Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated if older breast cancer survivors have a similar comorbidity burden 6–15 years after cancer diagnosis to matched women free of breast cancer at start of follow-up and if incident comorbidities are associated with all-cause mortality.
In this prospective cohort study, 1,361 older five-year early stage breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health system-matched women were followed for ten years. Adjudicated medical record review captured prevalent and incident comorbidities during follow-up or until death as collected from the National Death Index.
Older five-year breast cancer survivors did not acquire incident comorbidities more often than matched women free of breast cancer in the subsequent 10 years (HR=1.0, 95%CI: 0.93,1.1). Adjusted for cohort membership, women with incident comorbidities had a higher mortality rate than those without incident comorbidities (HR=4.8, 95%CI: 4.1,5.6). A breast cancer history continued to be a hazard for mortality 6–15 years after diagnosis (HR=1.3, 95%CI: 1.1,1.4).
We found that older breast cancer survivors who developed comorbidities had an increased all-cause mortality rate even after adjusting for age and prevalent comorbidity burden. Additionally, survivors acquire comorbidities at a rate similar to older women free of breast cancer. These results highlight the association between comorbidity burden and long-term mortality risk among older breast cancer survivors and their need for appropriate oncology and primary care follow-up.
breast cancer; survivorship; comorbidity; geriatrics; managed care; mortality
We examined racial/ethnic disparities in healthcare receipt among a nationally representative sample of male cancer survivors.
We identified adult men (age 18+) from the 2006–2010 National Health Interview Survey who reported a history of cancer. Four self-reported measures assessed healthcare receipt: primary care visit, specialist visit, flu vaccination, and pneumococcal vaccination. We used hierarchical logistic regression modeling, stratified by age (younger: <65, older: 65+), to examine racial/ethnic disparities in healthcare receipt.
In adjusted models, older African American and Hispanic survivors were approximately twice as likely as non-Hispanic Whites to not see a specialist (OR 1.78, CI 1.19–2.68 and OR 2.09, CI 1.18–3.70, respectively), not receive the flu vaccine (OR 2.21, CI 1.45–3.37 and OR 2.20, CI 1.21–4.01, respectively) and not receive the pneumococcal vaccine (OR 2.24, CI 1.54–3.24 and OR 3.10, CI 1.75–5.51, respectively).
Racial/ethnic disparities in healthcare receipt were evident among older, but not younger survivors, despite access to Medicare. This may have implications for their health and receipt of follow-up care if these survivors are less likely to see specialists, including oncologists, and get basic preventive care.
cancer; men; health care disparities; long-term survivors; health services
We sought to examine issues of generalizability in research on adolescent and young adult (AYA) cancer survivorship that relies on using community-based healthcare delivery system data.
Individuals aged 15 to 39 diagnosed with cancer between 1992 and 2006 were identified using data from community-based healthcare systems in California and Seattle. Loss to follow-up was defined as the first disenrollment (the end) of membership in the healthcare systems after cancer. Censoring occurred at death or study end (2009). We used Kaplan–Meier analysis to quantify follow-up, and multiple Cox regression to examine the association of follow-up loss with demographic and cancer characteristics.
Of 6828 eligible AYAs, most (93%) were aged between 20 and 39 years at diagnosis; 62% were female and 39% were non-White. Solid tumors accounted for 81% of diagnoses. The majority (89%) of patients continued to be members of the healthcare systems and available for follow-up 1 year after diagnosis. Approximately 60% remained enrolled 5 years after diagnosis. Loss to follow-up was associated with younger age at diagnosis, male gender, and African American or Hispanic race/ethnicity.
Data from community-based healthcare delivery systems offer an efficient way to identify large and diverse samples of AYA-onset cancer survivors. Differential loss to follow-up can threaten the generalizability of results from these studies and should be assessed quantitatively. Healthcare system data offer an alternative to studies requiring direct contact with participants.
survivorship; epidemiologic methods; healthcare research; bias
Late effects of breast cancer affect the quality of survivorship. Using administrative data, we compared the occurrence of almost all ICD9 codes among older breast cancer survivors to that among a matched comparison cohort to generate new hypotheses.
