Arup K. Sinha

Role of Caffeine Intake on Erectile Dysfunction in US Men: Results from NHANES 2001-2004

Objectives Caffeine is consumed by more than 85% of adults and little is known about its role on erectile dysfunction (ED) in population-based studies. We investigated the association of caffeine intake and caffeinated beverages with ED, and whether these associations vary among comorbidities for ED. Material and Method Data were analyzed for 3724 men (≥20 years old) who participated in the National Health and Nutrition Examination Survey (NHANES). ED was assessed by a single question during a self-paced, computer-assisted self-interview. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable logistic regression analyses using appropriate sampling weights were conducted. Results We found that men in the 3rd (85-170 mg/day) and 4th (171-303 mg/day) quintiles of caffeine intake were less likely to report ED compared to men in the lowest 1st quintile (0-7 mg/day) [OR: 0.58; 95% CI, 0.37–0.89; and OR: 0.61; 95% CI, 0.38–0.97, respectively], but no evidence for a trend. Similarly, among overweight/obese and hypertensive men, there was an inverse association between higher quintiles of caffeine intake and ED compared to men in the lowest 1st quintile, P≤0.05 for each quintile. However, only among men without diabetes we found a similar inverse association (Ptrend = 0.01). Conclusion Caffeine intake reduced the odds of prevalent ED, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive, but not among diabetic men. Yet, these associations are warranted to be investigated in prospective studies.

Five-year all-cause mortality rates across five categories of substantiated elder abuse occurring in the community

ABSTRACT Elder abuse increases the likelihood of early mortality, but little is known regarding which types of abuse may be resulting in the greatest mortality risk. This study included N = 1,670 cases of substantiated elder abuse and estimated the 5-year all-cause mortality for five types of elder abuse (caregiver neglect, physical abuse, emotional abuse, financial exploitation, and polyvictimization). Statistically significant differences in 5-year mortality risks were found between abuse types and across gender. Caregiver neglect and financial exploitation had the lowest survival rates, underscoring the value of considering the long-term consequences associated with different forms of abuse. Likewise, mortality differences between genders and abuse types indicate the need to consider this interaction in elder abuse case investigations and responses. Further mortality studies are needed in this population to better understand these patterns and implications for public health and clinical management of community-dwelling elder abuse victims.

Mammographic breast density is associated with the development of contralateral breast cancer

Women with dense mammographic breast density (BD) have a 2‐fold increased risk of developing primary breast cancer (BC). The authors hypothesized that dense mammographic BD also is associated with an increased risk of developing contralateral breast cancer (CBC).

Location of receipt of initial treatment and outcomes in long-term breast cancer survivors

Purpose Cancer outcomes differ depending on where treatment is received. We assessed differences in outcomes in long-term breast cancer survivors at a specialty care hospital by location of their initial treatment. Methods We retrospectively examined a cohort of women diagnosed with invasive early-stage breast cancer who did not experience recurrence for at least 5 years after the date of diagnosis and were evaluated at The University of Texas MD Anderson Cancer Center between January 1997 and August 2008. The location of initial treatment was categorized as MD Anderson (MDA-treated) or other (OTH-treated). Outcomes analyzed included recurrence-free survival (RFS), distant relapse-free survival (DRFS), and overall survival (OS). The Kaplan-Meier product-limit method was used to compare outcomes between the two groups. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results We identified 5,091 breast cancer survivors (median follow-up 8.6 years), of whom 89.1% were MDA-treated. The 10-year OS, RFS, and DRFS rates were 90.9%, 88.4%, and 89.0% in the MDA-treated group and 74.3%, 49.8%, and 52.7% in the OTH-treated group, respectively. We observed worse outcomes in the OTH-group in both the univariate analysis and the multivariable analysis (OS: HR = 4.8, 95% CI = 3.9–6.0; RFS: HR = 5.8, 95% CI = 4.8–7.0; DRFS: HR = 5.4, 95% CI = 4.5–6.6). Conclusion Long-term breast cancer survivors who initiated their treatment at MD Anderson had better outcomes. Location of initial treatment could be an independent risk factor for survival outcomes at specialty care hospitals. This analysis has limitations inherent to retrospective observational studies such as other unmeasured variables may be associated with worse prognosis.

