Objective

To assess the association between diabetes mellitus (DM) and the incidence and disease-specific mortality of endometrial cancer (EC).

Methods

MEDLINE, EMBASE and conference abstracts of the 2011-2013 Annual Meetings of Society of Gynecological Oncology were searched for reports of original cohort studies that enrolled diabetic and non-diabetic women who were free of EC at baseline to compare the incidence and disease-specific mortality of EC by DM status. The included reports were examined for demographic characteristics of study populations, study design, effect measures and risk of bias. Statistical heterogeneity was evaluated with Chi-square test of the Cochrane Q statistics at the 0.05 significance level and I(2) statistic. Publication bias was assessed by visual examination of a funnel plot and the Egger's test for small-study effects.

Results

Twenty-nine cohort studies (17 prospective, 12 retrospective) were eligible for this review, 23 of which reported EC incidence, five reported disease-specific mortality and one reported both. For incidence of EC among women with versus without DM, the summary relative risk (RR) was 1.89 (95%CI, 1.46-2.45; p<0.001) and the summary incidence rate ratio was 1.61 (95%CI, 1.51-1.71; p<0.001). The pooled RR of disease-specific mortality was 1.32 (95%CI, 1.10-1.60; p=0.003), while results in the studies reporting standardized mortality ratios were inconsistent. There remains considerable amount of clinical and methodological heterogeneity among the included studies; moreover, the hazard ratios for incident EC showed significant statistical heterogeneity and therefore were not quantitatively synthesized.

Conclusions

There is consistent evidence for an independent association between DM and an increased risk of incident EC, while the association between DM and EC-specific mortality remains uncertain. Further studies with better considerations for selection bias, information bias and confounding will further facilitate causal inference involving DM and EC.

BACKGROUND: Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited. METHODS: A total of 2050 older adults (≥60 years old) surviving for at least 1 year after a cancer diagnosis and 9474 older adults without a cancer history from the National Health and Nutrition Examination Survey (1999-2014) were included for analysis. The exposure variable, a 45-item frailty index (FI), was categorized on the basis of validated cutoffs (FI ≤ 0.10 [fit], 0.10 < FI ≤ 0.21 [prefrail], and FI > 0.21 [frail]). All-cause mortality was ascertained via the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for the FI, and this was followed by restricted cubic splines depicting dose-response curves. RESULTS: For older cancer survivors, the mean age at the baseline was 72.6 years (SD, 7.1 years); 5.9% were fit, 38.2% were prefrail, and 55.9% were frail. Older adults without a cancer history were slightly younger (mean age, 70.0 years) and less frail (47.9% were frail). At each level of the FI, cancer survivors (1.9 per 100 person-years for FI ≤ 0.10, 3.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 7.5 per 100 person-years for FI > 0.21) had higher mortality than their cancer-free counterparts (1.4 per 100 person-years for FI ≤ 0.10, 2.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 5.4 per 100 person-years for FI > 0.21). The multivariable model suggested a positive association between the FI and all-cause mortality for survivors (aHR for FI > 0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73-4.53) and participants without a cancer history (aHR for FI > 0.21 vs FI ≤ 0.10, 2.75; 95% CI, 2.29-3.32). Restricted cubic splines indicated that all-cause mortality risk increased with the FI in a monotonic pattern. CONCLUSIONS: Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history.

Background

Previous reports suggested risk of death and breast cancer varied by comorbidity and age in older women undergoing mammography. However, impacts of functional limitations remain unclear.

Methods

We used data from 238,849 women in the Breast Cancer Surveillance Consortium-Medicare linked database (1999-2015) who had screening mammogram at ages 66-94 years. We estimated risk of breast cancer, breast cancer death, and non-breast cancer death by function-related indicator (FRI) which incorporated 16 claims-based items and was categorized as an ordinal variable (0, 1, and 2+). Fine and Gray proportional sub-distribution hazards models were applied with breast cancer and death treated as competing events. Risk estimates by FRI scores were adjusted by age and NCI comorbidity index separately and stratified by these factors.

Results

Overall, 9,252 women were diagnosed with breast cancer, 406 died of breast cancer, and 41,640 died from non-breast cancer causes. The 10-year age-adjusted invasive breast cancer risk slightly decreased with FRI score [FRI = 0: 4.0%, 95% confidence interval (CI) = 3.8-4.1; FRI = 1: 3.9%, 95% CI = 3.7-4.2; FRI ≥ 2: 3.5%, 95% CI = 3.1-3.9). Risk of non-breast cancer death increased with FRI score (FRI = 0: 18.8%, 95% CI = 18.5-19.1; FRI = 1: 24.4%, 95% CI = 23.9-25.0; FRI ≥ 2: 39.8%, 95% CI = 38.8-40.9]. Risk of breast cancer death was low with minimal differences across FRI scores. NCI comorbidity index-adjusted models and stratified analyses yielded similar patterns.

Conclusions

Risk of non-breast cancer death substantially increases with FRI score, whereas risk of breast cancer death is low regardless of functional status.

Impact

Older women with functional limitations should be informed that they may not benefit from screening mammography.

Background

The cost-effectiveness of screening mammography beyond age 75 years remains unclear.

Objective

To estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden.

Design

Markov microsimulation model.

Data sources

SEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium.

Target population

U.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS).

Time horizon

Lifetime.

Perspective

National health payer.

Intervention

Screening mammography to age 75, 80, 85, or 90 years.

Outcome measures

Breast cancer death, survival, and costs.

Results of base-case analysis

Extending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer.

Results of sensitivity analysis

Costs per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography.

Limitation

No randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs.

Conclusion

Although annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer.

Primary funding source

National Cancer Institute and National Institutes of Health.

Introduction

Limited evidence exists on the impact of age and comorbidity on biopsy rates and findings among older women.

Materials and methods

We used data from 170,657 women ages 66-94 enrolled in the United States Breast Cancer Surveillance Consortium (BCSC). We estimated one-year rates of biopsy by type (any, fine-needle aspiration (FNA), core or surgical) and yield of the most invasive biopsy finding (benign, ductal carcinoma in situ (DCIS) and invasive breast cancer) by age and comorbidity. Statistical significance was assessed using Wald statistics comparing coefficients estimated from logistic regression models adjusted for age, comorbidity, BCSC registry, and interaction between age and comorbidity.

Results

Of 524,860 screening mammograms, 9830 biopsies were performed following 7930 exams (1.5%) within one year, specifically 5589 core biopsies (1.1%), 3422 (0.7%) surgical biopsies and 819 FNAs (0.2%). Biopsy rates per 1000 screens decreased with age (66-74:15.7, 95%CI:14.8-16.8), 75-84:14.5(13.5-15.6), 85-94:13.2(11.3,15.4), p_trend < 0.001) and increased with Charlson Comorbidity Score (CCS = 0:14.4 (13.5-15.3), CCS = 1:16.6 (15.2-18.1), CCS ≥2:19.0 (16.9-21.5), p_trend < 0.001).Biopsy rates increased with CCS at ages 66-74 and 75-84 but not 85-94. Core and surgical biopsy rates increased with CCS at ages 66-74 only. For each biopsy type, the yield of invasive breast cancer increased with age irrespective of comorbidity.

Discussion

Women aged 66-84 with significant comorbidity in a breast cancer screening population had higher breast biopsy rates and similar rates of invasive breast cancer diagnosis than their counterparts with lower comorbidity. A considerable proportion of these diagnoses may represent overdiagnoses, given the high competing risk of death from non-breast-cancer causes among older women.

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations.