Rebecca A. Silliman

Adjuvant Tamoxifen: Predictors of Use, Side Effects, and Discontinuation in Older Women

PURPOSE To identify predictors of adjuvant tamoxifen use, side effects, and discontinuation in older women. PATIENTS AND METHODS We followed a cohort of 303 women > or = 55 years of age diagnosed with stage I or stage II breast cancer for nearly 3 years. Data were collected from womens surgical records and from computer-assisted telephone interviews at 5, 21, and 33 months after primary tumor therapy. RESULTS Two hundred ninety-two (96%) of 303 patients in the study provided information about tamoxifen use. Tamoxifen use was reported by 189 patients (65%); 26 (15%) discontinued use during the follow-up period. Patients who were 65 to 74 years of age (relative to those 55 to 64 years of age), had stage II disease, were estrogen receptor-positive, saw a greater number of breast cancer physicians, and had better perceptions of their abilities to discuss treatment options with physicians had greater odds of tamoxifen use. Those who had better physical function, had received standard primary tumor therapy, and had obtained helpful breast cancer information from books or magazines had lesser odds of tamoxifen use. Patients > or = 75 years of age (relative to those 55 to 64 years of age) and patients with better emotional health had significantly lesser odds of reporting side effects. Patients who were estrogen receptor-positive were less likely to stop taking tamoxifen; patients who experienced side effects were more likely to stop taking tamoxifen. CONCLUSION Deviations from a prescribed course of adjuvant tamoxifen occur relatively frequently. The clinical consequences of this deviation need to be identified.

Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer

PURPOSE Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) -positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. PATIENTS AND METHODS Within six health care delivery systems, we identified women >or= 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. RESULTS Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). CONCLUSION Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

Breast Cancer Among the Oldest Old: Tumor Characteristics, Treatment Choices, and Survival

PURPOSE Few data are available on breast cancer characteristics, treatment, and survival for women age 80 years or older. PATIENTS AND METHODS We used the linked Surveillance, Epidemiology and End Results-Medicare data set from 1992 to 2003 to examine tumor characteristics, treatments (mastectomy, breast-conserving surgery [BCS] with radiation therapy or alone, or no surgery), and outcomes of women age 80 years or older (80 to 84, 85 to 89, > or = 90 years) with stage I/II breast cancer compared with younger women (age 67 to 79 years). We used Cox proportional hazard models to examine the impact of age on breast cancer-related and other causes of death. Analyses were performed within stage, adjusted for tumor and sociodemographic characteristics, treatments received, and comorbidities. Results In total, 49,616 women age 67 years or older with stage I/II disease were included. Tumor characteristics (grade, hormone receptivity) were similar across age groups. Treatment with BCS alone increased with age, especially after age 80. The risk of dying from breast cancer increased with age, significantly after age 80. For stage I disease, the adjusted hazard ratio of dying from breast cancer for women age > or = 90 years compared with women age 67 to 69 years was 2.6 (range, 2.0 to 3.4). Types of treatments received were significantly associated with age and comorbidity, with age as the stronger predictor (26% of women age > or = 80 years without comorbidity received BCS alone or no surgery compared with 6% of women age 67 to 79 years). CONCLUSION Women age > or = 80 years have breast cancer characteristics similar to those of younger women yet receive less aggressive treatment and experience higher mortality from early-stage breast cancer. Future studies should focus on identifying tumor and patient characteristics to help target treatments to the oldest women most likely to benefit.

