Publications by authors named "Lawrence H Kushi"

204 Publications

Positive predictive value and sensitivity of ICD-9-CM codes for identifying pediatric leukemia.

Pediatr Blood Cancer 2021 Nov 13:e29383. Epub 2021 Nov 13.

Department of Public Health Sciences, University of California, Davis, California, USA.

Background: To facilitate community-based epidemiologic studies of pediatric leukemia, we validated use of ICD-9-CM diagnosis codes to identify pediatric leukemia cases in electronic medical records of six U.S. integrated health plans from 1996-2015 and evaluated the additional contributions of procedure codes for diagnosis/treatment.

Procedures: Subjects (N = 408) were children and adolescents born in the health systems and enrolled for at least 120 days after the date of the first leukemia ICD-9-CM code or tumor registry diagnosis. The gold standard was the health system tumor registry and/or medical record review. We calculated positive predictive value (PPV) and sensitivity by number of ICD-9-CM codes received in the 120-day period following and including the first code. We evaluated whether adding chemotherapy and/or bone marrow biopsy/aspiration procedure codes improved PPV and/or sensitivity.

Results: Requiring receipt of one or more codes resulted in 99% sensitivity (95% confidence interval [CI]: 98-100%) but poor PPV (70%; 95% CI: 66-75%). Receipt of two or more codes improved PPV to 90% (95% CI: 86-93%) with 96% sensitivity (95% CI: 93-98%). Requiring at least four codes maximized PPV (95%; 95% CI: 92-98%) without sacrificing sensitivity (93%; 95% CI: 89-95%). Across health plans, PPV for four codes ranged from 84-100% and sensitivity ranged from 83-95%. Including at least one code for a bone marrow procedure or chemotherapy treatment had minimal impact on PPV or sensitivity.

Conclusions: The use of diagnosis codes from the electronic health record has high PPV and sensitivity for identifying leukemia in children and adolescents if more than one code is required.
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http://dx.doi.org/10.1002/pbc.29383DOI Listing
November 2021

Impact of the Affordable Care Act on Colorectal Cancer Incidence and Mortality.

Am J Prev Med 2021 Nov 8. Epub 2021 Nov 8.

Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, Connecticut; Center for Methods in Implementation and Prevention Science (CMIPS), Yale School of Public Health, Yale University, New Haven, Connecticut.

Introduction: The Patient Protection and Affordable Care Act eliminated cost sharing for preventive services, including colorectal cancer screening for individuals aged 50-75 years with private health insurance. This study examines the impact of the Affordable Care Act's removal of cost sharing for colorectal cancer screening on colorectal cancer incidence and mortality.

Methods: Trends in colorectal cancer incidence and colorectal cancer‒related mortality were modeled among 2,113,283 Kaiser Permanente Northern California members aged ≥50 years between 2003 and 2016 using an interrupted time-series design. As a sensitivity analysis, a controlled analysis utilized a comparison group of members covered with pre‒Affordable Care Act zero cost sharing for colorectal cancer screening. Analyses were performed in 2019 and 2020.

Results: The colorectal cancer incidence dropped by 17% around the time the Affordable Care Act was enacted (change in level incidence rate ratio; 95% CI=0.77, 0.90, 2-sided p-value <0.0001), followed by a 3% further decrease per year (95% CI=0.93, 1.00, p=0.05). A similar pattern was observed for colorectal cancer‒related mortality. The controlled results indicated that the elimination of cost sharing for screening due to the Affordable Care Act was associated with greater improvements in colorectal cancer outcomes among members previously covered by health plans with out-of-pocket costs for screening than among those with health plans with zero cost sharing for screening before the Affordable Care Act.

Conclusions: The elimination of cost sharing for colorectal cancer screening due to the Affordable Care Act was associated with a decrease in age-, race/ethnicity-, and sex-adjusted colorectal cancer incidence and colorectal cancer‒related mortality, implying that policies that remove barriers to screening, particularly financial burden from cost sharing, can result in improved colorectal cancer outcomes.
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http://dx.doi.org/10.1016/j.amepre.2021.08.025DOI Listing
November 2021

Plant-Based Dietary Patterns and Breast Cancer Recurrence and Survival in the Pathways Study.

Nutrients 2021 Sep 25;13(10). Epub 2021 Sep 25.

Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.

Plant-based diets are recommended for cancer survivors, but their relationship with breast cancer outcomes has not been examined. We evaluated whether long-term concordance with plant-based diets reduced the risk of recurrence and mortality among a prospective cohort of 3646 women diagnosed with breast cancer from 2005 to 2013. Participants completed food frequency questionnaires at diagnosis and 6-, 25-, and 72-month follow-up, from which we derived plant-based diet indices, including overall (PDI), healthful (hPDI), and unhealthful (uPDI). We observed 461 recurrences and 653 deaths over a median follow-up of 9.51 years. Using multivariable-adjusted Cox proportional hazards models, we estimated hazard ratios (HR) and 95% confidence intervals for breast cancer recurrence and all-cause, breast-cancer-specific, and non-breast-cancer mortality. Increased concordance with hPDI was associated with a reduced hazard of all-cause (HR 0.93, 95% CI: 0.83-1.05) and non-breast-cancer mortality (HR 0.83, 95% CI: 0.71-0.98), whereas increased concordance with uPDI was associated with increased hazards (HR 1.07, 95% CI: 0.96-1.2 and HR 1.20, 95% CI: 1.02-1.41, respectively). No associations with recurrence or breast-cancer-specific mortality were observed. In conclusion, healthful vs. unhealthful plant-based dietary patterns had differing associations with mortality. To enhance overall survival, dietary recommendations for breast cancer patients should emphasize healthful plant foods.
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http://dx.doi.org/10.3390/nu13103374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540603PMC
September 2021