Breast cancer patients sixty-five years or older diagnosed 1990–1994 in six integrated care settings and who survived at least five years were matched with a cohort of women without a history of breast cancer on care setting, age, and calendar time. We collected data on the occurrence of incident ICD9 codes beginning six years after the breast cancer diagnosis date and continuing to year fifteen, and comparable data for the matched woman. We calculated hazard ratios and 95% confidence intervals associating breast cancer survivorship with incidence of each ICD9 code. We used semi-Bayes methods to address multiple comparisons.
Older breast cancer survivors had about the same occurrence of diseases and conditions six to fifteen years after breast cancer diagnosis as comparable women. The median of 564 adjusted hazard ratios equaled 1.06, with interquartile range 0.92 to 1.3. The distribution of hazard ratios pertaining to cancer-related ICD codes was shifted towards positive associations, and the distribution pertaining to cardiovascular-related ICD codes was shifted towards negative associations.
In this hypothesis scanning study, we observed little difference in the occurrence of non-breast cancer-related diseases and conditions among older, long-term breast cancer survivors and comparable women without a history of breast cancer.
Breast neoplasms, complications; breast neoplasms, quality of life; breast neoplasms, late effects; breast neoplasms, survivorship
Little is known about the cognitive factors associated with adherence to anti-estrogen therapy. Our objective was to investigate the association between domain-specific cognitive function and adherence among women in a clinical prevention trial of oral anti-estrogen therapies. We performed a secondary analysis of Co-STAR, an ancillary study of the STAR breast cancer prevention trial in which postmenopausal women at increased breast cancer risk were randomized to tamoxifen or raloxifene. Co-STAR enrolled non-demented participants ≥65 years old to compare treatment effects on cognition. The cognitive battery assessed global cognitive function (Modified Mini-Mental State Exam), and specific cognitive domains of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, spatial ability, and fine motor speed. Adherence was defined by a ratio of actual time taking therapy per protocol ≥80% of expected time. Logistic regression was used to evaluate the association between cognitive test scores and adherence to therapy. The mean age of the 1,331 Co-STAR participants was 67.2±4.3 years. Mean 3MS score was 95.1 (4.7) and 14% were non-adherent. In adjusted analyses, the odds of non-adherence were lower for those with better scores on verbal memory [OR (95% CI): 0.75 (0.62, 0.92)]. Larger relative deficits in verbal memory compared to verbal fluency were also associated with non-adherence [1.28 (1.08, 1.51)]. Among non-demented older women, subtle differences in memory performance were associated with medication adherence. Differential performance across cognitive domains may help identify persons at greater risk for poor adherence.
adherence; cancer; cognition; elderly; tamoxifen; women
Routine follow-up care is recommended to promote the well-being of cancer survivors, but financial difficulties may interfere. Rural-urban disparities in forgoing healthcare due to cost have been observed in the general population; however, it is unknown whether this disparity persists among survivors. The purpose of this study was to examine rural-urban disparities in forgoing healthcare after cancer due to cost.
We analyzed data from 7804 cancer survivors in the 2006–2010 National Health Interview Survey. Logistic regression models, adjusting for sociodemographic and clinical characteristics, were used to assess rural-urban disparities in forgoing medical care, prescription medications, and dental care due to cost, stratified by age (younger: 18–64, older: 65+).
Compared to urban survivors, younger rural survivors were more likely to forgo medical care (p<0.001) and prescription medications (p<0.001) due to cost; older rural survivors were more likely to forgo medical (p<0.001) and dental care (p=0.05). Rural-urban disparities did not persist among younger survivors in adjusted analyses; however, older rural survivors remained more likely to forgo medical (OR=1.66, 95%CI=1.11–2.48) and dental care (OR=1.54, 95%CI=1.08–2.20).
Adjustment for health insurance and other sociodemographic characteristics attenuates rural-urban disparities in forgoing healthcare among younger survivors, but not older survivors. Financial factors relating to healthcare utilization among rural survivors should be a topic of continued investigation.
Addressing out-of-pocket costs may be an important step in reducing rural-urban disparities in healthcare, especially for older survivors. It will be important to monitor how healthcare reform efforts impact disparities observed in this vulnerable population.
cancer; long-term survivors; rural population; healthcare disparities; health services accessibility
Rural US adults have increased risk of poor outcomes after cancer, including increased cancer mortality. Rural-urban differences in health behaviors have been identified in the general population and may contribute to cancer health disparities, but have not yet been examined among US survivors. We examined rural-urban differences in health behaviors among cancer survivors and associations with self-reported health and health-related unemployment.
