Risk of admission to hospital with arterial or venous thromboembolism among patients diagnosed in the ambulatory setting with covid-19 compared with influenza: retrospective cohort study.

Objective: To measure the 90 day risk of arterial thromboembolism and venous thromboembolism among patients diagnosed with covid-19 in the ambulatory (ie, outpatient, emergency department, or institutional) setting during periods before and during covid-19 vaccine availability and compare results to patients with ambulatory diagnosed influenza. Design: Retrospective cohort study. Setting: Four integrated health systems and two national health insurers in the US Food and Drug Administration's Sentinel System. Participants: Patients with ambulatory diagnosed covid-19 when vaccines were unavailable in the US (period 1, 1 April-30 November 2020; n=272 065) and when vaccines were available in the US (period 2, 1 December 2020-31 May 2021; n=342 103), and patients with ambulatory diagnosed influenza (1 October 2018-30 April 2019; n=118 618). Main outcome measures: Arterial thromboembolism (hospital diagnosis of acute myocardial infarction or ischemic stroke) and venous thromboembolism (hospital diagnosis of acute deep venous thrombosis or pulmonary embolism) within 90 days after ambulatory covid-19 or influenza diagnosis. We developed propensity scores to account for differences between the cohorts and used weighted Cox regression to estimate adjusted hazard ratios of outcomes with 95% confidence intervals for covid-19 during periods 1 and 2 versus influenza. Results: 90 day absolute risk of arterial thromboembolism with covid-19 was 1.01% (95% confidence interval 0.97% to 1.05%) during period 1, 1.06% (1.03% to 1.10%) during period 2, and with influenza was 0.45% (0.41% to 0.49%). The risk of arterial thromboembolism was higher for patients with covid-19 during period 1 (adjusted hazard ratio 1.53 (95% confidence interval 1.38 to 1.69)) and period 2 (1.69 (1.53 to 1.86)) than for patients with influenza. 90 day absolute risk of venous thromboembolism with covid-19 was 0.73% (0.70% to 0.77%) during period 1, 0.88% (0.84 to 0.91%) during period 2, and with influenza was 0.18% (0.16% to 0.21%). Risk of venous thromboembolism was higher with covid-19 during period 1 (adjusted hazard ratio 2.86 (2.46 to 3.32)) and period 2 (3.56 (3.08 to 4.12)) than with influenza. Conclusions: Patients diagnosed with covid-19 in the ambulatory setting had a higher 90 day risk of admission to hospital with arterial thromboembolism and venous thromboembolism both before and after covid-19 vaccine availability compared with patients with influenza.

Association of COVID-19 vs Influenza With Risk of Arterial and Venous Thrombotic Events Among Hospitalized Patients.