Medication Regimen Complexity and Low Adherence in Older Community-Dwelling Adults With Substantiated Self-Neglect:

Objective: Determine whether medication regimen complexity predicts medication adherence levels in a sample of community-dwelling adults 65 years and older with Adult Protective Services–substantiated self-neglect. Methods: A cross-sectional analysis of baseline data (N = 31 participants) from a pilot intervention to increase medication adherence among the target group was performed. The Medication Regimen Complexity Index (MRCI) and the 8-item Morisky Medication Adherence Scale (MMAS-8)™ were the primary independent and dependent measures, respectively. A multivariable linear regression analysis, adjusting for potential confounders, was conducted to estimate the association between complexity and adherence. Results: Regimen complexity was high (mean MRCI = 19.6) and adherence was low (mean MMAS = 5.1). Even after controlling for confounders, increased complexity was significantly associated with lower adherence. Discussion: Older community-dwelling adults who self-neglect have complex medication regimens that contribute to low medication adherence. Medication regimen complexity may be a modifiable contributor to low adherence that can be targeted by future interventions to reduce self-neglect and its consequences.

Determinants of Weight Gain During Adjuvant Endocrine Therapy and Association of Such Weight Gain With Recurrence in Long-term Breast Cancer Survivors

Micro‐Abstract We conducted a retrospective study of breast cancer survivors to determine the risk factors for weight gain during endocrine therapy and the association of such weight gain with recurrence. Background: Weight gain is a negative prognostic factor in breast cancer (BC) patients. The risk factors for weight gain during adjuvant endocrine therapy (ET) and the extent to which such weight gain is associated with disease recurrence remain unclear. Patients and Methods: We retrospectively identified a cohort of women with a diagnosis of stage I‐III, hormone receptor–positive, human epidermal growth factor receptor 2‐negative BC from January 1997 to August 2008, who had received initial treatment at the MD Anderson Cancer Center, had completed 5 years of ET, and had remained free of locoregional or distant relapse or contralateral BC for ≥ 5 years after diagnosis. The weight change at the end of 5 years of ET was measured as the percentage of the change in weight from the start of ET, with a weight gain of > 5% considered clinically significant. Multivariable logistic regression and Cox proportional hazards models were used to assess the determinants of such weight gain and the risk of recurrence after 5 years. Results: Of 1282 long‐term BC survivors, 432 (33.7%) had a weight gain of > 5% after 5 years of ET. Women who were premenopausal at diagnosis were 1.40 times more likely than women who were postmenopausal at diagnosis to have a weight gain of > 5%. Asian women had the lowest risk of gaining weight. The recurrence risks of patients who had gained weight and those who had not were not significantly different. Conclusion: Premenopausal BC patients had an increased risk of weight gain after 5 years of ET; however, BC patients with a weight gain of > 5% did not have an increased risk of disease recurrence.

Long-term survival outcomes of triple-receptor negative breast cancer survivors who are disease free at 5 years and relationship with low hormone receptor positivity

Background:We counsel our triple-negative breast cancer (TNBC) patients that the risk of recurrence is highest in the first 5 years after diagnosis. However, there are limited data with extended follow-up on the frequency, characteristics, and predictors of late events.Methods:We queried the MD Anderson Breast Cancer Management System database to identify patients with stage I–III TNBC who were disease free at 5 years from diagnosis. The Kaplan–Meier method was used to estimate yearly recurrence-free interval (RFI), recurrence-free survival (RFS), and distant relapse-free survival (DRFS), as defined by the STEEP criteria. Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs).Results:We identified 873 patients who were disease free at least 5 years from diagnosis with median follow-up of 8.3 years. The 10-year RFI was 97%, RFS 91%, and DRFS 92%; the 15-year RFI was 95%, RFS 83%, and DRFS 84%. On a subset of patients with oestrogen receptor and progesterone receptor percentage recorded, low hormone receptor positivity conferred higher risk of late events on multivariable analysis for RFS only (RFI: HR=1.98, 95% CI=0.70–5.62, P-value=0.200; RFS: HR=1.94, 95% CI=1.05–3.56, P-value=0.034; DRFS: HR=1.72, 95% CI=0.92–3.24, P-value=0.091).Conclusions:The TNBC survivors who have been disease free for 5 years have a low probability of experiencing recurrence over the subsequent 10 years. Patients with low hormone receptor-positive cancers may have a higher risk of late events as measured by RFS but not by RFI or DRFS.

Association between tumor stage of first non-metastatic breast cancer and second contralateral breast cancer.

