Dr. Li is the co-Program Head of the Translational Research Program (TRP) and a Full Member in the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center (FHCRC), and is a Research Professor in the Department of Epidemiology at the University of Washington. He received his MD from the University of California, San Francisco, and his PhD in Epidemiology from the University of Washington. At FHCRC, Dr. Li works in the Cancer Epidemiology Research Cooperative (CERC), which is in FHCRC's Program in Epidemiology.
Dr. Li's research interests lie principally in the field of breast cancer and understanding factors related to its etiology and outcomes using a multidisciplinary approach. Currently, he is working on projects aimed at identifying novel biomarkers that could be used for the early detection of breast cancer, evaluating risk factors for different types of breast cancer, identifying predictors of poor outcomes among breast cancer survivors, and assessing disparities in cancer stage, treatment and survival by race/ethnicity.
Rho JH, Ladd JJ, Li CI, Potter JD, Zhang Y, Shelley D, Shibata D, Coppola D, Yamada H, Toyoda H, Tada T, Kumada T, Brenner DE, Hanash SM, Lampe PD. Protein and glycomic plasma markers for early detection of adenoma and colon cancer. Gut. 2016 Nov 7. [Epub ahead of print]
OBJECTIVE: To discover and confirm blood-based colon cancer early-detection markers. DESIGN: We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays. RESULTS: In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively. CONCLUSIONS: A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.
Farias AJ, Hansen RN, Zeliadt SB, Ornelas IJ, Li CI, Thompson B. The Association Between Out-of-Pocket Costs and Adherence to Adjuvant Endocrine Therapy Among Newly Diagnosed Breast Cancer Patients. Am J Clin Oncol. 2016 Nov 23. [Epub ahead of print]
OBJECTIVE: To determine how out-of-pocket costs for adjuvant endocrine therapy (AET) medication affects adherence among newly diagnosed breast cancer survivors with private health insurance who initiate therapy. MATERIALS AND METHODS: We examined medical and pharmacy claims for the 1-year period after initiating AET using the Truven Health Analytics MarketScan database. Adherence was defined as ≥80% proportion of days covered. Mean out-of-pocket costs for AET fill were measured as the sum of copayments, coinsurance, and deductibles and adjusted to 30-day amounts. Using a multivariable logistic regression model we calculated adjusted risk ratios controlling for age, comorbidities, type of surgery, use of chemotherapy and/or radiation therapy, average out-of-pocket costs for other services, and pharmacy use characteristics. RESULTS: Of the 6863 women 64 years and younger who were diagnosed with breast cancer and initiated AET, 73.9% were adherent (proportion of days covered≥80%). A total of 19% of patients had <$5 monthly out-of-pocket costs for AET, 30% had $5 to $9.99, 17% had $10 to $14.99, 10% had $15 to $19.99, and 25% had $20 or greater. Patients with out-of-pocket costs for AET between $10 and $14.99, $15 and $19.99, and >$20 were 6% to 8% less likely to be adherent compared with patients paying <$5.00, after controlling for covariates (P<0.05). Out-of-pocket costs for inpatient, outpatient, and other pharmacy services were not associated with adherence. CONCLUSIONS: A substantial proportion of privately insured patients are nonadherent to AET and out-of-pocket costs for AET medication are significantly associated with a greater likelihood of nonadherence.
Farias AJ, Ornelas IJ, Hohl SD, Zeliadt SB, Hansen RN, Li CI, Thompson B. Exploring the role of physician communication about adjuvant endocrine therapy among breast cancer patients on active treatment: a qualitative analysis. Support Care Cancer. 2017 Jan;25(1):75-83.