We identified rural (n=1,642) and urban (n=6,162) survivors from the cross-sectional National Health Interview Survey (2006–2010) and calculated the prevalence of smoking, physical activity, overweight/obesity, and alcohol consumption. Multivariable models were used to examine the associations of fair/poor health and health-related unemployment with health behaviors and rural-urban residence.
The prevalence of fair/poor health (rural 36.7%, urban 26.6%), health-related unemployment (rural 18.5%, urban 10.6%), smoking (rural 25.3%, urban 15.8%), and physical inactivity (rural 50.7%, urban 38.7%) was significantly higher in rural survivors (all p<.05); alcohol consumption was lower (rural 46.3%, urban 58.6%), and there were no significant differences in overweight/obesity (rural 65.4%, urban 62.6%). All health behaviors were significantly associated with fair/poor health and health-related unemployment in both univariate and multivariable models. After adjustment for behaviors, rural survivors remained more likely than urban survivors to report fair/poor health (OR= 1.21, 95%CI 1.03–1.43) and health-related unemployment (OR= 1.49, 95%CI 1.18–1.88).
Rural survivors may need tailored, accessible health promotion interventions to address health compromising behaviors and improve outcomes after cancer.
cancer survivors; smoking; physical activity; health status; employment
Pediatric obesity treatment programs report high attrition rates, but it is unknown if family experience and satisfaction contributes. This review surveys the literature regarding satisfaction in pediatric obesity and questions used in measurement. A systematic review of the literature was conducted using Med-line, PsychINFO, and CINAHL. Studies of satisfaction in pediatric weight management were reviewed, and related studies of obesity were included. Satisfaction survey questions were obtained from the articles or from the authors. Eighteen studies were included; 14 quantitative and 4 qualitative. Only one study linked satisfaction to attrition, and none investigated the association of satisfaction and weight outcomes. Most investigations included satisfaction as a secondary aim or used single-item questions of overall satisfaction; only one assessed satisfaction in noncompleters. Overall, participants expressed high levels of satisfaction with obesity treatment or prevention programs. Surveys focused predominantly on overall satisfaction or specific components of the program. Few in-depth studies of satisfaction with pediatric obesity treatment have been conducted. Increased focus on family satisfaction with obesity treatment may provide an avenue to lower attrition rates and improve outcomes. Enhancing measurement of satisfaction to yield actionable responses could positively influence outcomes, and a framework, via patient-centered care principles, is provided.
family involvement; patient satisfaction; pediatrics
To evaluate cardiovascular disease (CVD) risk factors in older breast cancer survivors compared with a group of women without breast cancer.
The retrospective study included (1) women aged 65 or more years who were initially diagnosed with stage I or II breast cancer from 1990 to 1994 in 6 US health plans and who survived at least 5 years postdiagnosis (cases) and (2) a matched comparison group. They were followed for a maximum of 15 years.
Data sources included medical charts and electronic health records. Cases (n = 1361) were matched on age, health plan site, and enrollment year to women in the comparison group (n = 1361). Subjects were followed to the first CVD outcome, health plan disenrollment, death, or study end. We compared rates of CVD in these 2 groups and used Cox proportional hazard models to estimate the hazard ratio (HR), considering body mass index, smoking history, diabetes, and hypertension.
The strongest predictors of CVD were smoking history (HR = 1.29; 95% confidence interval [CI], 1.15–1.46), diabetes (HR = 1.72; 95% CI, 1.48–1.99), and hypertension (HR = 1.48; 95% CI, 1.31–1.67) rather than breast cancer case-comparison status (HR = 0.97; 95% CI, 0.87–1.09).
Results suggest that long-term prognosis in breast cancer patients is affected by management of preexisting conditions. Assessment of comorbid conditions and effective management of diabetes and hypertension in older breast cancer survivors may lead to longer overall survival.
Breast cancer survivorship has increased and the association of long-term bone health with breast cancer and its treatment is unclear. This issue is important for older women who face an increased risk of osteoporotic fracture-related morbidity and mortality.
To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors and non-breast cancer comparisons.
A 10-year prospective cohort study beginning 5 years after a diagnosis of breast cancer for survivors and match date for comparison women.
The study was conducted within six integrated health care systems.
Women 65 years and older 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 non-breast cancer comparison cohort.