Importance: The incidence of arterial thromboembolism and venous thromboembolism in persons with COVID-19 remains unclear. Objective: To measure the 90-day risk of arterial thromboembolism and venous thromboembolism in patients hospitalized with COVID-19 before or during COVID-19 vaccine availability vs patients hospitalized with influenza. Design, Setting, and Participants: Retrospective cohort study of 41 443 patients hospitalized with COVID-19 before vaccine availability (April-November 2020), 44 194 patients hospitalized with COVID-19 during vaccine availability (December 2020-May 2021), and 8269 patients hospitalized with influenza (October 2018-April 2019) in the US Food and Drug Administration Sentinel System (data from 2 national health insurers and 4 regional integrated health systems). Exposures: COVID-19 or influenza (identified by hospital diagnosis or nucleic acid test). Main Outcomes and Measures: Hospital diagnosis of arterial thromboembolism (acute myocardial infarction or ischemic stroke) and venous thromboembolism (deep vein thrombosis or pulmonary embolism) within 90 days. Outcomes were ascertained through July 2019 for patients with influenza and through August 2021 for patients with COVID-19. Propensity scores with fine stratification were developed to account for differences between the influenza and COVID-19 cohorts. Weighted Cox regression was used to estimate the adjusted hazard ratios (HRs) for outcomes during each COVID-19 vaccine availability period vs the influenza period. Results: A total of 85 637 patients with COVID-19 (mean age, 72 [SD, 13.0] years; 50.5% were male) and 8269 with influenza (mean age, 72 [SD, 13.3] years; 45.0% were male) were included. The 90-day absolute risk of arterial thromboembolism was 14.4% (95% CI, 13.6%-15.2%) in patients with influenza vs 15.8% (95% CI, 15.5%-16.2%) in patients with COVID-19 before vaccine availability (risk difference, 1.4% [95% CI, 1.0%-2.3%]) and 16.3% (95% CI, 16.0%-16.6%) in patients with COVID-19 during vaccine availability (risk difference, 1.9% [95% CI, 1.1%-2.7%]). Compared with patients with influenza, the risk of arterial thromboembolism was not significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.04 [95% CI, 0.97-1.11]) or during vaccine availability (adjusted HR, 1.07 [95% CI, 1.00-1.14]). The 90-day absolute risk of venous thromboembolism was 5.3% (95% CI, 4.9%-5.8%) in patients with influenza vs 9.5% (95% CI, 9.2%-9.7%) in patients with COVID-19 before vaccine availability (risk difference, 4.1% [95% CI, 3.6%-4.7%]) and 10.9% (95% CI, 10.6%-11.1%) in patients with COVID-19 during vaccine availability (risk difference, 5.5% [95% CI, 5.0%-6.1%]). Compared with patients with influenza, the risk of venous thromboembolism was significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.60 [95% CI, 1.43-1.79]) and during vaccine availability (adjusted HR, 1.89 [95% CI, 1.68-2.12]). Conclusions and Relevance: Based on data from a US public health surveillance system, hospitalization with COVID-19 before and during vaccine availability, vs hospitalization with influenza in 2018-2019, was significantly associated with a higher risk of venous thromboembolism within 90 days, but there was no significant difference in the risk of arterial thromboembolism within 90 days.

Developing an algorithm across integrated healthcare systems to identify a history of cancer using electronic medical records.

OBJECTIVE: Tumor registries in integrated healthcare systems (IHCS) have high precision for identifying incident cancer but often miss recently diagnosed cancers or those diagnosed outside of the IHCS. We developed an algorithm using the electronic medical record (EMR) to identify people with a history of cancer not captured in the tumor registry to identify adults, aged 40-65 years, with no history of cancer. MATERIALS AND METHODS: The algorithm was developed at Kaiser Permanente Colorado, and then applied to 7 other IHCS. We included tumor registry data, diagnosis and procedure codes, chemotherapy files, oncology encounters, and revenue data to develop the algorithm. Each IHCS adapted the algorithm to their EMR data and calculated sensitivity and specificity to evaluate the algorithm's performance after iterative chart review. RESULTS: We included data from over 1.26 million eligible people across 8 IHCS; 55 601 (4.4%) were in a tumor registry, and 44848 (3.5%) had a reported cancer not captured in a registry. The common attributes of the final algorithm at each site were diagnosis and procedure codes. The sensitivity of the algorithm at each IHCS was 90.65%-100%, and the specificity was 87.91%-100%. DISCUSSION: Relying only on tumor registry data would miss nearly half of the identified cancers. Our algorithm was robust and required only minor modifications to adapt to other EMR systems. CONCLUSION: This algorithm can identify cancer cases regardless of when the diagnosis occurred and may be useful for a variety of research applications or quality improvement projects around cancer care.

A population-based survey to assess the association between cannabis and quality of life among colorectal cancer survivors.

