- Browse by Author
Browsing by Author "Cote, Michele L."
Now showing 1 - 10 of 11
Results Per Page
Sort Options
Item A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO(Springer Nature, 2021) Blackford, Amanda L.; Childs, Erica J.; Porter, Nancy; Petersen, Gloria M.; Rabe, Kari G.; Gallinger, Steven; Borgida, Ayelet; Syngal, Sapna; Cote, Michele L.; Schwartz, Ann G.; Goggins, Michael G.; Hruban, Ralph H.; Parmigiani, Giovanni; Klein, Alison P.; Epidemiology, Richard M. Fairbanks School of Public HealthIntroduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. Methods: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. Results: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). Discussion: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.Item Continuity of care and receipt of aggressive end of life care among women dying of ovarian cancer(Elsevier, 2021) Mullins, Megan A.; Ruterbusch, Julie J.; Clarke, Philippa; Uppal, Shitanshu; Cote, Michele L.; Wallner, Lauren P.; Medicine, School of MedicineObjective: To evaluate the association between post-diagnosis continuity of care and receipt of aggressive end of life care among women dying of ovarian cancer. Methods: This retrospective claims analysis included 6680 Medicare beneficiaries over age 66 with ovarian cancer who survived at least one year after diagnosis, had at least 4 outpatient evaluation and management visits and died between 2000 and 2016. We calculated the Bice-Boxerman Continuity of Care Index (COC) for each woman, and split COC into tertiles (high, medium, low). We compared late or no hospice use, >1 emergency department (ED) visit, intensive care unit (ICU) admission, >1 hospitalization, terminal hospitalization, chemotherapy, and invasive and/or life extending procedures among women with high or medium vs. low COC using multivariable adjusted logistic regression. Results: In this sample, 49.8% of women received aggressive care in the last month of life. Compared to women with low COC, women with high COC had 66% higher odds of chemotherapy (adjusted OR 1.66 CI 1.23-2.24) in the last two weeks of life. Women with high COC also had 16% greater odds of not enrolling in hospice compared to women with low COC (adjusted OR 1.16 CI 1.01-1.33). COC was not associated with late enrollment in hospice, hospital utilization, or aggressive procedures. Conclusions: COC at the end of life is complicated and may pose unique challenges in providing quality end of life care. Future work exploring the specific facets of continuity associated with quality end of life care is needed.Item Disparities in Adjuvant Treatment of High-Grade Endometrial Cancer in the Medicare Population(Elsevier, 2022) Corey, Logan; Cote, Michele L.; Ruterbusch, Julie J.; Winer, Ira; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Black women experience worse survival effects with high-grade endometrial cancer. Differences in adjuvant treatment have been proposed to be major contributors to this disparity. However, little is known about the differences in type or timing of adjuvant treatment as it relates to race and ethnicity in the Medicare population. Objective: This study aimed to examine patterns of adjuvant therapy and survival for non-Hispanic Black women vs non-Hispanic White women and Hispanic women who have undergone surgery for high-grade endometrial cancer in the Medicare population. Study design: We used the Medicare-linked Surveillance, Epidemiology, and End Results database to identify women who underwent surgery as a primary treatment for uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear-cell carcinoma, or serous carcinoma between the years 2000 and 2015. Women who did not identify as White or Black race or Hispanic ethnicity were excluded. Multinomial logistic regression was used to estimate odds ratios and 95% confidence intervals for receiving a treatment delay or not receiving adjuvant treatment (compared with those who received adjuvant treatment within 12 weeks) adjusted for clinical and demographic characteristics. Overall survival was stratified by race and ethnicity, route of surgery, operative complications, and type and timing of adjuvant therapy, which were analyzed using the Kaplan-Meier method. Cox proportional-hazards regression was used to estimate the hazard ratio of death by race and ethnicity adjusted for known predictors and surgical outcomes and adjuvant therapy patterns. Results: A total of 12,201 women met the study inclusion criteria. Non-Hispanic Black patients had a significantly worse 5-year overall survival than Hispanic and non-Hispanic White patients (30.9 months vs 51.0 months vs 53.6 months, respectively). Approximately 632 of 7282 patients (8.6%) who received adjuvant treatment experienced a treatment