Modeling risks of cardiovascular and cancer mortality following a diagnosis of loco-regional breast cancer.

Breast Cancer Res 2021 09 27;23(1):91. Epub 2021 Sep 27.

Department of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY, 161110032, USA.

Background: Many women with breast cancer also have a high likelihood of cardiovascular mortality, and while there are several cardiovascular risk prediction models, none have been validated in a cohort of breast cancer patients. We first compared the performance of commonly-used cardiovascular models, and then derived a new model where breast cancer and cardiovascular mortality were modeled simultaneously, to account for the competing risk endpoints and commonality of risk factors between the two events.

Methods: We included 20,462 women diagnosed with stage I-III breast cancer between 2000 and 2010 in Kaiser Permanente Northern California (KPNC) with follow-up through April 30, 2015, and examined the performance of the Framingham, CORE and SCOREOP cardiovascular risk models by area under the receiver operating characteristic curve (AUC), and observed-to -expected (O/E) ratio. We developed a multi-state model based on cause-specific hazards (CSH) to jointly model the causes of mortality.

Results: The extended models including breast cancer characteristics (grade, tumor size, nodal involvement) with CVD risk factors had better discrimination at 5-years with AUCs of 0.85 (95% CI 0.83, 0.86) for cardiovascular death and 0.80 (95% CI 0.78, 0.87) for breast cancer death compared with the existing cardiovascular models evaluated at 5 years AUCs ranging 0.71-0.78. Five-year calibration for breast and cardiovascular mortality from our multi-state model was also excellent (O/E = 1.01, 95% CI 0.91-1.11).

Conclusion: A model incorporating cardiovascular risk factors, breast cancer characteristics, and competing events, outperformed traditional models of cardiovascular disease by simultaneously estimating cancer and cardiovascular mortality risks.
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http://dx.doi.org/10.1186/s13058-021-01469-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474887PMC
September 2021

Individual- and neighborhood-level socioeconomic status and risk of aggressive breast cancer subtypes in a pooled cohort of women from Kaiser Permanente Northern California.

Cancer 2021 Aug 20. Epub 2021 Aug 20.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background: Low socioeconomic status (SES) has been associated with a higher risk of aggressive breast cancer (BC) subtypes, but few studies have examined the independent effects of both neighborhood-level socioeconomic status (nSES) and individual-level SES measures.

Methods: This study included 5547 women from the Pathways and Life After Cancer Epidemiology cohorts who were diagnosed with invasive BC. Generalized estimating equation models were used to examine associations of nSES (a composite score based on income, poverty, education, occupation, employment, rent, and house value) and individual-level SES (income and education) with BC subtypes: luminal B (LumB), Her2-enriched (Her2-e), and triple-negative breast cancer (TNBC) relative to luminal A (LumA). Models controlled for age, race, nativity, stage, days from diagnosis to survey, and study cohort and simultaneously for nSES and individual-level SES.

Results: In fully adjusted models, low nSES was significantly associated with the LumB (odds ratio for quartile 1 vs quartile 4 [OR ], 1.31; 95% confidence interval [CI], 1.11-1.54; P for trend = .005) and TNBC subtypes (OR , 1.32; 95% CI, 1.02-1.71; P for trend = .037) relative to LumA. Conversely, individual education was significantly associated with only the Her2-e subtype (odds ratio for high school degree or less vs postgraduate, 1.68; 95% CI, 1.03-2.75; P for trend = .030) relative to LumA. Individual income was not significantly associated with any BC subtype.

Conclusions: nSES and individual-level SES are independently associated with different BC subtypes; specifically, low nSES and individual-level education are independent predictors of more aggressive BC subtypes relative to LumA.
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http://dx.doi.org/10.1002/cncr.33861DOI Listing
August 2021

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Nat Commun 2021 07 7;12(1):4198. Epub 2021 Jul 7.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
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http://dx.doi.org/10.1038/s41467-021-24327-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263739PMC
July 2021

Childhood Socioeconomic Status and Menarche: A Prospective Study.

J Adolesc Health 2021 07;69(1):33-40

Division of Adolescent Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Purpose: The relationship between socioeconomic status (SES) and menarche has implications for understanding social level influences on early life development and adult disease, including breast cancer, but remains ill defined. We report here results from the Breast Cancer and the Environment Research Program, which permitted a longitudinal study of age at menarche in relationship to childhood SES in a diverse cohort of 1,069 girls across three urban areas of the United States.