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 conducted to evaluate the association between tamoxifen exposure and fracture risk.
Our analysis included 1,286 survivors and 1,286 comparison women with a mean age of 77.7 years in both groups. Survivor and comparison women were predominantly white and non-Hispanic, 81.6% and 85.2%, respectively. We observed no difference in fracture rates between groups (HR=1.1; 95%CI 0.9, 1.3). The protective effect of tamoxifen was not statistically significant (HR=0.9; 95%CI 0.6, 1.2).
Our findings suggest long-term survivors of early stage breast cancer diagnosed at age 65 and older are not at increased risk of osteoporotic fractures compared to age-matched non-breast cancer women. There appears to be no long-term protection from fractures following tamoxifen use.
Osteoporotic fractures; breast cancer survivors; postmenopausal women; cohort study; pharmacoepidemiology
While rural residents are more likely to be diagnosed with more advanced cancers and die of cancer, little is known about rural-urban disparities in self-reported health among survivors.
We identified adults with a self-reported cancer history from the National Health Interview Survey (2006–2010). Rural-urban residence was defined using US census definitions. Logistic regression with weighting to account for complex sampling was used to assess rural-urban differences in health status after accounting for differences in demographic characteristics.
Of the 7,804 identified cancer survivors, 20.8% were rural residents. This translates to a population of 2.8 million rural cancer survivors in the US. Rural survivors were more likely than urban survivors to be non-Hispanic white (p<.001), have less education (p<.001) and lack health insurance (p<.001). Rural survivors reported worse health in all domains. After adjustment for sex, race/ethnicity, age, marital status, education, insurance, time since diagnosis, and number of cancers, rural survivors were more likely to report fair/poor health [OR=1.39, 95%CI=1.20–1.62, psychological distress [OR=1.23, 1.00–1.50], ≥2 non-cancer comorbidities [OR=1.15, 1.01–1.32], and health-related unemployment [OR=1.66, 1.35–2.03].
We provide the first estimate of the proportion and number of US adult cancer survivors who reside in rural areas. Rural cancer survivors are at greater risk for a variety of poor health outcomes, even many years after their cancer diagnosis, and should be a target for interventions to improve their health and well-being.
cancer; survivors; rural health; health status; mental health; unemployment; comorbidity; health status disparities
To evaluate the impact of age on receipt of chemotherapy among low-income individuals with metastatic colorectal cancer.
Data Sources/Study Setting
North Carolina Medicaid enrollees with metastatic colorectal cancer diagnosed from 1999 to 2002 with colorectal as their only cancer (N=326).
Retrospective analysis using linked data from the North Carolina Cancer Registry and Medicaid claims.
Data Collection/Extraction Methods
Outcomes were chemotherapy use within one year of diagnosis and time to initiation of chemotherapy. Cox regression models were fit to evaluate the association between chemotherapy use and age, stratifying for comorbidity, and adjusting for patient, community, and health services characteristics.
Compared to 67.4% of patients aged <70 years, only 26.2% of patients ≥70 years received chemotherapy. After adjustment, younger patients with and without comorbidity were more likely to receive chemotherapy than older patients (hazard ratio (HR)=2.27, 95% confidence interval (CI) 1.41-3.66 and HR=6.33, 95% CI 2.87-13.96, respectively). Among those who received chemotherapy, the median time to receipt was 53 days, and did not differ significantly by age or comorbidity.
In this low-income cohort, older age was consistently associated with non-receipt of chemotherapy but not longer time to initiation of chemotherapy regardless of comorbidity status.
Colon cancer; Metastatic; Medicaid; Chemotherapy; Comorbidity
Although adjuvant radiotherapy (RT) following surgery for breast cancer improves overall survival, controversy exists about its long-term adverse impact on cardiovascular health in older survivors.
To determine whether incident cardiovascular disease (CVD) is associated with RT and whether tumor laterality modifies this association.
Women aged 65+ years diagnosed with stage I and II breast cancer between 1990 and 1994 were identified from three health plans. Women were followed through CVD outcomes, health plan disenrollment, death, or study end (December 31, 2004). The main independent variable was RT use. Adjusted HRs and 95% CIs were estimated using Cox proportional hazards models with time-dependent tamoxifen and RT use status. We adjusted for age, race, stage, estrogen receptor/progesterone receptor, hypertension, and diabetes.