delay. Delay in treatment of ≥12 weeks was significantly different by race and ethnicity (P=.034), with 12% of Hispanic, 9% of non-Hispanic Black, and 8% of non-Hispanic White women experiencing a delay. After adjustment for the number of complications, age, histology (endometrioid vs nonendometroid), International Federation of Gynecology and Obstetrics stage, marital status, comorbidity count, surgical approach, lymph node dissection, and urban-rural code, Hispanic women had a 71% increased risk of treatment delay (odds ratio, 1.71; 95% confidence interval, 1.23-2.38) for all stages of disease. In the same model, non-Hispanic Black race was independently predictive of decreased use of adjuvant treatment for the International Federation of Gynecology and Obstetrics stage II and higher (odds ratio, 1.32; 95% confidence interval, 1.04-1.68). Non-Hispanic Black race, number of perioperative complications, and nonendometrioid histology were predictive of worse survival in univariate models. Treatment delay was not independently predictive of worse 1- or 5-year survival at any stage. Conclusion: Non-Hispanic Black race was predictive of worse 5-year survival across all stages and was associated with omission of adjuvant treatment in International Federation of Gynecology and Obstetrics stage II or higher high-grade endometrial cancer. In unadjusted analyses, patients who experience treatment omission or delay experienced poorer overall survival, but these factors were not independently associated in multivariate analyses. This study suggests that race and ethnicity are independently associated with the type and timing of adjuvant treatment in patients with high-grade endometrial cancer. Further efforts to identify specific causes of barriers to care and timely treatment are imperative.Item Physician Influence on Variation in Receipt of Aggressive End-of-Life Care Among Women Dying of Ovarian Cancer(American Society of Clinical Oncology, 2022) Mullins, Megan A.; Uppal, Shitanshu; Ruterbusch, Julie J.; Cote, Michele L.; Clarke, Philippa; Wallner, Lauren P.; Epidemiology, Richard M. Fairbanks School of Public HealthPurpose: End-of-life care for women with ovarian cancer is persistently aggressive, but factors associated with overuse are not well understood. We evaluated physician-level variation in receipt of aggressive end-of-life care and examined physician-level factors contributing to this variation in the SEER-Medicare data set. Methods: Medicare beneficiaries with ovarian cancer who died between 2000 and 2016 were included if they were diagnosed after age 66 years, had complete Medicare coverage between diagnosis and death, and had outpatient physician evaluation and management for their ovarian cancer. Using multilevel logistic regression, we examined physician variation in no hospice enrollment, late hospice enrollment (≤ 3 days), > 1 emergency department visit, an intensive care unit stay, terminal hospitalization, > 1 hospitalization, receiving a life-extending or invasive procedure, and chemotherapy (in the last 2 weeks). Results: In this sample of 6,288 women, 51% of women received at least one form of aggressive end-of-life care. Most common were no hospice enrollment (28.9%), an intensive care unit stay (18.6%), and receipt of an invasive procedure (20.7%). For not enrolling in hospice, 9.9% of variation was accounted for by physician clustering (P < .01). Chemotherapy had the highest physician variation (12.4%), with no meaningful portion of the variation explained by physician specialty, volume, region, or patient characteristics. Conclusion: In this study, a meaningful amount of variation in aggressive end-of-life care among women dying of ovarian cancer was at the physician level, suggesting that efforts to improve the quality of this care should include interventions aimed at physician practices and decision making in end-of-life care.Item Psychosocial factors associated with genetic testing status among African American women with ovarian cancer: Results from the African American Cancer Epidemiology Study(Wiley, 2022) McBride, Colleen M.; Pathak, Sarita; Johnson, Courtney E.; Alberg, Anthony J.; Bandera, Elisa V.; Barnholtz-Sloan, Jill S.; Bondy, Melissa L.; Cote, Michele L.; Moorman, Patricia G.; Peres, Lauren C.; Peters, Edward S.; Schwartz, Ann G.; Terry, Paul D.; Schildkraut, Joellen M.; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Racial disparities in the uptake of cancer genetic services are well documented among African American (AA) women. Understanding the multiple social and psychological factors that can influence the uptake of genetic testing among AA women is needed. Methods: Data came from 270 AA women diagnosed with ovarian cancer and participating in a