Methods: We assessed the association of SES index quintiles with age at pubertal onset with breast budding and subsequent tempo to the age at menarche between 2004 and 2015 using multiple-event Cox regression models to estimate hazard ratios and 95% confidence intervals.

Results: In an unadjusted model, lower SES was predictive of both earlier pubertal onset and tempo and thus earlier age at menarche in trends across quintiles. After adjusting for the potentially mediating effects of body mass index, SES trends remained significant for both outcomes. After adjusting for both body mass index and race/ethnicity, the association with SES remained substantial for pubertal onset but was much diminished and nonsignificant for tempo and thus age at menarche.

Conclusions: These results suggest that a lower SES environment and social adversity affect the age at menarche primarily by hastening pubertal onset rather than by shortening tempo.
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http://dx.doi.org/10.1016/j.jadohealth.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243506PMC
July 2021

Diet Quality and Breast Cancer Recurrence and Survival: The Pathways Study.

JNCI Cancer Spectr 2021 Apr 2;5(2):pkab019. Epub 2021 Mar 2.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Background: Prior research suggests a relationship between overall diet quality and breast cancer survival, although few studies have reported on this topic. We evaluated whether 4 dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis were associated with risk of recurrence, cause-specific, and all-cause mortality.

Methods: A total of 3660 women diagnosed with invasive breast cancer were included. Diet was assessed an average of 2.3 (range = 0.7-18.7) months after diagnosis, from which 4 dietary quality indices were derived: the American Cancer Society guidelines (ACS), the alternate Mediterranean Diet Index (aMED), the Dietary Approaches to Stop Hypertension (DASH), and the 2015 Healthy Eating Index (HEI). Over 40 888 person-years of follow-up, 461 breast cancer recurrences, and 655 deaths were ascertained. Cox models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs).

Results: Adjusted comparisons between extreme quintiles showed all 4 dietary quality indices to be inversely associated with all-cause mortality, suggesting a 21%-27% lower risk (ACS HR = 0.73, 95% CI = 0.56 to 0.95; aMED HR = 0.79, 95% CI = 0.61 to 1.03; DASH HR = 0.76, 95% CI = 0.58 to 1.00; HEI HR = 0.77, 95% CI = 0.60 to 1.01). Similar patterns were noted for non-breast cancer mortality (ACS HR = 0.69, 95% CI = 0.48 to 0.98; aMED HR = 0.73, 95% CI = 0.50 to 1.05; DASH HR = 0.55, 95% CI = 0.38 to 0.79; HEI HR = 0.67, 95% CI = 0.48 to 0.94). None of the dietary quality indices were associated with recurrence or breast cancer-specific mortality.

Conclusion: Food intake patterns concordant with dietary quality indices consistent with recommendations for healthy eating may be beneficial for women with breast cancer.
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http://dx.doi.org/10.1093/jncics/pkab019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062847PMC
April 2021

Clustering of Social and Physical Pain Variables and Their Association With Mortality in Two Population-Based Cohorts.

Psychosom Med 2021 04;83(3):228-238

From the Division of Research (Kroenke, Alexeeff, Kushi, Kwan), Kaiser Permanente Northern California, Oakland, California; and University of Pittsburgh Department of Psychiatry (Matthews), Pittsburgh, Pennsylvania.

Objective: Social pain and physical pain are related bidirectionally, but how these variables cluster in the population is unknown.

Methods: This study included 2833 women from the Study of Women's Health Across the Nation (SWAN), a community-based cohort of middle-aged women, and 3972 women from the Pathways Study, a population-based cohort of women diagnosed with American Joint Committee on Cancer stages I-IV breast cancer diagnosed between 2005 and 2013. Women provided data on measures related to social pain (social network size, social support, loneliness, social well-being) and physical pain (sensitivity to pain, bodily pain) at study baseline. Analyzing each cohort separately, we used latent class analysis to evaluate social-physical pain clusters, logistic regression to evaluate predictors of categorization into clusters, and Cox proportional hazards models to evaluate associations of clusters with all-cause mortality. We also performed a meta-analysis to combine cohort mortality associations.

Results: Each cluster analysis produced a "low social-physical pain" cluster (SWAN, 48.6%; Pathways, 35.2%) characterized by low social and pain symptoms, a "high social-physical pain" cluster (SWAN, 17.9%; Pathways, 17.9%) characterized by high symptoms, and a "low social/high physical pain" cluster of women with high pain and compromised social functioning but otherwise low social symptoms (SWAN, 33.5%; Pathways, 46.9%). In meta-analysis, categorization into the high social-physical pain cluster was associated with elevated mortality (adjusted hazard ratio = 1.34, 95% confidence interval = 1.05-1.71, Q statistic = 0.782), compared with those in the low social-physical pain cluster.

