigned index year, matching with the year of breast cancer diagnosis of the corresponding case. Baseline comorbidities were measured over a 1-year period prior to the index date using two comorbidity indices, Rx-Risk-V and Aggregated Diagnosis Groups (ADG). Cox regression model was used to assess the development of seven specific comorbidities after the index date between women with breast cancer and non-cancer women. Results The most prevalent baseline comorbidity in the breast cancer cohort measured using the Rx-Risk-V model was cardiovascular conditions (39.0%), followed by pain/pain-inflammation (34.8%). The most prevalent category measured using the ADG model was major signs or symptoms (71.8%), followed by stable chronic medical conditions (52.2%). The risks of developing ischemic heart disease, heart failure, depression, diabetes, osteoporosis, and hypothyroidism were higher in women with breast cancer compared to women without cancer, with the hazard ratios ranging from 1.09 (95 CI% 1.03–1.16) for ischemic heart disease to 2.10 (95% CI 1.99–2.21) for osteoporosis in the model adjusted for baseline comorbidity measured using Rx-Risk-V score. Conclusion Women with breast cancer had a higher risk of developing new comorbidities than women without cancer. Development of coordinated care models to manage multiple chronic diseases among breast cancer patients is warranted.

Circulating lipids, mammographic density, and risk of breast cancer in the Nurses' Health Study and Nurses' Health Study II Abstract Purpose Epidemiologic evidence supports an association between high mammographic density and increased breast cancer risk yet etiologic mechanisms remain largely unknown. Mixed evidence exists as to whether circulating lipid levels influence mammographic density and breast cancer risk. Therefore, we examined these associations in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII), two large prospective cohorts with information on PMD and circulating lipid measures, long follow-up, and breast cancer risk factor and outcome data. Methods We conducted a nested case–control study among women in the NHS and NHSII. Percent mammographic density (PMD) was measured using Cumulus software, a computer-assisted method, on digitized film mammograms. Cross-sectional associations between circulating lipids [total cholesterol (n = 1,502), high-density lipoprotein (HDL-C; n = 579), and triglycerides (n = 655)] and PMD were evaluated among controls. All analyses were stratified by menopausal status at time of mammogram. Relative risks for breast cancer by lipid and PMD measures were estimated among postmenopausal women in the full nested case–control study (cases/controls for cholesterol, HDL-C, and triglycerides were 937/975, 416/449, and 506/537, respectively). Results There were no significant associations between circulating lipid levels and PMD among healthy women, irrespective of menopausal status. The association between PMD and breast cancer risk among postmenopausal women was not modified by circulating lipid levels (p interaction = 0.83, 0.80, and 0.34 for total cholesterol, HDL-C, and triglycerides, respectively). Conclusion Overall, no association was observed between lipid levels and PMD, and there was no evidence that lipid levels modified the association between PMD and breast cancer risk.

Ovarian Cancer in Women of African Ancestry (OCWAA) consortium: a resource of harmonized data from eight epidemiologic studies of African American and white women Abstract Purpose Although the incidence rate of epithelial ovarian cancer (EOC) is somewhat lower in African American (AA) than white women, survival is worse. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium will overcome small, study-specific sample sizes to better understand racial differences in EOC risk and outcomes. Methods We harmonized risk factors and prognostic characteristics from eight U.S. studies: the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles County Ovarian Cancer Study (LACOCS), the African American Cancer Epidemiology Study (AACES), the Cook County Case–Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), the Multiethnic Cohort Study (MEC), and the Southern Community Cohort Study (SCCS). Results Determinants of disparities for risk and survival in 1,146 AA EOC cases and 2,922 AA controls will be compared to 3,368 white EOC cases and 10,270 white controls. Analyses include estimation of population-attributable risk percent (PAR%) by race. Conclusion OCWAA is uniquely positioned to study the epidemiology of EOC in AA women compared with white women to address disparities. Studies of EOC have been underpowered to address factors that may explain AA-white differences in the incidence and survival. OCWAA promises to provide novel insight into disparities in ovarian cancer.