population-based, case-control study of ovarian cancer who were asked about genetic testing. Logistic regression analyses tested the associations of predisposing, enabling, and need factors with reported genetic testing uptake. Results: One-third of the sample (35%) reported having had genetic testing. In the multivariable model, AA women with higher incomes had more than double the odds of being tested than those with the lowest income (odds ratio [OR] for $25,000-$74,999, 2.04; 95% confidence interval [CI], 1.06-3.99; OR for ≥$75,000, 2.32; 95% CI, 0.92-5.94). AA women who reported employment discrimination were significantly less likely to report genetic testing than those who did not report job discrimination (OR, 0.39; 95% CI, 0.14-0.95). Marital status, Medicaid versus other insurance, prayer frequency, and perceived social support were significantly associated with genetic testing uptake in bivariate analyses but were not significant contributors in multivariable analyses. Conclusions: Consistent with other studies of AA women, a minority of African American Cancer Epidemiology Study participants had undergone genetic testing. Having a lower income and experiencing job discrimination decreased the likelihood of testing. These results provide foundational evidence supporting the need for interventions to improve the uptake of genetic testing among AA women by reducing cost barriers and providing credible assurances that genetic results will be kept private and not affect social factors such as employability.Item Racial Differences in the Tumor Immune Landscape and Survival of Women with High-Grade Serous Ovarian Carcinoma(American Association for Cancer Research, 2022) Peres, Lauren C.; Colin-Leitzinger, Christelle; Sinha, Sweta; Marks, Jeffrey R.; Conejo-Garcia, Jose R.; Alberg, Anthony J.; Bandera, Elisa V.; Berchuck, Andrew; Bondy, Melissa L.; Christensen, Brock C.; Cote, Michele L.; Doherty, Jennifer Anne; Moorman, Patricia G.; Peters, Edward S.; Segura, Carlos Moran; Nguyen, Jonathan V.; Schwartz, Ann G.; Terry, Paul D.; Wilson, Christopher M.; Fridley, Brooke L.; Schildkraut, Joellen M.; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. Methods: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n = 121 in each racial group). We measured TILs (CD3+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+FoxP3+), myeloid cells (CD11b+), and neutrophils (CD11b+CD15+) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race. Results: Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant. Conclusions: Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC. Impact: This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.Item Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent(Springer Nature, 2023-09-14) Kumar, Brijesh; Khatpe, Aditi S.; Guanglong, Jiang; Batic, Katie; Bhat-Nakshatri, Poornima; Granatir, Maggie M.; Addison, Rebekah Joann; Szymanski, Megan; Baldridge, Lee Ann; Temm, Constance J.; Sandusky, George; Althouse, Sandra K.; Cote, Michele L.; Miller, Kathy D.; Storniolo, Anna Maria; Nakshatri, Harikrishna; Surgery, School of MedicineThe biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.Item The Association between Mediated Deprivation and Ovarian Cancer Survival among African American Women(MDPI, 2023-10-04) Lawson, Andrew B.; Kim, Joanne; Johnson, Courtney; Ratnapradipa, Kendra L.; Alberg, Anthony J.; Akonde, Maxwell; Hastert, Theresa; Bandera, Elisa V.; Terry, Paul; Mandle, Hannah; Cote, Michele L.; Bondy, Melissa; Marks, Jeffrey; Peres, Lauren C.; Schildkraut, Joellen; Peters, Edward S.; Epidemiology, School of Public HealthBackground: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer. This study aimed to determine if clinical or diagnostic characteristics lie on a mediating pathway between socioeconomic status (SES) and deprivation and ovarian cancer survival in a minority population that experiences worse survival from ovarian cancer. Methods: We used mediation analysis to look at the direct and indirect causal effects of deprivation indices with main mediators of the SEER stage at diagnosis and residual disease. The analysis employed Bayesian structural equation models with variable selection. We applied a joint Bayesian structural model for the mediator, including a Weibull mixed model for the vital outcome with deprivation as exposure. We selected modifiers via a Monte Carlo model selection procedure. Results: The results suggest that high SES-related indices, such as Yost, Kolak urbanicity (URB), mobility (MOB) and SES dimensions, and concentrated disadvantage index (CDI), all have a significant impact on improved survival. In contrast, area deprivation index (ADI)/Singh, and area level poverty (POV) did not have a major impact. In some cases, the indirect