Conclusions: In two cohorts of women, latent class analysis produced similar sets of social-physical pain clusters, with the same proportion having both high social and pain symptoms; women in this cluster had elevated mortality.
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http://dx.doi.org/10.1097/PSY.0000000000000910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023720PMC
April 2021

"I Had to Make Them Feel at Ease": Narrative Accounts of How Women With Breast Cancer Navigate Social Support.

Qual Health Res 2021 05 28;31(6):1056-1068. Epub 2021 Feb 28.

Kaiser Permanente Northern California, Oakland, California, USA.

Social scientific studies of social support predominantly focus on the positive associations between social support and emotional well-being. The negative aspects of social support have received much less attention. We conducted semi-structured interviews of women with breast cancer ( = 47) to examine the emotional strain associated with social support and how recipients navigate it in ways that protect themselves and their relationships. Based on our analysis of narratives of women's lived experiences of breast cancer, we found that social support can be perceived negatively and associated with experiences of emotional strain. Interviewees engaged in strategies of avoidance, information control, and cognitive reframing to minimize emotional strain. We applied the concept of emotion work to understand the complexity of emotional strain in this context. The findings highlight the difficulties of social support from a recipient's perspective and emphasize the importance of perception and agency in navigating this experience.
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http://dx.doi.org/10.1177/1049732321989999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376224PMC
May 2021

Girls' Pubertal Timing and Tempo and Mental Health: A Longitudinal Examination in an Ethnically Diverse Sample.

J Adolesc Health 2021 06 23;68(6):1197-1203. Epub 2021 Feb 23.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.

Purpose: Earlier timing and faster tempo of puberty have been linked to adolescents' poor mental health. Previous research rarely adjusted for childhood mental health, did not use physical examination to assess puberty, and excluded Latinas and Asian Americans. This study addressed these limitations.

Methods: We followed 822 girls, recruited at ages 6-8, for 8 years. Breast and pubic hair development and anxiety and depressive symptoms were assessed prospectively and repeatedly. Structural equation models tested whether pubertal timing and tempo were associated with adolescent mental health symptoms and whether associations varied by ethnicity. Models were adjusted for childhood mental health symptoms, body mass index, and family income.

Results: Earlier breast development was associated with higher depressive symptoms among whites (β = -.19; p < .01) and higher anxiety symptoms among Latinas (β = -.26; p < .05), but lower depressive symptoms among Asians (β = .24, p < .05). Later pubic hair development (b = .24; p < .05) and faster pubic hair tempo (β = .26; p < .01) were associated with higher anxiety symptoms among Latinas. Faster pubic hair tempo was associated with lower depressive symptoms among Asians (β = -.34; p < .05). Tempo of breast development showed no associations.

Conclusions: Findings confirmed that earlier breast development was associated with higher mental health symptoms for Latina and white girls but was protective among Asians. Results for pubic hair and pubertal tempo were inconsistent, requiring future examination. While targeted interventions to prevent mental health problems among early-maturing girls are critical, there is variability among who might benefit most.
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http://dx.doi.org/10.1016/j.jadohealth.2021.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154636PMC
June 2021

The Adolescent and Young Adult (AYA) Horizon Study: An AYA Cancer Survivorship Cohort.

Cancer Epidemiol Biomarkers Prev 2021 05 22;30(5):857-866. Epub 2021 Feb 22.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background: In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States.

Methods: The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15-39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data.

Results: We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall ( = 1,679), and notably lower among minority groups compared with non-Hispanic white women.

Conclusions: Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements.

Impact: The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102328PMC
May 2021

Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.

Nat Commun 2021 02 12;12(1):970. Epub 2021 Feb 12.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.
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http://dx.doi.org/10.1038/s41467-021-21288-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880989PMC
February 2021

A prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting.

J Cancer Surviv 2021 Feb 9. Epub 2021 Feb 9.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Purpose: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown.

Methods: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture.

Results: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37).

Conclusions: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy.

Implications For Cancer Survivors: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.
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http://dx.doi.org/10.1007/s11764-021-00993-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349930PMC
February 2021

Effects of cooking methods on total isothiocyanate yield from cruciferous vegetables.

Food Sci Nutr 2020 Oct 9;8(10):5673-5682. Epub 2020 Sep 9.

Department of Cancer Prevention and Control Roswell Park Comprehensive Cancer Center Buffalo NY USA.

Cruciferous vegetables are primary sources of dietary isothiocyanates (ITCs), a group of phytochemicals showing promising cancer-chemopreventive activities in multiple cancer models. However, no study has thoroughly examined how cooking affects the yields of ITCs from cruciferous vegetables. In this study, a high-performance liquid chromatography (HPLC)-based cyclocondensation assay was performed to examine the ITC yields from four major cruciferous vegetables (broccoli, cabbage, cauliflower, and kale) under six cooking conditions (stir-frying, steaming, microwaving, boiling, stewing, and chip-baking for kale only) and measured the level of ITCs under the raw condition for a comprehensive list of cruciferous vegetables and ITC-containing condiments. A wide range of ITC yields was found across vegetables and condiments. Cooking significantly altered the ITC yields, showing an averagely four-fold increase by lightly cooking (stir-frying, steaming, and microwaving) and a 58% decrease by heavily cooking (boiling, stewing, and chip-baking). These findings will provide the evidence-based cooking guidance on cruciferous vegetable consumption and help better estimate dietary ITC exposure in epidemiologic studies.
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http://dx.doi.org/10.1002/fsn3.1836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590320PMC
October 2020

Early life household intactness and timing of pubertal onset in girls: a prospective cohort study.