260 Background: Female breast cancer survivors have an average lifetime risk of 4-8% to develop a contralateral breast cancer (CBC).It is unclear if the tumor stage of the first breast cancer is associated with the development of a second CBC. METHODS We performed a retrospective analysis of women who had a presenting diagnosis of non-metastatic breast cancer treated at MD Anderson Cancer Center between January 1997 and December 2013. Demographic, clinical, pathologic and treatment information were obtained from an institutional database. We excluded male patients, those treated outside MD Anderson, patients who underwent bilateral mastectomy, and those with unknown tumor characteristics. The primary endpoint was the development of CBC. The time to CBC was measured from the date of diagnosis of the first breast cancer. Patients who did not develop CBC were censored at death, or if alive, at the most recent follow-up visit. Index tumor stages were categorized as 0, I, II and III. RESULTS We analyzed 8,770 patients (median follow-up of 5.4 years), among whom 259 (3.0%) developed a CBC. The median follow-up time for stages 0-III was 4.9, 7.2, 5.2 and 3.9 years, respectively. The proportion of patients who developed a CBC by the stage of the index breast cancer was: stage 0: 0/403 (0.0%); stage I: 115/2,143 (5.4%); stage II: 110/4,220 (2.6%); stage III: 34/2,004 (1.7%). The overall median [quartile (Q) 1, Q3] time to the development of CBC was 3.2 (1.2, 6.3) years (stage 0: 0 (0.0, 0.0); stage I: 3.0 (1.2, 6.3); stage II: 4.4 (1.3, 6.9); stage III: 1.6 (0.8, 5.1) years). CONCLUSIONS Patients with stage 0 breast cancer appear to have lower risk of developing a second CBC compared to women presenting with invasive disease. A more detailed analysis of this observation, including incorporation of hormone receptor status and receipt of endocrine therapy, is warranted to determine whether this observation suggests differing biologic risks or treatment/selection bias.

Abstract P4-10-09: Relapse-free survival of triple negative breast cancer long term survivors and characterization of late events in MD Anderson experience

Background: Stage I-III TNBC patients have a high risk of disease relapse during the first 5 years after diagnosis. However, there is limited data on the risk of late relapse in TNBC survivors who are disease free at 5 years or more from diagnosis. We sought to characterize this risk in a cohort of TNBC long-term survivors from a large institutional database. Methods: The MD Anderson Breast Cancer Management System database was queried for TNBC survivors who were disease free 5 years or more from diagnosis. Demographic, tumor, and treatment data was extracted. Electronic medical records were searched to confirm pathology reports for invasive breast cancer diagnosis, triple negative receptor status, and hormone receptor percentage (%). The primary and secondary outcomes of interest were relapse free survival (RFS) and distant relapse free survival (DRFS). Patients were censored at time of developing a second primary breast cancer or at last follow-up time for those who were alive during the study. We used ACP-ASCO definition of ER and PR Results: We identified 1038 patients who had a median follow-up of 8.0 years. Receptor % information was available on 69% of patients, with 78% of them meeting current TNBC definition. From the total cohort of 130, 12.5% suffered event(s) that occurred after 5 years from diagnosis, with 86.2% of them occurring within 5-10 years of diagnosis. The event rate was 16.4% among patients with ER/PR 1-9% versus 11.3% among patients with ER/PR Conclusions: TNBC long term survivors are still at risk for relapse events after 5 years from diagnosis, and it is important to quantity this risk when counseling our patients. Frequency of late events was higher among patients with low hormone receptor positivity. Multivariate modeling of predictors of late recurrence is ongoing. Citation Format: Reddy SM, Sinha A, Syed M, Barcenas C, Valero V. Relapse-free survival of triple negative breast cancer long term survivors and characterization of late events in MD Anderson experience. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-10-09.

Comparison of the global statistical test and composite outcome for secondary analyses of multiple coronary heart disease outcomes.

Multiple outcomes (or multiple endpoints), such as mortality and recurrent myocardial infarction, are increasingly common in clinical trials and are often of interest in secondary analyses. Traditionally, a clinical trial protocol is built around a single event as its primary outcome, with several secondary outcomes specified, the analyses for which lack the same level of power. To accommodate all the relevant outcomes and to increase the power of the comparison in trials evaluating the efficacy of treatments for coronary heart disease, investigators often chose to construct a composite outcome. The more conventional composite outcome fails to account for the relative importance and the relationship (correlation) among its components. The purpose of this work is to demonstrate the usefulness of the Global Statistical Test, which considers the correlation between multiple outcomes, as an alternative strategy for these situations and to demonstrate its effect on hypothesis testing and power analysis issues in comparison with the traditional composite outcome analysis. Data from the cardiovascular clinical trial Systolic Hypertension in the Elderly Population are used as an example.