Breast Cancer in Older Women: Quality of Life and Psychosocial Adjustment in the 15 Months After Diagnosis

PURPOSE We examined the health-related quality of life (QOL) of a cohort of older women with breast cancer after their diagnosis. PATIENTS AND METHODS Six hundred ninety-one women aged 65 years and older were interviewed approximately 3 months after breast cancer surgery and two additional times in the following year using standardized QOL measures. Demographic factors, breast cancer treatments, and comorbid conditions were used to model ratings of health-related QOL over time. Self-perceived health and psychosocial adjustment at 15 months after surgery were modeled. RESULTS Physical and mental health scores declined significantly in the follow-up year, independent of age. However, a cancer-specific psychosocial instrument showed significant improvement in scores. Better 3-month physical and mental health scores, as well as better emotional social support, predicted more favorable self-perceived health 15 months after surgery. Psychosocial adjustment at 15 months was significantly predicted by better mental health, emotional social support, and better self-rated interaction with health care providers assessed at 3 months. CONCLUSION Contrary to reports from younger women with breast cancer, we observed significant declines in the physical and mental health of older women in the 15 months after breast cancer surgery, whereas scores on a cancer-specific psychosocial QOL measure improved over time, consistent with patterns in younger women. Predictive models indicate that older women with impaired physical functioning, mental health, and emotional social support after surgery have poorer self-perceived health and psychosocial adjustment 1 year later. Interventions to address the physical and emotional needs of older women with breast cancer should be developed and evaluated to determine their impact on subsequent health-related QOL.

Sexuality after treatment for early prostate cancer: exploring the meanings of "erectile dysfunction".

AbstractOBJECTIVE: To explore perceptions of the impact of erectile dysfunction on men who had undergone definitive treatment for early nonmetastatic prostate cancer. DESIGN: Seven focus groups of men with early prostate cancer. The groups were semistructured to explore men’s experiences and quality-of-life concerns associated with prostate cancer and its treatment. SETTING: A staff model health maintenance organization, and a Veterans Affairs medical center. PATIENTS: Forty-eight men who had been treated for early prostate cancer 12 to 24 months previously. RESULTS: Men confirmed the substantial effect of sexual dysfunction on the quality of their lives. Four domains of quality of life related to men’s sexuality were identified: 1) the qualities of sexual intimacy; 2) everyday interactions with women; 3) sexual imagining and fantasy life; and 4) men’s perceptions of their masculinity. Erectile problems were found to affect men in both their intimate and nonintimate lives, including how they saw themselves as sexual beings. CONCLUSIONS: Erectile dysfunction, the most common side effect of treatment for early prostate cancer, has far-reaching effects upon men’s lives. Assessment of quality of life related to sexual dysfunction should address these broad impacts of erectile function on men’s lives. Physicians should consider these effects when advising men regarding treatment options. Physicians caring for patients who have undergone treatment should address these psychosocial issues when counseling men with erectile dysfunction.

A most stubborn bias: No adjustment method fully resolves confounding by indication in observational studies

OBJECTIVE To evaluate the effectiveness of methods that control for confounding by indication, we compared breast cancer recurrence rates among women receiving adjuvant chemotherapy with 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 between 1990 and 1994, our crude analysis suggested that 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 (PSs), and instrumental variable (IV) methods. RESULTS 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. CONCLUSION 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.

Statin Prescriptions and Breast Cancer Recurrence Risk: A Danish Nationwide Prospective Cohort Study

BACKGROUND Accumulating evidence suggests that statins affect diseases other than cardiovascular disease, including cancer, and that these effects may depend on the lipid solubility of specific statins. Though many studies have reported an association between statin use and breast cancer incidence, the relationship between statin use and breast cancer recurrence has not been well studied. METHODS We conducted a nationwide, population-based prospective cohort study of all female residents in Denmark diagnosed with stage I-III invasive breast carcinoma who were reported to the Danish Breast Cancer Cooperative Group registry between 1996 and 2003 (n = 18,769). Women were followed for a median of 6.8 years after diagnosis. Prescriptions for lipophilic and hydrophilic statins were ascertained from the national electronic pharmacy database. Associations between statin prescriptions and breast cancer recurrence were estimated with generalized linear models and Cox proportional hazards regression with adjustment for age and menopausal status at diagnosis; histological grade; estrogen receptor status; receipt of adjuvant therapy; type of primary surgery received; pre-diagnosis hormone replacement therapy; and co-prescriptions of aspirin, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, or anticoagulants. All statistical tests were two-sided. RESULTS Most prescriptions for lipophilic statins in the study population were for simvastatin. Exclusive simvastatin users experienced approximately 10 fewer breast cancer recurrences per 100 women after 10 years of follow-up (adjusted 10-year risk difference = -0.10, 95% confidence interval = -0.11 to -0.08), compared with women who were not prescribed a statin. Exclusive hydrophilic statin users had approximately the same risk of breast cancer recurrence as women not prescribed a statin over follow-up (adjusted 10-year risk difference = 0.05, 95% confidence interval = -0.01 to 0.11). CONCLUSIONS Simvastatin, a highly lipophilic statin, was associated with a reduced risk of breast cancer recurrence among Danish women diagnosed with stage I-III breast carcinoma, whereas no association between hydrophilic statin use and breast cancer recurrence was observed.