BMC Pediatr 2020 10 28;20(1):464. Epub 2020 Oct 28.

Kaiser Permanente Division of Research, 2000 Broadway, CA, 94612, Oakland, USA.

Background: Girls who experience early-life familial stress may have heightened risk of early puberty, which has adverse implications for adolescent and adult health. We assessed the association between household intactness and pubertal onset using a racially/ethnically diverse cohort of girls from Northern California.

Methods: A prospective cohort study of 26,044 girls born in 2003-10. Girls living with both parents from birth up to 6 years were considered to come from "intact" households while others constituted "non-intact" households. Pubertal development was measured using pediatrician-assessed Tanner staging for breast and pubic hair. Pubertal onset was defined as the transition from Tanner Stage 1 to 2+ for breast (thelarche) and pubic hair (pubarche). Menarche data was collected from routine well-child questionnaires. Weibull regression models accommodating left, right, and interval censoring were used to determine risk of earlier thelarche and pubarche, and logistic regressions were used to assess the risk of early menarche (age < 12).

Results: Girls exposed to non-intact households before age 2 years were at increased risk for earlier thelarche and pubarche with significant effect modification by race/ethnicity, compared with girls from intact households. The associations were strongest among Black girls (adjusted hazard ratio [HR]: 1.60, 95% confidence interval [CI]: 1.29,1.98; HR: 1.42, 95%CI: 1.15,1.77 for thelarche and pubarche, respectively). There were no significant associations among Asian/Pacific Islanders. Girls who lived in non-intact households before age 2 years were also at increased risk for earlier menarche, but without race/ethnic interaction. Adjustment for prepubertal obesity did not change these associations. Associations between living in non-intact households after age 2 years and early puberty were weaker but still significant.

Conclusions: Exposure to a non-intact household early in life may increase the risk of early puberty in girls. Future psychosocial interventions focused on improving family cohesiveness and efforts to reduce childhood stress among families that are non-intact may mitigate these negative associations, thereby preventing future adverse health effects of early puberty and health disparities.
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http://dx.doi.org/10.1186/s12887-020-02345-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592583PMC
October 2020

Material and psychological financial hardship related to employment disruption among female adolescent and young adult cancer survivors.

Cancer 2020 01 12;127(1):137-148. Epub 2020 Oct 12.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: The importance of addressing adverse financial effects of cancer among adolescents and young adults (AYAs) is paramount as survival improves. In the current study, the authors examined whether cancer-related employment disruption was associated with financial hardship among female AYA cancer survivors in North Carolina and California.

Methods: AYA cancer survivors identified through the North Carolina Central Cancer Registry and the Kaiser Permanente Northern/Southern California tumor registries responded to an online survey. Disrupted employment was defined as reducing hours, taking temporary leave, or stopping work completely because of cancer. Financial hardship was defined as material conditions or psychological distress related to cancer. Descriptive statistics and chi-square tests were used to characterize the invited sample and survey respondents. Marginal structural binomial regression models were used to estimate prevalence differences (PDs) and 95% confidence intervals (95% CIs).

Results: Among 1328 women employed at the time of their diagnosis, women were a median age of 34 years at the time of diagnosis and 7 years from diagnosis at the time of the survey and approximately 32% experienced employment disruption. A substantial percentage reported financial hardship related to material conditions (27%) or psychological distress (50%). In adjusted analyses, women with disrupted employment had a 17% higher burden of material conditions (95% CI, 10%-23%) and an 8% higher burden of psychological distress (95% CI, 1%-16%) compared with those without disruption.

Conclusions: Financial hardship related to employment disruption among female AYA cancer survivors can be substantial. Interventions to promote job maintenance and transition back to the workforce after treatment, as well as improved workplace accommodations and benefits, present an opportunity to improve cancer survivorship.
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http://dx.doi.org/10.1002/cncr.33190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736150PMC
January 2020

Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations.

Gynecol Oncol 2020 12 1;159(3):804-810. Epub 2020 Oct 1.

Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States of America.

Objective: To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations.

Methods: Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy.

Results: A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%).

Conclusion: A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.
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http://dx.doi.org/10.1016/j.ygyno.2020.09.021DOI Listing
December 2020

Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.

Nat Commun 2020 09 4;11(1):4423. Epub 2020 Sep 4.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.
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http://dx.doi.org/10.1038/s41467-020-18246-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473862PMC
September 2020

Urinary polycyclic aromatic hydrocarbons in relation to anthropometric measures and pubertal development in a cohort of Northern California girls.

Environ Epidemiol 2020 Aug 6;4(4):e0102. Epub 2020 Jul 6.