Influence of physical activity on active surveillance discontinuation in men with low-risk prostate cancer Abstract Purpose Epidemiologic data suggest that high levels of physical activity (PA) may reduce the risk of disease progression in men with prostate cancer (PCa), but it is unknown whether PA can delay the requirement for definitive treatment for those on active surveillance (AS). We investigated the influence of PA post-diagnosis on AS discontinuation in men with low-risk disease. Methods The effect of PA on the time to AS discontinuation was assessed in 421 patients, of whom 107 underwent additional PCa treatment over a median of 2.5 years. Results Using Cox regression models, we found that PA was not significantly associated with time to curative treatment initiation. Prostate-specific antigen (PSA) most proximal to AS initiation (HR, 1.11; 95% CI 1.03 to 1.21) and the number of positive cores (HR, 1.34; 95% CI 1.12 to 1.61) at diagnosis were associated with a significantly increased risk of discontinuing AS. Conclusion Our findings suggest that PA during AS for PCa does not significantly influence time to curative treatment.

Trajectories of body mass index, from adolescence to older adulthood, and pancreatic cancer risk; a population-based case–control study in Ontario, Canada Abstract Purpose Pancreatic cancer has the highest fatality rate of all cancers. Adulthood obesity is an established risk factor for pancreatic cancer; however, life-course obesity is not well understood. The aim of this study was to evaluate the association between body mass index (BMI) trajectories throughout the life-course and pancreatic cancer risk. Methods A population-based case–control study was conducted (2011–2013) in Ontario, Canada. Cases were recruited from the Ontario pancreas cancer study (n = 310) and controls from the Ontario cancer risk factor study (n = 1258). Questionnaires captured self-reported height and weight at four timepoints (adolescence, 20 s, 30–40 s, 50–60 s). BMI trajectories were identified using latent class growth mixture modeling. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression. Results Five BMI trajectories were identified: stable-normal weight (38.9%), progressively overweight (42.2%), persistent overweight (12.6%), progressive obesity (4.2%), and persistent obesity (2.1%). The persistent overweight (OR = 1.55; 95% CI 1.02, 2.39) and progressive obesity trajectories (OR = 1.49; 95% CI 0.77, 2.87) compared to stable-normal weight were associated with increased odds of pancreatic cancer. When BMI was evaluated separately the strongest associations with pancreatic cancer emerged in young and mid-adulthood. Conclusion BMI trajectories characterized by overweight in early adulthood were associated with increased pancreatic cancer risk suggesting a life-course approach to disease risk.

Clinical characteristics and survival patterns of subsequent sarcoma, breast cancer, and melanoma after childhood cancer in the DCOG-LATER cohort Abstract Purpose Childhood cancer survivors are at increased risk of developing subsequent malignant neoplasms (SMNs). We compared survival and clinical characteristics of survivors with SMNs (sarcoma, breast cancer, or melanoma) and a population-based sample of similar first malignant neoplasm (FMN) patients. Methods We assembled three case series of solid SMNs observed in a cohort of 5-year Dutch childhood cancer survivors diagnosed 1963–2001 and followed until 2014: sarcoma (n = 45), female breast cancer (n = 41), and melanoma (n = 17). Each SMN patient was sex-, age-, and calendar year-matched to 10 FMN patients in the population-based Netherlands Cancer Registry. We compared clinical and histopathological characteristics by Fisher's exact tests and survival by multivariable Cox regression and competing risk regression analyses. Results Among sarcoma-SMN patients, overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.23–2.87] and sarcoma-specific mortality (HR 1.91, 95% CI 1.16–3.13) were significantly worse compared to sarcoma-FMN patients (foremost for soft-tissue sarcoma), with 15-year survival rates of 30.8% and 61.6%, respectively. Overall survival did not significantly differ for breast-SMN versus breast-FMN patients (HR 1.14, 95% CI 0.54–2.37), nor for melanoma-SMN versus melanoma-FMN patients (HR 0.71, 95% CI 0.10–5.00). No significant differences in tumor characteristics were observed between breast-SMN and breast-FMN patients. Breast-SMN patients were treated more often with mastectomy without radiotherapy/chemotherapy compared to breast-FMN patients (17.1% vs. 5.6%). Conclusions Survival of sarcoma-SMN patients is worse than sarcoma-FMN patients. Although survival and tumor characteristics appear similar for breast-SMN and breast-FMN patients, treatment differs; breast-SMN patients less often receive breast-conserving therapy. Larger studies are necessary to substantiate these exploratory findings.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com