Blood pressure and survival in the oldest old.

OBJECTIVES: To determine the relationship between blood pressure (BP) and all‐cause mortality in subjects aged 80 and older with hypertension.

Health behavior changes after genetic risk assessment for Alzheimer disease: The REVEAL study

Risk information for Alzheimer disease (AD) may be communicated through susceptibility gene disclosure, even though this is not currently in clinical use. The REVEAL Study is the first randomized clinical trial of risk assessment for AD with apolipoprotein E (APOE) genotype and numerical risk estimate disclosure. We examined whether APOE genotype and numerical risk disclosure to asymptomatic individuals at high risk for AD alters health behaviors. One hundred sixty-two participants were randomized to either intervention (APOE disclosure) or control (no genotype disclosure) groups. Subjects in both groups received numerical lifetime risk estimates of future AD development based on sex and family history of AD. The intervention group received their APOE genotype. Subjects were informed that no proven preventive measures for AD existed and given an information sheet on preventative therapies under investigation. Participants who learned they were ϵ4 positive were significantly more likely than ϵ4 negative participants to report AD-specific health behavior change 1 year after disclosure (adjusted odds ratio: 2.73; 95% confidence interval: 1.14, 6.54; P=0.02). Post hoc analyses revealed similar significant associations between numerical lifetime risk estimates and self-report of AD-specific health behavior change. Despite lack of preventive measures for AD, knowledge of APOE genotype, numerical lifetime risk, or both, influences health behavior.

Measuring patients' perceptions of the outcomes of treatment for early prostate cancer.

Background. Compared with careful attention to the physical (eg, urinary, bowel, sexual) dysfunction that may follow treatment, little attention has been given to the behavioral, emotional, and interpersonal changes that the diagnosis of early prostate cancer and subsequent physical dysfunction may bring. Objective. To construct patient‐centered measures of the outcomes of treatment for early prostate cancer. Research Design. Qualitative study followed by survey of early prostate cancer patients and group of comparable patients with no history of prostate cancer. Analysis of focus groups identified relevant domains of quality of life, which were represented by Likert scale items included in survey questionnaires. Psychometric analyses of survey data defined scales evaluated with respect to internal consistency and validity. Results. Qualitative analysis identified three domains: urinary control, sexuality, and uncertainty about the cancer and its treatment. Psychometric analysis defined 11 scales. Seven were generically relevant to most older men: urinary control (eg, embarrassment with leakage), sexual intimacy (eg, anxiety about completing intercourse), sexual confidence (eg, comfort with sexuality), marital affection (eg, emotional distance from spouse/partner), masculine self esteem (eg, feeling oneself a whole man), health worry (eg, apprehensiveness about health changes), and PSA concern (eg, closely attending to ones PSA). Four scales were specific to the treatment experience: perceived cancer control, quality of treatment decision making, regret of treatment choice, and cancer‐related outlook. Conclusion. The scales provide definition and metrics for patient‐centered research in this area. They complement measures of physical dysfunction and bring into resolution outcomes of treatment that have gone unnoticed in previous studies.