BACKGROUND: As more states legalize cannabis for medical and recreational use, people increasingly use cannabis to treat medical conditions and associated symptoms. The prevalence and utility of cannabis for cancer-related symptoms may be clarified by examining cannabis use among patients with a common cancer diagnosis. We aimed to determine the prevalence of cannabis use among colorectal cancer (CRC) survivors and its associations with quality of life (QoL) and cancer-related symptomatology. METHODS: A cross-sectional survey of patient-reported QoL outcomes and behaviors, including cannabis use, was conducted within the Patient Outcomes To Advance Learning network's (PORTAL) CRC Cohort. The cohort included a population-based sample of healthcare system members ≥18 years old diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2016. We assessed the association between cannabis use and QoL using the European Organization for Research and Treatment of Cancer QLQ-C30 summary score. RESULTS: Of the 1784 respondents, 293 (16.4%) reported cannabis use following CRC diagnosis. Current tobacco smokers were more likely to use cannabis compared to former or never tobacco smokers (adjusted odds ratio [aOR] 2.71, 95% confidence interval [CI] 1.56 to 4.70). Greater alcohol use (> 4 drinks per month versus ≤4 drinks per month) was associated with cannabis use (aOR 2.17, 95% CI 1.65 to 2.85). There was an association between cannabis use and cancer stage at diagnosis, with stage 3 or 4 CRC patients more likely to use cannabis than stage 1 or 2 CRC patients (aOR 1.68, 95% CI 1.25 to 2.25). After adjusting for demographics, medical comorbidities, stage and site of CRC diagnosis, and prescription opioid use, people who used cannabis had significantly lower QoL than people who did not use cannabis (difference of - 6.14, 95% CI - 8.07 to - 4.20). CONCLUSION: Among CRC survivors, cannabis use was relatively common, associated with more advanced stages of disease, associated with tobacco and alcohol use, and not associated with better QoL. Clinicians should inquire about cannabis use among their patients and provide evidence-based recommendations for cancer-related symptoms.

Long-Term Patterns of Oral Anticancer Agent Adoption, Duration, and Switching in Patients With CML.

BACKGROUND: Oral tyrosine kinase inhibitors (TKIs) have been the standard of care for chronic myeloid leukemia (CML) since 2001. However, few studies have evaluated changes in the treatment landscape of CML over time. This study assessed the long-term treatment patterns of oral anticancer therapies among patients with CML. METHODS: This retrospective cohort study included patients newly diagnosed with CML between January 1, 2000, and December 31, 2016, from 10 integrated healthcare systems. The proportion of patients treated with 5 FDA-approved oral TKI agents-bosutinib, dasatinib, imatinib, nilotinib, and ponatinib-in the 12 months after diagnosis were measured, overall and by year, between 2000 and 2017. We assessed the use of each oral agent through the fourth-line setting. Multivariable logistic regression estimated the odds of receiving any oral agent, adjusting for sociodemographic and clinical characteristics. RESULTS: Among 853 patients with CML, 81% received an oral agent between 2000 and 2017. Use of non-oral therapies decreased from 100% in 2000 to 5% in 2005, coinciding with imatinib uptake from 65% in 2001 to 98% in 2005. Approximately 28% of patients switched to a second-line agent, 9% switched to a third-line agent, and 2% switched to a fourth-line agent. Adjusted analysis showed that age at diagnosis, year of diagnosis, and comorbidity burden were statistically significantly associated with odds of receiving an oral agent. CONCLUSIONS: A dramatic shift was seen in CML treatments away from traditional, nonoral chemotherapy toward use of novel oral TKIs between 2000 and 2017. As the costs of oral anticancer agents reach new highs, studies assessing the long-term health and financial outcomes among patients with CML are warranted.

Predictors of Long-Term Survival among High-Grade Serous Ovarian Cancer Patients.

BACKGROUND: Relatively little is known about factors associated with long-term survival (LTS) following a diagnosis of ovarian cancer. METHODS: We conducted a retrospective study of high-grade serous ovarian cancer (HGSOC) to explore predictors of LTS (defined as ≥7 years of survival) using electronic medical record data from a network of integrated health care systems. Multivariable logistic regression with forward selection was used to compare characteristics of women who survived ≥7 years after diagnosis (n = 148) to those who died within 7 years of diagnosis (n = 494). RESULTS: Our final model included study site, age, stage at diagnosis, CA-125, comorbidity score, receipt of chemotherapy, BMI, and four separate comorbid conditions: weight loss, depression, hypothyroidism, and liver disease. Of these, only younger age, lower stage, and depression were statistically significantly associated with LTS. CONCLUSIONS: We did not identify any new characteristics associated with HGSOC survival. IMPACT: Prognosis of ovarian cancer generally remains poor. Large, pooled studies of ovarian cancer are needed to identify characteristics that may improve survival.