Environmental Health Investigations Branch, California Department of Public Health, Richmond, California.

Background: Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous, environmental chemicals that may have endocrine disrupting capabilities. We investigated whether childhood exposure to PAHs was associated with adiposity and pubertal timing in a longitudinal study of 404 girls enrolled in the Northern California site of the Breast Cancer and the Environment Research Program cohort.

Methods: Baseline urinary samples from girls aged 6-8-years-old were assayed for 2-naphthol, fluorene metabolites, phenanthrene metabolites, 1-hydroxypyrene, and sum of PAH metabolites. Mixed-effects linear models were used to estimate how concentrations of PAH metabolites were related to changes in girl's body mass index (BMI) and waist-to-height ratio from age 7 through 16 years old. Accelerated failure time models were used to estimate age of pubertal onset (Tanner stages 2 or higher for breast and pubic hair development).

Results: Higher adiposity measurements among high tertiles of baseline PAH metabolites were evident at age 7 years old and increased thereafter (i.e., BMI for all PAH metabolites, waist-to-height ratio for fluorene and phenanthrene metabolites) or leveled off (i.e., waist-to-height ratio for 2-naphthol, 1-hydroxypyrene, sum of PAHs). Among girls overweight/obese at baseline, median age of breast development onset for high tertiles was 9.1-9.4 years old compared with 10-10.2 years old for low tertiles for all PAH metabolites; in contrast, found no association or slightly later onset of breast development for girls with normal weight at baseline.

Discussion: These results suggest that exposure to specific PAHs during childhood may influence adiposity throughout adolescence and effect pubertal timing.
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http://dx.doi.org/10.1097/EE9.0000000000000102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423521PMC
August 2020

Streamlining genetic testing for women with ovarian cancer in a Northern California health care system.

Gynecol Oncol 2020 10 7;159(1):221-228. Epub 2020 Aug 7.

Kaiser Permanente Northern California, Division of Research, Oakland, CA, United States of America.

Objective: Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing.

Methods: A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system.

Results: Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process.

Conclusion: Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.
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http://dx.doi.org/10.1016/j.ygyno.2020.07.027DOI Listing
October 2020

Obesity and related conditions and risk of inflammatory breast cancer: a nested case-control study.

Breast Cancer Res Treat 2020 Sep 20;183(2):467-478. Epub 2020 Jul 20.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Purpose: Inflammatory breast cancer (IBC) is a rare, poorly understood and aggressive tumor. We extended prior findings linking high body mass index (BMI) to substantial increased IBC risk by examining BMI associations before and after adjustment for well-characterized comorbidities using medical record data for diabetes, insulin resistance, and disturbances of cholesterol metabolism in a general community healthcare setting.

Methods: We identified 247 incident IBC cases diagnosed at Kaiser Permanente Northern California between 2005 and 2017 and 2470 controls matched 10:1 on birth year and geographic area and with ≥ 13 months of continuous enrollment prior to diagnosis/index date. We assessed exposures from 6 years up to one year prior to the diagnosis/index date, using logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

Results: Before adjustment for comorbidities, ORs (95% CIs) for BMI of 25-< 30, 30-< 35, and ≥ 35 compared to < 25 kg/m were 1.5 (0.9-2.3), 2.0 (1.2-3.1), and 2.5 (1.4-4.4), respectively. After adjustment for pre-diabetes/diabetes, HDL-C and triglyceride levels, and dyslipidemia, corresponding ORs were 1.3 (0.8-2.1), 1.6 (0.9-2.9), and 1.9 (1.0-3.5). The OR for HDL-C levels < 50 mg/dL compared to ≥ 65 mg/dL was 2.0 (1.2-3.3) in the adjusted model. In a separate model the OR for a triglyceride/HDL-C ratio ≥ 2.50 compared to < 1.62 was 1.7 (1.1-2.8) after adjustment for BMI, pre-diabetes/diabetes, and dyslipidemia. Results did not differ significantly by estrogen receptor status.

Conclusions: Obesity and measures of insulin resistance independently increased IBC risk as did obesity and low HDL-C levels. These findings, if confirmed, have implications for IBC prevention.
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http://dx.doi.org/10.1007/s10549-020-05785-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257005PMC
September 2020

American Cancer Society guideline for diet and physical activity for cancer prevention.

CA Cancer J Clin 2020 07 9;70(4):245-271. Epub 2020 Jun 9.

Cancer Control, American Cancer Society, Atlanta, Georgia.

The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
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http://dx.doi.org/10.3322/caac.21591DOI Listing
July 2020

Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations.

Gynecol Oncol 2020 05 4;157(2):521-528. Epub 2020 Mar 4.

Kaiser Permanente Northern California, Division of Research, Oakland, CA, United States of America; Kaiser Permanente Northern California Gynecologic Cancer Program, United States of America. Electronic address:

Objective: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months.

Methods: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale.

Results: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034).

Conclusions: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2020.02.027DOI Listing
May 2020

Distinct trajectories of moderate to vigorous physical activity and sedentary behavior following a breast cancer diagnosis: the Pathways Study.