PURPOSE: To better understand how physicians communicate with breast cancer patients about adjuvant endocrine therapy (AET), we explored, from the breast cancer patient's perspective, dimensions of the patient-provider communication among women who were on active AET treatment. METHODS: Qualitative methods using semi-structured in-depth interviews were conducted with breast cancer patients (n = 22) who filled a prescription for AET in the previous 12 months. Interview questions aimed to elicit experiences with AET. We reviewed and coded interview transcripts using qualitative principles of inductive reasoning to identify concepts and themes from interview data. RESULTS: We grouped emergent themes into four major functions of physician-patient communication: (1) information exchange, (2) decision-making to take and continue AET, (3) enabling patient self-management and monitoring potential side effects, and (4) emotional support. Physicians exchanged information with patients in a way that they understood and enhanced patient's health literacy regarding the benefits and knowledge of AET. Physicians empowered patients to make decisions about their care. Patients expressed trust and confidence in their physician which helped them seek care when needed. Patients reported a high degree of self-efficacy to self-manage AET and were continuing treatment despite potential side effects. CONCLUSIONS: The results from our study suggest that women's interactions and communication with their physician may be an important factor that contributes to the continued use of AET. Physicians who can communicate information about AET treatment benefits, purpose, and expectations in a way that patients can understand is a critical aspect of care that needs to be further studied.
Garrison CB, Lastwika KJ, Zhang Y, Li CI, Lampe PD. Proteomic Analysis, Immune Dysregulation, and Pathway Interconnections with Obesity. J Proteome Res. 2017 Jan 6;16(1):274-287.
Proteomic studies can offer information on hundreds to thousands of proteins and potentially provide researchers with a comprehensive understanding of signaling response during stress and disease. Large data sets, such as those obtained in high-dimensional proteomic studies, can be leveraged for pathway analysis to discover or describe the biological implications of clinical disease states. Obesity is a worldwide epidemic that is considered a risk factor for numerous other diseases. We performed analysis on plasma proteomic data from 3 separate sample sets of postmenopausal women to identify the pathways that are altered in subjects with a high body mass index (BMI) compared to normal BMI. We found many pathways consistently and significantly associated with inflammation dysregulated in plasma from obese/overweight subjects compared to plasma from normal BMI subjects. These pathways indicate alterations of soluble inflammatory regulators, cellular stress, and metabolic dysregulation. Our results highlight the importance of high-dimensional pathway analysis in complex diseases as well as provide information on the interconnections between pathways that are dysregulated with obesity. Specifically, overlap of obesity related pathways with those activated during cancer and infection could help describe why obesity is a risk factor for disease and help devise treatment options that mitigate its effect.
Kaplan RC, Strizich G, Aneke-Nash C, Dominguez-Islas C, Bužková P, Strickler H, Rohan T, Pollak M, Kuller L, Kizer JR, Cappola A, Li CI, Psaty BM, Newman A. Insulinlike Growth Factor Binding Protein-1 and Ghrelin Predict Health Outcomes Among Older Adults: Cardiovascular Health Study Cohort. J Clin Endocrinol Metab. 2017 Jan 1;102(1):267-278.
Context: Multiple diseases may explain the association of the growth hormone/insulinlike growth factor-I (GH/IGF-I) axis with longevity. Objective: To relate circulating GH/IGF-I system protein levels with major health events. Design and Setting: This is a cohort study set in 4 US communities. Participants: Adults (N = 2268) 65 years and older free of diabetes and cardiovascular disease. Measurements: We assessed insulinlike growth factor binding protein-1 (IGFBP-1) and ghrelin in fasting and 2-hour oral glucose tolerance test (OGTT) blood samples, as well as fasting IGF-I and IGFBP-3. Hazard ratios for mortality and a composite outcome for first incident myocardial infarction, stroke, heart failure, hip fracture, or death were adjusted for sociodemographic, behavioral, and physiological covariates. Results: During 13,930 person-years of follow-up, 48.1% of individuals sustained one or more components of the composite outcome and 31.8% died. Versus the lowest quartiles, the highest quartiles of fasting and 2-hour ghrelin were associated with 27% higher (95% confidence interval [CI]: 6%, 53%) and 39% higher (95% CI: 14%, 71%) risks of the composite outcome, respectively. The highest quartile of 2-hour IGFBP-1 was associated with 35% higher (95% CI: 1%, 52%) risk of the composite end point. Similarly, higher mortality was significantly associated with higher fasting and 2-hour ghrelin levels and with 2-hour IGFBP-1 level. When examined together, 2-hour post-OGTT levels of IGFBP-1 and ghrelin tended to predict outcomes better than fasting levels. Conclusions: Circulating IGFBP-1 and ghrelin measured during an OGTT predicted major health events and death in older adults, which may explain the influence of the GH/IGF-I axis on lifespan and health.