In the full cohort (N = 806), RT was not associated with greater risk of CVD (maximum follow-up was 14 years). However, within the RT-exposed group (N = 340), women treated for left-side breast cancer had a significant increased risk of CVD outcomes (HR = 1.53, 95% CI: 1.06–2.21) compared with women with right-sided tumors.
Laterality is critical to understanding the effect of RT on CVD. Studies of more contemporary cohorts of women treated with RT should incorporate this variable to determine whether the risk persists with refinements in the dosing and delivery of RT.
As some irradiation to the heart is unavoidable even with refined modern RT techniques, continued effort is required to minimize such exposures, especially in older women with left-sided tumors.
To test the feasibility and utility of a bedside geriatric assessment (GA) to detect impairment in multiple geriatric domains in older adults initiating chemotherapy for acute myelogenous leukemia (AML).
Prospective observational cohort study.
Single academic institution.
Individuals aged 60 and older with newly diagnosed AML and planned chemotherapy.
Bedside GA was performed during inpatient exmination for AML. GA measures included the modified Mini-Mental State Examination; Center for Epidemiologic Studies Depression Scale; Distress Thermometer, Pepper Assessment Tool for Disability (includes self- reported activities of daily living (ADLs), instrumental ADLs, and mobility questions); Short Physical Performance Battery (includes timed 4-m walk, chair stands, standing balance); grip strength, and Hematopoietic Cell Transplantation Comorbidity Index.
Of 54 participants (mean age 70.8 ± 6.4) eligible for this analysis, 92.6% completed the entire GA battery (mean time 44.0 ± 14 minutes). The following impairments were detected: cognitive impairment, 31.5%; depression, 38.9%; distress, 53.7%; impairment in ADLs, 48.2%; impaired physical performance, 53.7%; and comorbidity, 46.3%. Most were impaired in one (92.6%) or more (63%) functional domains. For the 38 participants rated as having good performance status according to standard oncologic assessment (Eastern Cooperative Oncology Performance Scale score ≤1), impairments in individual GA measures ranged from 23.7% to 50%. Significant variability in cognitive, emotional, and physical status was detected even after stratification according to tumor biology (cytogenetic risk group classification).
Inpatient GA was feasible and added new information to standard oncology assessment, which may be important for stratifying therapeutic risk in older adults with AML.
geriatric assessment; acute myelogenous leukemia; cancer; functional status; elderly
Many elderly cancer patients experience increased cancer-related morbidity and mortality compared to younger patients. In soft tissue sarcoma, adjuvant radiotherapy is an integral part of definitive therapy for limb preservation. We hypothesized that age-related disparities exist in the use of radiation.
We used SEER data to conduct a retrospective cohort study among patients 25 years or older diagnosed from 1998 to 2004 with non-metastatic, biopsy-proven, high-grade soft tissue sarcoma in the extremities undergoing a limb-sparing procedure. Patients were stratified according to age (<50, 50-70, and >70). Logistic regression was used to determine the association between age and radiotherapy use, adjusting for histology, location, size, surgery, gender, race, and marital status. A Cox proportional hazards model was used to compare disease-specific and all-cause mortality.
Among 1,354 eligible patients; 37.1% were older than age 70, 44.3% female, and 84.4% Caucasian. While almost three-quarters (73.8%) of the cohort received radiotherapy, receipt decreased from 78.2% in patients younger than age 50 to 69.6% in patients older than age 70 (test of trend p=0.006). After adjusting for demographic and tumor factors, older patients remained less likely to receive radiotherapy (odds ratio=0.66, 95% confidence interval (CI)=0.47-0.92) and more likely to experience disease-specific death (hazard ratio=2.4, CI=1.4-4.1) as compared to the youngest group.
Older adults appear less likely to receive definitive therapy for soft tissue sarcoma of the extremities. In the absence of clinical trials and treatment guidelines tailored to this population, under-treatment may disadvantage the elderly with increased cancer-related morbidity and mortality.
sarcoma; radiotherapy; age factors; healthcare disparities; treatment
To evaluate objective physical performance measures as predictors of survival and subsequent disability in older patients with cancer.
Longitudinal cohort study.
Health, Aging and Body Composition (Health ABC) Study.
Four hundred twenty-nine individuals diagnosed with cancer during the first 6 years of follow-up of the Health ABC Study.