Health-related quality of life among US adults with cancer: Potential roles of complementary and alternative medicine for health promotion and well-being.

OBJECTIVES: We estimated prevalence of complementary and alternative medicine (CAM) use by reason for use (treatment, wellness, or both) among non-institutionalized adults with cancer in the United States. We also examined health-related quality of life (HRQOL) outcomes among adults with cancer who used CAM. METHODS: We used data from the 2012 National Health Interview Survey (NHIS), which represents non-institutionalized adults with cancer (n = 2967 unweighted). Using a cross-sectional design with survey sampling techniques, we estimated past year prevalence of CAM use. We ran multivariable logistic regression analyses to investigate the odds of perceived benefits of CAM. RESULTS: In the past 12 months, 35.1% of adults with cancer reported using some form of CAM. Among CAM users, 56.0% used CAM for both treatment and wellness, and 32.4% used CAM for wellness only. Only 11.6% used CAM for treatment only. Regardless of reason for use, the most commonly used CAM types in the past year were herbal therapies (56.8%), chiropractic (27.1%), and massage (24.9%). Among CAM users, those using CAM for wellness only and for a combination of treatment and wellness reported significantly higher odds of "a better sense of controlling health" and "improved overall health and feeling better" compared with treatment only users. Similar patterns were found in other HRQOL outcomes, but they were not statistically different. CONCLUSIONS: CAM is widely used among adults with cancer for wellness only or a combination of treatment and wellness. Given improved HRQOL outcomes, CAM may be a promising approach for enhancing health promotion and well-being among adults with cancer.

Opioid Use During Pregnancy, Observations of Opioid Use, and Secular Trend From 2006 to 2014 at HealthPartners Medical Group.

OBJECTIVES: To determine the prevalence of opioid use before, during, and after pregnancy and describe its use based on patient-specific characteristics. Determine secular trend of opioid use 2006 to 2014. MATERIALS AND METHODS: Retrospective cohort study. A large Upper Midwest integrated health care system and insurer. Female individuals age 10 to 50 years with a delivery diagnosis from July 1, 2006 through June 30, 2014. MAIN OUTCOME MEASURE: prevalence of opioid use before, during, and after pregnancy; description of opioid use during these time periods. RESULTS: From 11,565 deliveries among 9690 unique women, 862 (7.5%) deliveries were associated with significant opioid use. Significant opioid use was associated with single marital status, Cesarean section, Medicaid coverage, tobacco use, depression, anxiety, bipolar disorder, substance use disorder, nonopioid analgesic use, and referral to physical therapy, psychotherapy, or pain specialists. From 2006 to 2014 opioid use decreased from 9% to 6% before, during, and after pregnancy with a rate of change per year of -0.2%. DISCUSSION: Known risk factors including tobacco and alcohol use, mental health diagnoses, substance use disorder, or Medicaid enrollment may enable enhanced assessments and targeted interventions to reduce unnecessary prescribing and use of opioids among pregnant women and those who might become pregnant. Strategies to decrease opioid use during pregnancy should be considered by health care systems and health plans to reduce opioid prescribing in this patient population.

The Cancer Research Network: a platform for epidemiologic and health services research on cancer prevention, care, and outcomes in large, stable populations.