J Cancer Surviv 2020 06 4;14(3):393-403. Epub 2020 Mar 4.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Purpose: To identify distinct trajectories of total moderate-to-vigorous physical activity (MVPA) and sedentary behavior following a breast cancer diagnosis and their correlates.

Methods: The analysis examined 3000 female breast cancer survivors within Kaiser Permanente Northern California between 2006 and 2013. Self-reported time spent on total MVPA and sedentary behaviors were assessed at baseline (mean = 1.8 months post-diagnosis) and at 6 and 24 months follow up. Trajectory groups were identified using group-based trajectory modeling and K-means for longitudinal data analysis. Trajectory groups were named by baseline activity level (high, medium, or low) and direction of change (increaser, decreaser, or maintainer).

Results: Trajectory analyses identified three MVPA trajectories [high decreaser (7%), medium decreaser (35%), low maintainer (58%)] and four sedentary behavior trajectories [high maintainer (18%), high decreaser (27%), low increaser (24%), and low maintainer (31%)]. Women with higher education (ORs: 1.63-4.37), income (OR: 1.37), dispositional optimism (ORs: 1.60-1.86), and social support (OR: 1.33) were more likely to be high or medium decreasers of MVPA (all P < 0.05). High maintainers and high decreasers of sedentary behavior were more likely to have higher education (OR: 1.84) and social support (ORs: 1.42-1.86), but lower income (OR: 0.66; all P < 0.05).

Conclusions: In the 24 months following breast cancer diagnosis, 42% of survivors decreased MVPA and 73% maintained or increased time on sedentary behavior. Socioeconomic status and stress coping at diagnosis predicted subsequent PA trajectory.

Implications For Cancer Survivors: It is important to prioritize exercise intervention and counseling during early stage of breast cancer survivorship, especially in survivors who are at high risk of becoming physically inactive post-diagnosis.
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http://dx.doi.org/10.1007/s11764-020-00856-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955660PMC
June 2020

Impact of the Affordable Care Act on Colorectal Cancer Outcomes: A Systematic Review.

Am J Prev Med 2020 04 31;58(4):596-603. Epub 2020 Jan 31.

Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut.

Context: The Patient Protection and Affordable Care Act increases healthcare access and includes provisions that directly impact access to and cost of evidence-based colorectal cancer screening. The Affordable Care Act's removal of cost sharing for colorectal cancer screening as well as Medicaid expansion have been hypothesized to increase screening and improve other health outcomes. However, since its passage in 2010, there is little consensus on the Affordable Care Act's impact.

Evidence Acquisition: Data from March 2010 to June 2019 were reviewed and 21 relevant studies were identified; 19 studies examined colorectal cancer screening with most finding increased screening rates.

Evidence Synthesis: Eleven studies found significant increases, 5 found nonsignificant increases, 3 found nonsignificant decreases, and 1 study found a significant decrease in colorectal cancer screening. Three studies examined the impact on colorectal cancer incidence and stage of diagnosis, where a significant 2.4% increase in early diagnosis was found in one and a nonsignificant increase in incidence in another. However, survival improved after Medicaid expansion.

Conclusions: Free preventive colorectal cancer screening and Medicaid expansion because of passage of the Affordable Care Act have been, in general, positively associated with modest improvements in screening rates across the country. Future studies are needed that investigate the longer-term impact of the Affordable Care Act on colorectal cancer morbidity and mortality rates, as screening is only the first step in treatment of cancerous and precancerous lesions, preventing them from progressing. Moreover, more studies examining subpopulations are needed to better assess where gaps in care remain.
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http://dx.doi.org/10.1016/j.amepre.2019.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175922PMC
April 2020

Adjuvant endocrine therapy for breast cancer patients: impact of a health system outreach program to improve adherence.

Breast Cancer Res Treat 2020 Feb 23;180(1):219-226. Epub 2020 Jan 23.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Purpose: Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5 years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC) on adherence and discontinuation of AET among patients who initiated AET.

Methods: We assembled a retrospective cohort of all KPNC patients diagnosed with HR+, stage I-III BC initiating AET before (n = 4287) and after (n = 3580) implementation of the outreach program. We compared adherence proportions and discontinuation rates before and after program implementation, both crude and adjusted for age, race/ethnicity, education, income, and stage. We conducted a pooled analysis of data from six Cancer Research Network (CRN) sites that had not implemented programs for improving AET adherence, using identical methods and time periods, to assess possible secular trends.

Results: In the pre-outreach period, estimated adherence in years 1, 2, and 3 following AET initiation was 75.2%, 71.0%, and 67.3%; following the outreach program, the estimates were 79.4%, 75.6%, and 72.2% (p-values < .0001 for pairwise comparisons). Results were comparable after adjusting for clinical and demographic factors. The estimated cumulative incidence of discontinuation was 0.22 (0.21-0.24) and 0.18 (0.17-0.19) at 3 years for pre- and post-outreach groups (p-value < .0001). We found no evidence of an increase in adherence between the study periods at the CRN sites with no AET adherence program.