The associations between precancer measures of physical performance (20-m usual gait speed, 400-m long-distance corridor walk (LDCW), and grip strength) and overall survival and a short-term outcome of 2-year progression to disability or death were evaluated. Cox proportional hazards and logistic regression models, stratified for metastatic disease, respectively, were used for outcomes.
Mean age was 77.2, 36.1% were women, and 45.7% were black. Faster 20-m usual walking speed was associated with a lower risk of death in the metastatic group (hazard ratio = 0.89, 95% confidence interval (CI) = 0.79–0.99) and lower 2-year progression to disability or death in the nonmetastatic group (odds ratio (OR) = 0.77, 95% CI = 0.64–0.94). Ability to complete the 400-m LDCW was associated with lower 2-year progression to disability or death in the nonmetastatic group (OR = 0.24, 95% CI = 0.10–0.62). There were no associations between grip strength and disability or death.
Lower extremity physical performance tests (usual gait speed and 400-m LDCW) were associated with survival and 2-year progression to disability or death. Objective physical performance measures may help inform pretreatment evaluations in older adults with cancer.
physical performance; elderly; cancer; disability; survival
Abstractor training is a key element in creating valid and reliable data collection procedures. The choice between in-person vs. remote or simultaneous vs. sequential abstractor training has considerable consequences for time and resource utilization. We conducted a web-based (webinar) abstractor training session to standardize training across six individual Cancer Research Network (CRN) sites for a study of breast cancer treatment effects in older women (BOWII). The goals of this manuscript are to describe the training session, its participants and participants' evaluation of webinar technology for abstraction training.
A webinar was held for all six sites with the primary purpose of simultaneously training staff and ensuring consistent abstraction across sites. The training session involved sequential review of over 600 data elements outlined in the coding manual in conjunction with the display of data entry fields in the study's electronic data collection system. Post-training evaluation was conducted via Survey Monkey©. Inter-rater reliability measures for abstractors within each site were conducted three months after the commencement of data collection.
Ten of the 16 people who participated in the training completed the online survey. Almost all (90%) of the 10 trainees had previous medical record abstraction experience and nearly two-thirds reported over 10 years of experience. Half of the respondents had previously participated in a webinar, among which three had participated in a webinar for training purposes. All rated the knowledge and information delivered through the webinar as useful and reported it adequately prepared them for data collection. Moreover, all participants would recommend this platform for multi-site abstraction training. Consistent with participant-reported training effectiveness, results of data collection inter-rater agreement within sites ranged from 89 to 98%, with a weighted average of 95% agreement across sites.
Conducting training via web-based technology was an acceptable and effective approach to standardizing medical record review across multiple sites for this group of experienced abstractors. Given the substantial time and cost savings achieved with the webinar, coupled with participants' positive evaluation of the training session, researchers should consider this instructional method as part of training efforts to ensure high quality data collection in multi-site studies.
To evaluate the effectiveness of methods that control for confounding by indication, we compared breast cancer recurrence rates among women receiving adjuvant chemotherapy versus those who did not.
Study Design and Setting
In a medical record review-based study of breast cancer treatment in older women (n=1798) diagnosed 1990-1994, our crude analysis suggested adjuvant chemotherapy was positively associated with recurrence [hazard ratio (HR)=2.6 (95% confidence interval (CI)=1.9, 3.5)]. We expected a protective effect, so postulated that the crude association was confounded by indications for chemotherapy. We attempted to adjust for this confounding by restriction, multivariable regression, propensity scores [PS], and instrumental variable [IV] methods.
After restricting to women at high-risk for recurrence (n=946), chemotherapy was not associated with recurrence [HR=1.1 (95% CI=0.7, 1.6)] using multivariable regression. PS adjustment yielded similar results [HR=1.3 (95% CI=0.8, 2.0)]. The IV-like method yielded a protective estimate [HR=0.9; (95% CI=0.2, 4.3)]; however imbalances of measured factors across levels of the IV suggested residual confounding.
Conventional methods do not control for unmeasured factors, which often remain important when addressing confounding by indication. PS and IV analysis methods can be useful under specific situations, but neither method adequately controlled confounding by indication in this study.
confounding by indication; propensity score; instrumental variable; non-randomized studies; breast cancer; chemotherapy
Little is known about the risk of recurrence more than five years after diagnosis among older breast cancer survivors. A community-based population of women ≥65 years diagnosed with early stage breast cancer who survived disease-free for five years was followed for five additional years or until a diagnosis of breast cancer recurrence, second primary, death or loss to follow-up. These five-year disease-free survivors (N=1277) had primary breast cancers that were node negative (77%) and estrogen receptor positive or unknown (86%). Five percent (N=61) developed a recurrence between five and ten years after diagnosis; 25% local, 9.8% regional, and 66% distant. Women who were node positive (Hazard Ratio [HR]=3.9; 95% Confidence Interval [CI]=1.5,10); had poorly differentiated tumors (HR=2.5; 95% CI=0.9, 6.6); or who received breast conserving surgery without radiation therapy (HR=2.4; 95%CI=1.0, 5.8) had higher recurrence rates compared with node negative, well differentiated, and receipt of mastectomy, respectively. Not receiving adjuvant tamoxifen, compared with receiving adjuvant tamoxifen, was also positively associated with late recurrence among women with estrogen receptor positive/unknown tumors. While relatively few women experience a late recurrence, most recurrences present as advanced disease, which is difficult to treat in older women. This study of late recurrence emphasizes that the risk, although small, is not negligible even in this group at high risk for death due to competing causes.
Breast cancer; recurrence; primary therapy; cancer survivorship; older women
To identify factors associated with delayed radiotherapy (RT) in older women with early stage breast cancer.
We studied 541 women ages 65+ diagnosed with early stage breast cancer from 1990–1994 at five integrated healthcare delivery systems and treated with breast conserving surgery and RT, but not chemotherapy. We examined whether demographic, tumor, or treatment characteristics were associated with RT delays of >8 weeks post-surgery using chi-square tests and multivariable logistic regression.
Seventy-six women (14%) had delayed RT, with a median delay of 14 weeks. Non-white and Hispanic women were much more likely than White women to have delayed RT (OR=3.3, 95%CI: 1.7, 10) in multivariable analyses that controlled for demographic and clinical variables.
Of women receiving BCS and radiation in this cohort, 14% experienced delayed RT, even though they had insurance and access to care in integrated delivery systems. Women receiving delayed care were more likely to be non-White and Hispanic. Timely RT should be facilitated through physician and patient education, navigation, and notification programs to improve quality of care. Future research should examine modifiable barriers to RT timeliness and whether delays impact long-term outcomes.
breast cancer; radiotherapy; socioeconomic status; integrated delivery system
Randomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use and impact of these therapies on risk of recurrence among ductal carcinoma in situ patients diagnosed and treated in the community setting.
We identified 2,995 patients diagnosed with ductal carcinoma in situ between 1990 and 2001 and treated with breast-conserving surgery at three large health plans. Medical charts were reviewed to confirm diagnosis and treatment and to obtain information on subsequent breast cancers. On a subset of patients, slides from the index ductal carcinoma in situ were reviewed for histopathologic features. Cumulative incidence curves were generated and Cox regression was used to examine changes in five-year risk of recurrence across diagnosis years, with and without adjusting for trends in use of adjuvant therapies.
Use of radiotherapy increased from 25.8% in 1990-1991 to 61.3% in 2000-2001; tamoxifen increased from 2.3% to 34.4%. A total of 245 patients had a local recurrence within five years of their index ductal carcinoma in situ. The five-year risk of any local recurrence decreased from 14.3% (95% confidence interval 9.8 to 18.7) for patients diagnosed in 1990-1991 to 7.7% (95% confidence interval 5.5 to 9.9) for patients diagnosed in 1998-1999; invasive recurrence decreased from 7.0% (95% confidence interval 3.8 to 10.3) to 3.1% (95% confidence interval 1.7 to 4.6). In Cox models, the association between diagnosis year and risk of recurrence was modestly attenuated after accounting for use of adjuvant therapy. Between 1990-1991 and 2000-2001, the proportion of patients with tumors with high nuclear grade decreased from 46% to 32% (P = 0.03) and those with involved surgical margins dropped from 15% to 0% (P = 0.03).
The marked increase in the 1990s in the use of adjuvant therapy for ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting only partially explains the 50% decline in risk of recurrence. Changes in pathology factors have likely also contributed to this decline.
Annual surveillance mammography is recommended for follow-up of women with a history of breast cancer. We examined surveillance mammography among breast cancer survivors who were enrolled in integrated healthcare systems.
Women in this study were 65 or older when diagnosed with early stage invasive breast cancer (N = 1,762). We assessed mammography use during 4 years of follow-up, using generalized estimating equations to account for repeated measurements.
Eighty-two percent had mammograms during the first year after treatment; the percentage declined to 68.5% in the fourth year of follow-up. Controlling for age and comorbidity, women who were at higher risk of recurrence by being diagnosed at stage II or receiving breast-conserving surgery (BCS) without radiation therapy were less likely to have yearly mammograms (compared to stage I, odds ratio [OR] for stage IIA 0.72, confidence interval [CI] 0.59, 0.87, OR for stage IIB 0.75, CI 0.57, 1.0; compared to BCS with radiation, OR 0.58, CI 0.43, 0.77). Women with visits to a breast cancer surgeon or oncologist were more likely to receive mammograms (OR for breast cancer surgeon 6.0, CI 4.9, 7.4, OR for oncologist 7.4, CI 6.1, 9.0).
Breast cancer survivors who are at greater risk of recurrence are less likely to receive surveillance mammograms. Women without a visit to an oncologist or breast cancer surgeon during a year have particularly low rates of mammography. Improvements to surveillance care for breast cancer survivors may require active participation by primary care physicians and improvements in cancer survivorship programs by healthcare systems.
breast cancer; surveillance; mammography; survivors
Millions of women receive clinical breast examination (CBE) each year, as either a breast cancer screening test or a diagnostic test for breast symptoms. While screening CBE had moderately high specificity (∼94%) in clinical trials, community clinicians may be comparatively inexperienced and may conduct relatively brief examinations, resulting in even higher specificity but lower sensitivity.
To estimate the specificity of screening and diagnostic CBE in clinical practice and identify patient factors associated with specificity.
Retrospective cohort study.
Breast-cancer-free female health plan enrollees in 5 states (WA, OR, CA, MA, and MN) who received CBE (N = 1,484).
Medical charts were abstracted to ascertain breast cancer risk factors, examination purpose (screening vs diagnostic), and results (true-negative vs false-positive). Women were considered “average-risk” if they had neither a family history of breast cancer nor a prior breast biopsy and “increased-risk” otherwise.
Among average- and increased-risk women, respectively, the specificity (true-negative proportion) of screening CBE was 99.4% [95% confidence interval (CI): 98.8–99.7%] and 97.1% (95% CI: 95.7–98.0%), and the specificity of diagnostic CBE was 68.7% (95% CI: 59.7–76.5%) and 57.1% (95% CI: 51.1–63.0%). The odds of a true-negative screening CBE (specificity) were significantly lower among women at increased risk of breast cancer (adjusted odds ratio 0.21; 95% CI: 0.10–0.46).
Screening CBE likely has higher specificity among community clinicians compared to examiners in clinical trials of breast cancer screening, even among women at increased breast cancer risk. Highly specific examinations, however, may have relatively low sensitivity for breast cancer. Diagnostic CBE, meanwhile, is relatively nonspecific.
breast cancer; sensitivity and specificity; screening; physical examination
A substantial literature describes age-dependent variations in breast cancer treatment, showing that older women are less likely to receive standard treatment than are younger women. We sought to identify patient and tumor characteristics associated with the non-receipt of standard primary tumor and systemic adjuvant therapies.
We studied 1,859 women aged 65 years or older with stage I and II breast cancer diagnosed between 1990 and 1994 who were cared for in six geographically dispersed community-based health care systems. We collected demographic, tumor, treatment, and comorbidity data from electronic data sources, including cancer registry, administrative, and clinical databases, and from subjects’ medical records.
Women 75 years of age or older and those with higher comorbidy indices were more likely to receive non-standard primary tumor therapy; to not receive axillary lymph node dissection; and to not receive radiation therapy following breast conserving surgery. Asian women were less likely to receive breast conserving surgery and African American women were less likely to be prescribed tamoxifen. Although non-receipt of most therapies was associated with a lower baseline risk of recurrence, an important minority of high risk women (16–30%) did not received guideline therapies.
Age is an independent risk factor for non-receipt of effective cancer therapies, even when comorbidity and risk of recurrence are taken into account. Information regarding treatment effectiveness in this age group and tools that allow physicians and patients to estimate the benefits versus the risks of therapies, taking into account age and comorbidity burden, are critically needed.
breast cancer; older women; patterns of care