effects have very wide credible intervals, so the total effect is not well estimated despite the estimation of the direct effect. Conclusions: First, it is clear that commonly used indices such as Yost, or CDI both significantly impact the survival experience of Black women diagnosed with epithelial ovarian cancer. In addition, the Kolak dimension indices (URB, MOB, mixed immigrant: MICA and SES) also demonstrate a significant association, depending on the mediator. Mediation effects differ according to the mediator chosen.Item Trends and racial disparities in aggressive end of life care for a national sample of women with ovarian cancer(Wiley, 2021) Mullins, Megan A.; Ruterbusch, Julie J.; Clarke, Philippa; Uppal, Shitanshu; Wallner, Lauren P.; Cote, Michele L.; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: The clinical landscape has moved toward less aggressive end-of-life care for women with ovarian cancer. However, whether there has been a decline in the use of aggressive end-of-life services is unknown. The authors evaluated current national trends and racial disparities in end-of-life care among women with ovarian cancer using the Surveillance, Epidemiology, and End Results-Medicare-linked data set. Methods: In total, 7756 Medicare beneficiaries aged >66 years with ovarian cancer who died between 2007 and 2016 were identified. The authors examined trends and racial disparities in late hospice or no hospice use, >1 emergency department (ED) visit, intensive care unit admission, >1 hospitalization, terminal hospitalization, chemotherapy, and invasive and/or life-extending procedures using multivariable logistic regression. Results: The median hospice length of stay did not change over time; however, women were increasingly admitted to the intensive care unit and had multiple ED visits in the last month of life (P < .001). Not enrolling in hospice at the end of life and terminal hospitalizations decreased over time (P < .001). Non-White women were more likely to receive aggressive end-of-life care, particularly for hospital-related utilization and life-extending procedures, whereas non-Hispanic Black women were more likely to have >1 ED visit (odds ratio, 2.04; 95% CI, 1.57-2.64) or life-extending procedures (odds ratio, 1.89; 95% CI, 1.45-2.48) compared with non-Hispanic White women. Conclusions: Despite clinical guidelines and increasing emphasis on reducing aggressive end-of-life care, the use of aggressive end-of-life care for women with ovarian cancer persists, and care is most aggressive for non-White women.Item Trends in hospice referral timing and location among individuals dying of ovarian cancer: persistence of missed opportunities(BMJ, 2023-07-03) Mullins, Megan A.; Ruterbusch, Julie J.; Cote, Michele L.; Uppal, Shitanshu; Wallner, Lauren P.; Epidemiology, Richard M. Fairbanks School of Public HealthObjective: To evaluate trends, racial disparities, and opportunities to improve the timing and location of hospice referral for women dying of ovarian cancer. Methods: This retrospective claims analysis included 4258 Medicare beneficiaries over age 66 diagnosed with ovarian cancer who survived at least 6 months after diagnosis, died between 2007 and 2016, and enrolled in a hospice. We examined trends in timing and clinical location (outpatient, inpatient hospital, nursing/long-term care, other) of hospice referrals and associations with patient race and ethnicity using multivariable multinomial logistic regression. Results: In this sample, 56% of hospice enrollees were referred to a hospice within a month of death, and referral timing did not vary by patient race. Referrals were most commonly inpatient hospital (1731 (41%) inpatient, 703 (17%) outpatient, 299 (7%) nursing/long-term care, 1525 (36%) other), with a median of 6 inpatient days prior to hospice enrollment. Only 17% of hospice referrals were made in an outpatient clinic, but participants had a median of 1.7 outpatient visits per month in the 6 months prior to hospice referral. Referral location varied by patient race, with non-Hispanic black people experiencing the most inpatient referrals (60%). Hospice referral timing and location trends did not change between 2007 and 2016. Compared with individuals referred to a hospice in an outpatient setting, individuals referred from an inpatient hospital setting had more than six times the odds of a referral in the last 3 days of life (OR=6.5, 95% CI 4.4 to 9.8) versus a referral more than 90 days before death. Conclusion: Timeliness of hospice referral is not improving over time despite opportunities for earlier referral across multiple clinical settings. Future work delineating how to capitalize on these opportunities is essential for improving the timeliness of hospice care.