Farias AJ, Hansen RN, Zeliadt SB, Ornelas IJ, Li CI, Thompson B. Factors Associated with Adherence to Adjuvant Endocrine Therapy Among Privately Insured and Newly Diagnosed Breast Cancer Patients: A Quantile Regression Analysis. J Manag Care Spec Pharm. 2016;22(8):969-78.
BACKGROUND: Adherence to adjuvant endocrine therapy (AET) for estrogen receptor-positive breast cancer remains suboptimal, which suggests that women are not getting the full benefit of the treatment to reduce breast cancer recurrence and mortality. The majority of studies on adherence to AET focus on identifying factors among those women at the highest levels of adherence and provide little insight on factors that influence medication use across the distribution of adherence. OBJECTIVE: To understand how factors influence adherence among women across low and high levels of adherence. METHODS: A retrospective evaluation was conducted using the Truven Health MarketScan Commercial Claims and Encounters Database from 2007-2011. Privately insured women aged 18-64 years who were recently diagnosed and treated for breast cancer and who initiated AET within 12 months of primary treatment were assessed. Adherence was measured as the proportion of days covered (PDC) over a 12-month period. Simultaneous multivariable quantile regression was used to assess the association between treatment and demographic factors, use of mail order pharmacies, medication switching, and out-of-pocket costs and adherence. The effect of each variable was examined at the 40th, 60th, 80th, and 95th quantiles. RESULTS: Among the 6,863 women in the cohort, mail order pharmacies had the greatest influence on adherence at the 40th quantile, associated with a 29.6% (95% CI = 22.2-37.0) higher PDC compared with retail pharmacies. Out-of-pocket cost for a 30-day supply of AET greater than $20 was associated with an 8.6% (95% CI = 2.8-14.4) lower PDC versus $0-$9.99. The main factors that influenced adherence at the 95th quantile were mail order pharmacies, associated with a 4.4% higher PDC (95% CI = 3.8-5.0) versus retail pharmacies, and switching AET medication 2 or more times, associated with a 5.6% lower PDC versus not switching (95% CI = 2.3-9.0). CONCLUSIONS: Factors associated with adherence differed across quantiles. Addressing the use of mail order pharmacies and out-of-pocket costs for AET may have the greatest influence on improving adherence among those women with low adherence.
Chen L, Li CI, Tang MT, Porter P, Hill DA, Wiggins CL, Cook LS. Reproductive Factors and Risk of Luminal, HER2-Overexpressing, and Triple-Negative Breast Cancer Among Multiethnic Women. Cancer Epidemiol Biomarkers Prev. 2016 Sep;25(9):1297-304.
BACKGROUND: Reproductive factors are among the most well-established risk factors for breast cancer. However, their associations with different breast cancer subtypes defined by joint estrogen receptor (ER)/progesterone receptor (PR)/HER2 status remain unclear. METHODS: We assessed relationships between reproductive factors and risks of luminal A (ER(+)/HER2(-)), luminal B (ER(+)/HER2(+)), triple-negative (TN; ER(-)/PR(-)/HER2(-)), and HER2-overexpressing (H2E; ER(-)/HER2(+)) breast cancers in a population-based case-case study consisting of 2,710 women ages 20-69 years diagnosed between 2004 and 2012. ORs and 95% confidence intervals (CI) were estimated with luminal A cases serving as the reference group using polytomous logistic regression. RESULTS: Earlier age at first full-term pregnancy and age at menopause were positively associated with odds of TN breast cancer (Ptrend: 0.003 and 0.024, respectively). Parity was associated with a 43% (95% CI, 1.08-1.89) elevated odds of H2E breast cancer, and women who had ≥3 full-term pregnancies had a 63% (95% CI, 1.16-2.29, Ptrend = 0.013) increased odds of this subtype compared with nulliparous women. Breast feeding for ≥36 months was associated with a 49% (OR 0.51; 95% CI, 0.27-0.99) lower odds of TN breast cancer. CONCLUSION: Our results suggest that reproductive factors contribute differently to risks of the major molecular subtypes of breast cancer. IMPACT: African American and Hispanic women have higher incidence rates of the more aggressive TN and H2E breast cancers and their younger average age at first pregnancy, higher parity, and less frequent breast feeding could in part contribute to this disparity.