PURPOSE: The ability to collect data on patients for long periods prior to, during, and after a cancer diagnosis is critical for studies of cancer etiology, prevention, treatment, outcomes, and costs. We describe such data capacities within the Cancer Research Network (CRN), a cooperative agreement between the National Cancer Institute (NCI) and organized health care systems across the United States. METHODS: Data were extracted from each CRN site's virtual data warehouse using a centrally written and locally executed program. We computed the percent of patients continuously enrolled ≥1, ≥5, and ≥10 years before cancer diagnosis in 2012-2015 (year varied by CRN site). To describe retention after diagnosis, we computed the cumulative percentages enrolled, deceased, and disenrolled each year after the diagnosis for patients diagnosed in 2000. RESULTS: Approximately 8 million people were enrolled in ten CRN health plans on December 31, 2014 or 2015 (year varied by CRN site). Among more than 30,000 recent cancer diagnoses, 70 % were enrolled for ≥5 years and 56 % for ≥10 years before diagnosis. Among 25,274 cancers diagnosed in 2000, 28 % were still enrolled in 2010, 45 % had died, and 27 % had disenrolled from CRN health systems. CONCLUSIONS: Health plan enrollment before cancer diagnosis was generally long in the CRN, and the proportion of patients lost to follow-up after diagnosis was low. With long enrollment histories among cancer patients pre-diagnosis and low post-diagnosis disenrollment, the CRN provides an excellent platform for epidemiologic and health services research on cancer incidence, outcomes, and costs.

A Successful Multifaceted Trial to Improve Hypertension Control in Primary Care: Why Did it Work?

BACKGROUND: It is important to understand which components of successful multifaceted interventions are responsible for study outcomes, since some components may be more important contributors to the intervention effect than others. OBJECTIVE: We conducted a mediation analysis to determine which of seven factors had the greatest effect on change in systolic blood pressure (BP) after 6 months in a trial to improve hypertension control. DESIGN: The study was a preplanned secondary analysis of a cluster-randomized clinical trial. Eight clinics in an integrated health system were randomized to provide usual care to their patients (n = 222), and eight were randomized to provide a telemonitoring intervention (n = 228). PARTICIPANTS: Four hundred three of 450 trial participants completing the 6-month follow-up visit were included. INTERVENTIONS: Intervention group participants received home BP telemonitors and transmitted measurements to pharmacists, who adjusted medications and provided advice to improve adherence to medications and lifestyle modification via telephone visits. MAIN MEASURES: Path analytic models estimated indirect effects of the seven potential mediators of intervention effect (defined as the difference between the intervention and usual care groups in change in systolic BP from baseline to 6 months). The potential mediators were change in home BP monitor use, number of BP medication classes, adherence to BP medications, physical activity, salt intake, alcohol use, and weight. KEY RESULTS: The difference in change in systolic BP was 11.3 mmHg. The multivariable mediation model explained 47 % (5.3 mmHg) of the intervention effect. Nearly all of this was mediated by two factors: an increase in medication treatment intensity (24 %) and increased home BP monitor use (19 %). The other five factors were not significant mediators, although medication adherence and salt intake improved more in the intervention group than in the usual care group. CONCLUSIONS: Most of the explained intervention effect was attributable to the combination of self-monitoring and medication intensification. High adherence at baseline and the relatively low intensity of resources directed toward lifestyle change may explain why these factors did not contribute to the improvement in BP.

Fracture risk in older, long-term survivors of early-stage breast cancer.

OBJECTIVES: To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors. DESIGN: A 10-year prospective cohort study beginning 5 years after a diagnosis of breast cancer for survivors and match date for comparison women. SETTING: Six integrated healthcare systems. PARTICIPANTS: Women aged 65 and older (1,286 survivors, 1,286 comparison women, mean age 77.7 in both groups, white, non-Hispanic: survivors, 81.6%; comparison women, 85.2%) who were alive and recurrence free 5 years after a diagnosis of early-stage breast cancer and matched on age, study site, and enrollment year to a comparison cohort without breast cancer. MEASUREMENTS: Cox proportional hazards models were used to estimate the association between fracture risk and survivor-comparison status, adjusting for drugs and risk factors associated with bone health. A subanalysis was used to evaluate the association between tamoxifen exposure and fracture risk. RESULTS: No difference was observed in fracture rates between groups (hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.9-1.3). The protective effect of tamoxifen was not statistically significant (HR = 0.9, 95% CI = 0.6-1.2). CONCLUSION: Long-term survivors of early-stage breast cancer diagnosed at age 65 and older are not at greater risk of osteoporotic fractures than age-matched women without breast cancer. There appears to be no long-term protection from fractures with tamoxifen use.

Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer.

PURPOSE: The aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations. METHODS: We determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network. RESULTS: We found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history-based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome-associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred. CONCLUSION: The information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines.

Patient characteristics associated with medication adherence.

OBJECTIVE: Despite evidence indicating therapeutic benefit for adhering to a prescribed regimen, many patients do not take their medications as prescribed. Non-adherence often leads to morbidity and to higher health care costs. The objective of the study was to assess patient characteristics associated with medication adherence across eight diseases. DESIGN: Retrospective data from a repository within an integrated health system was used to identify patients ≥18 years of age with ICD-9-CM codes for primary or secondary diagnoses for any of eight conditions (depression, hypertension, hyperlipidemia, diabetes, asthma or chronic obstructive pulmonary disease, multiple sclerosis, cancer, or osteoporosis). Electronic pharmacy data was then obtained for 128 medications used for treatment. METHODS: Medication possession ratios (MPR) were calculated for those with one condition and one drug (n=15,334) and then for the total population having any of the eight diseases (n=31,636). The proportion of patients adherent (MPR ≥80%) was summarized by patient and living-area (census) characteristics. Bivariate associations between drug adherence and patient characteristics (age, sex, race, education, and comorbidity) were tested using contingency tables and chi-square tests. Logistic regression analysis examined predictors of adherence from patient and living area characteristics. RESULTS: Medication adherence for those with one condition was higher in males, Caucasians, older patients, and those living in areas with higher education rates and higher income. In the total population, adherence increased with lower comorbidity and increased number of medications. Substantial variation in adherence was found by condition with the lowest adherence for diabetes (51%) and asthma (33%). CONCLUSIONS: The expectation of high adherence due to a covered pharmacy benefit, and to enhanced medication access did not hold. Differences in medication adherence were found across condition and by patient characteristics. Great room for improvement remains, specifically for diabetes and asthma.

KRAS testing and epidermal growth factor receptor inhibitor treatment for colorectal cancer in community settings.

BACKGROUND: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. METHODS: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care. RESULTS: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009). CONCLUSIONS: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care. IMPACT: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States.

Age, comorbidity, and breast cancer severity: impact on receipt of definitive local therapy and rate of recurrence among older women with early-stage breast cancer.

BACKGROUND: The definitive local therapy options for early-stage breast cancer are mastectomy and breast-conserving surgery followed by radiation therapy. Older women and those with comorbidities frequently receive breast-conserving surgery alone. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of definitive therapy have not been well-studied. STUDY DESIGN: In a cohort of 1,837 women aged 65 years and older receiving treatment for early-stage breast cancer in 6 integrated health care delivery systems in 1990-1994 and followed for 10 years, we examined predictors of receiving nondefinitive local therapy and assessed the impact on breast cancer recurrence within levels of severity, defined as level of risk for recurrence. RESULTS: Age and comorbidity were associated with receipt of nondefinitive therapy. Compared with those at low risk, women at the highest risk were less likely to receive nondefinitive therapy (odds ratio = 0.32; 95% CI, 0.22-0.47), and women at moderate risk were about half as likely (odds ratio = 0.54; 95% CI, 0.35-0.84). Nondefinitive local therapy was associated with higher rates of recurrence among women at moderate (hazard ratio = 5.1; 95% CI, 1.9-13.5) and low risk (hazard ratio = 3.2; 95% CI, 1.1-8.9). The association among women at high risk was weak (hazard ratio = 1.3; 95% CI, 0.75-2.1). CONCLUSIONS: Among these older women with early-stage breast cancer, decisions about therapy partially balanced breast cancer severity against age and comorbidity. However, even among women at low risk, omitting definitive local therapy was associated with increased recurrence.