Conclusion: Adherence and discontinuation after AET initiation improved modestly following implementation of the outreach program.
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http://dx.doi.org/10.1007/s10549-020-05539-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035197PMC
February 2020

Serum bone markers and risk of osteoporosis and fragility fractures in women who received endocrine therapy for breast cancer: a prospective study.

Breast Cancer Res Treat 2020 Feb 7;180(1):187-195. Epub 2020 Jan 7.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Purpose: Osteoporosis and fragility fracture are major bone toxicities of aromatase inhibitors (AIs) for postmenopausal hormone receptor-positive breast cancer. Except for a few small studies on bone turnover markers and reduced bone mineral density after AI treatment, data on the associations of bone markers and risk of osteoporosis or fracture from prospective studies are lacking.

Methods: In a prospective study of 1709 women on AIs, two bone turnover markers, BALP and TRACP, and two bone regulatory markers, RANKL and OPG, were measured and examined in relation to risk of osteoporosis and fragility fractures during a median follow-up time of 6.1 years.

Results: Higher levels of BALP and TRACP were both associated with increased risk of osteoporosis and higher BALP/TRACP ratios were associated with lower risk of osteoporosis, but no associations were observed for fracture risk. Higher levels of OPG were associated with increased risk of fracture, whereas higher levels of RANKL were associated with lower risk. As a result, OPG/RANKL ratios were positively associated with fracture risk [hazard ratio (HR) = 2.49, 95% confidence interval (CI) 1.34-4.61]. After controlling for age and fracture history, the associations became non-significant but a suggestive trend remained (HR = 1.80, 95% CI 0.96-3.37).

Conclusion: Our study provides suggestive evidence for the potential utility of OPG/RANKL ratios in predicting risk of fracture in women treated with AIs for breast cancer. Further validation may be warranted.
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http://dx.doi.org/10.1007/s10549-019-05518-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171589PMC
February 2020

Validity of state cancer registry treatment information for adolescent and young adult women.

Cancer Epidemiol 2020 02 5;64:101652. Epub 2019 Dec 5.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, US.

Background: Population-based cancer registries collect information on first course of treatment that may be utilized in research on cancer care quality, yet few studies have investigated the validity of this information. We examined the accuracy and completeness of registry-based treatment information in a cohort of adolescent and young adult women.

Methods: Women diagnosed with breast cancer, lymphoma, thyroid cancer, cervical/uterine cancer or ovarian cancer at ages 15-39 during 2003-2014 were identified using data from the North Carolina Central Cancer Registry (CCR) (N = 2342). CCR data were linked to Medicaid and private insurance claims data, and claims were reviewed for the 12 months following diagnosis to identify cancer treatments received. Using claims data as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of CCR data for receipt of chemotherapy, radiation and hormone therapy. We also compared dates of treatment initiation between the two data sources.

Results: For all cancer types combined, the sensitivity of the CCR data was high for chemotherapy (86%) and moderate for radiation (74%). PPVs were 82% and 83% for chemotherapy and radiation, respectively. Both the sensitivity (67%) and PPV (70%) were lower for hormone therapy for breast cancer. For all three treatment types, dates of initiation in the registry and the claims differed by ≤30 days for most women.

Conclusions: In this cohort of young women, population-based cancer registry data on chemotherapy receipt was reasonably accurate and complete in comparison with insurance claims. Radiation and hormone therapy appeared to be less complete.
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http://dx.doi.org/10.1016/j.canep.2019.101652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983329PMC
February 2020

Environmental Tobacco Smoke Exposure in Relation to Family Characteristics, Stressors and Chemical Co-Exposures in California Girls.

Int J Environ Res Public Health 2019 10 30;16(21). Epub 2019 Oct 30.

Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612, USA.

Childhood environmental tobacco smoke (ETS) exposure is a risk factor for adverse health outcomes and may disproportionately burden lower socioeconomic status groups, exacerbating health disparities. We explored associations of demographic factors, stressful life events, and chemical co-exposures, with cotinine levels, among girls in the CYGNET Study. Data were collected from families of girls aged 6-8 years old in Northern California, through clinic exams, questionnaires and biospecimens (n = 421). Linear regression and factor analysis were conducted to explore predictors of urinary cotinine and co-exposure body burdens, respectively. In unadjusted models, geometric mean cotinine concentrations were higher among Black (0.59 ug/g creatinine) than non-Hispanic white (0.27), Asian (0.32), or Hispanic (0.34) participants. Following adjustment, living in a rented home, lower primary caregiver education, and lack of two biologic parents in the home were associated with higher cotinine concentrations. Girls who experienced parental separation or unemployment in the family had higher unadjusted cotinine concentrations. Higher cotinine was also associated with higher polybrominated diphenyl ether and metals concentrations. Our findings have environmental justice implications as Black and socio-economically disadvantaged young girls experienced higher ETS exposure, also associated with higher exposure to other chemicals. Efforts to reduce ETS and co-exposures should account for other disparity-related factors.
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http://dx.doi.org/10.3390/ijerph16214208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862570PMC
October 2019
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